ORCID Profile
0000-0003-2064-7699
Current Organisations
UNSW Sydney
,
George Institute for Global Health
,
Imperial College London
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Publisher: Public Library of Science (PLoS)
Date: 19-10-2004
Publisher: BMJ
Date: 03-2002
DOI: 10.1136/IP.8.1.66
Abstract: Cohort studies have contributed important scientific knowledge regarding the determinants of chronic diseases. Despite the need for etiologic investigations, this design has been infrequently used in injury prevention research. To describe the baseline findings of the New Zealand Blood Donors' Health Study, a large prospective study designed to investigate relationships between lifestyle, psychosocial factors, and serious injury due to road crashes, falls, self harm, assault, work, sport, and recreation. Participants were recruited from fixed and mobile collection sites of a voluntary non-profit blood donor program. Baseline exposure data (for ex le risk taking behaviors, alcohol and marijuana use, sleep habits, and depression) were collected using a self administered questionnaire. Outcome data regarding serious injury will be collected prospectively through computerized record linkage of participants' unique identifiers to national morbidity and mortality databases. In total, 22 389 participants enrolled in the study (81% response rate). The erse study population included 36% aged 16-24 years, 20% rural residents, and large variability in exposures of interest. For ex le, in the 12 months before recruitment, 21% had driven a motor vehicle when they considered themselves over the legal limit for alcohol, and 11% had been convicted of traffic violations (excluding parking infringements). Twelve per cent had seriously considered attempting suicide sometime in their life. This is the first, large scale cohort study investigating determinants of serious injury in New Zealand and among the largest worldwide. Preliminary findings from prospective analyses that can inform injury prevention policy are expected within five years.
Publisher: American Diabetes Association
Date: 03-08-2009
DOI: 10.2337/DC09-0959
Abstract: To assess the magnitude and independence of the effects of routine blood pressure lowering and intensive glucose control on clinical outcomes in patients with long-standing type 2 diabetes. This was a multicenter, factorial randomized trial of perindopril-indapamide versus placebo (double-blind comparison) and intensive glucose control with a gliclazide MR–based regimen (target A1C ≤6.5%) versus standard glucose control (open comparison) in 11,140 participants with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. Annual event rates and risks of major macrovascular and microvascular events considered jointly and separately, renal events, and death during an average 4.3 years of follow-up were assessed, using Cox proportional hazards models. There was no interaction between the effects of routine blood pressure lowering and intensive glucose control for any of the prespecified clinical outcomes (all P & 0.1): the separate effects of the two interventions for the renal outcomes and death appeared to be additive on the log scale. Compared with neither intervention, combination treatment reduced the risk of new or worsening nephropathy by 33% (95% CI 12–50%, P = 0.005), new onset of macroalbuminuria by 54% (35–68%, P & 0.0001), and new onset of microalbuminuria by 26% (17–34%). Combination treatment was associated with an 18% reduction in the risk of all-cause death (1–32%, P = 0.04). The effects of routine blood pressure lowering and intensive glucose control were independent of one another. When combined, they produced additional reductions in clinically relevant outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2008
Publisher: Elsevier BV
Date: 12-2007
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2004
DOI: 10.1161/01.STR.0000106480.76217.6F
Abstract: Background and Purpose— The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) showed that blood pressure lowering reduced stroke risk in patients with a history of cerebrovascular events. Here, we report the consistency of treatment effects across different stroke subtypes and among major clinical subgroups. Methods— PROGRESS was a randomized, double-blind trial among 6105 people with a prior history of cerebrovascular events. Participants were assigned to active treatment (perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). Results— During a mean of 3.9 years of follow-up, active treatment reduced the absolute rates of ischemic stroke from 10% to 8% (relative risk reduction [RRR], 24% 95% confidence interval [CI], 10 to 35) and the absolute rates of intracerebral hemorrhage from 2% to 1% (RRR, 50% 95% CI, 26 to 67). The relative risk of any stroke during follow-up was reduced by 26% (95% CI, 12 to 38) among patients whose baseline cerebrovascular event was an ischemic stroke and by 49% (95% CI, 18 to 68) among those whose baseline event was an intracerebral hemorrhage. There was no evidence that treatment effects were modified by other drug therapies (antiplatelet or other antihypertensive agents), residual neurological signs, atrial fibrillation, or the time since the last cerebrovascular event. Conclusions— Beneficial effects of a perindopril-based treatment regimen were observed for all stroke types and all major clinical subgroups studied. These data suggest that effective blood pressure–lowering therapy should be routinely considered for all patients with a history of cerebrovascular events.
Publisher: Oxford University Press (OUP)
Date: 24-05-2005
DOI: 10.1093/IJE/DYI104
Abstract: Although smoking is a major risk factor for cardiovascular disease, it has been suggested that Asians may be less susceptible to the adverse effects of smoking than Caucasians. This may have contributed to the high prevalence of smoking, and the low quitting rates, in Asian men. Worldwide, smoking rates are increasing for women, amongst whom cardiovascular awareness is relatively poor. An in idual participant data analysis of 40 cohort studies was carried out, involving 463 674 Asians (33% female) and 98 664 Australasians (45% female). Cox proportional hazard models, stratified by study and sex where appropriate, were employed. The HR [95% confidence interval (CI)], comparing current smokers with non-smokers, for coronary heart disease (CHD) was 1.60 (1.49-1.72) haemorrhagic stroke 1.19 (1.06-1.33) ischaemic stroke 1.38 (1.24-1.54). There was a clear dose-response relationship between the number of cigarettes smoked per day and both CHD and stroke, with no significant difference (P >/= 0.20) between populations from Asia and Australia/New Zealand. Although there was no sex difference for stroke in the effect of amount smoked (P = 0.16), for CHD, women tended to have higher hazard ratios than men (P = 0.011). Quitting gave a clear benefit, which was not significantly different between the sexes or regions (P > 0.63). The HR (CI) for ex-smokers compared with current smokers was 0.71 (0.64-0.78) for CHD and 0.84 (0.76-0.92) for stroke. Unless urgent public health measures are put into place, the impact of the smoking epidemic in Asia, and among women, will be enormous. Tobacco control policies that specifically target these populations are essential.
Publisher: Public Library of Science (PLoS)
Date: 19-01-2012
Publisher: Springer Science and Business Media LLC
Date: 03-05-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-02-2008
DOI: 10.1212/01.WNL.0000308819.43401.87
Abstract: The apolipoprotein E (APOE) polymorphism is an established risk factor for intracerebral hemorrhage (ICH) that is related to cerebral amyloid angiopathy in the white population. Among Asian populations, although ICH represents up to one third of all strokes and has high rates of mortality and morbidity, the role of the APOE polymorphism has not been well studied. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, double-blind, placebo-controlled trial of a blood pressure lowering regimen in subjects with prior cerebrovascular disease. APOE status was determined for 5,671 patients, including 2,148 Asians (38%). During the 3.9 years of follow-up, ICH occurred in 99 patients. Overall, carrying an epsilon 2 or epsilon 4 allele of the APOE polymorphism was associated with an adjusted hazard ratio (HR(a)) of 1.85 (95% CI = 1.24 to 2.76). In Asian patients the risk of ICH for epsilon 2 or epsilon 4 carriers was 2.11 (95% CI = 1.28 to 3.47) and 1.48 (95% CI = 0.76 to 2.87) in Europeans. Carriers of the epsilon 2 or epsilon 4 allele had an increased risk of both incident and recurrent ICH, and both cortical and deep ICH, and most risk estimates were higher in Asians than in Europeans. For both ethnic groups and for subtypes of ICH active treatment more than halved the risk of ICH and the treatment effects were not different in carriers of the epsilon 2 or epsilon 4 allele and in those with the epsilon 3 epsilon 3 genotype. There is a strong association between APOE genotype and the risk of intracerebral hemorrhage (ICH). In Asian patients the role of APOE polymorphisms in ICH is much broader than was previously supposed.
Publisher: American Diabetes Association
Date: 25-05-2021
DOI: 10.2337/DC20-2664
Abstract: To develop a frailty index (FI) and explore the relationship of frailty to subsequent adverse outcomes on the effectiveness and safety of more intensive control of both blood glucose and blood pressure (BP), among participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Cox proportional hazard models were used to estimate the effectiveness and safety of intensive glucose control and BP intervention according to frailty (defined as FI & .21) status. The primary outcomes were macro- and microvascular events. The secondary outcomes were all-cause mortality, cardiovascular mortality, severe hypoglycemia, and discontinuation of BP treatment due to hypotension/dizziness. There were 11,140 participants (mean age, 65.8 years 42.5% women, 25.7% frail). Frailty was an independent predictor of all primary outcomes and secondary outcomes. The effect of intensive glucose treatment on primary outcomes showed some evidence of attenuation in the frail: hazard ratios for combined major macro- and microvascular events 1.03 (95% CI 0.90–1.19) in the frail versus 0.84 (95% CI 0.74–0.94) in the nonfrail (P = 0.02). A similar trend was observed with BP intervention. Severe hypoglycemia rates (per 1,000 person-years) were higher in the frail: 8.39 (6.15–10.63) vs. 4.80 (3.84–5.76) in nonfrail (P & 0.001). There was no significant difference in discontinuation of BP treatment between frailty groups. It was possible to retrospectively estimate frailty in a trial population, and this FI identified those at higher risk of poor outcomes. Participants with frailty had some attenuation of benefit from intensive glucose-lowering and BP-lowering treatments.
Publisher: Elsevier BV
Date: 07-2015
Publisher: Portland Press Ltd.
Date: 28-11-2009
DOI: 10.1042/CS20070404
Abstract: The role of oxidative damage in the aetiology of coronary disease remains controversial, as clinical trials investigating the effect of antioxidants have not generally been positive. In the present study, 227 coronary cases, identified from a cohort study, were matched, by age and gender, with 420 controls in a nested case-control design. Stored plasma s les were analysed for F2-isoprostanes by stable isotope dilution MS, and specifically oxidized forms of apoA-I (apolipoprotein A-I) by HPLC of HDL (high-density lipoprotein). Median values of F2-isoprostanes were higher in plasma s les that contained oxidized apoA-I compared with s les with undetectable oxidized apoA-I (1542 compared with 1165 pmol/l). F2-Isoprostanes were significantly correlated with variants of non-oxidized apoA-II (r=−0.15) and were associated with HDL-cholesterol (P& .0001). F2-Isoprostanes in cases (median, 1146 pmol/l) were not different from controls (1250 pmol/l) the odds ratio (95% confidence interval) for a 1 S.D. increase in F2-isoprostanes was 1.08 (0.91–1.29). Similarly, there was no independent association between the presence of oxidized apoA-I, detected in approx. 20% of the s les, and coronary risk. In conclusion, we found no evidence of associations between markers of lipid (F2-isoprostanes) and protein (oxidized apoA-I) oxidation and the risk of fatal or non-fatal coronary heart disease in a general population. This may be due to a true lack of association or insufficient power.
Publisher: Wiley
Date: 04-05-2021
DOI: 10.1111/DOM.14391
Abstract: To estimate the associations between risk factors and cognitive decline (CD)/dementia, and the sex differences in these risk factors in in iduals with type 2 diabetes, while accounting for the competing risk of death. The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial of 11,140 in iduals with type 2 diabetes was used to estimate the odds of CD/dementia using multinomial logistic regression. During a median 5‐year follow‐up, 1827 participants (43.2% women) had CD/dementia (1718 with CD only 21 with dementia only 88 with CD and dementia), and 929 (31.0% women) died without CD/dementia. Women had lower odds of CD/dementia than men (odds ratio [OR] [95% confidence interval], 0.88 [0.77, 1.00]) older age, higher total cholesterol, HbA1c, waist circumference, waist‐to‐height ratio, moderately increased albumin‐creatinine ratio, stroke/transient ischaemic attack and retinal disease were each associated with greater odds of CD/dementia higher years at education completion, baseline cognitive function, taller stature and current alcohol use were inversely associated. Higher waist circumference (women‐to‐men ratio of ORs [ROR], 1.05 [1.00, 1.10] per 5 cm) and presence of anxiety/depression (ROR, 1.28 [1.01, 1.63]) were associated with greater ORs for CD/dementia in women than men. Several risk factors were associated with CD/dementia. Higher waist circumference and mental health symptoms were more strongly associated with CD/dementia in women than men. Further studies should examine the mechanisms that underlie these sex differences.
Publisher: Springer Science and Business Media LLC
Date: 21-12-2011
DOI: 10.1007/S00125-011-2404-1
Abstract: There is conflicting evidence regarding appropriate glycaemic targets for patients with type 2 diabetes. Here, we investigate the relationship between HbA(1c) and the risks of vascular complications and death in such patients. Eleven thousand one hundred and forty patients were randomised to intensive or standard glucose control in the Action in Diabetes and Vascular disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Glycaemic exposure was assessed as the mean of HbA(1c) measurements during follow-up and prior to the first event. Adjusted risks for each HbA(1c) decile were estimated using Cox models. Possible differences in the association between HbA(1c) and risks at different levels of HbA(1c) were explored using linear spline models. There was a non-linear relationship between mean HbA(1c) during follow-up and the risks of macrovascular events, microvascular events and death. Within the range of HbA(1c) studied (5.5-10.5%), there was evidence of 'thresholds', such that below HbA(1c) levels of 7.0% for macrovascular events and death, and 6.5% for microvascular events, there was no significant change in risks (all p > 0.8). Above these thresholds, the risks increased significantly: every 1% higher HbA(1c) level was associated with a 38% higher risk of a macrovascular event, a 40% higher risk of a microvascular event and a 38% higher risk of death (all p < 0.0001). In patients with type 2 diabetes, HbA(1c) levels were associated with lower risks of macrovascular events and death down to a threshold of 7.0% and microvascular events down to a threshold of 6.5%. There was no evidence of lower risks below these levels but neither was there clear evidence of harm.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-09-2013
DOI: 10.1161/CIRCULATIONAHA.113.002717
Abstract: Recent evidence suggests that visit-to-visit variability in systolic blood pressure (SBP) and maximum SBP are predictors of cardiovascular disease. However, it remains uncertain whether these parameters predict the risks of macrovascular and microvascular complications in patients with type 2 diabetes mellitus. The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) was a factorial randomized controlled trial of blood pressure lowering and blood glucose control in patients with type 2 diabetes mellitus. The present analysis included 8811 patients without major macrovascular and microvascular events or death during the first 24 months after randomization. SBP variability (defined as standard deviation) and maximum SBP were determined during the first 24 months after randomization. During a median 2.4 years of follow-up from the 24-month visit, 407 major macrovascular (myocardial infarction, stroke, or cardiovascular death) and 476 microvascular (new or worsening nephropathy or retinopathy) events were observed. The association of major macrovascular and microvascular events with SBP variability was continuous even after adjustment for mean SBP and other confounding factors (both P .05 for trend). Hazard ratios (95% confidence intervals) for the highest tenth of SBP variability were 1.54 (0.99–2.39) for macrovascular events and 1.84 (1.19–2.84) for microvascular events in comparison with the lowest tenth. For maximum SBP, hazard ratios (95% confidence intervals) for the highest tenth were 3.64 (1.73–7.66) and 2.18 (1.04–4.58), respectively. Visit-to-visit variability in SBP and maximum SBP were independent risk factors for macrovascular and microvascular complications in type 2 diabetes mellitus. URL: www.clinicaltrials.gov . Unique Identifier: NCT00145925.
Publisher: AMPCo
Date: 06-2000
Publisher: Elsevier BV
Date: 2015
Publisher: Elsevier BV
Date: 08-2000
DOI: 10.1016/S0735-1097(00)00736-1
Abstract: The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, on carotid atherosclerosis in patients with coronary, cerebrovascular or peripheral vascular disease. Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models. It has been hypothesized that the clinical benefits of ACE inhibitors may, therefore, be mediated by effects on atherosclerosis. Six hundred seventeen patients were randomized in equal proportions to ramipril (5-10 mg daily) or placebo. At baseline, two years and four years, carotid atherosclerosis was assessed by B-mode ultrasound, and left ventricular mass was assessed by M-mode echocardiography. Blood pressure (BP) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group (p<0.001). There was no difference between groups in the changes in common carotid artery wall thickness (p = 0.58) or in carotid plaque (p = 0.93). Left ventricular mass index decreased by 3.8 g/m2 (4%) in the ramipril group compared with the placebo group (2p = 0.04). The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events. It is more likely that the benefits are due to lower BP, reduced left ventricular mass or other factors such as reversal of endothelial dysfunction.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2009
Publisher: Elsevier BV
Date: 02-2001
Publisher: Elsevier BV
Date: 04-2008
DOI: 10.1038/KI.2008.5
Abstract: Recent epidemiological studies have shown a J-shaped association between the risk of stroke and systolic blood pressure (SBP) levels in people with chronic kidney disease (CKD). The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, placebo-controlled trial demonstrating that perindopril-based blood pressure (BP) lowering reduced the risk of stroke in 6105 participants with prior cerebrovascular disease. We estimated the effects of therapy on the risk of recurrent stroke in 1757 of these participants with stage 3 or greater CKD according to baseline BP and the relationship between achieved follow-up BP and the risk of stroke. Active therapy produced comparable and significant reductions in the risk of stroke across all baseline SBP levels. The age- and gender-adjusted incidence of stroke increased significantly in a log-linear relationship for achieved SBP levels and strokes per 1000 person-years. This association persisted after adjusting for potential confounding factors. We found that perindopril-based BP lowering effectively prevented recurrent stroke in people with CKD, across a wide range of BP levels, without evidence of an increased risk of stroke in people with low BP levels.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2015
DOI: 10.1161/CIRCOUTCOMES.114.001235
Abstract: Despite effective treatments to reduce cardiovascular disease risk, their translation into practice is limited. Using a parallel arm cluster-randomized controlled trial in 60 Australian primary healthcare centers, we tested whether a multifaceted quality improvement intervention comprising computerized decision support, audit/feedback tools, and staff training improved (1) guideline-indicated risk factor measurements and (2) guideline-indicated medications for those at high cardiovascular disease risk. Centers had to use a compatible software system, and eligible patients were regular attendees (Aboriginal and Torres Strait Islander people aged ≥35 years and others aged ≥45 years). Patient-level analyses were conducted using generalized estimating equations to account for clustering. Median follow-up for 38 725 patients (mean age, 61.0 years 42% men) was 17.5 months. Mean monthly staff support was hour/site. For the coprimary outcomes, the intervention was associated with improved overall risk factor measurements (62.8% versus 53.4% risk ratio 1.25 95% confidence interval, 1.04–1.50 P =0.02), but there was no significant differences in recommended prescriptions for the high-risk cohort (n=10 308 56.8% versus 51.2% P =0.12). There were significant treatment escalations (new prescriptions or increased numbers of medicines) for antiplatelet (17.9% versus 2.7% P .001), lipid-lowering (19.2% versus 4.8% P .001), and blood pressure–lowering medications (23.3% versus 12.1% P =0.02). In Australian primary healthcare settings, a computer-guided quality improvement intervention, requiring minimal support, improved cardiovascular disease risk measurement but did not increase prescription rates in the high-risk group. Computerized quality improvement tools offer an important, albeit partial, solution to improving primary healthcare system capacity for cardiovascular disease risk management. URL: www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=336630 . Australian New Zealand Clinical Trials Registry No. 12611000478910.
Publisher: BMJ
Date: 21-10-2004
Publisher: Oxford University Press (OUP)
Date: 26-02-2013
Publisher: Wiley
Date: 06-2016
DOI: 10.1111/JCH.12835
Publisher: Medical Journals Sweden AB
Date: 2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2000
Publisher: Elsevier BV
Date: 12-2001
Publisher: Oxford University Press (OUP)
Date: 05-2004
Publisher: Elsevier BV
Date: 2008
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.SURG.2015.01.002
Abstract: Information on the use of major surgery in India is scarce. In this study we aimed to bridge this gap by auditing hospital claims from Rajiv Aarogyasri Community Health Insurance Scheme, which provides access to free hospital care through state-funded insurance to 68 million beneficiaries, an estimated 81% of population in the states of Telangana and Andhra Pradesh. Publicly available deidentified hospital claim data for all surgery procedures conducted between mid-2008 and mid-2012 were compiled across all 23 districts in Telangana and Andhra Pradesh. A total of 677,332 operative admissions (80% at private hospitals) were recorded at an annual rate of 259 per 100,000 beneficiaries, with male subjects accounting for 56% of admissions. Injury was the most common cause for operative admission (27%) with operative correction of long bone fractures being the most common procedure (20%) identified in the audit. Diseases of the digestive (16%), genitourinary (12%), and musculoskeletal (10%) systems were other leading causes for operative admissions. Most hospital bed-days were used by admissions for injuries (31%) and diseases of the digestive (17%) and musculoskeletal system (11%) costing 19%, 13%, and 11% of reimbursement. Operations on the circulatory system (8%) accounted for 21% of reimbursements. Annual per capita cost of operative claims was US$1.48. The use of surgery by an insured population in India continued to be low despite access to financing comparable with greater spending countries, highlighting need for strategies, beyond traditional health financing, that prioritize improvement in access, delivery, and use of operative care.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Oxford University Press (OUP)
Date: 03-05-2016
DOI: 10.1093/IJE/DYW053
Publisher: AMPCo
Date: 05-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-1995
Publisher: Wiley
Date: 02-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-04-2009
DOI: 10.1161/CIRCULATIONAHA.108.819201
Abstract: Background— The rate of cardiovascular disease is widely considered to be increasing throughout India. Precise and reliable data on fatal and nonfatal cardiovascular disease, however, are few, and little is known about the use of preventive therapies. This is particularly true for rural regions. Methods and Results— Data were collected from 53 villages in the Godavari region of Andhra Pradesh. Mortality data were obtained from a verbal autopsy-based mortality surveillance system during a 12-month period in 2003 to 2004. The prevalence of nonfatal cardiovascular disease and the use of preventive therapies were estimated from a stratified random s le of 4535 adults (≥30 years of age) in 2005. Cardiovascular disease was the leading cause of mortality, accounting for at least 32% of all deaths. The average age at cardiovascular death was 65 years, and 51% of all cardiovascular deaths occurred in patients years of age. Among adults, the prevalence of coronary heart disease was estimated to be 4.8% (95% CI, 4.1 to 5.5), and the prevalence of cerebrovascular disease was estimated at 2.0% (95% CI, 1.5 to 2.4). Among in iduals with either diagnosis, 14% (95% CI, 10 to 18) reported taking aspirin, 41% (95% CI, 36 to 47) took a blood pressure-lowering medication, and 5% (95% CI, 3 to 7) reported using a cholesterol-lowering medication. Conclusion— This region has a large disease burden attributable to cardiovascular disease with significant underuse of proven, low-cost preventive medications.
Publisher: Mary Ann Liebert Inc
Date: 11-2005
Abstract: There is much interest in promoting healthy heart awareness among women. However, little is known about the reasons behind the lower rates of heart disease among women compared with men, and why this risk difference diminishes with age. Previous comparative studies have generally had insufficient numbers of women to quantify such differences reliably. We carried out an in idual participant data meta-analysis of 39 cohort studies (32 from Asian countries and 7 from Australia and New Zealand). Cox models were used to estimate hazard ratios (HR) for coronary death, comparing men to women. Further adjustments were made for several proven coronary risk factors to quantify their contributions to the sex differential. Sex interactions were tested for the same risk factors. During 4 million person-years of follow-up, there were 1989 (926 female) deaths from coronary heart disease (CHD). The age-adjusted and study-adjusted male/female HR (95% confidence interval [95% CI]) was 2.05 (1.89-2.22). At baseline, 54% of men vs. 7% of women were current smokers hence, adjustment for smoking explained the largest component (20%) of this HR. A significant sex interaction was observed between systolic blood pressure (SBP) and CHD mortality such that a 10 mm Hg increase was associated with a 15% greater increase in the relative risk (RR) of coronary death in women compared with men (p = 0.002). Only a small amount of the sex differential in coronary death could be explained by differences in the prevalence of classic risk factors. Alternative explanations are required to explain the age-related attenuation of the sex difference in CHD risk.
Publisher: Hindawi Limited
Date: 12-2002
Abstract: Introduction Among in iduals with a history of myocardial infarction (MI), higher levels of blood pressure (BP) are associated with increased long-term risks of death from coronary heart disease. Treatment with a BPlowering regimen, based on omapatrilat may result in greater clinical benefits than treatment with a regimen based on a regular angiotensin-converting enzyme (ACE) inhibitor because of more favourable effects on the renin-angiotensin-aldosterone system. Methods Seven hundred and twenty-three clinically stable patients with a history of MI or unstable angina, and a mean entry BP of 134/77 mmHg, were randomised to six months treatment with omapatrilat 40 mg, omapatrilat 20 mg, or matching placebo. Results After six months, mean BP levels (systolic/diastolic) in the omapatrilat 40 mg group were reduced by 4.3/ 2.9 mmHg (95% confidence interval 1.3 to 7.2/1.2 to 4.6). Mean BP levels in the omapatrilat 20 mg group were reduced by 4.6/1.0 mmHg (1.6 to 7.6/—0.7 to 2.6) in comparison with the placebo group. Both doses of omapatrilat also produced significant decreases in plasma ACE activity and significant increases in levels of plasma renin activity, atrial natriuretic peptide, endothelin and homocysteine (p .05 for all). Premature discontinuations were more frequent with omapatrilat than with placebo (p .001 for 20 mg and 40 mg). Conclusions Omapatrilat produced changes in BP, neurohormone and biochemical parameters that were similar for the two doses. The long-term clinical implications of the observed effects are uncertain and a large-scale randomised trial would be required to reliably establish the effects of omapatrilat on the risks of major vascular disease events among patients with coronary heart disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2008
DOI: 10.1161/STROKEAHA.107.504498
Abstract: Background and Purpose— There are few reports on proinflammatory cytokines and risk of primary or recurrent stroke. We studied the association of interleukin (IL)-6, IL-18, and tumor necrosis factor-α (TNF-α) with recurrent stroke in a nested case-control study derived from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). Methods— We performed a nested case-control study of 591 strokes (472 ischemic, 83 hemorrhagic, 36 unknown subtype) occurring during a randomized, placebo-controlled multicenter trial of perindopril-based therapy in 6105 patients with a history of stroke or transient ischemic attack. Controls were matched for age, treatment group, sex, region, and most recent qualifying event at entry to the parent trial. Results— IL-6 and TNF-α, but not IL-18, were associated with risk of recurrent ischemic stroke independently of conventional risk markers. Adjusted odds ratios comparing the highest to lowest third of their distributions were 1.33 (95% CI, 1.00 to 1.78) for IL-6 and 1.46 (1.02 to 2.10) for TNF-α. No inflammatory marker was associated with hemorrhagic stroke risk. In multivariable models, IL-6 and TNF-α fully explained observed associations of C-reactive protein and fibrinogen with risk of ischemic stroke, but TNF-α retained borderline significance after full adjustment. Conclusions— Inflammatory markers associated with the acute-phase response (IL-6, TNF-α, C-reactive protein, and fibrinogen, but not IL-18) are associated with risk of recurrent stroke. These markers are dependent on each other in multivariable models, and once all were included, only TNF-α retained a borderline association. Markers of generalized inflammation of the acute-phase response are associated with recurrent stroke, rather than IL-6, C-reactive protein, or fibrinogen in particular.
Publisher: Springer Science and Business Media LLC
Date: 06-2015
DOI: 10.1007/S00134-015-3757-6
Abstract: To compare the effect of intensive versus conventional blood glucose control in patients with traumatic brain injury. In a large international randomized trial patients were randomly assigned to a target blood glucose (BG) range of either 4.5-6.0 mmol/L (intensive control) or <10 mmol/L (conventional control). Patients with traumatic brain injury (TBI) were identified at randomization and data were collected to examine the extended Glasgow outcome score (includes mortality) at 24 months. Of the 6104 randomized patients, 391 satisfied diagnostic criteria for TBI 203 (51.9%) were assigned to intensive and 188 (48.1%) to conventional control the primary outcome was available for 166 (81.8%) and 149 (79.3%) patients, respectively. The two groups had similar baseline characteristics. At 2 years 98 (58.7%) patients in the intensive group and 79 (53.0%) in the conventional group had a favorable neurological outcome (odds ratio [OR] 1.26, 95% CI 0.81-1.97 P = 0.3) 35 patients (20.9%) in the intensive group and 34 (22.8%) in the conventional group had died (OR 0.90, 95% CI 0.53-1.53 P = 0.7) moderate hypoglycemia (BG 2.3-3.9 mmol/L 41-70 mg/dL) occurred in 160/202 (79.2%) and 17/188 (9.0%), respectively (OR 38.3, 95% CI 21.0-70.1 P < 0.0001) severe hypoglycemia (BG ≤ 2.2 mmol/L ≤40 mg/dL) in 10 (4.9%) and 0 (0.0%), respectively (OR 20.5 95% CI 1.2-351.6, P = 0.003). Although patients with traumatic brain injury randomly assigned to intensive compared to conventional glucose control experienced moderate and severe hypoglycemia more frequently, we found no significant difference in clinically important outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2007
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-03-2015
DOI: 10.1161/CIRCRESAHA.116.304723
Abstract: Despite the vast amount of evidence on the benefits of blood pressure lowering accumulated to date, elevated blood pressure is still the leading risk factor for disease and disability worldwide. The purpose of this review is to summarize the epidemiological evidence underpinning the association between blood pressure and a range of conditions. This review focuses on the association between systolic and diastolic blood pressures and the risk of cardiovascular and renal disease. Evidence for and against the existence of a J-shaped curve association between blood pressure and cardiovascular risk, and differences in the predictive power of systolic, diastolic, and pulse pressure, are described. In addition, global and regional trends in blood pressure levels and management of hypertension are reviewed.
Publisher: Elsevier BV
Date: 04-2000
Publisher: Springer Science and Business Media LLC
Date: 22-08-2005
Abstract: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study is examining the effects of long-term fibrate therapy on coronary heart disease (CHD) event rates in patients with diabetes mellitus. This article describes the trial's run-in phase and patients' baseline characteristics. FIELD is a double-blind, placebo-controlled trial in 63 centres in 3 countries evaluating the effects of fenofibrate versus placebo on CHD morbidity and mortality in 9795 patients with type 2 diabetes mellitus. Patients were to have no indication for lipid-lowering therapy on randomization, but could start these or other drugs at any time after randomization. Follow-up in the study was to be for a median duration of not less than 5 years and until 500 major coronary events (fatal coronary heart disease plus nonfatal myocardial infarction) had occurred. About 2100 patients (22%) had some manifestation of cardiovascular disease (CVD) at baseline and thus high risk status. Less than 25% of patients without CVD had a (UKPDS determined) calculated 5-year CHD risk of %, but nearly all had a 5-year stroke risk of %. Despite this, half of the cohort were obese (BMI 30), most were men, two-thirds were aged over 60 years, and substantial proportions had NCEP ATP III features of the metabolic syndrome independent of their diabetes, including low HDL (60%), high blood pressure measurement or treatment for hypertension (84%), high waist measurement (68%), and raised triglycerides (52%). After a 6-week run-in period before randomisation with all participants receiving 200 mg comicronized fenofibrate, there were declines in total and LDL cholesterol (10%) and triglycerides (26%) and an increase in HDL cholesterol (6.5%). The study will show the effect of PPAR-alpha agonist action on CHD and other vascular outcomes in patients with type 2 diabetes including substantial numbers with low to moderate CVD risk but with the various components of the metabolic syndrome. The main results of the study will be reported in late 2005.
Publisher: Elsevier BV
Date: 11-2009
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.AHJ.2009.05.034
Abstract: Developing countries are experiencing increasing levels of cardiovascular disease (CVD). Although there is a good understanding of how to deliver CVD prevention programs in developed countries, there are few data regarding strategies for CVD prevention in resource-poor settings. This study aimed to implement and evaluate a CVD prevention program in a rural area of India. The 2 strategies of CVD prevention to be investigated are an algorithm-based care approach and a health-promotion c aign. A factorial, cluster-randomized trial design will be used to evaluate these, in which villages will be exposed to one, both, or neither of the interventions for a period of about 12 months. Surveys of households in every village will be used to assess outcomes in all high-risk in iduals and a s le of the general adult population. The primary outcome of the algorithm-based component of this study will be the percentage of high-risk in iduals that have been "identified"-defined as having received a cardiovascular-risk assessment in the last 12 months. The primary outcome for the health-promotion component will be the percentage of the adult population with correct knowledge about the effects of 6 behavioral determinants of cardiovascular risk (green-leafy vegetables, fruits, oily foods, salt, smoking, physical activity). Secondary outcomes include a range of measures defining uptake of different preventive strategies. This study will provide evidence about the effectiveness of a simple practical mechanism of CVD preventive care specifically designed for delivery in a resource-poor area in India.
Publisher: Oxford University Press (OUP)
Date: 02-2003
DOI: 10.1093/IJE/DYG022
Abstract: To investigate the association between risk of motor vehicle driver injury and body mass index (BMI). In a cohort study of 10 525 New Zealand men and women, BMI was assessed in 1992-1993 (baseline), and data on deaths and hospitalizations for motor vehicle driver injury were obtained by record linkage to national health databases for the period 1988-1998. Hazard ratios (HR) and CI were estimated by Cox regression. During a mean 10.3 years of follow-up, 139 fatal and non-fatal driver injury cases occurred (85 before baseline and 54 after). A U-shaped association was observed between driver injury risk and BMI, both crudely and after adjustment for covariates, which included age, sex, driving exposure, and alcohol intake (P-values for quadratic trend /=28.7 kg/m(2) HR = 2.00, 95% CI: 1.18-3.39) and lowest (<23.5 kg/m(2) HR = 2.17, 95% CI: 1.27-3.73) quartiles of BMI were twice as likely to have experienced a driver injury during the follow-up period as participants in the reference quartile (25.9-28.6 kg/m(2) HR = 1.00). Further research is needed to corroborate or refute the hypothesis that BMI is a risk factor for serious motor vehicle driver injury.
Publisher: Elsevier BV
Date: 04-2002
Publisher: Medical Journals Sweden AB
Date: 2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-11-2011
DOI: 10.1161/CIRCULATIONAHA.111.055269
Abstract: A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10 95% confidence interval, 0.86–1.41), cohort studies (risk ratio, 0.94 95% confidence interval, 0.81–1.10), or case-control studies (risk ratio, 0.60 95% confidence interval, 0.41–0.88). Substantial statistical heterogeneity was evident for the case-control studies (I 2 =66%, P =0.01), but not for the cohort studies (I 2 =0%, P =0.48) or randomized trials (I 2 =30%, P =0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. We found no evidence that statins were associated with intracerebral hemorrhage if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs.
Publisher: Wiley
Date: 16-07-2021
DOI: 10.1111/DOM.14493
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2011
Publisher: Oxford University Press (OUP)
Date: 08-2008
DOI: 10.1038/AJH.2008.223
Publisher: Elsevier BV
Date: 08-2014
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.JCHF.2014.04.008
Abstract: This study sought to review the literature for risk prediction models in patients with heart failure and to identify the most consistently reported independent predictors of risk across models. Risk assessment provides information about patient prognosis, guides decision making about the type and intensity of care, and enables better understanding of provider performance. MEDLINE and EMBASE were searched from January 1995 to March 2013, followed by hand searches of the retrieved reference lists. Studies were eligible if they reported at least 1 multivariable model for risk prediction of death, hospitalization, or both in patients with heart failure and reported model performance. We ranked reported in idual risk predictors by their strength of association with the outcome and assessed the association of model performance with study characteristics. Sixty-four main models and 50 modifications from 48 studies met the inclusion criteria. Of the 64 main models, 43 models predicted death, 10 hospitalization, and 11 death or hospitalization. The discriminatory ability of the models for prediction of death appeared to be higher than that for prediction of death or hospitalization or prediction of hospitalization alone (p = 0.0003). A wide variation between studies in clinical settings, population characteristics, s le size, and variables used for model development was observed, but these features were not significantly associated with the discriminatory performance of the models. A few strong predictors emerged for prediction of death the most consistently reported predictors were age, renal function, blood pressure, blood sodium level, left ventricular ejection fraction, sex, brain natriuretic peptide level, New York Heart Association functional class, diabetes, weight or body mass index, and exercise capacity. There are several clinically useful and well-validated death prediction models in patients with heart failure. Although the studies differed in many respects, the models largely included a few common markers of risk.
Publisher: Oxford University Press (OUP)
Date: 20-05-2008
Abstract: Large-scale observational studies show that lower blood pressure is associated with lower cardiovascular risk in both men and women although some studies have suggested that different outcomes between the sexes may reflect different responses to blood pressure-lowering treatment. The aims of these overview analyses were to quantify the effects of blood pressure-lowering treatment in each sex and to determine if there are important differences in the proportional benefits of treatment between men and women. Thirty-one randomized trials that included 103,268 men and 87,349 women contributed to these analyses. For each outcome and each comparison summary estimates of effect and 95% confidence intervals were calculated for men and women using a random-effects model. The consistency of the effects of each treatment regimen across the sexes was examined using chi(2) tests of homogeneity. Achieved blood pressure reductions were comparable for men and women in every comparison made. For the primary outcome of total major cardiovascular events there was no evidence that men and women obtained different levels of protection from blood pressure lowering or that regimens based on angiotensin-converting-enzyme inhibitors, calcium antagonists, angiotensin receptor blockers, or diuretics/beta-blockers were more effective in one sex than the other (all P-homogeneity > 0.08). All of the blood pressure-lowering regimens studied here provided broadly similar protection against major cardiovascular events in men and women. Differences in cardiovascular risks between sexes are unlikely to reflect differences in response to blood pressure-lowering treatments.
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.CYTO.2009.12.014
Abstract: The pro-inflammatory cytokines, interleukin (IL)-18 and tumour necrosis factor-alpha (TNFalpha) may play a role in coronary heart disease (CHD). We aimed to extend data on their relationships to the risk of CHD in generally healthy populations. During 5.5years follow-up in the Fletcher Challenge general population cohort there were 256 CHD cases, and 615 controls were matched for age and sex. Baseline plasma levels of IL-18 and TNFalpha were related to CHD risk in available s les (77%). Plasma levels of IL-18 (11% increase in mean, p=0.01) and TNFalpha (10% increase in mean p=0.024) were significantly elevated in CHD cases versus controls. In univariable models IL-18 was associated with CHD risk (odds ratio [OR] upper third to lower third, 1.63 95% CI 1.08, 2.46), but TNFalpha was not (OR 1.33 95% CI 0.87, 2.02).After adjusting for major CHD risk factors and CRP, the association of IL-18 with CHD risk was attenuated (OR 1.69 95% CI 0.94, 3.03). IL-18, but not TNFalpha, had a non-negligible association with CHD risk, although the association of IL-18 with risk was weak after full adjustment. These cytokines may play a role in CHD pathology, but may not be robust risk biomarkers.
Publisher: Oxford University Press (OUP)
Date: 12-09-2018
Publisher: Massachusetts Medical Society
Date: 03-08-2000
Publisher: Elsevier BV
Date: 06-2005
Publisher: Massachusetts Medical Society
Date: 09-10-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2009
DOI: 10.1161/CIRCOUTCOMES.108.808469
Abstract: Background— Statins reduce the rates of heart attacks, strokes, and revascularization procedures (ie, major vascular events) in a wide range of circumstances. Randomized controlled trial data from 20 536 adults have been used to estimate the cost-effectiveness of prescribing statin therapy in the United States for people at different levels of vascular disease risk and to explore whether wider use of generic statins beyond the populations currently recommended for treatment in clinical guidelines is indicated. Methods and Results— Randomized controlled trial data, an internally validated vascular disease model, and US costs of statin therapy and other medical care were used to project lifetime risks of vascular events and evaluate the cost-effectiveness of 40 mg simvastatin daily. For an average of 5 years, allocation to simvastatin reduced the estimated US costs of hospitalizations for vascular events by ≈20% (95% CI, 15 to 24) in the different subcategories of participants studied. At a daily cost of $1 for 40 mg generic simvastatin, the estimated costs of preventing a vascular death within the 5-year study period ranged from a net saving of $1300 (95% CI, $15 600 saving to $13 200 cost) among participants with a 42% 5-year major vascular event risk to a net cost of $216 500 ($123 700 to $460 000 cost) among those with a 12% 5-year risk. The costs per life year gained with lifetime simvastatin treatment ranged from $2500 (−$40 to $3820) in people aged 40 to 49 years with a 42% 5-year major vascular event risk to $10 990 ($9430 to $14 700) in people aged 70 years and older with a 12% 5-year risk. Conclusions— Treatment with generic simvastatin appears to be cost-effective for a much wider population in the United States than that recommended by current guidelines.
Publisher: Wiley
Date: 13-09-2020
Publisher: Oxford University Press (OUP)
Date: 06-2007
Publisher: Apollo - University of Cambridge Repository
Date: 2016
DOI: 10.17863/CAM.15790
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.PCAD.2010.02.010
Abstract: The global population of in iduals with diabetes is important and rapidly growing. Because of the link between diabetes and cardiovascular disease (CVD), it is expected that diabetes will be an important driver of the future burden of CVD around the world. A connection between diabetes and CVD was suspected as earlier as in the mid 19th century. However, CVD in diabetes received less attention until the advent in the 20th century of treatments that allowed people with diabetes to live long enough to experience CVD. Since then the relationship between diabetes and CVD has been extensively investigated and characterised. The present article outlines the important contribution the Framingham Heart Study has made to the recognition of diabetes as a cardiovascular risk factor and the way in which the study has informed the association between other risk factors and CVD in the presence of diabetes, the changing pattern of the risk with time, and the quantification of CVD risk in the presence of diabetes. Through this contribution, Framingham has largely influenced our understanding of CVD in people with diabetes. Lines of investigation regarding cardiovascular health in this population are still wide open, and the Framingham Study continues to be part of this journey.
Publisher: Massachusetts Medical Society
Date: 07-10-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2006
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2009
DOI: 10.1161/STROKEAHA.108.540633
Abstract: Background and Purpose— Cerebral white matter hyperintensities (WMHs) are believed to be the consequence of small vessel disease, and it is uncertain whether their extent predicts the risk of dementia in patients with vascular disease history. Method— Brain MRI was performed in 226 participants of the PROGRESS study. WMH severity was assessed using a visual rating scale. During follow-up, patients were classified for incident severe cognitive deterioration (including dementia) using standard criteria. Results— Over 4-year follow-up, the incidence of severe cognitive deterioration ranged from 1.1 to 9.1 per 100 person-years in patients with respectively no or severe WMHs at baseline. In multivariable analysis, incident severe cognitive deterioration was associated with baseline severe WMHs (odds ratio=7.7, P .005). Conclusion— Higher WMH load is a strong predictor of dementia and cognitive decline in patients with cerebrovascular disease history.
Publisher: BMJ
Date: 18-01-2050
Abstract: To investigate the association between motor vehicle driver injury and socioeconomic status. Cohort study with prospective and retrospective outcomes. New Zealand. 10 525 adults (volunteer s le of a multi-industry workforce, n=8008 and a random s le of urban electoral rolls, n=2517). Motor vehicle driver injury resulting in admission of the driver to hospital or the driver's death, or both, during the period 1988-98 hospitalisation and mortality data were obtained by record linkage to national health databases. After adjustment for age and sex, driver injury risk was inversely associated with both occupational status (p for linear trend <0.0001) and educational level (p for linear trend =0.007). Participants in the lowest approximate quartile of occupational status were four times as likely (HR 4.17, 95% CI 2.31 to 7.55) to have experienced a driver injury during follow up as participants in the highest approximate quartile. Participants who had been to secondary school for less than two years were twice as likely (HR 2.26, 95% CI 1.34 to 3.81) to have experienced a driver injury as those who had been to university or polytechnic. There was little evidence that driver injury risk was associated with neighbourhood income (p for linear trend =0.12) CONCLUSIONS: Occupational status and educational level seem to be important determinants of driver injury risk. Driver injury countermeasures should be targeted to people in low status occupations, as well as to people with comparatively little formal education.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2006
DOI: 10.1161/01.STR.0000221212.36860.C9
Abstract: Background and Purpose— The relationship between baseline and recurrent vascular events may be important in the targeting of secondary prevention strategies. We examined the relationship between initial event and various types of further vascular outcomes and associated effects of blood pressure (BP)–lowering. Methods— Subsidiary analyses of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial that established the benefits of BP–lowering in 6105 patients (mean age 64 years, 30% female) with cerebrovascular disease, randomly assigned to either active treatment (perindopril for all, plus indapamide in those with neither an indication for, nor a contraindication to, a diuretic) or placebo(s). Results— Stroke subtypes and coronary events were associated with 1.5- to 6.6-fold greater risk of recurrence of the same event (hazard ratios, 1.51 to 6.64 P =0.1 for large artery infarction, P .0001 for other events). However, 46% to 92% of further vascular outcomes were not of the same type. Active treatment produced comparable reductions in the risk of vascular outcomes among patients with a broad range of vascular events at entry (relative risk reduction, 25% P .0001 for ischemic stroke 42%, P =0.0006 for hemorrhagic stroke 17%, P =0.3 for coronary events P homogeneity=0.4). Conclusions— Patients with previous vascular events are at high risk of recurrences of the same event. However, because they are also at risk of other vascular outcomes, a broad range of secondary prevention strategies is necessary for their treatment. BP–lowering is likely to be one of the most effective and generalizable strategies across a variety of major vascular events including stroke and myocardial infarction.
Publisher: Elsevier BV
Date: 11-2016
Publisher: Oxford University Press (OUP)
Date: 03-2003
DOI: 10.1016/S0195-668X(02)00804-7
Abstract: To determine the effects of a perindopril-based blood pressure lowering regimen on major cardiac events among hypertensive and non-hypertensive patients with a history of cerebrovascular disease. A total of 6105 in iduals with a history of stroke or transient ischaemic attack were randomly assigned active treatment (n=3051) or placebo (n=3054). Active treatment comprised the angiotensin-converting-enzyme inhibitor perindopril (4 mg daily), with the addition of the diuretic indapamide at the discretion of treating physicians. Over a mean of 3.9 years of follow-up, active treatment reduced blood pressure by 9/4 mm Hg compared with placebo and reduced the primary outcome, stroke, by 28%. Major coronary events occurred in 269 participants (active 3.8%, placebo 5.0%) and heart failure was diagnosed in 264 participants (active 3.7%, placebo 4.9%). Active treatment reduced the risk of major coronary events by 26% (95% CI: 6-42% p=0.02) and the risk of congestive heart failure by 26% (5-42% p=0.02). For each of these outcomes, there was no clear evidence of differences between the treatment effects in participants classified as hypertensive or non-hypertensive, and those with or without a history of coronary heart disease. Among in iduals with cerebrovascular disease, blood pressure lowering with a regimen involving perindopril and indapamide not only reduced the risk of stroke, but also substantially reduced the risks of cardiac outcomes.
Publisher: Oxford University Press (OUP)
Date: 08-07-2005
Abstract: To evaluate the role of plasma lipids in recurrent vascular events, including stroke, among in iduals with established cerebrovascular disease. Plasma total cholesterol, HDL cholesterol, and triglycerides were measured at baseline among in iduals participating in the Perindopril Protection Against Recurrent Stroke (PROGRESS) study, a randomized clinical trial of blood pressure lowering among patients with previous stroke or transient ischaemic attack. A series of nested case-control studies were used to investigate the association between each of these lipid variables and the risk of subsequent haemorrhagic stroke, ischaemic stroke, myocardial infarction (MI), and heart failure. A total of 895 patients were selected as cases (83 haemorrhagic stroke, 472 ischaemic stroke, 206 MI, and 258 heart failure) and each was matched with one to three controls. After adjustment for other major cardiovascular risk factors, none of the lipid variables was associated with the risk of either stroke subtype. There were significant positive and negative associations for total cholesterol and HDL, respectively, with the risk of MI the odds ratio comparing the highest and lowest thirds of each of these lipid variables was 2.00 (95% CI: 1.30-3.09) for total cholesterol and 0.58 (95% CI: 0.37-0.90) for HDL. HDL was inversely associated with the risk of heart failure however, this result was of borderline statistical significance (P=0.05). Lipid variables are associated with the risk of MI, but not recurrent stroke, in patients with established cerebrovascular disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2007
Publisher: Informa UK Limited
Date: 2004
DOI: 10.1080/08037050410029605
Abstract: Analyses of the risks of stroke were conducted for subjects with and without diabetes, participating in a randomized, double-blind, placebo-controlled trial of a perindopril-based blood pressure lowering regimen in 6105 people with prior stroke or transient ischaemic attack (TIA), followed for a median of 3.9 years. Seven hundred and sixty-one patients had diabetes at baseline. Diabetes increased the risk of recurrent stroke by 35% (95% CI 10-65%) principally through an effect on ischaemic stroke (1.53, 95% CI 1.23-1.90). Active treatment reduced blood pressure by 9.5/4.6 mmHg in patients with diabetes and by 8.9/3.9 mmHg in patients without diabetes. The proportional risk reductions achieved for stroke in patients with diabetes, 38% (95% CI 8-58%), and patients without diabetes, 28% (95% CI 16-39%), were not significantly different (p homogeneity = 0.5). The absolute reduction in the risk of recurrent stroke in the patients with diabetes was equivalent to one stroke avoided among every 16 (95% CI 9-111) patients treated for 5 years. Diabetes is an important risk factor for stroke in patients with established cerebrovascular disease. Treatment with the ACE inhibitor perindopril with discretionary use of the diuretic indapamide produced reductions in the risk of recurrent stroke in patients with diabetes that were at least as great as those achieved in patients without diabetes.
Publisher: Wiley
Date: 17-03-2021
Publisher: Elsevier BV
Date: 09-2007
DOI: 10.1111/J.1538-7836.2007.02677.X
Abstract: While meta-analyses of prospective studies have established that plasma levels of several hemostatic variables are associated with the risk of coronary heart disease (CHD), these have been suggested to be acute-phase reactant proteins. This study examines their associations with inflammatory markers [C-reactive protein (CRP) and interleukin-6 (IL-6)] and the effect of adjustment on their associations with CHD risk. In a nested case-control study, 247 CHD cases and 473 controls were matched for age and sex from 10 529 men and women in the Fletcher Challenge cohort. Plasma levels of all hemostatic variables except von Willebrand factor (VWF) and lipoprotein (a) [Lp(a)] showed significant associations with CRP and IL-6. Fibrinogen, VWF, tissue plasminogen activator antigen (t-PA), D-dimer, Lp(a), CRP and IL-6 levels were significantly associated with risk of CHD. After adjustment for conventional risk factors, CRP, D-dimer and IL-6 levels were significantly associated with risk of CHD. On further adjustments for the other six hemostatic and inflammatory variables these associations were reduced, but remained significant for D-dimer and IL-6 odds ratios (95% CI), comparing the highest to lowest third, were 3.10 (1.25-7.67) and 2.79 (1.11-6.99), respectively. The associations of plasma levels of some hemostatic variables (fibrinogen, VWF, t-PA and Lp(a) but not fibrin D-dimer) with CHD risk are attenuated when inflammatory markers (CRP and IL-6) as well as conventional risk factors are included in multivariable analyses. D-dimer and IL-6 each have the potential to increase the prediction of CHD, in addition to conventional risk factors.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1038/KI.2012.401
Abstract: The effect of intensive glucose control on major kidney outcomes in type 2 diabetes remains unclear. To study this, the ADVANCE trial randomly assigned 11,140 participants to an intensive glucose-lowering strategy (hemoglobin A1c target 6.5% or less) or standard glucose control. Treatment effects on end-stage renal disease ((ESRD), requirement for dialysis or renal transplantation), total kidney events, renal death, doubling of creatinine to above 200 μmol/l, new-onset macroalbuminuria or microalbuminuria, and progression or regression of albuminuria, were then assessed. After a median of 5 years, the mean hemoglobin A1c level was 6.5% in the intensive group, and 7.3% in the standard group. Intensive glucose control significantly reduced the risk of ESRD by 65% (20 compared to 7 events), microalbuminuria by 9% (1298 compared to 1410 patients), and macroalbuminuria by 30% (162 compared to 231 patients). The progression of albuminuria was significantly reduced by 10% and its regression significantly increased by 15%. The results were almost identical in analyses taking account of potential competing risks. The number of participants needed to treat over 5 years to prevent one ESRD event ranged from 410 in the overall study to 41 participants with macroalbuminuria at baseline. Thus, improved glucose control will improve major kidney outcomes in patients with type 2 diabetes.
Publisher: Elsevier BV
Date: 02-2008
Abstract: We describe the prevalence of stage III and IV chronic kidney disease in Thailand from a representative s le of in iduals aged 35 years and above using a stratified, multistage, cluster-s ling method. Population estimates were calculated by applying s ling weights from the 2000 Thai census. Glomerular filtration rates were estimated from serum creatinine using the Cockroft-Gault and the simplified Modification of Diet in Renal Disease (MDRD) formulae. The prevalence of stage III disease among in iduals aged 35 years and above was estimated to be about 20% using the Cockroft-Gault formula and about 13% from the MDRD formula. Stage IV disease was present in about 0.9 and 0.6% of this population using the respective formulae. The highest prevalence rates were observed in less well-developed rural areas and the lowest in developed urban areas. The prevalence of chronic kidney disease was significantly higher than that reported in in iduals over 40 years old from the United States for both stage III and IV disease and higher than the reported incidence in Taiwan and Australia. This high prevalence of chronic kidney disease in Thailand has obvious implications for the health of its citizens and for the allocation of health-care resources.
Publisher: Elsevier BV
Date: 03-2014
Publisher: Springer Science and Business Media LLC
Date: 06-10-2010
DOI: 10.1007/S00134-010-2039-6
Abstract: To determine the effect of random assignment to fluid resuscitation with albumin or saline on organ function and mortality in patients with severe sepsis. Pre-defined subgroup analysis of a randomized controlled trial conducted in the intensive care units of 16 hospitals in Australia and New Zealand. Of 1,218 patients with severe sepsis at baseline, 603 and 615 were assigned to receive albumin and saline, respectively. The two groups had similar baseline characteristics. During the first 7 days mean arterial pressure was similar in the two groups, but patients assigned albumin had a lower heart rate on days 1 and 3 (p = 0.002 and p = 0.03, respectively) and a higher central venous pressure on days 1-3 (p < 0.005 each day). There was no difference in the renal or total Sequential Organ Failure Assessment score of the two groups 113/603 (18.7%) of patients assigned albumin were treated with renal replacement therapy compared to 112/615 (18.2%) assigned saline (p = 0.98). The unadjusted relative risk of death for albumin versus saline was 0.87 [95% confidence interval (CI) 0.74-1.02] for patients with severe sepsis and 1.05 (0.94-1.17) for patients without severe sepsis (p = 0.06 for heterogeneity). From multivariate logistic regression analysis adjusting for baseline factors in patients with complete baseline data (919/1,218, 75.5%), the adjusted odds ratio for death for albumin versus saline was 0.71 (95% CI: 0.52-0.97 p = 0.03). Administration of albumin compared to saline did not impair renal or other organ function and may have decreased the risk of death.
Publisher: AMPCo
Date: 10-2002
Publisher: Springer Science and Business Media LLC
Date: 08-2017
Publisher: BMJ
Date: 05-2019
DOI: 10.1136/BMJOPEN-2018-028698
Abstract: Previous research from the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) and others has shown that pharmacological blood pressure (BP)- lowering substantially reduces the risk of major cardiovascular events, including ischaemic heart disease, heart failure and stroke. In this new phase, the aim is to conduct in idual patient-level data (IPD) meta-analyses involving eligible BP-lowering randomised controlled trials (RCTs) to address uncertainties relating to efficacy and safety of BP-lowering treatment. RCTs investigating the effect of pharmacological BP-lowering, with a minimum of 1000 patient-years of follow-up in each trial arm, are eligible. Our systematic review identified 100 potentially eligible trials. We requested their investigators/sponsors to contribute baseline, follow-up and outcomes data. As of June 2018, the collaboration has obtained data from 49 trials (n=315 046 participants), with additional data currently in the process of being transferred from four RCTs (n=34 642 participants). In addition, data harmonisation has commenced. Scientific activities of the collaboration are overseen by the Steering Committee with input from all collaborators. Detailed protocols for in idual meta-analyses will be developed and registered on public platforms. Ethics approval has been obtained for this new and extended phase of the BPLTTC, the largest collaboration of de-identified IPD from RCTs. It offers an efficient and ethical manner of re-purposing existing data to answer clinically important questions relating to BP treatment as well as methodological questions relating to IPD meta-analyses. Among the immediate impacts will include reliable quantification of effects of treatment modifiers, such as baseline BP, age and prior disease, on both vascular and non-vascular outcomes. Analyses will further assess the impact of BP-lowering on important, but less well understood, outcomes, such as new-onset diabetes and renal disease. Findings will be published in peer-reviewed medical journals on behalf of the collaboration.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2008
DOI: 10.1097/01.HJH.0000320754.38732.46
Abstract: ADVANCE was planned to investigate the effects of routine blood pressure lowering with the fixed combination perindopril-indapamide on major vascular events in people with type 2 diabetes, irrespective of initial blood pressures or the use of other blood pressure-lowering drugs, including angiotensin-converting enzyme inhibitors. A total of 11140 in iduals with type 2 diabetes were randomly assigned to fixed combination perindopril-indapamide or matching placebo, after a 6-week run-in period. The primary outcomes were composites of major macrovascular and major microvascular events, analysed jointly and separately, by intention to treat. Active treatment reduced blood pressure by 5.6/2.2 mmHg compared with placebo and the relative risks of all deaths, cardiovascular deaths and major vascular events, by 14% (P = 0.025), 18% (P = 0.027) and 9% (P = 0.041), respectively. There were also reductions in total coronary events (14% P = 0.02) and total renal events (21% P < 0.0001). Study treatment was well tolerated, with 73% and 74% of participants who received active treatment and placebo, respectively, still adherent to randomized therapy after an average of 4.3 years of follow-up. Routine treatment with the fixed combination perindopril-indapamide, on top of all concomitant protective therapies, was well tolerated and reduced the risks of death and vascular disease irrespective of the initial level of blood pressure. The results suggest that for every 79 patients so treated, one death would be averted over 5 years.
Publisher: Massachusetts Medical Society
Date: 06-01-2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2012
DOI: 10.1161/STROKEAHA.112.651448
Abstract: Observational studies demonstrate strong associations between blood pressure and bleeding complications of antithrombotic therapy. The objective was to determine whether blood pressure lowering reduces risks of bleeding in patients on antithrombotic therapy. This is a subsidiary analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial. A total of 6105 patients with cerebrovascular disease were randomly assigned to either active treatment (perindopril±indapamide) or placebo(s). The outcomes were intracranial and extracranial bleeding. There were 4876 (80%) patients on antithrombotic therapy at baseline. Over a mean follow-up of 3.9 years, 119 intracranial and 123 extracranial bleeding events were observed. Among patients with and without antithrombotic therapy, active treatment lowered blood pressure by 8.9/4.0 and 9.3/3.8 mm Hg and reduced the risks of intracranial bleeding by 46% (95% CI, 7%–69%) and 70% (39%–85%), respectively. However, active treatment did not reduce the risks of extracranial bleeding significantly in either group. Among patients on antithrombotic therapy, the lowest risk of intracranial bleeding was observed in participants with the lowest follow-up systolic blood pressure levels (median, 113 mm Hg). Blood pressure lowering provides protection against intracranial bleeding among patients with cerebrovascular disease including those receiving antithrombotic therapy. This trial was not registered because patients were enrolled before July 1, 2005.
Publisher: Elsevier BV
Date: 04-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2006
Publisher: Springer Science and Business Media LLC
Date: 29-11-2012
Abstract: Setting priorities for the prevention and management of heart failure requires an empirical understanding of the pattern of disease burden. We aim to describe the methods for a systematic review of the literature on burden of heart failure in low- and middle-income countries (LMIC) and how this information will be synthesized to produce useful estimates that can inform policy and practice. We will conduct a comprehensive search strategy for articles published between 1995 and April 2012 related to incidence, prevalence and treatment of heart failure in LMIC. Populations will be coded as urban, rural, or combined and studies classified as national, sub-national, healthcare system-based, or community level. Details from eligible studies will be extracted independently by two reviewers using a pre-designed data extraction form that will cover information on demographics, diagnostic criteria including disease incidence and prevalence, medical history, medication history, and hospital- or community-based management and outcomes. We will assess the reporting and methodological quality of the included studies and conduct a quantitative summary of reported outcomes where appropriate. Currently, there are important gaps in our knowledge on the burden of heart failure in LMIC and this systematic review aims to provide useful information that improves our knowledge in this field. Results are expected to be publicly available in early 2013.
Publisher: WHO Press
Date: 2009
Publisher: Oxford University Press (OUP)
Date: 04-04-2009
Abstract: Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk in different groups of patients. Whether these effects can be generalized to the broad group of patients with vascular disease is unknown. Therefore, we undertook a combined analysis using in idual data from ADVANCE, EUROPA, and PROGRESS to determine the consistency of the treatment effect of perindopril-based regimen in patients with vascular disease or at high risk of vascular disease. We studied all-cause mortality and major cardiovascular outcomes during a follow-up of about 4 years in the 29 463 patients randomly assigned a perindopril-based treatment regimen or placebo. The perindopril-based regimens were associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.89 95% confidence interval (CI) 0.82-0.96 P = 0.006], cardiovascular mortality (HR 0.85 95% CI 0.76-0.95 P = 0.004), non-fatal myocardial infarction (HR 0.80 95% CI 0.71-0.90 P < 0.001), stroke (HR 0.82 95% CI 0.74-0.92 P = 0.002), and heart failure (HR 0.84 95% CI 0.72-0.96 P = 0.015). Results were consistent in subgroups with different clinical characteristics, concomitant medication use, and across all strata of baseline blood pressure. This study provides strong evidence for a consistent cardiovascular protection with an ACE-inhibitor treatment regimen (perindopril-indapamide) by improving survival and reducing the risk of major cardiovascular events across a broad spectrum of patients with vascular disease.
Publisher: Springer Science and Business Media LLC
Date: 25-11-2013
Publisher: BMJ
Date: 2004
Abstract: To investigate the association of marital status with risk of motor vehicle driver injury. A cohort study with prospective and retrospective outcomes. New Zealand. A total of 10,525 adults (a volunteer s le of a multi-industry workforce, n = 8008 and a random s le of urban electoral rolls, n = 2517). EXPOSURE VARIABLE: Self reported marital status, assessed from a questionnaire administered in 1992-93 (baseline). Motor vehicle driver injury resulting in admission of the driver to hospital and/or the driver's death, during the period 1988-98 hospitalisation and mortality data were obtained by record linkage to national health databases. During 108 741 person-years of follow up, 139 driver injury cases occurred (85 before baseline, 54 after). After adjustment for age, sex, and study cohort, never married participants had twice the risk of driver injury (hazard ratio [HR] 2.06, 95% confidence interval [CI] 1.35 to 3.16) as married participants (HR 1.00). The relative risk for never married participants was slightly higher (HR 2.29), though less precise (95% CI 1.39 to 3.76), after further adjustment for alcohol intake, driving exposure, area of residence, body mass index, and occupational status. After taking age, sex, and other variables into account, never married people had a substantially higher risk of driver injury than married people. While requiring corroboration, these findings imply that it may be appropriate for driver injury countermeasures to be targeted to never married people.
Publisher: Public Library of Science (PLoS)
Date: 17-10-2017
Publisher: American Diabetes Association
Date: 22-03-2016
DOI: 10.2337/DC15-2322
Abstract: The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial reported that intensive glucose control prevents end-stage kidney disease (ESKD) in patients with type 2 diabetes, but uncertainty about the balance between risks and benefits exists. Here, we examine the long-term effects of intensive glucose control on risk of ESKD and other outcomes. Survivors, previously randomized to intensive or standard glucose control, were invited to participate in post-trial follow-up. ESKD, defined as the need for dialysis or kidney transplantation, or death due to kidney disease, was documented overall and by baseline CKD stage, along with hypoglycemic episodes, major cardiovascular events, and death from other causes. A total of 8,494 ADVANCE participants were followed for a median of 5.4 additional years. In-trial HbA1c differences disappeared by the first post-trial visit. The in-trial reductions in the risk of ESKD (7 vs. 20 events, hazard ratio [HR] 0.35, P = 0.02) persisted after 9.9 years of overall follow-up (29 vs. 53 events, HR 0.54, P & 0.01). These effects were greater in earlier-stage CKD (P = 0.04) and at lower baseline systolic blood pressure levels (P = 0.01). The effects of glucose lowering on the risks of death, cardiovascular death, or major cardiovascular events did not differ by levels of kidney function (P & 0.26). Intensive glucose control was associated with a long-term reduction in ESKD, without evidence of any increased risk of cardiovascular events or death. These benefits were greater with preserved kidney function and with well-controlled blood pressure.
Publisher: BMJ
Date: 03-2018
DOI: 10.1136/BMJOPEN-2017-019335
Abstract: To assess the relationship between risk factor clusters and cardiovascular disease (CVD) incidence in Asian and Caucasian populations and to estimate the burden of CVD attributable to each cluster. Asia Pacific Cohort Studies Collaboration. In idual participant data from 34 population-based cohorts, involving 314 024 participants without a history of CVD at baseline. Clusters were 11 possible combinations of four in idual risk factors (current smoking, overweight, blood pressure (BP) and total cholesterol). Cox regression models were used to obtain adjusted HRs and 95% CIs for CVD associated with in idual risk factors and risk factor clusters. Population-attributable fractions (PAFs) were calculated. During a mean follow-up of 7 years, 6203 CVD events were recorded. The ranking of HRs and PAFs was similar for Australia and New Zealand (ANZ) and Asia clusters including BP consistently showed the highest HRs and PAFs. The BP–smoking cluster had the highest HR for people with two risk factors: 4.13 (3.56 to 4.80) for Asia and 3.07 (2.23 to 4.23) for ANZ. Corresponding PAFs were 24% and 11%, respectively. For in iduals with three risk factors, the BP–smoking–cholesterol cluster had the highest HR (4.67 (3.92 to 5.57) for Asia and 3.49 (2.69 to 4.53) for ANZ). Corresponding PAFs were 13% and 10%. Risk factor clusters act similarly on CVD risk in Asian and Caucasian populations. Clusters including elevated BP were associated with the highest excess risk of CVD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-07-2005
DOI: 10.1161/CIRCULATIONAHA.104.525527
Abstract: Background— B-type natriuretic peptide (BNP), C-reactive protein (CRP), and renin are elevated in persons at risk for cardiovascular disease. However, data that directly compare these markers in the prediction of myocardial infarction (MI) are limited. Methods and Results— N-terminal-proBNP (NT-proBNP), CRP, and renin were measured in baseline blood s les from a nested case-control study of the 6105 participants of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among in iduals with previous stroke or transient ischemic attack. Each of 206 subjects who experienced MI, either fatal or nonfatal, during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. Most MI cases (67%) occurred in subjects without a history of coronary heart disease. NT-proBNP, CRP, and renin each predicted MI the odds ratio for subjects in the highest compared with the lowest quarter was 2.2 (95% CI, 1.3 to 3.6) for NT-proBNP, 2.2 (95% CI, 1.3 to 3.6) for CRP, and 1.7 (95% CI, 1.1 to 2.8) for renin. NT-proBNP and renin, but not CRP, remained predictors of MI after adjustment for all other predictors, including LDL and HDL cholesterol levels. In iduals with both NT-proBNP and renin in their highest quarters had 4.5 times the risk of MI compared with subjects with both biological markers in their lowest quarters. Conclusions— NT-proBNP and renin, but not CRP, are independent predictors of MI risk after stroke or transient ischemic attack, providing information additional to that provided by classic risk factors, and may enable more effective targeting of MI prevention strategies.
Publisher: Elsevier BV
Date: 03-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2004
DOI: 10.1097/00004872-200403000-00030
Abstract: To assess the consistency of the benefits of blood pressure lowering on secondary stroke risk by age, sex and geographic region of recruitment. Randomized, placebo-controlled trial. Participants were randomized to the angiotensin-converting enzyme (ACE) inhibitor perindopril (plus the diuretic indapamide if not indicated or contraindicated) or to placebo(s) over a mean follow-up of 3.9 years. Main analyses used Cox proportional hazards models on an intention-to-treat basis. Subgroup results were standardized for the proportion (42%) taking single-drug therapy. A total of 172 centres in Asia, Australia, New Zealand and Europe. Patients (n = 6105) with a history of stroke or transient ischaemic attack, of whom 50% were aged over 65 years at baseline, 30% were women and 39% were from Asia. Stroke, coronary heart disease and major vascular events. Overall, treatment reduced stroke by 28% [95% confidence interval (CI) 17-38%] and major vascular events by 26% (16-44%), with separately significant reductions across subgroups defined by age ( or = 65 years), sex and region (Asia or not). Treatment was safe and well tolerated, and the absolute benefits were large 5 years' treatment would be expected to avert at least one major vascular event among every 20 patients in all age, sex and region subgroups. There was some evidence of particularly large benefits among younger participants and those from Asia. Blood pressure lowering reduces secondary stroke risk, with large absolute benefits across groups defined by age, sex and geographic region.
Publisher: Public Library of Science (PLoS)
Date: 04-02-2013
Publisher: Elsevier BV
Date: 02-2001
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2003
DOI: 10.1161/01.HYP.0000088322.85804.96
Abstract: The insertion/deletion ( I/D ) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 in iduals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly ( P .0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.
Publisher: Elsevier BV
Date: 07-2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2011
Publisher: Public Library of Science (PLoS)
Date: 12-08-2014
Publisher: Wiley
Date: 11-10-2020
DOI: 10.1111/DOM.14199
Abstract: Obesity is associated with severe COVID‐19 outcomes, yet, it is unclear whether the risk of COVID‐19 mortality associated with obesity is similar between the sexes. We used data from the UK Biobank to assess the risk of COVID‐19 mortality associated with various anthropometric measures in women and men. To put these results in context, we also compared these estimates with those for mortality from influenza neumonia and coronary heart disease (CHD). The analyses included 502 493 in iduals (54% women), of whom 410 (36% women) died from COVID‐19, 549 (36% women) died from influenza neumonia and 3355 (19% women) died from CHD. A higher body mass index (BMI), waist circumference, waist‐to‐hip ratio and waist‐to‐height ratio were each associated with a greater risk of death from COVID‐19, influenza neumonia and CHD in both sexes, with the exception of the association between higher BMI and the risk of influenza neumonia death in men. A higher BMI was associated with a stronger risk of COVID‐19 mortality in women than men the women‐to‐men ratio of hazard ratios was 1.20 (95% confidence interval 1.00 1.43). This study demonstrates the role of obesity in COVID‐19 mortality and shows that the relative effects of a higher BMI on COVID‐19 mortality may be stronger in women than men.
Publisher: Springer Science and Business Media LLC
Date: 09-2001
Abstract: Patients with Type II (non-insulin-dependent) diabetes mellitus are at increased risk of macrovascular and microvascular disease, both of which are reduced by controlling raised blood pressure in hypertensive patients. Intensive glycaemic control has also been shown to reduce microvascular disease but the effects on macrovascular disease remain uncertain. This study will examine the hypotheses that lowering blood pressure with an ACE inhibitor-diuretic combination and intensively controlling gylcaemia with a sulphonylurea-based regimen in high-risk patients with Type II diabetes (both hypertensive and non-hypertensive) reduces the incidence of macrovascular and microvascular disease. The study is a 2 x 2 factorial randomised controlled trial that will include 10000 adults with Type II diabetes at high risk of vascular disease. Following 6 weeks on open label perindopril-indapamide combination, eligible patients are randomised to continued perindopril-indapamide or matching placebo, and to an intensive gliclazide MR-based glucose control regimen or usual guidelines-based therapy. Primary outcomes are, first, the composite of nonfatal stroke, non-fatal myocardial infarction or cardiovascular death and, second, the composite of new or worsening nephropathy or diabetic eye disease. The scheduled average duration of treatment and follow-up is 4.5 years. The study will be conducted in approximately 200 centres in Australasia, Asia, Europe and North America. ADVANCE is designed to provide reliable evidence on the balance of benefits and risks conferred by blood pressure lowering therapy and intensive glucose control therapy in high-risk diabetic patients, regardless of initial blood pressure or glucose concentrations.
Publisher: BMJ
Date: 2012
Publisher: Elsevier BV
Date: 03-2009
Publisher: Elsevier BV
Date: 09-2001
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-09-2005
DOI: 10.1161/CIRCULATIONAHA.104.501163
Abstract: Background— The prevalence of white matter hyperintensities (WMHs) detected on cerebral MRI is associated with hypertension, but it is not known whether blood pressure lowering can arrest their progression. We report here the results of an MRI substudy of PROGRESS (Perindopril Protection Against Recurrent Stroke Study), a randomized trial of blood pressure lowering in subjects with cerebrovascular disease. Methods and Results— The substudy comprised 192 participants who had a cerebral MRI both at baseline and after a mean follow-up time of 36 months (SD=6.0 months). At the first MRI, WMHs were graded with a visual rating scale from A (no WMH) to D (severe WMH). Participants were assigned to a combination of perindopril plus indapamide (or their placebos 58%) or to single therapy with perindopril (or placebo). At the time of the second MRI, the blood pressure reduction in the active arm compared with the placebo arm was 11.2 mm Hg for systolic blood pressure and 4.3 mm Hg for diastolic blood pressure. Twenty-four subjects (12.5%) developed new WMHs at follow-up. The risk of new WMH was reduced by 43% (95% CI −7% to 89%) in the active treatment group compared with the placebo group ( P =0.17). The mean total volume of new WMHs was significantly reduced in the active treatment group (0.4 mm 3 [SE=0.8]) compared with the placebo group (2.0 mm 3 [SE=0.7] P =0.012). This difference was greatest for patients with severe WMH at entry, 0.0 mm 3 (SE=0) in the active treatment group versus 7.6 mm 3 (SE=1.0) in the placebo group ( P .0001). Conclusions— These results indicate that an active blood pressure–lowering regimen stopped or delayed the progression of WMHs in patients with cerebrovascular disease.
Publisher: BMJ
Date: 03-2017
DOI: 10.1136/HEARTJNL-2016-310216
Abstract: To quantify contemporary differences in cardiovascular disease (CVD) risk factor assessment and management between women and men in Australian primary healthcare services. Records of routinely attending patients were s led from 60 Australian primary healthcare services in 2012 for the Treatment of Cardiovascular Risk using Electronic Decision Support study. Multivariable logistic regression models were used to compare the rate of CVD risk factor assessment and recommended medication prescriptions, by gender. Of 53 085 patients, 58% were female. Adjusting for demographic and clinical characteristics, women were less likely to have sufficient risk factors measured for CVD risk assessment (OR (95% CI): 0.88 (0.81 to 0.96)). Among 13 294 patients (47% women) in the CVD/high CVD risk subgroup, the adjusted odds of prescription of guideline-recommended medications were greater for women than men: 1.12 (1.01 to 1.23). However, there was heterogeneity by age (p <0.001), women in the CVD/high CVD risk subgroup aged 35-54 years were less likely to be prescribed the medications (0.63 (0.52 to 0.77)), and women in the CVD/high CVD risk subgroup aged ≥65 years were more likely to be prescribed the medications (1.34 (1.17 to 1.54)) than their male counterparts. Women attending primary healthcare services in Australia were less likely than men to have risk factors measured and recorded such that absolute CVD risk can be assessed. For those with, or at high risk of, CVD, the prescription of appropriate preventive medications was more frequent in older women, but less frequent in younger women, compared with their male counterparts. 12611000478910, Pre-results.
Publisher: Public Library of Science (PLoS)
Date: 21-08-2012
Publisher: Springer Science and Business Media LLC
Date: 31-01-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2009
DOI: 10.1161/STROKEAHA.109.563932
Abstract: Background and Purpose— Patients with cerebral amyloid angiopathy (CAA) are at high risk for intracerebral hemorrhage (ICH), but no effective prevention strategies have been established. The objective is to determine whether lowering of blood pressure (BP) provides protection for this high-risk patient group. Methods— This study is a subsidiary analysis of the PROGRESS trial—a randomized, placebo-controlled trial that established the beneficial effects of BP lowering in patients with cerebrovascular disease 6105 patients were randomly assigned to either active treatment (perindopril for all participants plus indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo. Outcomes were probable CAA-related ICH as defined by the Boston criteria, probable hypertension-related ICH, and unclassified ICH. Results— Over a mean follow-up of 3.9 years, 16 probable CAA-related ICH, 51 probable hypertension-related ICH, and 44 unclassified ICH occurred. Active treatment reduced the risk of CAA-related ICH by 77% (95% CI, 19%–93%), that of hypertension-related ICH by 46% (95% CI, 4%–69%), and that of unclassified ICH by 43% (95% CI, −5%–69%). There was no evidence of differences in the magnitude of the effects of treatment among different types of ICH ( P homogeneity=0.4). Conclusions— BP-lowering treatment is likely to provide protection against all types of ICH.
Publisher: American Association for Cancer Research (AACR)
Date: 12-2006
DOI: 10.1158/1055-9965.EPI-06-0368
Abstract: Background: Pancreatic cancer accounts for about 220,000 deaths each year. Known risk factors are smoking and type 2 diabetes. It remains to be seen whether these risk factors are equally important in Asia and whether other modifiable risk factors have important associations with pancreatic cancer. Methods: An in idual participant data analysis of 30 cohort studies was carried out, involving 420,310 Asian participants (33% female) and 99,333 from Australia/New Zealand (45% female). Cox proportional hazard models, stratified by study and sex and adjusted for age, were used to quantify risk factors for death from pancreatic cancer. Results: During 3,558,733 person-years of follow-up, there were 324 deaths from pancreatic cancer (54% Asia and 33% female). Mortality rates (per 100,000 person-years) from pancreatic cancer were 10 for men and 8 for women. The following are age-adjusted hazard ratios (95% confidence interval) for death from pancreatic cancer: for current smoking, 1.61 (1.12-2.32) for diabetes, 1.76 (1.15-2.69) for a 2-cm increase in waist circumference, 1.08 (1.02-1.14). All three relationships remained significant (P & 0.05) after adjustment for other risk factors. There was no evidence of heterogeneity in the strength of these associations between either cohorts from Asia and Australia/New Zealand or between the sexes. In men, the combination of cigarette smoking and diabetes more than doubled the likelihood of pancreatic cancer (2.47 95% confidence interval, 1.17-5.21) in both regions. Conclusions: Smoking, obesity, and diabetes are important and are potentially modifiable risk factors for pancreatic cancer in populations of the Asia-Pacific region. Activities to prevent them can be expected to lead to a major reduction in the number of deaths from this cancer, particularly in Asia with its enormous population. (Cancer Epidemiol Biomarkers Prev 2006 (12):2435–40)
Publisher: JMIR Publications Inc.
Date: 08-12-2014
DOI: 10.2196/MHEALTH.3568
Publisher: Massachusetts Medical Society
Date: 27-05-2004
DOI: 10.1056/NEJMOA040232
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2015
DOI: 10.1161/HYPERTENSIONAHA.114.04421
Abstract: Blood pressure–lowering treatment reduces cardiovascular risk in patients with diabetes mellitus, but the effect varies between in iduals. We sought to identify which patients benefit most from such treatment in a large clinical trial in type 2 diabetes mellitus. In Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) participants (n=11 140), we estimated the in idual patient 5-year absolute risk of major adverse cardiovascular events with and without treatment by perindopril–indapamide (4/1.25 mg). The difference between treated and untreated risk is the estimated in idual patient’s absolute risk reduction (ARR). Predictions were based on a Cox proportional hazards model inclusive of demographic and clinical characteristics together with the observed relative treatment effect. The group-level effect of selectively treating patients with an estimated ARR above a range of decision thresholds was compared with treating everyone or those with a blood pressure /90 mm Hg using net benefit analysis. In ADVANCE, there was wide variation in treatment effects across in idual patients. According to the algorithm, 43% of patients had a large predicted 5-year ARR of ≥1% (number-needed-to-treat [NNT 5 ] ≤100) and 40% had an intermediate predicted ARR of 0.5% to 1% (NNT 5 =100–`200). The proportion of patients with a small ARR of ≤0.5% (NNT 5 ≥200) was 17%. Provided that one is prepared to treat at most 200 patients for 5 years to prevent 1 adverse outcome, prediction-based treatment yielded the highest net benefit. In conclusion, a multivariable treatment algorithm can identify those in iduals who benefit most from blood pressure–lowering therapy in terms of ARR of major adverse cardiovascular events and may be used to guide treatment decisions in in idual patients with diabetes. URL: www.clinicaltrials.gov . Unique identifier: NCT00145925.
Publisher: Elsevier BV
Date: 10-2002
DOI: 10.1111/J.1467-842X.2002.TB00346.X
Abstract: To determine whether capture-recapture analysis provides more reliable estimates of the cumulative incidence and prevalence of leg ulcers in Auckland, New Zealand. A population-based, cross-sectional study was conducted in the Central and North Auckland health districts of New Zealand in 1998. Cases were identified through health professional referral and by self-notification. All ages and ulcer types were investigated. Both traditional and capture-recapture methods of analysis were used to estimate the cumulative incidence and prevalence of leg ulcers in the study population. Four hundred and twenty-six people with current leg ulcers were identified during the 12-month study period. Using traditional methods of analysis, the annual cumulative incidence rate of leg ulcers in Auckland was 32 per 100,000, with a point prevalence of 39 per 100,000 and a period prevalence of 79 per 100,000 per year. Results from capture-recapture analysis, however, suggest an annual cumulative incidence rate of 252 per 100,000, with a point prevalence of 248 per 100,000 and a period prevalence of 530 per 100,000 per year. The traditional method of calculating cumulative incidence and prevalence clearly under-estimates the frequency of leg ulcers in the Auckland region. Capture-recapture analysis provides a more reliable estimate of disease frequency, since cases that remain unidentified in the population are considered.
Publisher: Springer Science and Business Media LLC
Date: 2001
Abstract: Random errors in the measurement of 10 commonly investigated cardiovascular risk factors (systolic and diastolic blood pressure, blood cholesterol, blood glucose, pulse rate, body mass index (BMI), cigarette consumption, passive smoking, alcohol intake and physical exercise) were assessed in a general population cohort (n = 2517) and a workforce cohort (n = 8008). Random errors were estimated from regression dilution ratios (lower ratios imply greater random error, and a ratio of one implies no random error). All of the risk factors, except for BMI (which had regression dilution ratios of 0.93 and 0.98 in the two cohorts), were measured with substantial levels of random error. Particularly low regression dilution ratios were observed for physical exercise (0.28 and 0.39) and pulse rate (0.47 and 0.56). For each of these risk factors, with the possible exception of BMI, associations with long-term average values could be importantly biased toward the null unless appropriate corrections are made.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2013
DOI: 10.1161/STROKEAHA.111.680728
Abstract: To determine the interrelationships between baseline Mini-Mental State Examination (MMSE) score and risk of overall dementia, post-recurrent stroke dementia, and dementia without recurrent stroke among patients with a history of stroke. Prospective cohort study among participants enrolled in the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) for whom baseline MMSE score was available. Baseline MMSE score was ided into 4 categories: 30, 29–27, 26–24, and . Participants were followed for incident dementia and recurrent stroke. Logistic regression models were used to examine the association between MMSE score and dementia. Of the 6080 participants included in this analysis, 2493 had an MMSE score of 30, 1768 had a score of 29–28, 1369 had a score of 26–24, and 450 had a score of . Average follow-up time was 3.8 years. There were 407 cases of dementia, 106 of which were preceded by a recurrent stroke. The risk of overall dementia increased with decreasing MMSE score. However, the impact of MMSE score on the risk of dementia without recurrent stroke was much stronger than the impact of MMSE score on the risk of post-recurrent stroke dementia. For those with MMSE score , the risk of dementia without recurrent stroke was 47.89 (95% confidence interval, 28.57–80.26), whereas the risk of post-recurrent stroke dementia was only 7.17 (95% confidence interval, 3.70–13.89). Higher MMSE scores were even less strongly associated with the risk of post-recurrent stroke dementia. Patients with stroke with low MMSE scores are at high risk of dementia over time, even in the absence of a recurrent stroke, and should therefore be followed closely for further cognitive decline.
Publisher: Elsevier BV
Date: 03-2012
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.IJCARD.2014.07.108
Abstract: Our objective was to investigate the actual incidence and clinical determinants of cough leading to discontinuation of ACE-inhibitors. Cough is the most frequent reason to stop ACE-inhibitor treatment. We studied 27,492 ACE-inhibitor naïve patients randomized to the ACE-inhibitor perindopril or placebo using in idual data of 3 clinical trials. Multivariate logistic regression analysis was used to study the incidence of cough in relation to baseline clinical characteristics including racial background. In 27,492 patients with cardiovascular disease, 1076 patients discontinued ACE-inhibitor perindopril due to cough (3.9%), 703 patients during run-in period of 4 weeks and 373 patients during a mean four years of follow-up. Significant determinants of cough were female gender (OR 1.92 95% CI 1.68-2.18), age above 65 years (OR 1.53 95% CI 1.35-1.73), and concomitant use of lipid-lowering agents (OR 1.37 95% CI 1.18-1.59). A simple clinical risk score composed of these 3 predictors of cough mounted to an odds ratio of 4.4 (95% CI 3.1-5.4) in the subjects with highest score (i.e. all determinants present). Racial background was not related to a differential incidence of cough in patients of Caucasian or Asian descendent (OR 1.11 95% CI 0.92-1.39). This large combined analysis of randomized clinical trials in 27,492 patients showed an overall lower incidence of cough leading to discontinuation of ACE-inhibitors (3.9%) as compared to literature. Clinical determinants of such cough are older age, female gender and concomitant use of lipid-lowering agents. In contrast, racial differences were not related to the incidence of cough.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-06-2016
DOI: 10.1161/CIRCULATIONAHA.115.008728
Abstract: With one-fifth of the world’s total population, China’s prevention and control of cardiovascular disease (CVD) may affect the success of worldwide efforts to achieve sustainable CVD reduction. Understanding China’s current cardiovascular epidemic requires awareness of the economic development in the past decades. The rapid economic transformations (industrialization, marketization, urbanization, globalization, and informationalization) contributed to the aging demography, unhealthy lifestyles, and environmental changes. The latter have predisposed to increasing cardiovascular risk factors and the CVD pandemic. Rising CVD rates have had a major economic impact, which has challenged the healthcare system and the whole society. With recognition of the importance of health, initial political steps and national actions have been taken to address the CVD epidemic. Looking to the future, we recommend that 4 priorities should be taken: pursue multisectorial government and nongovernment strategies targeting the underlying causes of CVD (the whole-of-government and whole-of-society policy) give priority to prevention reform the healthcare system to fit the nature of noncommunicable diseases and conduct research for evidence-based, low-cost, simple, sustainable, and scalable interventions. By pursuing the 4 priorities, the pandemic of CVD and other major noncommunicable diseases in China will be reversed and the global sustainable development goal achieved.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2011
DOI: 10.1161/STROKEAHA.110.606764
Abstract: Despite clear evidence that blood pressure (BP) lowering is effective for prevention of cardiovascular events among patients with isolated systolic hypertension and systolic–diastolic hypertension, there is ongoing uncertainty about its effects in those with isolated diastolic hypertension. The objective of the present analysis is to determine whether BP lowering provides benefits to patients with isolated diastolic hypertension. Patients with cerebrovascular disease and hypertension at baseline (n=4283) were randomly assigned to either active treatment (perindopril in all participants plus indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). The primary outcome was total major vascular events. There were 1923 patients with isolated systolic hypertension (systolic BP ≥140 mm Hg and diastolic BP mm Hg), 315 with isolated diastolic hypertension (systolic BP mm Hg and diastolic BP ≥90 mm Hg), and 2045 with systolic–diastolic hypertension (systolic BP ≥140 mm Hg and diastolic BP ≥90 mm Hg) at baseline. Active treatment reduced the relative risk of major vascular events by 27% (95% CI, 10% to 41%) among patients with isolated systolic hypertension, by 28% (−29% to 60%) among those with isolated diastolic hypertension, and by 32% (17% to 45%) among those with systolic–diastolic hypertension. There was no evidence of differences in the magnitude of the effects of treatment among different types of hypertension ( P homogeneity=0.89). BP lowering is likely to provide a similar level of protection against major vascular events for patients with isolated diastolic hypertension as for those with isolated systolic hypertension and systolic–diastolic hypertension. This trial was not registered because patients were enrolled before July 1, 2005.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2010
Publisher: Oxford University PressOxford
Date: 30-06-2009
DOI: 10.1093/ACPROF:OSO/9780198525738.003.0011
Abstract: This chapter presents estimates of blood pressure distributions by age, sex, and world region to estimate the burden of coronary heart disease (CHD) attributable to raised blood pressure worldwide in the year 2000. It summarizes work produced for the WHO Global Burden of Disease 2000 study and the World Health Report 2002, which included estimates of the burden of disease attributable to a variety of risk factors including blood pressure.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2005
DOI: 10.1161/01.HYP.0000151103.02424.C3
Abstract: B-type natriuretic peptide (BNP) and C-reactive protein (CRP) are elevated in persons at risk for congestive heart failure (CHF). However, limited data are available directly comparing BNP-related peptides and CRP in persons at risk of CHF. To evaluate amino terminal–pro-BNP (NT-proBNP) and CRP, separately and together, for assessment of risk of CHF, we performed a nested case-control study of the 6105 participants of the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure–lowering regimen among in iduals with previous stroke or transient ischemic attack (TIA). Each of 258 subjects who developed CHF resulting in death, hospitalization, or withdrawal of randomized therapy during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. NT-proBNP and CRP predicted CHF the odds ratio for subjects in the highest compared with the lowest quarter was 4.5 (95% confidence interval, 2.7 to 7.5) for NT-proBNP and 2.9 (confidence interval, 1.9 to 4.7) for CRP, and each remained a predictor of CHF after adjustment for all other predictors. Screening for both markers provided better prognostic information than screening for either alone. Elevation of NT-proBNP above 50 pmol/L and CRP above 0.84 mg/L predicted CHF with sensitivity of 64% and specificity of 66%. NT-proBNP and CRP predicted CHF in subjects receiving perindopril-based therapy. We conclude that NT-proBNP and CRP are independent predictors of CHF risk after stroke or TIA. Moreover, NT-proBNP and CRP may be markers of mechanisms of CHF pathogenesis distinct from those responsive to angiotensin-converting enzyme inhibitor–based therapy.
Publisher: Springer Science and Business Media LLC
Date: 15-11-2018
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.JACC.2005.06.085
Abstract: In 1,049 patients with stable ischemic heart disease (IHD), brain natriuretic peptide (BNP) and amino terminal pro-brain natriuretic peptide (NTproBNP) correlated closely (r = 0.09, p < 0.001) and were similarly related to left ventricular ejection fraction (LVEF) (r = -0.50 and -0.46, respectively), age (0.44 and 0.47), and creatinine clearance (-0.51 and -0.51). Receiver-operating characteristic curves for detection of LVEF <30% were similar (area under the curves = 0.83 and 0.80, both p < 0.001), and both peptides had strong negative predictive value (95% and 94%). Both independently predicted all-cause mortality and/or heart failure with closely overlapping event-free survival curves BNP and NTproBNP display strong, near-identical test performance in ruling about severely reduced LVEF and in prediction of all-cause mortality or heart failure in stable IHD. The aim of this work was to test B-type natriuretic peptides for assessment of function and prognosis in stable ischemic heart disease (IHD) and to compare brain natriuretic peptide (BNP) with amino terminal pro-brain natriuretic peptide (NTproBNP), including the relative effects of age and renal function on test performance. Brain natriuretic peptide and NTproBNP are emerging diagnostic and prognostic markers in heart failure and acute coronary syndromes. Their performance in assessing function and prognosis in stable IHD is unknown. Whether one marker is superior and the relative effects of age and renal function on test performance are uncertain. In 1,049 patients with stable IHD, left ventricular ejection fraction (LVEF) was measured by radionuclide scanning and creatinine clearance estimated by the Cockroft-Gault equation. Age, gender, and body mass index were recorded. Twelve-month all-cause mortality or admission with heart failure was prospectively recorded BNP and NTproBNP were measured by radioimmunoassay. Brain natriuretic peptide and NTproBNP correlated closely (r = 0.90, p < 0.001) and had similar relationships to LVEF (r = -0.50 and -0.46, respectively, both p < 0.001), age (0.44 and 0.47, both p < 0.001), and creatinine clearance (-0.51 and -0.51, both p < 0.001). Areas under receiver-operating characteristic curves for detection of LVEF <30% were similar (0.83 and 0.80, both p < 0.001) with strong negative predictive values for both (95% and 94%). Both markers independently predicted the clinical end point with closely overlapping event-free survival curves. In stable IHD, BNP and NTproBNP display strong and near-identical test performance in ruling out severely reduced LVEF and in prediction of all-cause mortality or heart failure despite significant effects of age, gender, and renal function on levels of both markers.
Publisher: Elsevier BV
Date: 03-2000
DOI: 10.1016/S1071-9164(00)00007-5
Abstract: Beta-blocker therapy has been shown to improve left ventricular (LV) ejection fraction and reduce LV volumes in patients with heart failure caused by ischemic heart disease. However, the possible mechanisms of this improvement and the effects of such treatment on regional wall motion have not been established. In a substudy of the Australia-New Zealand trial of carvedilol in patients with heart failure caused by ischemic heart disease, the effects of treatment on LV regional wall motion were assessed using 2-dimensional echocardiography. One hundred nineteen patients from 10 centers were included on this substudy. Patients were randomly assigned to treatment with carvedilol or placebo. Echocardiography was performed before randomization and after 6 and 12 months of treatment. LV regional wall motion was assessed using a semiquantitative scoring system. LV wall motion score index (WMSI) was reduced from 2.40 to 2.29 after 6 and 12 months in the carvedilol group and remained unchanged in the placebo group (2-tailed P = .005, carvedilol vs placebo). The percentage of myocardium with normal function also significantly improved with carvedilol treatment. Carvedilol improved LV regional WMSI in patients with heart failure caused by ischemic heart disease. These results indicate a mechanism by which beta-blocker therapy may benefit patients with heart failure and are consistent with an intrinsic improvement in LV function after treatment with carvedilol.
Publisher: Wiley
Date: 11-2002
DOI: 10.1046/J.1445-2197.2002.02549.X
Abstract: Heterotopic bone formation is a well-established complication of major hip surgery, but traditional reviews of the published literature may have underestimated its frequency. A systematic overview of all the relevant studies was performed to determine reliably the incidence of any heterotopic bone formation and the incidence of each Brooker equivalent grade. Separate estimates were made for patients with total hip replacement and patients with acetabular fracture repair. A computer-based search identified 218 studies with data on the incidence of heterotopic bone formation after either hip replacement or acetabular fracture repair. These studies included data from an estimated 59 121 operated hips among patients that received total hip replacement and an estimated 998 hips among patients that underwent acetabular fracture repair. In these studies, the incidence of any heterotopic bone formation was 43% after total hip replacement and 51% after acetabular fracture repair. The incidence of severe heterotopic bone formation was 9% and 19%, respectively. These results suggest that heterotopic bone formation occurs more frequently after total hip replacement than is generally believed. It is possible that heterotopic bone formation is a more important cause of postoperative disability than has previously been recognized and that effective prophylactic regimens might improve outcome in substantial numbers of patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2006
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-11-2019
Abstract: Information is scarce regarding effects of antihypertensive medication on blood pressure variability ( BPV ) and associated clinical outcomes. We examined whether antihypertensive treatment changes BPV over time and whether such change (decline or increase) has any association with long‐term mortality in an elderly hypertensive population. We used data from a subset of participants in the Second Australian National Blood Pressure study (n=496) aged ≥65 years who had 24‐hour ambulatory blood pressure recordings at study entry (baseline) and then after a median of 2 years while on treatment (follow‐up). Weighted day‐night systolic BPV was calculated for both baseline and follow‐up as a weighted mean of daytime and nighttime blood pressure standard deviations. The annual rate of change in BPV over time was calculated from these BPV estimates. Furthermore, we classified both BPV estimates as high and low based on the baseline median BPV value and then classified BPV changes into stable: low BPV , stable: high BPV , decline: high to low , and increase: low to high . We observed an annual decline (mean± SD : −0.37±1.95 95% CI, −0.54 to −0.19 P .001) in weighted day‐night systolic BPV between baseline and follow‐up. Having constant stable: high BPV was associated with an increase in all‐cause mortality (hazard ratio: 3.03 95% CI, 1.67–5.52) and cardiovascular mortality (hazard ratio: 3.70 95% CI, 1.62–8.47) in relation to the stable: low BPV group over a median 8.6 years after the follow‐up ambulatory blood pressure monitoring. Similarly, higher risk was observed in the decline: high to low group. Our results demonstrate that in elderly hypertensive patients, average BPV declined over 2 years of follow‐up after initiation of antihypertensive therapy, and having higher BPV (regardless of any change) was associated with increased long‐term mortality.
Publisher: Elsevier BV
Date: 02-2001
DOI: 10.1016/S0140-6736(00)04042-3
Abstract: Statins inhibit the same biochemical pathway as aminobisphosphonates, therefore these cholesterol-lowering agents may have a beneficial effect on osteoporosis. This possibility has been supported by the finding that some statins also stimulate bone formation, and by observational studies suggesting that patients using statins have higher bone densities and lower fracture rates than controls. To assess whether statins have clinically significant effects on bone, we studied the frequency of fractures in a large randomised controlled trial of these agents. 9014 patients (17% women, median age 62 years) with ischaemic heart disease were randomly assigned pravastatin 40 mg daily or placebo and followed up for a mean of 6.0 years. Fractures were ascertained from adverse-event reports. 101 patients in the placebo group were admitted to hospital for fracture compared with 107 in the pravastatin group (hazard ratio 1.05 [95% CI 0.80-1.37]). When patients with fractures not necessitating hospital admission were added, the total number of patients having a fracture was 183 in the placebo group and 175 in the pravastatin group (0.94 [0.77-1.16]). Separate analyses for women alone and for in iduals aged 65 years and over gave similar results. These findings offer no support for the hypothesis that statins have a significant effect on fracture risk. However, this study was not of an osteoporotic population, and fracture rate, although clinically important, is an insensitive index of effects on bone. Statins should not be used to prevent osteoporosis until there is evidence for their efficacy based on randomised controlled trials.
Publisher: Elsevier BV
Date: 12-2003
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.IJMEDINF.2015.05.003
Abstract: Despite their potential for improving health outcomes, mobile-based home monitoring systems for heart failure have not yet been taken up widely by the patients and providers. To design and iteratively move towards a personalised mobile health monitoring system for patients living with heart failure, according to their health care and usability needs. We present an iterative approach to refining a remote health monitoring system that is based on interactions between different actors (patients, clinicians, social scientists and engineers) and supports the collection of quantitative and qualitative information about user experience and engagement. Patients were provided with tablet computers and commercially available sensing devices (a blood pressure monitor, a set of weighing scales, and a pulse oximeter) in order to complete physiological measurements at home, answer symptom-specific questionnaires, review their personal readings, view educational material on heart failure self-management, and communicate with their health professionals. The system supported unobtrusive remote software upgrades via an application distribution channel and the activation or deactivation of functional components by health professionals during run-time operation. We report early findings from the application of this approach in a cohort of 26 heart failure patients (mean age 72±15 years), their caregivers and healthcare professionals who participated in the SUPPORT-HF (Seamless User-centred Proactive Provision Of Risk-stratified Treatment for Heart Failure) study over a one-year study period (mean patient follow-up duration=270±62 days). The approach employed in this study led to several system upgrades dealing in particular with patient requirements for better communication with the development team and personalised self-monitoring interfaces. Engagement with the system was constantly high throughout the study and during the last week of the evaluation, 23 patients (88%) used the system at least once and 16 patients (62%) at least three times. Designers of future mobile-based home monitoring systems for heart failure and other chronic conditions could leverage the described approach as a means of meeting patients' needs during system use within the home environment and facilitating successful uptake.
Publisher: BMJ
Date: 02-08-2006
Publisher: BMJ
Date: 14-05-2014
Abstract: There is ongoing controversy regarding a 'J-curve' phenomenon such that low and high blood pressure (BP) levels are associated with increased risks of recurrent stroke. We aimed to determine whether large treatment-related BP reductions are associated with increased risks of recurrent stroke. Data are from the PROGRESS trial, where 6105 patients with cerebrovascular disease were randomly assigned to either active treatment (perindopril ± indapamide) or placebo(s). There were no BP criteria for entry. BP was measured at every visit, and participant groups defined by reduction in systolic BP (SBP) from baseline were used for the analyses. Outcome was recurrent stroke. During a mean follow-up of 3.9 years, 727 recurrent strokes were observed. There were clear associations between the magnitude of SBP reduction and the risk of recurrent stroke. After adjustment for cardiovascular risk factors and randomised treatment, annual incidence was 2.08%, 2.10%, 2.31% and 2.96% for participant groups defined by SBP reductions of ≥ 20, 10-19, 0-9 and <0 mm Hg, respectively (p=0.0006 for trend). The present analysis provided no evidence of an increase in recurrent stroke associated with larger reductions in SBP produced by treatment among patients with cerebrovascular disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-11-2013
Publisher: Wiley
Date: 16-09-2020
Publisher: Public Library of Science (PLoS)
Date: 09-12-2016
Publisher: Oxford University Press (OUP)
Date: 09-07-2015
Publisher: Elsevier BV
Date: 12-2000
DOI: 10.1016/S0140-6736(00)03257-8
Abstract: The LIPID study is a major trial of secondary prevention of coronary-heart-disease events that includes hospital admission with unstable angina (as well as myocardial infarction) as a qualifying event. In this substudy of LIPID, we compared subsequent cardiovascular risks and the effects of pravastatin in patients with previous unstable angina or previous myocardial infarction. 3260 patients diagnosed with unstable angina and 5754 with acute myocardial infarction 3-36 months previously were randomly assigned 40 mg pravastatin daily or placebo over a mean of 6.0 years. The risk reduction of a range of cardiovascular events was estimated by means of the hazard ratio in Cox's proportional hazards model. Among patients assigned placebo, survival in the two diagnosis groups was similar. The relative risk reduction for mortality with pravastatin was 20.6% in the myocardial infarction group and 26.3% in the unstable angina group (p=0.55). Pravastatin significantly reduced the rates of all prespecified coronary endpoints in the myocardial infarction group. In patients with previous unstable angina, coronary heart disease mortality, total mortality, myocardial infarction, a need for coronary revascularisation, the number of admissions to hospital, and the number of days in hospital were significantly lower with pravastatin. Overall, hospital admission for unstable angina was the most common endpoint (24.6% of the placebo group 22.3% of the pravastatin group). Patients who have survived acute myocardial infarction or unstable angina have a similar long-term prognosis, a high occurrence of subsequent unstable angina, and benefit similarly from therapy with pravastatin.
Publisher: Oxford University Press (OUP)
Date: 03-2003
Publisher: Oxford University Press (OUP)
Date: 10-2002
Abstract: To determine the effects on homocysteine levels of two doses of folic acid compared to placebo, where the high dose is typical of that provided by pharmacological intervention and the low dose approximates that provided by dietary supplementation. The PACIFIC study was a double-blind, placebo-controlled, factorial randomized trial. Seven hundred and twenty-three in iduals with a history of myocardial infarction or unstable angina were recruited from 28 clinical cardiology centres in Australia and New Zealand and randomized to folic acid 2.0 mg daily, folic acid 0.2 mg daily or placebo. The primary outcome, homocysteine, was measured using a fluorescence polarization immunoassay. Compared to placebo, 2.0 mg folic acid reduced homo-cysteine by 1.8 micromol x 1(-1) [95% confidence interval (CI) 1.3-2.3] and 0.2 mg reduced homocysteine by 1.2 micromol x 1(-1) [95% CI 0.8-1.7). The higher dose reduced homocysteine significantly more than the lower dose (P=001). Both doses of folic acid reduced homocysteine, but the effects of the 2.0 mg dose were about one third greater than the 0.2 mg dose. Fortification of foods with folic acid should result in population-wide lower levels of homocysteine but high-dose pharmacological supplementation would produce greater reductions for high-risk in iduals.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2007
Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1016/J.JACC.2008.08.049
Abstract: Cardiovascular disease (CVD) was the leading cause of death globally in 2005, responsible for 17.5 million deaths, more than 80% of which occurred in low- and middle-income countries (LMIC). In these regions, CVD occurs at a much younger age than in high-income countries, thereby contributing disproportionately to lost potential years of healthy life as well as lost economic productivity. Many effective interventions for CVD prevention and management are now affordable for all but the very poorest countries, but large treatment gaps still exist because of poor prescribing practices, limited availability of medicines, and lack of appropriately skilled health care providers. Despite the increasing awareness of the growing epidemic of CVD in LMIC, this public health priority has received little attention from those who determine the international health agenda. Although the burden of CVD is already enormous in developing countries, there exists a window of opportunity to prevent the epidemic reaching its full potential magnitude. This requires the rapid deployment of strategies already proven to be effective in high-income countries. Such strategies need to be tailored for LMIC for them to be affordable, effective, and accessible to disadvantaged groups and the burgeoning middle classes. Ideally, the control of CVD in these countries would involve a dual approach in which evidence-based clinical strategies for CVD prevention and treatment are complemented by evidence-based population level strategies. We propose that upgrading primary health care services is a central requirement for the control of the CVD epidemics facing the developing world.
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1038/KI.2013.553
Publisher: American Medical Association (AMA)
Date: 04-09-2013
Publisher: Wiley
Date: 06-12-2001
DOI: 10.1046/J.1440-1681.2001.03581.X
Abstract: 1. Diabetes is a major global public health problem. The prevalence of this disease is predicted to increase sharply in the coming decades, particularly in less-developed regions of the world. 2. Most premature morbidity and mortality associated with diabetes relates to markedly increased risks of major cardiovascular diseases, such as myocardial infarction and stroke (macrovascular events), as well as microvascular complications, such as nephropathy and retinopathy. 3. Hypertension is a prevalent and important risk factor for vascular events in these patients. However, observational data demonstrate a continuous relationship between blood pressure and risk of vascular events, suggesting that even those in iduals considered normotensive may benefit from blood pressure lowering. 4. Trials of blood pressure lowering among mostly hypertensive in iduals with diabetes have demonstrated benefit of intervention on macrovascular and microvascular outcomes. Recent data may suggest additional effects of angiotensin- converting enzyme inhibitors independent of blood pressure lowering. 5. Issues where data are lacking with respect to blood pressure lowering in diabetes include the effects of blood pressure lowering among non-hypertensive in iduals and the effects of blood pressure lowering regimens based on different classes of drug. 6. Data expected to address some of these issues are being collected. These include a prospective meta-analysis of blood pressure-lowering trials with large numbers of patients with diabetes. A new large-scale randomised trial, ADVANCE (Action in Diabetes and Vascular Disease), is also described.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2003
DOI: 10.1097/00004872-200306005-00003
Abstract: To determine the effects of a perindopril-based blood pressure lowering regimen in hypertensive and non-hypertensive patients with a history of stroke or transient ischaemic attack (TIA). 6105 subjects from 172 centres in Asia, Australasia, and Europe were randomised to receive active treatment (n = 3051) or placebo (n = 3054). Active treatment consisted of a flexible regimen based on the angiotensin-converting enzyme inhibitor perindopril (4 mg daily), with the addition of the diuretic indapamide, at the discretion of treating physicians. The primary outcome was total stroke (fatal or non-fatal). Analysis was by intention to treat. Active treatment reduced blood pressure by 9/4 mmHg over 4 years of follow-up. 307 (10%) in iduals assigned active treatment suffered a stroke, compared with 420 (14%) assigned placebo [relative risk reduction 28% (95% confidence interval 17-38), P < 0.0001]. Active treatment also reduced the risks of total major vascular events [26% (16-34)] including non-fatal myocardial infarction [38% (14-55)], severe cognitive decline [19% (4-32)], stroke-related dementia [34% (3-55)] and disability [18% (8-28)]. There were similar reductions in the risk of stroke in hypertensive and non-hypertensive subgroups (P < 0.01). Combination therapy with perindopril plus indapamide lowered blood pressure by 12/5 mmHg and stroke risk by 43%. Single-drug therapy lowered blood pressure by 5/3 mmHg and produced no significant fall in the risk of stroke. The blood-pressure lowering regimen used in Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) reduced the risks of stroke and other serious events in hypertensive and non-hypertensive subjects with a history of stroke (whatever the subtype) or transient ischaemic attack. Combination therapy with perindopril and indapamide produced larger blood pressure reductions and larger stroke reductions than monotherapy with perindopril alone. Treatment with these two agents should be considered routinely for all patients with a history of previous stroke or TIA, whether hypertensive or normotensive.
Publisher: Oxford University Press (OUP)
Date: 06-03-2009
DOI: 10.1093/IJE/DYP150
Abstract: In Caucasian populations, adult height is inversely associated with cardiovascular disease (CVD) risk and positively related to some cancers. However, there are few data from Asian populations and from women. We sought to determine the sex- and region-specific associations between height and cardiovascular outcomes, and deaths due to cancer, respiratory and injury in populations from the Asia-Pacific region. Thirty-nine studies from the Asia Pacific Cohort Studies Collaboration database were included. We used Cox proportional hazard regression models to estimate the associations between height and pre-specified outcomes. A total of 510,800 participants with 21,623 deaths were included. Amongst men, inverse linear associations were observed between height and coronary heart disease (CHD), stroke, CVD, injury and total mortality. The hazard ratios [95% confidence intervals, (CI)] for a 1-SD (= 6 cm) increment in height ranged from 0.85 (0.80-0.91) for injury to 0.97 (0.95-0.98) for total mortality. Similar trends were found between height and CHD, haemorrhagic stroke and CVD in women. A positive linear association was observed between height and cancer mortality. For each standard deviation greater height, the risk of cancer was increased by 5% (2-8%) and 9% (5-14%) in men and women, respectively. No regional difference was observed between Asian and Australasian cohorts. Adjusting for markers of education did not alter the results. The opposing relationships of height with CVD and cancer suggest that care is required in setting national policies on childhood nutrition lest they have unintended consequences on the incidence of major non-communicable diseases.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2005
DOI: 10.1161/01.STR.0000181754.38408.4C
Abstract: Background and Purpose— Several prospective studies have shown significant associations between plasma fibrinogen, viscosity, C-reactive protein (CRP), fibrin d -dimer, or tissue plasminogen activator (tPA) antigen and the risk of primary cardiovascular events. Little has been published on the associations of these variables with recurrent stroke. We studied such associations in a nested case-control study derived from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). Methods— Nested case-control study of ischemic (n=472) and hemorrhagic (n=83) strokes occurring during a randomized, placebo-controlled multicenter trial of perindopril-based therapy in 6105 patients with a history of stroke or transient ischemic attack. Controls were matched for age, treatment group, sex, region, and most recent qualifying event at entry to the parent trial. Results— Fibrinogen and CRP were associated with an increased risk of recurrent ischemic stroke after accounting for the matching variables and adjusting for systolic blood pressure, smoking, peripheral vascular disease, and statin and antiplatelet therapy. The odds ratio for the last compared with the first third of fibrinogen was 1.34 (95% CI, 1.01 to 1.78) and for CRP was 1.39 (95% CI, 1.05 to 1.85). After additional adjustment for each other, these 2 odds ratios stayed virtually unchanged. Plasma viscosity, tPA, and d -dimer showed no relationship with recurrent ischemic stroke, although tPA was significant for lacunar and large artery subtypes. Although each of these variables showed a negative relationship with recurrent hemorrhagic stroke, none of these relationships achieved statistical significance. Conclusions— Fibrinogen and CRP are risk predictors for ischemic but not hemorrhagic stroke, independent of potential confounders.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2003
Publisher: BMJ
Date: 13-10-2013
Publisher: Elsevier BV
Date: 05-2008
Publisher: Elsevier BV
Date: 08-2012
Publisher: Elsevier BV
Date: 11-2010
Publisher: Elsevier BV
Date: 03-2012
Publisher: Elsevier BV
Date: 07-2018
Publisher: Elsevier BV
Date: 03-1990
DOI: 10.1016/0140-6736(90)90878-9
Abstract: The associations of diastolic blood pressure (DBP) with stroke and with coronary heart disease (CHD) were investigated in nine major prospective observational studies: total 420,000 in iduals, 843 strokes, and 4856 CHD events, 6-25 (mean 10) years of follow-up. The combined results demonstrate positive, continuous, and apparently independent associations, with no significant heterogeneity of effect among different studies. Within the range of DBP studied (about 70-110 mm Hg), there was no evidence of any "threshold" below which lower levels of DBP were not associated with lower risks of stroke and of CHD. Previous analyses have described the uncorrected associations of DBP measured just at "baseline" with subsequent disease rates. But, because of the diluting effects of random fluctuations in DBP, these substantially underestimate the true associations of the usual DBP (ie, an in idual's long-term average DBP) with disease. After correction for this "regression dilution" bias, prolonged differences in usual DBP of 5, 7.5, and 10 mm Hg were respectively associated with at least 34%, 46%, and 56% less stroke and at least 21%, 29%, and 37% less CHD. These associations are about 60% greater than in previous uncorrected analyses. (This regression dilution bias is quite general, so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths.) The DBP results suggest that for the large majority of in iduals, whether conventionally "hypertensive" or "normotensive", a lower blood pressure should eventually confer a lower risk of vascular disease.
Publisher: American Medical Association (AMA)
Date: 2006
DOI: 10.1001/ARCHNEUR.63.1.NOC50221
Abstract: Patients with stroke or transient ischemic attack are at high risk of another stroke, and there is need for improved strategies to predict recurrent stroke. To assess the prognostic value of levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size in patients with previous stroke or transient ischemic attack. A nested case-control study of participants of the Perindopril Protection Against Recurrent Stroke Study was performed. The Perindopril Protection Against Recurrent Stroke Study was a placebo-controlled trial of a perindopril erbumine-based, blood pressure-lowering regimen that reduced ischemic stroke risk by 24% among in iduals with previous stroke or transient ischemic attack. Each of 252 patients who experienced ischemic stroke during a mean follow-up of 3.9 years was matched to 1 to 3 control patients. Matching variables were age, sex, treatment allocated, region, and most recent qualifying event at randomization. Risk of ischemic stroke predicted by baseline levels of sVCAM-1, NT-proBNP, C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size. Levels of sVCAM-1 and NT-proBNP predicted recurrent ischemic stroke. The odds ratio for patients in the highest, as compared with the lowest, quarter was 2.24 (95% confidence interval, 1.35-3.73) for sVCAM-1 level and 1.62 (95% confidence interval, 0.98-2.69) for NT-proBNP level, after adjustment for matching and other risk factors. Patients in the highest quarters for both sVCAM-1 and NT-proBNP levels had 3.6 times the risk of recurrent ischemic stroke compared with patients in the lowest quarters for both biologic markers. Level of sVCAM-1 was similarly predictive of ischemic stroke in patients allocated to placebo and perindopril-based therapy. Baseline plasma levels of C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size did not predict recurrent ischemic stroke risk. Measurement of sVCAM-1 and NT-proBNP levels provides prognostic information for recurrent ischemic stroke beyond traditional risk factors.
Publisher: Public Library of Science (PLoS)
Date: 26-03-2019
Publisher: Oxford University Press (OUP)
Date: 28-07-2004
DOI: 10.1093/IJE/DYH163
Publisher: Oxford University Press (OUP)
Date: 10-06-2010
Abstract: The efficacy of angiotensin-converting enzyme (ACE)-inhibitors in stable coronary artery disease (CAD) may be increased by targeting the therapy to those patients most likely to benefit. However, these patients cannot be identified by clinical characteristics. We developed a genetic profile to predict the treatment benefit of ACE-inhibitors exist and to optimize therapy with ACE-inhibitors. In 8907 stable CAD patients participating in the randomized placebo-controlled EUROPA-trial, we analysed 12 candidate genes within the pharmacodynamic pathway of ACE-inhibitors, using 52 haplotype-tagging-single nucleotide polymorphisms (SNPs). The primary outcome was the reduction in cardiovascular mortality, non-fatal myocardial infarction, and resuscitated cardiac arrest during 4.2 years of follow-up. Multivariate Cox regression was performed with multiple testing corrections using permutation analysis. Three polymorphisms, located in the angiotensin-II type I receptor and bradykinin type I receptor genes, were significantly associated with the treatment benefit of perindopril after multivariate adjustment for confounders and correction for multiple testing. A pharmacogenetic score, combining these three SNPs, demonstrated a stepwise reduction of risk in the placebo group and a stepwise decrease in treatment benefit of perindopril with an increasing scores (interaction P < 0.0001). A pronounced treatment benefit was observed in a subgroup of 73.5% of the patients [hazard ratio (HR) 0.67 95% confidence interval (CI) 0.56-0.79], whereas no benefit was apparent in the remaining 26.5% (HR 1.26 95% CI 0.97-1.67) with a trend towards a harmful effect. In 1051 patients with cerebrovascular disease from the PROGRESS-trial, treated with perindopril or placebo, an interaction effect of similar direction and magnitude, although not statistically significant, was observed. The current study is the first to identify genetic determinants of treatment benefit of ACE-inhibitor therapy. We developed a genetic profile which predicts the treatment benefit of ACE-inhibitors and which could be used to optimize therapy.
Publisher: Elsevier BV
Date: 10-2004
Publisher: Springer Science and Business Media LLC
Date: 30-04-2008
DOI: 10.1007/S10198-008-0108-3
Abstract: Cerebrovascular disease (or stroke) is one of the main causes of long-term disability and the second leading cause of death worldwide. The economic impact of stroke is clearly seen, as it is the largest single cause of bed occupancy in hospitals in England and accounts for 6% of hospital costs. This analysis is the first to quantify the economic consequences of a blood pressure lowering regimen based on the PROGRESS study (perindopril-based regimen), for reducing future cardiovascular events. A Markov decision analytical model was used to estimate the cost per quality adjusted life year (QALY) of blood pressure lowering in the treatment of patients presenting with a cerebrovascular event. The health states are based upon Barthel indices for which resource utilisation and health benefits have previously been estimated. The participants for the economic analysis were obtained from the PROGRESS study database. 6,105 clinical study participants were recruited through both primary and secondary care centres. The mean age was 64 years 70% were male in the original study. In the PROGRESS study, blood pressure lowering by a perindopril-based regimen was compared to standard care. Cost per quality adjusted life year for the duration of the study (4 years) and for a time span of 20 years. Using only direct hospital medical costs, the cost per QALY for a perindopril based regimen is pound 6,927 for the base study period and pound 10,133 for a 20-year time period. These results are sensitive to the cost of perindopril, the cost of the stroke unit, length of stay, and to a lesser extent, the cost of indapamide. This analysis demonstrates a cost-effective treatment for patients suffering a cerebrovascular event with a blood pressure lowering regimen. The findings of this study are in line with current decisions and guidance by the national institute for health and clinical excellence (NICE) in England.
Publisher: American Medical Association (AMA)
Date: 12-05-2003
Publisher: Springer Science and Business Media LLC
Date: 2004
Publisher: Elsevier BV
Date: 06-2001
DOI: 10.1016/S0735-1097(01)01269-4
Abstract: We sought to assess plasma concentrations of the amino (N)-terminal portion of pro-brain natriuretic peptide (N-BNP) and adrenomedullin for prediction of adverse outcomes and responses to treatment in 297 patients with ischemic left ventricular (LV) dysfunction who were randomly assigned to receive carvedilol or placebo. Although neurohormonal status has known prognostic significance in heart failure, the predictive power of either N-BNP or adrenomedullin in chronic ischemic LV dysfunction has not been previously reported. Plasma N-BNP and adrenomedullin were measured in 297 patients with chronic ischemic (LV) dysfunction before randomization to carvedilol or placebo, added to established treatment with a converting enzyme inhibitor and loop diuretic (with or without digoxin). The patients' clinical outcomes, induding mortality and heart failure events, were recorded for 18 months. Above-median N-BNP and adrenomedullin levels conferred increased risks (all p < 0.001) of mortality (risk ratios [95% confidence intervals]: 4.67 [2-10.9] and 3.92 [1.76-8.7], respectively) and hospital admission with heart failure (4.7 [2.2-10.3] and 2.4 [1.3-4.5], respectively). Both of these predicted death or heart failure independent of age, New York Heart Association functional class, LV ejection fraction, previous myocardial infarction or previous admission with heart failure. Carvedilol reduced the risk of death or heart failure in patients with above-median levels of N-BNP or adrenomedullin, or both, to rates not significantly different from those observed in patients with levels below the median value. In patients with established ischemic LV dysfunction, plasma N-BNP and adrenomedullin are independent predictors of mortality and heart failure. Carvedilol reduced mortality and heart failure in patients with higher pre-treatment plasma N-BNP and adrenomedullin.
Publisher: Elsevier BV
Date: 11-2003
DOI: 10.1016/S0140-6736(03)14739-3
Abstract: The benefits of reducing blood pressure on the risks of major cardiovascular disease are well established, but uncertainty remains about the comparative effects of different blood-pressure-lowering regimens. We aimed to estimate effects of strategies based on different drug classes (angiotensin-converting-enzyme [ACE] inhibitors, calcium antagonists, angiotensin-receptor blockers [ARBs], and diuretics or beta blockers) or those targeting different blood pressure goals, on the risks of major cardiovascular events and death. We did seven sets of prospectively-designed overviews with data from 29 randomised trials (n=162341). The trial eligibility criteria, primary outcomes, and main hypotheses were specified before the result of any contributing trial was known. In placebo-controlled trials the relative risks of total major cardiovascular events were reduced by regimens based on ACE inhibitors (22% 95% CI 17-27) or calcium antagonists (18% 5-29). Greater risk reductions were produced by regimens that targeted lower blood pressure goals (15% 5-24). ARB-based regimens reduced the risks of total major cardiovascular events (10% 4-17) compared with control regimens. There were no significant differences in total major cardiovascular events between regimens based on ACE inhibitors, calcium antagonists, or diuretics or beta blockers, although ACE-inhibitor-based regimens reduced blood pressure less. There was evidence of some differences between active regimens in their effects on cause-specific outcomes. For every outcome other than heart failure, the difference between randomised groups in achieved blood pressure reduction was directly related to the observed difference in risk. Treatment with any commonly-used regimen reduces the risk of total major cardiovascular events, and larger reductions in blood pressure produce larger reductions in risk.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2005
DOI: 10.1161/01.STR.0000181115.59173.42
Abstract: Background and Purpose— Patients with atrial fibrillation have a high risk of stroke and other vascular events even if anticoagulated. The primary objective here is to determine whether routine blood pressure–lowering provides additional protection for this high-risk patient group. Methods— This study was a subsidiary analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS)—a randomized, placebo-controlled trial that established the beneficial effects of blood pressure–lowering in a heterogeneous group of patients with cerebrovascular disease. A total of 6105 patients were randomly assigned to either active treatment (2 to 4 mg perindopril for all participants plus 2.0 to 2.5 mg indapamide for those without an indication for or a contraindication to a diuretic) or matching placebo(s). Outcomes are total major vascular events, cause-specific vascular outcomes, and death from any cause. Results— There were 476 patients with atrial fibrillation at baseline, of whom 51% were taking anticoagulants. In these patients, active treatment lowered mean blood pressure by 7.3/3.4 mm Hg and was associated with a 38% (95% confidence interval [CI], 6 to 59) reduction in major vascular events and 34% (95% CI, −13 to 61) reduction in stroke. The benefits of blood pressure–lowering in patients with atrial fibrillation were achieved irrespective of the use of anticoagulant therapy ( P homogeneity=0.8) or the presence of hypertension ( P homogeneity=0.4). Conclusions— For most patients with atrial fibrillation, routine blood pressure–lowering is likely to provide protection against major vascular events additional to that conferred by anticoagulation.
Publisher: Springer Science and Business Media LLC
Date: 18-08-2009
DOI: 10.1007/S00125-009-1484-7
Abstract: The relationship between cognitive function, cardiovascular disease and premature death is not well established in patients with type 2 diabetes. We assessed the effects of cognitive function in 11,140 patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Furthermore, we tested whether level of cognitive function altered the beneficial effects of the BP-lowering and glycaemic-control regimens in the trial. Cognitive function was assessed using the Mini Mental State Examination at baseline, and defined by scores 28-30 ('normal', n = 8,689), 24-27 ('mild dysfunction', n = 2,231) and <24 ('severe dysfunction', n = 212). Risks of major cardiovascular events, death and hypoglycaemia and interactions with treatment were assessed using Cox proportional hazards analysis. Relative to normal function, both mild and severe cognitive dysfunction significantly increased the multiple-adjusted risks of major cardiovascular events (HR 1.27, 95% CI 1.11-1.46 and 1.42, 95% CI 1.01-1.99 both p < 0.05), cardiovascular death (1.41, 95% CI 1.16-1.71 and 1.56, 95% CI 0.99-2.46 both p <or= 0.05) and all-cause death (1.33, 95% CI 1.16-1.54 and 1.50, 95% CI 1.06-2.12 both p < 0.03). Severe, but not mild, cognitive dysfunction increased the risk of severe hypoglycaemia (HR 2.10, 95% CI 1.14-3.87 p = 0.018). There was no evidence of heterogeneity of treatment effects on cardiovascular outcomes in subgroups defined by cognitive function at baseline. Cognitive dysfunction is an independent predictor of clinical outcomes in patients with type 2 diabetes, but does not modify the effects of BP lowering or glucose control on the risks of major cardiovascular events. ClinicalTrials.gov NCT00145925.
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.PCAD.2010.03.002
Abstract: Around one-quarter of the world's adult population are defined as "hypertensive" however a much greater proportion are at risk of blood pressure-related disease because of the nature of the association between blood pressure and cardiovascular risk. The Framingham Study, together with other landmark observational studies, has been instrumental in elucidating this relationship. As early as the 1960s, Framingham showed that the association between blood pressure and cardiovascular risk was continuous and linear and was consistent across different age groups and for a range of major cardiovascular events. As the first major observational study to include substantial numbers of women, it was also able to debunk the myth that women "could tolerate blood pressure well". In more recent decades, Framingham has been central to the development of the notion of absolute risk and the importance of blood pressure alongside other risk factors. Much of our current understanding of the role blood pressure in cardiovascular disease can be attributed to decades of high quality research from Framingham.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2014
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Stephen MacMahon.