ORCID Profile
0000-0002-8094-1841
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University College Hospital
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University College London
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2015
Publisher: Elsevier BV
Date: 07-2020
Publisher: Cold Spring Harbor Laboratory
Date: 02-11-2019
DOI: 10.1101/19010785
Abstract: Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction can lead to timely intervention and better outcomes. Through summary statistics of meta-analyses of published genome-wide association studies performed in over 1.2 million of in iduals, we combined 9 PRS gathering genomic variants associated to cardiovascular and renal diseases and their key risk factors into one logistic regression model, to predict micro- and macrovascular endpoints of diabetes. Its clinical utility in predicting complications of diabetes was tested in 4098 participants with diabetes of the ADVANCE trial followed during a period of 10 years and replicated it in three independent non-trial cohorts. The prediction model adjusted for ethnicity, sex, age at onset and diabetes duration, identified the top 30% of ADVANCE participants at 3.1-fold increased risk of major micro- and macrovascular events (p=6.3×10 −21 and p=9.6×10 −31 , respectively) and at 4.4-fold (p=6.8×10 −33 ) increased risk of cardiovascular death compared to the remainder of T2D subjects. While in ADVANCE overall, combined intensive therapy of blood pressure and glycaemia decreased cardiovascular mortality by 24%, the prediction model identified a high-risk group in whom this therapy decreased mortality by 47%, and a low risk group in whom the therapy had no discernable effect. Patients with high PRS had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years. This novel polygenic prediction model identified people with diabetes at low and high risk of complications and improved targeting those at greater benefit from intensive therapy while avoiding unnecessary intensification in low-risk subjects.
Publisher: SAGE Publications
Date: 02-2017
Abstract: Understanding patients’ perspective towards HIV screening in Malaysia is pivotal to explore challenges faced by these in iduals. This would be beneficial for developing local plans to improve the health-seeking behaviours among population at risk of HIV/AIDS. A qualitative research methodology was adopted to explore HIV/AIDS patients’ views about disease screening. A semi-structured interview guide was used for in-depth patient interviews. All interviews were audio-recorded and were subjected to a standard content analysis framework for data analysis. Most patients were positive about screening and the value of knowing about their status early. However, fear of social stigma, discrimination, lack of support system and lack of public understanding were identified as major concerns affecting their willingness to be screened. They were concerned about mandatory screening being implemented without improvement in support system and public education. Reluctance to seek HIV screening is an important factor contributing to transmission in developing countries. In the Malaysian context, efforts should be made to strengthen screening strategies especially in the most-at-risk populations to monitor the epidemic and target prevention strategies. In a multicultural context, HIV preventive strategies must include disease awareness, including measure to tackle barriers towards screening.
Publisher: American Diabetes Association
Date: 12-07-2014
DOI: 10.2337/DC13-2625
Abstract: We investigated microvascular event risk in people with type 2 diabetes and assessed whether N-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) improved prediction. We performed a case-cohort study, including 439 incident cases of microvascular events (new or worsening nephropathy or retinopathy) and 2,946 noncase subjects identified from participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. NT-proBNP and hsTnT were measured in stored plasma s les using automated commercial assays. After adjustment for age, sex, and randomized treatment, the hazard ratios for microvascular events per 1-SD increase in the log-transformed hsTnT and NT-proBNP were 1.67 (95% CI 1.51–1.85) and 1.63 (1.44–1.84), respectively. After further adjustment for classical and diabetes-related cardiovascular disease risk factors, the hazard ratios attenuated to 1.40 (1.24–1.58) and 1.41 (1.24–1.60), respectively. While the C statistic did not improve on addition of hsTnT or NT-proBNP for the total microvascular end point, a combination of both markers improved the prediction of nephropathy (P = 0.033) but not retinopathy (P = 0.72). The corresponding net reclassification indices in a three–risk category model (& %, 10–15%, and & % 5-year risk) for all microvascular events were 7.31% (95% CI 2.24–12.79) for hsTNT addition, 6.23% (1.74–11.5) for NT-proBNP addition, and 7.1% (1.5–12.9) for both markers together. These data suggest that cardiac biomarkers moderately improve microvascular event risk prediction, in particular the risk of nephropathy. Further studies examining the value of this approach for trial design and clinical use are warranted.
Publisher: Oxford University Press (OUP)
Date: 16-11-2019
DOI: 10.1093/AJH/HPY169
Abstract: The influence of age on balance of benefit vs. potential harm of blood pressure (BP)-lowering therapy for elderly hypertensives is unclear. We evaluated the modifying effects of age on BP lowering for various adverse outcomes in hypertensive patients older than 60 years without specified comorbidities. All relevant randomized controlled trials (RCTs) were systematically identified. Coronary heart disease, stroke, heart failure (HF), cardiovascular death, major adverse cardiovascular events (MACE), renal failure (RF), and all-cause death were assessed. Meta-regression analysis was used to explore the relationship between achieved systolic BP (SBP) and the risk of adverse events. Random-effects meta-analysis was used to pool the estimates. Our study included 18 RCTs (n = 53,993). Meta-regression analysis showed a lower achieved SBP related with a lower risk of stroke and cardiovascular death, but an increased risk of RF. The regression slopes were comparable between populations stratifying by age 75 years. In subgroup analysis, the relative risks of a more aggressive BP lowering strategy were similar between patients aged older or less than 75 years for all outcomes except for RF (P for interaction = 0.02). Compared to treatment with final achieved SBP 140–150 mm Hg, a lower achieved SBP (& mm Hg) was significantly associated with decreased risk of stroke (relative risk = 0.68 95% confidence interval = 0.55–0.85), HF (0.77 0.60–0.99), cardiovascular death (0.68 0.52–0.89), and MACE (0.83 0.69–0.99). To treat hypertension in the elderly, age had trivial effect modification on most outcomes, except for renal failure. Close monitoring of renal function may be warranted in the management of elderly hypertension.
Publisher: American Diabetes Association
Date: 25-07-2016
DOI: 10.2337/DC16-0588
Abstract: Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis in type 2 diabetes, but the relationship between other vascular diseases and PAD has been poorly investigated. We examined the impact of previous microvascular and macrovascular disease on the risk of major PAD in patients with type 2 diabetes. We analyzed 10,624 patients with type 2 diabetes free from baseline major PAD in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) clinical trial. The primary composite outcome was major PAD defined as PAD-induced death, peripheral revascularization, lower-limb utation, or chronic ulceration. The secondary end points were the PAD components considered separately. Major PAD occurred in 620 (5.8%) participants during 5 years of follow-up. Baseline microvascular and macrovascular disease were both associated with subsequent risk of major PAD after adjustment for age, sex, region of origin, and randomized treatments. However, only microvascular disease remained significantly associated with PAD after further adjustment for established risk factors. The highest risk was observed in participants with a history of macroalbuminuria (hazard ratio 1.91 [95% CI 1.38–2.64], P & 0.0001) and retinal photocoagulation therapy (1.60 [1.11–2.32], P = 0.01). Baseline microvascular disease was also associated with a higher risk of chronic lower-limb ulceration (2.07 [1.56–2.75], P & 0.0001) and utation (1.59 [1.15–2.22], P = 0.006), whereas baseline macrovascular disease was associated with a higher rate of angioplasty procedures (1.75 [1.13–2.73], P = 0.01). Microvascular disease, particularly macroalbuminuria and retinal photocoagulation therapy, strongly predicts major PAD in patients with type 2 diabetes, but macrovascular disease does not.
Publisher: Oxford University Press (OUP)
Date: 21-02-2012
DOI: 10.1093/NDT/GFS022
Abstract: Diabetes and chronic kidney disease (CKD) are both associated with an increased risk of cancer but it is unclear whether diabetes complicated by CKD further augments an in idual's cancer risk. The aim of our study was to determine the association of CKD [defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min] with the overall and site-specific risks of incident cancers among in iduals with Type 2 diabetes. Cox proportional hazard regression models and competing risk analyses were used to examine the univariate and multivariate adjusted associations between reduced kidney function and the overall and site-specific risks of cancer in participants enrolled in the Action in Diabetes and Vascular disease: Preterax and Diamicron MR controlled evaluation (ADVANCE) trial. Over a median follow-up of 5.0 years, 700 malignant neoplasms occurred in the 11 140 (6.4%) participants. There was no increase in overall cancer risk [adjusted hazard ratio: 1.07 (95% confidence interval: 0.89-1.29, P = 0.50)] or site-specific cancer risk for in iduals with CKD (defined as eGFR < 60 mL/min) compared to those without CKD at baseline. These results were robust to multiple methods and thresholds used to estimate CKD. Mild to moderate CKD does not increase the risk of cancer in people with Type 2 diabetes. ADVANCE is registered with ClincalTrial.gov (number NCT00145925).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2009
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: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2022
DOI: 10.2215/CJN.00180122
Abstract: Hyperkalemia after starting renin-angiotensin system inhibitors has been shown to be subsequently associated with a higher risk of cardiovascular and kidney outcomes. However, whether to continue or discontinue the drug after hyperkalemia remains unclear. Data came from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, which included a run-in period where all participants initiated angiotensin-converting enzyme inhibitor–based therapy (a fixed combination of perindopril and indapamide). The study population was taken as patients with type 2 diabetes with normokalemia (serum potassium of 3.5 to .0 mEq/L) at the start of run-in. Potassium was remeasured 3 weeks later when a total of 9694 participants were classified into hyperkalemia (≥5.0 mEq/L), normokalemia, and hypokalemia ( .5 mEq/L) groups. After run-in, patients were randomized to continuation of the angiotensin-converting enzyme inhibitor–based therapy or placebo major macrovascular, microvascular, and mortality outcomes were analyzed using Cox regression during the following 4.4 years (median). During active run-in, 556 (6%) participants experienced hyperkalemia. During follow-up, 1505 participants experienced the primary composite outcome of major macrovascular and microvascular events. Randomized treatment of angiotensin-converting enzyme inhibitor–based therapy significantly decreased the risk of the primary outcome (38.1 versus 42.0 per 1000 person-years hazard ratio, 0.91 95% confidence interval, 0.83 to 1.00 P =0.04) compared with placebo. The magnitude of effects did not differ across subgroups defined by short-term changes in serum potassium during run-in ( P for heterogeneity =0.66). Similar consistent treatment effects were also observed for all-cause death, cardiovascular death, major coronary events, major cerebrovascular events, and new or worsening nephropathy ( P for heterogeneity ≥0.27). Continuation of angiotensin-converting enzyme inhibitor–based therapy consistently decreased the subsequent risk of clinical outcomes, including cardiovascular and kidney outcomes and death, regardless of short-term changes in serum potassium. Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), NCT00145925
Publisher: Elsevier BV
Date: 11-2021
Publisher: Springer Science and Business Media LLC
Date: 17-09-2014
DOI: 10.1007/S00125-014-3369-7
Abstract: Data are inconsistent regarding the associations between age, age at diagnosis of diabetes, diabetes duration and subsequent vascular complications. The associations between age (or age at diagnosis), diabetes duration and major macrovascular events, all-cause death and major microvascular events were examined in 11,140 patients with type 2 diabetes randomly allocated to intensive or standard glucose control in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Rates were calculated by 5 year baseline age (or age at diagnosis) and diabetes duration strata. Risks were estimated using Cox models adjusted for treatment assignment and HbA1c. The mean age (±SD) was 65.8 ± 6.4 years, age at diagnosis was 57.8 ± 8.7 years and diabetes duration was 7.9 ± 6.4 years. Diabetes duration was associated with the risk of macrovascular events (HR 1.13 [95% CI 1.08, 1.17]), microvascular events (1.28 [1.23, 1.33]) and death (1.15 [1.10, 1.20]) whereas age (or age at diagnosis) was only associated with the risk of macrovascular events (1.33 [1.27, 1.39]) and death (1.56 [1.48, 1.64]). No interaction was observed between diabetes duration, age and the risk of macrovascular events or death (both p > 0.4). However, an interaction was observed between diabetes duration, age and the risk of microvascular events (p = 0.002), such that the effects of increasing diabetes duration were greatest at younger rather than older age. In patients with type 2 diabetes, age or age at diagnosis and diabetes duration are independently associated with macrovascular events and death whereas only diabetes duration is independently associated with microvascular events and this effect is greater in the youngest patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2020
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: 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: Europa Digital & Publishing
Date: 08-2013
DOI: 10.4244/EIJV9I4A78
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2018
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: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.DIABRES.2017.03.015
Abstract: The relationship between educational level and the risk of all-cause mortality is well established, whereas the association with vascular events in in iduals with type 2 diabetes is not well described. Any association may reflect a link with common cardiovascular or lifestyle-based risk factors. The relationships between the highest level of educational attainment and major cardiovascular events, microvascular complications and all-cause mortality were explored in a cohort of 11,140 in iduals with type 2 diabetes. Completion of formal education before the age of 16 was categorized as a low level of education. Regional differences between Asia, East Europe and Established Market Economies were also assessed. During a median of 5years of follow up, 1031 (9%) patients died, 1147 (10%) experienced a major cardiovascular event and 1136 (10%) a microvascular event. After adjustment for baseline characteristics and risk factors, in iduals with lower education had an increased risk of cardiovascular events (hazard ratio (HR) 1.31, 95% CI 1.16-1.48, p<0.0001), microvascular events (HR 1.23, 95% CI 1.08-1.39, p=0.0013) and all-cause mortality (HR 1.34, 95% CI 1.18-1.52, p<0.0001). In regional analyses the increased risk of studied outcomes associated with lower education was weakest in Established Market Economies and strongest in East Europe. A low level of education is associated with an increased risk of vascular events and death in patients with type 2 diabetes, independently of common lifestyle associated cardiovascular risk factors. The effect size varies between geographical regions.
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.JACC.2022.08.802
Abstract: Renal denervation (RDN) has been shown to lower blood pressure (BP), but its effects on cardiovascular events have only been preliminarily evaluated. Time in therapeutic range (TTR) of BP is associated with cardiovascular events. This study sought to assess the impact of catheter-based RDN on TTR and its association with cardiovascular outcomes in the GSR (Global SYMPLICITY Registry). Patients with uncontrolled hypertension were enrolled and treated with radiofrequency RDN. Office and ambulatory systolic blood pressure (OSBP and ASBP) were measured at 3, 6, 12, 24, and 36 months postprocedure and used to derive TTR. TTR through 6 months was assessed as a predictor of cardiovascular events from 6 to 36 months using a Cox proportional hazard regression model. As of March 1, 2022, 3,077 patients were enrolled: 42.2% were female mean age was 60.5 ± 12.2 years baseline OSBP was 165.6 ± 24.8 mm Hg and baseline ASBP was 154.3 ± 18.7 mm Hg. Patients were prescribed 4.9 ± 1.7 antihypertensive medications at baseline and 4.8 ± 1.9 at 36 months. At 36 months, mean changes were -16.7 ± 28.4 and -9.0 ± 20.2 mm Hg for OSBP and ASBP, respectively. TTR through 6 months was 30.6%. A 10% increase in TTR after RDN through 6 months was associated with significant risk reductions from 6 to 36 months of 15% for major adverse cardiovascular events (P < 0.001), 11% cardiovascular death (P = 0.010), 15% myocardial infarction (P = 0.023), and 23% stroke (P < 0.001). There were sustained BP reductions and higher TTR through 36 months after RDN. A 10% increase in TTR through 6 months was associated with significant risk reductions in major cardiovascular events from 6 to 36 months. (Global SYMPLICITY Registry [GSR] DEFINE NCT01534299).
Publisher: American Diabetes Association
Date: 11-12-2013
DOI: 10.2337/DC13-1165
Abstract: Current methods of risk stratification in patients with type 2 diabetes are suboptimal. The current study assesses the ability of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) to improve the prediction of cardiovascular events and death in patients with type 2 diabetes. A nested case-cohort study was performed in 3,862 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Seven hundred nine (18%) patients experienced a major cardiovascular event (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and 706 (18%) died during a median of 5 years of follow-up. In Cox regression models, adjusting for all established risk predictors, the hazard ratio for cardiovascular events for NT-proBNP was 1.95 per 1 SD increase (95% CI 1.72, 2.20) and the hazard ratio for hs-cTnT was 1.50 per 1 SD increase (95% CI 1.36, 1.65). The hazard ratios for death were 1.97 (95% CI 1.73, 2.24) and 1.52 (95% CI 1.37, 1.67), respectively. The addition of either marker improved 5-year risk classification for cardiovascular events (net reclassification index in continuous model, 39% for NT-proBNP and 46% for hs-cTnT). Likewise, both markers greatly improved the accuracy with which the 5-year risk of death was predicted. The combination of both markers provided optimal risk discrimination. NT-proBNP and hs-cTnT appear to greatly improve the accuracy with which the risk of cardiovascular events or death can be estimated in patients with type 2 diabetes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2009
DOI: 10.1161/HYPERTENSIONAHA.109.133041
Abstract: The relative importance of various blood pressure indices on cardiovascular risk in people with type 2 diabetes mellitus has not been established. This study compares the strengths of the associations between different baseline blood pressure variables (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], and mean arterial pressure) and the 4.3-year risk of major cardiovascular events in the Action in Diabetes and Vascular Disease: Preterax and Diamicron-Modified Release Controlled Evaluation Study. Mean (SD) age for the 11 140 participants was 65.8 years (6.4 years). During follow-up, 1000 major cardiovascular events, 559 major coronary events, and 468 cardiovascular deaths were recorded. After adjustment for age, sex, and treatment allocation, the hazard ratios (95% CIs) associated with 1 increment in SD for the risk of major cardiovascular events were 1.17 (1.10 to 1.24) for SBP 1.20 (1.13 to 1.28) for PP 1.12 (1.05 to 1.19) for mean arterial pressure and 1.04 (0.98 to 1.11) for DBP. The areas under the receiver operating characteristic curve were slightly higher for SBP and PP compared with mean arterial pressure and DBP for major cardiovascular and coronary events. Using achieved instead of baseline blood pressure values marginally improved the effect estimates for SBP, DBP, and mean arterial pressure, with no significant differences in the areas under the receiver operating characteristic curve between models with SBP and those with PP. In conclusion, SBP and PP are the 2 best and DBP is the least effective determinant of the risk of major cardiovascular outcomes in the relatively old patients with type 2 diabetes mellitus participating in the Action in Diabetes and Vascular Disease: Preterax and Diamicron-Modified Release Controlled Evaluation Study. However, SBP may be the simplest and most useful predictor across a wider range of age groups and populations.
Publisher: Springer Science and Business Media LLC
Date: 08-06-2016
DOI: 10.1007/S00421-016-3407-X
Abstract: Endurance exercise improves cardiovascular health and reduces mortality risk. Augmentation index (AIx) reflects adverse loading exerted on the heart and large arteries and predicts future cardiovascular disease. The purpose of this study was to establish whether endurance athletes possess lower AIx and aortic blood pressure compared to healthy controls, and to determine the association between AIx and cardiorespiratory fitness. Forty-six endurance athletes and 43 healthy controls underwent central BP and AIx measurements by non-invasive applanation tonometry before a maximal exercise test. Peak oxygen uptake ([Formula: see text]) was assessed by pulmonary analysis. Relative to controls, athletes had significantly lower brachial diastolic blood pressure (BP, -4.8 mmHg, p < 0.01), central systolic BP (-3.5 mmHg, p = 0.07), and AIx at a heart rate of 75 beats min(-1) (AIx@75, -11.9 %, p < 0.001). No AIx@75 differences were observed between athletes and controls when adjusted for age and [Formula: see text] [athletes vs controls mean (%) ± SE: -6.9 ± 2.2 vs -5.7 ± 2.3, p = 0.76]. Relative to men with low [Formula: see text], those with moderate and high [Formula: see text] had lower age-adjusted AIx@75 (p < 0.001). In women, those with high [Formula: see text] had lower AIx@75 than those with low and moderate [Formula: see text] (p < 0.01). The lower AIx@75 in endurance athletes is partly mediated by [Formula: see text]. While an inverse relationship between AIx@75 and [Formula: see text] was found in men, women with the highest [Formula: see text] possessed lowest AIx@75 compared to females with moderate or poor cardiorespiratory fitness. We recommend aerobic training aimed at achieving a minimum [Formula: see text] of 45 ml kg(-1) min(-1) to decrease the risk of future cardiovascular events and all-cause mortality.
Publisher: Informa UK Limited
Date: 28-09-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2021
DOI: 10.1161/HYPERTENSIONAHA.120.16109
Abstract: Isolated systolic hypertension (ISH) is the most common form of hypertension and is highly prevalent in older people. We recently showed differences between upper-arm cuff and invasive blood pressure (BP) become greater with increasing age, which could influence correct identification of ISH. This study sought to determine the difference between identification of ISH by cuff BP compared with invasive BP. Cuff BP and invasive aortic BP were measured in 1695 subjects (median 64 years, interquartile range [55–72], 68% male) from the INSPECT (Invasive Blood Pressure Consortium) database. Data were recorded during coronary angiography among 29 studies, using 21 different cuff BP devices. ISH was defined as ≥130/ mm Hg using cuff BP compared with invasive aortic BP as the reference. The prevalence of ISH was 24% (n=407) according to cuff BP but 38% (n=642) according to invasive aortic BP. There was fair agreement (Cohen κ, 0.36) and 72% concordance between cuff and invasive aortic BP for identifying ISH. Among the 28% of subjects (n=471) with misclassification of ISH status by cuff BP, 20% (n=96) of the difference was due to lower cuff systolic BP compared with invasive aortic systolic BP (mean, −16.4 mm Hg [95% CI, −18.7 to −14.1]), whereas 49% (n=231) was from higher cuff diastolic BP compared with invasive aortic diastolic BP (+14.2 mm Hg [95% CI, 11.5−16.9]). In conclusion, compared with invasive BP, cuff BP fails to identify ISH in a sizeable portion of older people and demonstrates the need to improve cuff BP measurements.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2014
DOI: 10.1161/HYPERTENSIONAHA.113.02252
Abstract: The objective of the present analysis was to determine the effects of a fixed combination of perindopril and indapamide in combination with calcium channel blockers (CCBs) in patients with type 2 diabetes mellitus. The Action in Diabetes and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE) trial was a factorial randomized controlled trial. A total of 11 140 patients with type 2 diabetes mellitus were randomly assigned to fixed combination of perindopril–indapamide (4/1.25 mg) or placebo. Effects of randomized treatment on mortality and major cardiovascular outcomes were examined in subgroups defined by baseline use of CCBs. Patients on CCB at baseline (n=3427) constituted a higher risk group compared with those not on CCB (n=7713), with more extensive use of antihypertensive and other protective therapies. Active treatment reduced the relative risk of death by 28% (95% confidence interval, 10%–43%) among patients with CCB at baseline compared with 5% (−12% to 20%) among those without CCB ( P homogeneity=0.02) and 14% (2%–25%) for the whole population. Similarly, the relative risk reduction for major cardiovascular events was 12% (−8% to 28%) versus 6% (−10% to 19%) for those with and without CCB at baseline although the difference was not statistically significant ( P homogeneity=0.38). There was no detectable increase in adverse effects in those receiving CCB. The combination of perindopril and indapamide with CCBs seems to provide further protection against mortality in patients with type 2 diabetes mellitus.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 21-06-2023
Publisher: Springer Science and Business Media LLC
Date: 08-01-2018
Publisher: Oxford University Press (OUP)
Date: 25-03-2019
Abstract: Several studies and registries have demonstrated sustained reductions in blood pressure (BP) after renal denervation (RDN). The long-term safety and efficacy after RDN in real-world patients with uncontrolled hypertension, however, remains unknown. The objective of this study was to assess the long-term safety and efficacy of RDN, including its effects on renal function. The Global SYMPLICITY Registry is a prospective, open-label registry conducted at 196 active sites worldwide in hypertensive patients receiving RDN treatment. Among 2237 patients enrolled and treated with the SYMPLICITY Flex catheter, 1742 were eligible for follow-up at 3 years. Baseline office and 24-h ambulatory systolic BP (SBP) were 166 ± 25 and 154 ± 18 mmHg, respectively. SBP reduction after RDN was sustained over 3 years, including decreases in both office (−16.5 ± 28.6 mmHg, P & 0.001) and 24-h ambulatory SBP (−8.0 ± 20.0 mmHg P & 0.001). Twenty-one percent of patients had a baseline estimated glomerular filtration rate (eGFR) & mL/min/1.73 m2. Between baseline and 3 years, renal function declined by 7.1 mL/min/1.73 m2 in patients without chronic kidney disease (CKD eGFR ≥60 mL/min/1.73 m2 baseline eGFR 87 ± 17 mL/min/1.73 m2) and by 3.7 mL/min/1.73 m2 in patients with CKD (eGFR & mL/min/1.73 m2 baseline eGFR 47 ± 11 mL/min/1.73 m2). No long-term safety concerns were observed following the RDN procedure. Long-term data from the Global SYMPLICITY Registry representing the largest available cohort of hypertensive patients receiving RDN in a real-world clinical setting demonstrate both the safety and efficacy of the procedure with significant and sustained office and ambulatory BP reductions out to 3 years.
Publisher: Springer Science and Business Media LLC
Date: 17-01-2018
DOI: 10.1038/S41387-017-0012-Y
Abstract: We aimed to evaluate the relationship between BMI and the risk of renal disease in patients with type 2 diabetes in the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) study. Participants were ided into six baseline BMI categories: .5 (underweight, n = 58) ≥18.5 to (normal, n = 2894) ≥25 to (overweight, n = 4340) ≥30 to (obesity grade 1, n = 2265) ≥35 to (obesity grade 2, n = 744) and ≥40 kg/m 2 (obesity grade 3, n = 294) those underweight were excluded. The composite outcome “major renal event” was defined as development of new macroalbuminuria, doubling of creatinine, end stage renal disease, or renal death. These outcomes and development of new microalbuminuria were considered in idually as secondary endpoints. During 5-years of follow-up, major renal events occurred in 487 (4.6%) patients. The risk increased with higher BMI. Multivariable-adjusted HRs (95% CIs), compared to normal weight, were: 0.91 (0.72–1.15) for overweight 1.03 (0.77–1.37) for obesity grade 1 1.42 (0.98–2.07) for grade 2 and 2.16 (1.34–3.48) for grade 3 ( p for trend = 0.006). These findings were similar across subgroups by randomised interventions (intensive versus standard glucose control and perindopril-indapamide versus placebo). Every additional unit of BMI over 25 kg/m 2 increased the risk of major renal events by 4 (1–6)%. Comparable results were observed with the risk of secondary endpoints. Higher BMI is an independent predictor of major renal events in patients with type 2 diabetes. Our findings encourage weight loss to improve nephroprotection in these patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-09-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2017
DOI: 10.1161/HYPERTENSIONAHA.117.09359
Abstract: Visit-to-visit variability in systolic blood pressure (SBP) is a risk factor for cardiovascular events. However, whether it provides additional predictive information beyond traditional risk factors, including mean SBP, in the long term is unclear. The ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) was a randomized controlled trial in patients with type 2 diabetes mellitus ADVANCE-ON (ADVANCE-Observational) followed-up patients subsequently. In these analyses, 9114 patients without major macrovascular or renal events or death during the first 24 months were included. Data on SBP from 6 visits during the first 24 months after randomization were used to estimate visit-to-visit variability in several ways: the primary measure was the standard deviation. Events accrued during the following 7.6 years. The primary outcome was a composite of major macrovascular and renal events and all-cause mortality. Standard deviation of SBP was log-linearly associated with an increased risk of the primary outcome ( P .001) after adjustment for mean SBP and other cardiovascular risk factors. The hazard ratio (HR 95% confidence interval [CI]) in the highest, compared with the lowest, tenth of the standard deviation was 1.39 (1.15–1.69). Results were similar for major macrovascular events alone and all-cause mortality alone (both P .01). Addition of standard deviation of SBP significantly improved 8-year risk classification (continuous net reclassification improvement, 5.3%). Results were similar for other measures of visit-to-visit variability, except maximum SBP. Visit-to-visit variability in SBP is an independent predictor of vascular complications and death, which improves risk prediction beyond that provided by traditional risk factors, including mean SBP.
Publisher: BMJ
Date: 02-2021
DOI: 10.1136/BMJOPEN-2020-043625
Abstract: Whether ACE inhibitors (ACEi) or angiotensin II receptor blocker (ARB) therapy should be continued, initiated or ceased in patients with COVID-19 is uncertain. Given the widespread use of ACEi/ARBs worldwide, guidance on the use of these drugs is urgently needed. This prospective meta-analysis aims to pool data from randomised controlled trials (RCTs) to assess the safety and efficacy of ACEi/ARB therapy in adults infected with SARS-CoV-2. RCTs will be eligible if they compare patients with COVID-19 randomised to ACEi/ARB continuation or commencement versuss no ACEi/ARB therapy study duration ≥14 days recruitment completed between March 2020 and May 2021. The primary outcome will be all-cause mortality at ≤30 days. Secondary outcomes will include mechanical ventilation, admission to intensive care or cardiovascular events at short-term follow-up (≤30 days) and all-cause mortality at longer-term follow-up ( month). Prespecified subgroup analyses will assess the effect of sex age comorbidities smoking status ethnicity country of origin on all-cause mortality. A search of ClinicalTrials.gov has been performed, which will be followed by a formal search of trial registers, preprint servers, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify RCTs that meet inclusion criteria. To date, a search of ClinicalTrials.gov identified 21 potentially eligible trials for this meta-analysis. We will request trial investigators/sponsors to contribute standardised grouped tabular outcome data. Ethics approval and informed consent will be the responsibility of the in idual RCTs. Dissemination of results will occur by peer-reviewed publication. The results of our analysis can inform public health policy and clinical decision making regarding ACEi/ARB use in patients with COVID-19 on a global scale.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2022
Publisher: American Diabetes Association
Date: 27-10-2018
DOI: 10.2337/DC17-1467
Abstract: To assess the association between 2-year changes in urine albumin-to-creatinine ratio (UACR) and the risk of clinical outcomes in type 2 diabetes. We analyzed data from 8,766 participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Post-Trial Observational Study (ADVANCE-ON). Change in UACR was calculated from UACR measurements 2 years apart, classified into three groups: decrease in UACR of ≥30%, minor change, and increase in UACR of ≥30%. By analyzing changes from baseline UACR groups, categorized into thirds, we repeated these analyses accounting for regression to the mean (RtM). The primary outcome was the composite of major macrovascular events, renal events, and all-cause mortality secondary outcomes were these components. Cox regression models were used to estimate hazard ratios (HRs). Over a median follow-up of 7.7 years, 2,191 primary outcomes were observed. Increases in UACR over 2 years independently predicted a greater risk of the primary outcome (HR for ≥30% UACR increase vs. minor change: 1.26 95% CI 1.13-1.41), whereas a decrease in UACR was not significantly associated with lower risk (HR 0.93 95% CI 0.83-1.04). However, after allowing for RtM, the effect of "real" decrease in UACR on the primary outcome was found to be significant (HR 0.84 95% CI 0.75-0.94), whereas the estimated effect on an increase was unchanged. Changes in UACR predicted changes in the risk of major clinical outcomes and mortality in type 2 diabetes, supporting the prognostic utility of monitoring albuminuria change over time.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2019
DOI: 10.1161/HYPERTENSIONAHA.118.12060
Abstract: Discontinuation of angiotensin-converting enzyme (ACE) inhibitor is recommended if patients experience ≥30% acute increase in serum creatinine after starting this therapy. However, the long-term effects of its continuation or discontinuation on major clinical outcomes after increases in serum creatinine are unclear. In the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation), 11 140 diabetes mellitus patients were randomly assigned to perindopril-indapamide or placebo after a 6-week active run-in period. The current study included 11 066 participants with 2 serum creatinine measurements recorded before and during the active run-in period (3 weeks apart). Acute increase in creatinine was determined using these 2 measurements and classified into 4 groups: increases in serum creatinine of %, 10% to 19%, 20% to 29%, and ≥30%. The primary study outcome was the composite of major macrovascular events, new or worsening nephropathy, and all-cause mortality. An acute increase in serum creatinine was associated with an elevated risk of the primary outcome ( P for trend .001). The hazard ratios were 1.11 (95% CI, 0.97–1.28) for those with an increase of 10% to 19%, 1.34 (1.07–1.66) for 20% to 29%, and 1.44 (1.15–1.81) for ≥30%, compared with %. However, there was no evidence of heterogeneity in the benefit of randomized treatment effects on the outcome across subgroups defined by acute serum creatinine increase ( P for heterogeneity=0.94). Acute increases in serum creatinine after starting perindopril-indapamide were associated with greater risks of subsequent major clinical outcomes. However, the continuation of angiotensin-converting enzyme inhibitor-based therapy reduced the long-term risk of major clinical outcomes, irrespective of acute increase in creatinine. URL: www.clinicaltrials.gov . Unique identifier: NCT00145925.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2010
Publisher: Springer Science and Business Media LLC
Date: 06-07-2021
DOI: 10.1007/S00125-021-05491-7
Abstract: Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk. We developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies. The 10 wPRS, first principal component of ethnicity, sex, age at onset and diabetes duration were included into one logistic regression model to predict micro- and macrovascular outcomes in 4098 participants in the ADVANCE study and 17,604 in iduals with type 2 diabetes in the UK Biobank study. The model showed a similar predictive performance for cardiovascular and renal complications in different cohorts. It identified the top 30% of ADVANCE participants with a mean of 3.1-fold increased risk of major micro- and macrovascular events ( p = 6.3 × 10 −21 and p = 9.6 × 10 −31 , respectively) and a 4.4-fold ( p = 6.8 × 10 −33 ) higher risk of cardiovascular death. While in ADVANCE overall, combined intensive blood pressure and glucose control decreased cardiovascular death by 24%, the model identified a high-risk group in whom it decreased the mortality rate by 47%, and a low-risk group in whom it had no discernible effect. High-risk in iduals had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years. This novel multiPRS model stratified in iduals with type 2 diabetes according to risk of complications and helped to target earlier those who would receive greater benefit from intensive therapy.
Publisher: Wiley
Date: 29-05-2019
DOI: 10.1111/DOM.13755
Publisher: Wiley
Date: 30-10-2020
DOI: 10.1111/DOM.13878
Abstract: To assess the effects of intensive glucose control on the risk of major clinical outcomes according to estimated glomerular filtration rate (eGFR) levels in people with type 2 diabetes. Of 11 140 ADVANCE trial participants, 11 096 with baseline eGFR measurements were included, and classified into three eGFR groups: ≥90 mL/min/1.73 m
Publisher: American Diabetes Association
Date: 10-04-2014
DOI: 10.2337/DC13-2727
Abstract: Moderate alcohol consumption has been associated with a reduced risk of mortality and coronary artery disease. The relationship between cardiovascular health and alcohol use in type 2 diabetes is less clear. The current study assesses the effects of alcohol use among participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial. The effects of alcohol use were explored using Cox regression models, adjusted for potential confounders. The study end points were cardiovascular events (cardiovascular death, myocardial infarction, and stroke), microvascular complications (new or worsening nephropathy or retinopathy), and all-cause mortality. During a median of 5 years of follow-up, 1,031 (9%) patients died, 1,147 (10%) experienced a cardiovascular event, and 1,136 (10%) experienced a microvascular complication. Compared with patients who reported no alcohol consumption, those who reported moderate consumption had fewer cardiovascular events (adjusted hazard ratio [aHR] 0.83 95% CI 0.72–0.95 P = 0.008), less microvascular complications (aHR 0.85 95% CI 0.73–0.99 P = 0.03), and lower all-cause mortality (aHR 0.87 96% CI 0.75–1.00 P = 0.05). The benefits were particularly evident in participants who drank predominantly wine (cardiovascular events aHR 0.78, 95% CI 0.63–0.95, P = 0.01 all-cause mortality aHR 0.77, 95% CI 0.62–0.95, P = 0.02). Compared with patients who reported no alcohol consumption, those who reported heavy consumption had dose-dependent higher risks of cardiovascular events and all-cause mortality. In patients with type 2 diabetes, moderate alcohol use, particularly wine consumption, is associated with reduced risks of cardiovascular events and all-cause mortality.
Publisher: Springer Science and Business Media LLC
Date: 27-08-2021
Publisher: Oxford University Press (OUP)
Date: 11-10-2022
DOI: 10.1093/CVR/CVAC130
Abstract: Raised blood pressure (BP) is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high- and low-resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in BP control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally, there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanization, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity, and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial, and environmental determinants, and strengthening health systems implement a well-designed customized quality-of-care improvement framework.
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.JACC.2013.08.1616
Abstract: Catheter-based radiofrequency ablation technology to disrupt both efferent and afferent renal nerves has recently been introduced to clinical medicine after the demonstration of significant systolic and diastolic blood pressure reductions. Clinical trial data available thus far have been obtained primarily in patients with resistant hypertension, defined as standardized systolic clinic blood pressure ≥ 160 mm Hg (or ≥ 150 mm Hg in patients with type 2 diabetes) despite appropriate pharmacologic treatment with at least 3 antihypertensive drugs, including a diuretic agent. Accordingly, these criteria and blood pressure thresholds should be borne in mind when selecting patients for renal nerve ablation. Secondary forms of hypertension and pseudoresistance, such as nonadherence to medication, intolerance of medication, and white coat hypertension, should have been ruled out, and 24-h ambulatory blood pressure monitoring is mandatory in this context. Because there are theoretical concerns with regard to renal safety, selected patients should have preserved renal function, with an estimated glomerular filtration rate ≥ 45 ml/min/1.73 m(2). Optimal periprocedural management of volume status and medication regimens at specialized and experienced centers equipped with adequate infrastructure to cope with potential procedural complications will minimize potential patient risks. Long-term safety and efficacy data are limited to 3 years of follow-up in small patient cohorts, so efforts to monitor treated patients are crucial to define the long-term performance of the procedure. Although renal nerve ablation could have beneficial effects in other conditions characterized by elevated renal sympathetic nerve activity, its potential use for such indications should currently be limited to formal research studies of its safety and efficacy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-11-2016
DOI: 10.1161/CIRCULATIONAHA.116.023233
Abstract: Clinical lipid measurements do not show the full complexity of the altered lipid metabolism associated with diabetes mellitus or cardiovascular disease. Lipidomics enables the assessment of hundreds of lipid species as potential markers for disease risk. Plasma lipid species (310) were measured by a targeted lipidomic analysis with liquid chromatography electrospray ionization–tandem mass spectrometry on a case-cohort (n=3779) subset from the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation). The case-cohort was 61% male with a mean age of 67 years. All participants had type 2 diabetes mellitus with ≥1 additional cardiovascular risk factors, and 35% had a history of macrovascular disease. Weighted Cox regression was used to identify lipid species associated with future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) and cardiovascular death during a 5-year follow-up period. Multivariable models combining traditional risk factors with lipid species were optimized with the Akaike information criteria. C statistics and NRIs were calculated within a 5-fold cross-validation framework. Sphingolipids, phospholipids (including lyso- and ether- species), cholesteryl esters, and glycerolipids were associated with future cardiovascular events and cardiovascular death. The addition of 7 lipid species to a base model (14 traditional risk factors and medications) to predict cardiovascular events increased the C statistic from 0.680 (95% confidence interval [CI], 0.678–0.682) to 0.700 (95% CI, 0.698–0.702 P .0001) with a corresponding continuous NRI of 0.227 (95% CI, 0.219–0.235). The prediction of cardiovascular death was improved with the incorporation of 4 lipid species into the base model, showing an increase in the C statistic from 0.740 (95% CI, 0.738–0.742) to 0.760 (95% CI, 0.757–0.762 P .0001) and a continuous net reclassification index of 0.328 (95% CI, 0.317–0.339). The results were validated in a subcohort with type 2 diabetes mellitus (n=511) from the LIPID trial (Long-Term Intervention With Pravastatin in Ischemic Disease). The improvement in the prediction of cardiovascular events, above traditional risk factors, demonstrates the potential of plasma lipid species as biomarkers for cardiovascular risk stratification in diabetes mellitus. URL: clinicaltrials.gov . Unique identifier: NCT00145925.
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1038/KI.2012.383
Abstract: Albuminuria and a reduced glomerular filtration rate are conventional predictors of a future decline in kidney function in patients with type 2 diabetes mellitus. Using a nested case-control study we assessed whether circulating transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7) levels more accurately predict renal end points than the conventional markers. Cases were defined as those who developed a renal end point (doubling of serum creatinine to at least 200 μmol/l, the need for renal replacement therapy, or death due to renal disease) during the study. Using propensity scoring, two controls were selected for each of 281 cases. Participants who developed renal end points had significantly higher total TGF-β1, lower BMP-7 levels, and a higher total TGF-β1 to BMP-7 ratio at baseline. A graded increase in risk was found in in iduals with lower BMP-7 levels (odds ratio 24.07, for the lowest to the highest tertile), or significantly higher TGF-β1 levels (odds ratio for the highest to the lowest tertile, 8.43). The area under the receiver operating characteristic curve (c-statistic) for the conventional predictors was 0.73. Using BMP-7 and total and active TGF-β1, the c-statistic was 0.94 (significantly higher to conventional predictors). Thus, our results suggest these novel kidney markers are better predictors of renal progression than the conventional predictors in patients with type 2 diabetes mellitus.
Publisher: American Diabetes Association
Date: 23-06-2015
DOI: 10.2337/DC15-ER07A
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.JACC.2017.05.064
Abstract: Hypertension (HTN) is the single greatest cardiovascular risk factor worldwide. HTN management is usually guided by brachial cuff blood pressure (BP), but questions have been raised regarding accuracy. This comprehensive analysis determined the accuracy of cuff BP and the consequent effect on BP classification compared with intra-arterial BP reference standards. Three in idual participant data meta-analyses were conducted among studies (from the 1950s to 2016) that measured intra-arterial aortic BP, intra-arterial brachial BP, and cuff BP. A total of 74 studies with 3,073 participants were included. Intra-arterial brachial systolic blood pressure (SBP) was higher than aortic values (8.0 mm Hg 95% confidence interval [CI]: 5.9 to 10.1 mm Hg p < 0.0001) and intra-arterial brachial diastolic BP was lower than aortic values (-1.0 mm Hg 95% CI: -2.0 to -0.1 mm Hg p = 0.038). Cuff BP underestimated intra-arterial brachial SBP (-5.7 mm Hg 95% CI: -8.0 to -3.5 mm Hg p < 0.0001) but overestimated intra-arterial diastolic BP (5.5 mm Hg 95% CI: 3.5 to 7.5 mm Hg p < 0.0001). Cuff and intra-arterial aortic SBP showed a small mean difference (0.3 mm Hg 95% CI: -1.5 to 2.1 mm Hg p = 0.77) but poor agreement (mean absolute difference 8.0 mm Hg 95% CI: 7.1 to 8.9 mm Hg). Concordance between BP classification using the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure cuff BP (normal, pre-HTN, and HTN stages 1 and 2) compared with intra-arterial brachial BP was 60%, 50%, 53%, and 80%, and using intra-arterial aortic BP was 79%, 57%, 52%, and 76%, respectively. Using revised intra-arterial thresholds based on cuff BP percentile rank, concordance between BP classification using cuff BP compared with intra-arterial brachial BP was 71%, 66%, 52%, and 76%, and using intra-arterial aortic BP was 74%, 61%, 56%, and 65%, respectively. Cuff BP has variable accuracy for measuring either brachial or aortic intra-arterial BP, and this adversely influences correct BP classification. These findings indicate that stronger accuracy standards for BP devices may improve cardiovascular risk management.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2020
DOI: 10.1161/HYPERTENSIONAHA.120.14874
Abstract: Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening c aign aiming to improve awareness of blood pressure at the in idual and population level. Adults (≥18 years) recruited through opportunistic s ling were screened at sites in 92 countries during May 2019. Ideally, 3 blood pressure readings were measured for each participant, and data on lifestyle factors and comorbidities were collected. Hypertension was defined as a systolic blood pressure ≥140 mm Hg, or a diastolic blood pressure ≥90 mm Hg (mean of the second and third readings) or taking antihypertensive medication. When necessary, multiple imputation was used to estimate participants’ mean blood pressure. Mixed-effects models were used to evaluate associations between blood pressure and participant characteristics. Of 1 508 130 screenees 482 273 (32.0%) had never had a blood pressure measurement before and 513 337 (34.0%) had hypertension, of whom 58.7% were aware, and 54.7% were on antihypertensive medication. Of those on medication, 57.8% were controlled to /90 mm Hg, and 28.9% to /80 mm Hg. Of all those with hypertension, 31.7% were controlled to /90 mm Hg, and 350 825 (23.3%) participants had untreated or inadequately treated hypertension. Of those taking antihypertensive medication, half were taking only a single drug, and 25% reported using aspirin inappropriately. This survey is the largest ever synchronized and standardized contemporary compilation of global blood pressure data. This c aign is needed as a temporary substitute for systematic blood pressure screening in many countries worldwide.
Publisher: American Diabetes Association
Date: 23-06-2015
DOI: 10.2337/DC15-ER07
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2019
DOI: 10.1161/HYPERTENSIONAHA.118.12414
Abstract: The optimal blood pressure (BP) goal in patients with diabetes mellitus remains controversial. We examined whether benefits and risks of intensified antihypertensive therapy in diabetes mellitus are influenced by either baseline BP or cardiovascular disease (CVD) risk. We studied 10 948 people with diabetes mellitus, at moderate-to-high risk, in the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation). Cox models were used to determine whether baseline BP category or CVD risk modified the outcomes of combination perindopril-indapamide treatment, compared with placebo. During 4.3 years of follow-up, treatment with perindopril-indapamide versus placebo reduced mortality and major vascular (macrovascular or microvascular) events. There was no evidence of differences in these effects, regardless of baseline systolic BP (evaluated down to mm Hg P for heterogeneity, 0.85), diastolic BP (evaluated down to mm Hg P =0.49), or whether 10-year CVD risk was ≥20% or % ( P =0.08). The effects of randomized treatment on discontinuation of treatment because of cough or hypotension/dizziness were also statistically consistent across subgroups defined by baseline BP and CVD risk (all P ≥0.08). Adults with diabetes mellitus appear to benefit from more intensive BP treatment even at levels of BP and CVD risk that some guidelines do not currently recommend for intervention. URL: www.clinicaltrials.gov . Unique identifier: NCT00751972.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-09-2022
Abstract: Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin‐angiotensin system inhibitors (RASi) in adults with COVID‐19. We therefore performed a meta‐analysis to assess the safety and efficacy of RASi in adults with COVID‐19. MEDLINE, EMBASE, ClinicalTrials.gov , and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID‐19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all‐cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow‐up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all‐cause mortality (7.2% versus 7.5% relative risk [RR], 0.95 [95% CI, 0.69–1.30]) either overall or in subgroups defined by COVID‐19 severity or trial type. Network meta‐analysis identified no difference between angiotensin‐converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6% RR, 0.59 [95% CI, 0.33–1.06]), but increased risk of acute kidney injury (7.0% versus 3.6% RR, 1.82 [95% CI, 1.05–3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. This meta‐analysis of randomized controlled trials evaluating angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers versus control in patients with COVID‐19 found no difference in all‐cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID‐19.
Publisher: Cold Spring Harbor Laboratory
Date: 26-05-2020
DOI: 10.1101/2020.05.19.20106781
Abstract: Angiotensin converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2) - the cause of COVID-19 disease. It has been hypothesized that use of renin-angiotensin system (RAS) inhibiting medications in patients with hypertension, increases the expression of ACE2 and thereby increases the risk of COVID-19 infection and severe outcomes or death. However, the effect of RAS-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. We examined how hypertension, its major metabolic co-phenotypes and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterised by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. Collectively, our data indicate that neither hypertension nor antihypertensive treatment are likely to alter in idual risk of SARS-CoV-2 infection or influence clinical outcomes in COVID-19 through changes of ACE2 expression. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.
Publisher: Massachusetts Medical Society
Date: 12-11-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2023
DOI: 10.1161/HYPERTENSIONAHA.123.21283
Abstract: The Global SYMPLICITY Registry DEFINE (Denervation Findings in Real World) investigates radiofrequency renal denervation (RDN) in a broad range of patients with hypertension. We evaluated whether the number or type of antihypertensive medications were associated with increased long-term blood pressure (BP) reductions and cardiovascular outcomes following radiofrequency RDN. Patients underwent radiofrequency RDN and were categorized by baseline number (0–3 and ≥4) and different combinations of medication classes. BP changes were compared between groups through 36 months. In idual and composite major adverse cardiovascular events were analyzed. Of 2746 evaluable patients, 18% were prescribed 0 to 3 and 82% prescribed ≥4 classes. At 36 months, office systolic BP significantly decreased ( P .0001) by −19.0±28.3 and −16.2±28.6 mm Hg in the 0 to 3 and ≥4 class groups, respectively. Twenty-four–hour mean systolic BP significantly decreased ( P .0001) by −10.7±19.7 and −8.9±20.5 mm Hg, respectively. BP reduction was similar between the medication subgroups. Antihypertensive medication classes decreased from 4.6±1.4 to 4.3±1.5 ( P .0001). Most decreased (31%) or had no changes (47%) to the number of medications, while 22% increased. The number of baseline antihypertensive medication classes was inversely related to the change in prescribed classes at 36 months ( P .001). Cardiovascular event rates were generally low. More patients in the ≥4 compared with 0 to 3 medication classes had myocardial infarction at 36 months (2.8% versus 0.3% P =0.009). Radiofrequency RDN reduced BP safely through 36 months, independent of the number and type of baseline antihypertensive medication classes. More patients decreased than increased their number of medications. Radiofrequency RDN is a safe and effective adjunctive therapy regardless of antihypertensive medication regimen. URL: www.clinicaltrials.gov Unique identifier: NCT01534299.
Publisher: American Diabetes Association
Date: 04-2008
DOI: 10.2337/DC07-1657
Abstract: OBJECTIVE—The objective of this study was to describe prevalent vascular retinal lesions among patients with type 2 diabetes enrolled in the ADVANCE Retinal Measurements (AdRem) study, a substudy of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. RESEARCH DESIGN AND METHODS—Seven-field stereoscopic photographs of both eyes were obtained at the baseline assessment of the ADVANCE trial. All photographs were graded in a central reading center. Gradable retinal images were received from 1,605 patients. RESULTS—The number of patients with any retinopathy (Early Treatment of Diabetic Retinopathy Study [ETDRS] score ≥20) was 645 (40.2% [95% CI 37.8–42.6]) of these, 35 (2.2% [1.6–3.0]) had severe diabetic retinopathy (ETDRS score ≥50). Focal arterial narrowing, venous beading, and arteriovenous nicking were present in 3.8, 5.1, and 9.8% of participants, respectively. Among participants included in this study, Chinese and South-Asian patients had more retinopathy than Caucasians, as defined both by ETDRS score (49.4, 46.0, and 31.3%, respectively P & 0.001, adjusted for age, sex, A1C, systolic blood pressure, and duration of diabetes) and specific vascular lesions (e.g., arteriovenous nicking 12.3, 8.5, and 7.5%, respectively adjusted P & 0.005). A1C, duration of diabetes, and systolic blood pressure were similarly associated with increased retinal lesions in Chinese, South-Asian, and Caucasian patients. CONCLUSIONS—Using a sensitive diagnostic procedure, more than one-third of patients with type 2 diabetes enrolled in the AdRem study had retinal lesions at baseline. Despite differences in prevalence and severity of retinopathy among Chinese, South-Asian, and Caucasian patients included in this study, the cross-sectional associations among established risk factors for retinopathy and retinal lesions were similar across ethnic groups.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-07-2023
DOI: 10.1097/HJH.0000000000003510
Abstract: Hypertension management is directed by cuff blood pressure (BP), but this may be inaccurate, potentially influencing cardiovascular disease (CVD) events and health costs. This study aimed to determine the impact on CVD events and related costs of the differences between cuff and invasive SBP. Microsimulations based on Markov modelling over one year were used to determine the differences in the number of CVD events (myocardial infarction or coronary death, stroke, atrial fibrillation or heart failure) predicted by Framingham risk and total CVD health costs based on cuff SBP compared with invasive (aortic) SBP. Modelling was based on international consortium data from 1678 participants undergoing cardiac catheterization and 30 separate studies. Cuff underestimation and overestimation were defined as cuff SBP less than invasive SBP and cuff SBP greater than invasive SBP, respectively. The proportion of people with cuff SBP underestimation versus overestimation progressively increased as SBP increased. This reached a maximum ratio of 16 : 1 in people with hypertension grades II and III. Both the number of CVD events missed (predominantly stroke, coronary death and myocardial infarction) and associated health costs increased stepwise across levels of SBP control, as cuff SBP underestimation increased. The maximum number of CVD events potentially missed (11.8/1000 patients) and highest costs ($241 300 USD/1000 patients) were seen in people with hypertension grades II and III and with at least 15 mmHg of cuff SBP underestimation. Cuff SBP underestimation can result in potentially preventable CVD events being missed and major increases in health costs. These issues could be remedied with improved cuff SBP accuracy.
Publisher: American Diabetes Association
Date: 07-08-2015
DOI: 10.2337/DC15-0925
Abstract: This study explored whether activation of the receptor for advanced glycation end products (RAGE) is implicated in the development of diabetes complications. A case-cohort study was performed in 3,763 participants with prevalent diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. The hazard ratios (HRs) for death, major cardiovascular events, and new or worsening nephropathy were derived using Cox regression models, and the ability of sRAGE and AGE levels to reclassify the risk of nephropathy was assessed. After adjustment for a range of possible confounders and other risk factors, sRAGE levels were associated with all-cause mortality (HR 1.11 for a 1-SD increase of log sRAGE [95% CI 1.00–1.22] P = 0.045) and new or worsening nephropathy (HR 1.20 for a 1-SD increase of log sRAGE [95% CI 1.02–1.41] P = 0.032). Circulating AGE levels were also independently associated with new or worsening nephropathy (HR 1.21 for a 1-SD increase [95% CI 1.08–1.36] P = 0.001). Both markers also significantly improved the accuracy with which the 5-year risk of new or worsening nephropathy could be predicted (net reclassification index in continuous model, 0.25 for sRAGE and 0.24 for AGE levels). In adults with type 2 diabetes, increased levels of sRAGE are independently associated with new or worsening kidney disease and mortality over the next 5 years. Higher levels of AGE are also associated with an increased risk of adverse renal outcomes. The AGE/RAGE axis may be of importance in the prevention and management of diabetes complications.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-04-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-09-2012
Abstract: A higher resting heart rate is associated with an increased probability of cardiovascular complications and premature death in patients with type 2 diabetes mellitus. The impact of heart rate on the risk of developing microvascular complications, such as diabetic retinopathy and nephropathy, is, however, unknown. The present study tests the hypothesis that a higher resting heart rate is associated with an increased incidence and a greater progression of microvascular complications in patients with type 2 diabetes mellitus. The relation between baseline resting heart rate and the development of a major microvascular event was examined in 11 140 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study. Major microvascular events were defined as a composite of new or worsening nephropathy or new or worsening retinopathy. Patients with a higher baseline heart rate were at increased risk of a new major microvascular complication during follow‐up (adjusted hazard ratio: 1.13 per 10 beats per minute 95% confidence interval: 1.07–1.20 P .001). The excess hazard was evident for both nephropathy (adjusted hazard ratio: 1.16 per 10 beats per minute 95% confidence interval: 1.08–1.25) and retinopathy (adjusted hazard ratio: 1.11 per 10 beats per minute 95% confidence interval: 1.02–1.21). Patients with type 2 diabetes mellitus who have a higher resting heart rate experience a greater incidence of new‐onset or progressive nephropathy and retinopathy. URL: www.clinicaltrials.gov . Unique identifier: NCT00145925. tatic/html rehome rehome.asp
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2016
Publisher: Oxford University Press (OUP)
Date: 27-10-2020
DOI: 10.1093/EURHEARTJ/EHAA794
Abstract: Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)—the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.
Publisher: Oxford University Press (OUP)
Date: 29-08-2013
Abstract: Self-monitoring and self-titration of antihypertensives (self-management) is a novel intervention which improves blood pressure control. However, little evidence exists regarding the cost-effectiveness of self-monitoring of blood pressure in general and self-management in particular. This study aimed to evaluate whether self-management of hypertension was cost-effective. A cohort Markov model-based probabilistic cost-effectiveness analysis was undertaken extrapolating to up to 35 years from cost and outcome data collected from the telemonitoring and self-management in hypertension trial (TASMINH2). Self-management of hypertension was compared with usual care in terms of lifetime costs, quality adjusted life years and cost-effectiveness using a UK Health Service perspective. Sensitivity analyses examined the effect of different time horizons and reduced effectiveness over time from self-management. In the long-term, when compared with usual care, self-management was more effective by 0.24 and 0.12 quality adjusted life years (QALYs) gained per patient for men and women, respectively. The resultant incremental cost-effectiveness ratio for self-management was £1624 per QALY for men and £4923 per QALY for women. There was at least a 99% chance of the intervention being cost-effective for both sexes at a willingness to pay threshold of £20,000 per QALY gained. These results were robust to sensitivity analyses around the assumptions made, provided that the effects of self-management lasted at least two years for men and five years for women. Self-monitoring with self-titration of antihypertensives and telemonitoring of blood pressure measurements not only reduces blood pressure, compared with usual care, but also represents a cost-effective use of health care resources.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2021
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.JACC.2022.06.039
Abstract: Standard measures of blood pressure (BP) do not account for both the magnitude and duration of exposure to elevated BP over time. The purpose of this study was to assess the association between cumulative systolic blood pressure (SBP) load and risk of cardiovascular events in patients with type 2 diabetes. A post hoc analysis of patients with type 2 diabetes followed by the ADVANCE-ON (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation - Observational Study). Cumulative SBP load was defined as the area under curve for SBP values ≥130 mm Hg ided by the area under curve for all measured SBP values over a 24-month exposure period. HRs for the association between cumulative SBP load with major cardiovascular events and death were estimated using Cox models. Over a median 7.6 years of follow-up, 1,469 major cardiovascular events, 1,615 deaths, and 660 cardiovascular deaths were observed in 9,338 participants. Each 1-SD increase in cumulative SBP load was associated with a 14% increase in major cardiovascular events (HR: 1.14 95% CI: 1.09-1.20), 13% increase in all-cause mortality (HR: 1.13 95% CI: 1.13-1.18), and 21% increase in cardiovascular death (HR: 1.21 95% CI: 1.13-1.29). For the prediction of cardiovascular events and death, cumulative SBP load outperformed mean SBP, time-below-target SBP, and visit-to-visit SBP variability in terms of Akaike information criterion and net reclassification indexes. Cumulative SBP load may provide better prediction of major cardiovascular events compared with traditional BP measures among patients with type 2 diabetes. These findings reinforce the importance of both the magnitude and duration of exposure to elevated SBP in assessing cardiovascular risk. (Action in Diabetes and Vascular Disease Preterax and Diamicron MR Controlled Evaluation Post Trial Observational Study [ADVANCE-ON] NCT00949286).
Publisher: Elsevier BV
Date: 09-2007
Publisher: Xia & He Publishing
Date: 2006
DOI: 10.3727/000000006783991953
Abstract: The Wilms' tumor suppressor gene product (WT1) regulates expression of growth control genes. Microarray analysis of gene expression profiles of hormone-treated LNCaP prostate cancer cell lines transfected with either wild-type WT1 or a zinc finger mutant form, DDS (R394W), revealed significantly altered patterns of expression. Validation studies using quantitative real-time PCR confirmed the differential expression of the tumor progression gene, vascular endothelial growth factor (VEGF). WT1-LNCaP cells had significantly reduced levels of VEGF mRNA when compared to vector control cells in contrast, DDS-LNCaP cells showed elevated levels of VEGF transcripts. To address a functional role for WT1 overexpression, we investigated whether induction of VEGF expression, by the synthetic androgen R1881, would be disrupted in wild-type or mutant WT1-transfected LNCaP cells. Hormone treatment failed to elevate VEGF transcript levels above uninduced baseline levels in WT1-LNCaP cells, despite 48 h of treatment with 5 nM R1881. Consistent with our quantitative real-time PCR analysis, immunofluorescent staining of VEGF protein was reduced in WT1-LNCaP cells in both the presence and absence of R1881 treatment. Conversely, VEGF levels increased in vector control and DDS-LNCaP cells treated with 5 nM R1881. Not only do these studies point out the regulatory potential of WT1 for VEGF, but they also indicate an altered function for the mutant DDS isoform. Because VEGF is associated with neovascularization and promotion of metastasis in a variety of solid tumors including prostate cancer, a better understanding of the regulation of VEGF expression by transcription factors, such as WT1, is important for halting disease progression.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2016
Publisher: American Medical Association (AMA)
Date: 06-2015
DOI: 10.1001/JAMADERMATOL.2014.3593
Abstract: The total cost of psoriasis in the United States is unknown. Defining the US economic burden of psoriasis is needed because it provides the foundation for research, advocacy, and educational efforts. To determine the US economic burden of psoriasis from a societal perspective. PubMed and MEDLINE databases were searched between January 1, 2008, and September 20, 2013, for economic investigations on the direct, indirect, intangible, and comorbidity costs of adult psoriasis in the United States. The base year costs were adjusted to 2013 US dollars using the Consumer Price Index for All Urban Consumers and multiplied by the estimated number of US patients with psoriasis in 2013 to determine the 2013 psoriasis cost burden. Among 100 identified articles, 22 studies were included in the systematic review. The direct psoriasis costs ranged from $51.7 billion to $63.2 billion, the indirect costs ranged from $23.9 billion to $35.4 billion, and medical comorbidities were estimated to contribute $36.4 billion annually in 2013 US dollars. Patients with psoriasis would pay a lifetime cost of $11,498 for relief of physical symptoms and emotional health however, intangible cost data are limited. The annual US cost of psoriasis amounted to approximately $112 billion in 2013. The economic burden of psoriasis is substantial and significant in the United States.
Publisher: Springer Science and Business Media LLC
Date: 13-07-2019
Publisher: American Diabetes Association
Date: 06-07-2017
DOI: 10.2337/DC17-0509
Abstract: This study examined the in idual and combined effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and hs-CRP on the prediction of heart failure incidence or progression in patients with type 2 diabetes. A nested case-cohort study was conducted in 3,098 participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. A higher value of each biomarker was significantly associated with a higher risk of heart failure incidence or progression, after adjustment for major risk factors. The hazard ratios per 1-SD increase were 3.06 (95% CI 2.37, 3.96) for NT-proBNP, 1.50 (1.27, 1.77) for hs-cTnT, 1.48 (1.27, 1.72) for IL-6, and 1.32 (1.12, 1.55) for hs-CRP. The addition of NT-proBNP to the model including conventional risk factors meaningfully improved 5-year risk-predictive performance (C statistic 0.8162 to 0.8800 continuous net reclassification improvement [NRI] 73.1% categorical NRI [& %, 5–10%, & % 5-year risk] 24.2%). In contrast, the addition of hs-cTnT, IL-6, or hs-CRP did not improve the prediction metrics consistently in combination or when added to NT-proBNP. Only NT-proBNP strongly and consistently improved the prediction of heart failure in patients with type 2 diabetes beyond a wide range of clinical risk factors and biomarkers.
Publisher: Massachusetts Medical Society
Date: 09-10-2014
Publisher: Springer Science and Business Media LLC
Date: 23-03-2013
Abstract: Self-monitoring of hypertension with self-titration of antihypertensives (self-management) results in lower systolic blood pressure for at least one year. However, few people in high risk groups have been evaluated to date and previous work suggests a smaller effect size in these groups. This trial therefore aims to assess the added value of self-management in high risk groups over and above usual care. The targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR) trial will be a pragmatic primary care based, unblinded, randomised controlled trial of self-management of blood pressure (BP) compared to usual care. Eligible patients will have a history of stroke, coronary heart disease, diabetes or chronic kidney disease and will be recruited from primary care. Participants will be in idually randomised to either usual care or self-management. The primary outcome of the trial will be difference in office SBP between intervention and control groups at 12 months adjusted for baseline SBP and covariates. 540 patients will be sufficient to detect a difference in SBP between self-management and usual care of 5 mmHg with 90% power. Secondary outcomes will include self-efficacy, lifestyle behaviours, health-related quality of life and adverse events. An economic analysis will consider both within trial costs and a model extrapolating the results thereafter. A qualitative analysis will gain insights into patients’ views, experiences and decision making processes. The results of the trial will be directly applicable to primary care in the UK. If successful, self-management of blood pressure in people with stroke and other high risk conditions would be applicable to many hundreds of thousands of in iduals in the UK and beyond. ISRCTN87171227
Publisher: Wiley
Date: 16-12-2013
DOI: 10.1111/DOM.12238
Abstract: The aim of this study was to assess associations between patient characteristics, intensification of blood glucose-lowering treatment through oral glucose-lowering therapy and/or insulin and effective glycaemic control in type 2 diabetes. 11 140 patients from the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) trial who were randomized to intensive glucose control or standard glucose control and followed up for a median of 5 years were categorized into two groups: effective glycaemic control [haemoglobin A1c (HbA1c) ≤ 7.0% or a proportionate reduction in HbA1c over 10%] or ineffective glycaemic control (HbA1c > 7.0% and a proportionate reduction in HbA1c less than or equal to 10%). Therapeutic intensification was defined as addition of an oral glucose-lowering agent or commencement of insulin. Pooled logistic regression models examined the associations between patient factors, intensification and effective glycaemic control. A total of 7768 patients (69.7%), including 3198 in the standard treatment group achieved effective glycaemic control. Compared to patients with ineffective control, patients with effective glycaemic control had shorter duration of diabetes and lower HbA1c at baseline and at the time of treatment intensification. Treatment intensification with addition of an oral agent or commencement of insulin was associated with a 107% [odds ratio, OR: 2.07 (95% confidence interval, CI: 1.95-2.20)] and 152% [OR: 2.52 (95% CI: 2.30-2.77)] greater chance of achieving effective glycaemic control, respectively. These associations were robust after adjustment for several baseline characteristics and not modified by the number of oral medications taken at the time of treatment intensification. Effective glycaemic control was associated with treatment intensification at lower HbA1c levels at all stages of the disease course and in both arms of the ADVANCE trial.
Publisher: Elsevier BV
Date: 07-2022
Publisher: Springer Science and Business Media LLC
Date: 27-07-2017
Publisher: Elsevier BV
Date: 07-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2015
Publisher: Elsevier BV
Date: 05-2023
Publisher: Elsevier BV
Date: 05-2023
Publisher: The Endocrine Society
Date: 07-10-2019
Abstract: Weight loss is strongly recommended for overweight and obese adults with type 2 diabetes. Unintentional weight loss is associated with increased risk of all-cause mortality, but few studies have examined its association with cardiovascular outcomes in patients with diabetes. To evaluate 2-year weight change and subsequent risk of cardiovascular events and mortality in established type 2 diabetes. The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation was an international, multisite 2×2 factorial trial of intensive glucose control and blood pressure control. We examined 5 categories of 2-year weight change: & % loss, 4% to 10% loss, stable (±& %), 4% to 10% gain, and & % gain. We used Cox regression with follow-up time starting at 2 years, adjusting for intervention arm, demographics, cardiovascular risk factors, and diabetes medication use from the 2-year visit. Among 10 081 participants with valid weight measurements, average age was 66 years. By the 2-year examination, 4.3% had & % weight loss, 18.4% had 4% to 10% weight loss, and 5.3% had & % weight gain. Over the following 3 years of the trial, & % weight loss was strongly associated with major macrovascular events (hazard ratio [HR], 1.75 95% confidence interval [CI], 1.26-2.44), cardiovascular mortality (HR, 2.76 95% CI, 1.87-4.09), all-cause mortality (HR, 2.79 95% CI, 2.10-3.71), but not major microvascular events (HR, 0.91 95% CI, 0.61-1.36), compared with stable weight. There was no evidence of effect modification by baseline body mass index, age, or type of diabetes medication. In the absence of substantial lifestyle changes, weight loss may be a warning sign of poor health meriting further workup in patients with type 2 diabetes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2020
Publisher: Elsevier BV
Date: 02-1990
DOI: 10.1016/0888-7543(90)90571-B
Abstract: In a previous report, we described a contiguous restriction map of chromosome band 11p13 that localized the Wilms tumor locus to a small group of NotI fragments. In an effort to identify and isolate the 11p13-associated sporadic Wilms tumor locus, we developed a panel of NotI fragment-specific DNA probes. These probes were selected from genomic libraries constructed using the Chinese hamster ovary-human somatic cell hybrid carrying only human 11p. The libraries were prepared from NotI-digested DNA after size selection by pulsed-field gel electrophoresis. The selected NotI fragments had been previously targeted on the basis of deletion mapping as having a high probability of containing the Wilms tumor locus. We used these newly identified 11p13-specific probes to improve the resolution of the restriction map spanning the Wilms tumor locus. The locus has been defined by a homozygous deletion in a sporadic Wilms tumor. Using these probes, the region of homozygous deletion in this tumor and presumably all or part of the Wilms tumor gene have been confined to two small SfiI fragments spanning less than 350 kb.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2015
DOI: 10.1161/HYPERTENSIONAHA.114.05010
Abstract: This study aimed to assess the safety and effectiveness of renal denervation using the Symplicity system in real-world patients with uncontrolled hypertension (NCT01534299). The Global SYMPLICITY Registry is a prospective, open-label, multicenter registry. Office and 24-hour ambulatory blood pressures (BPs) were measured. Change from baseline to 6 months was analyzed for all patients and for subgroups based on baseline office systolic BP, diabetic status, and renal function a cohort with severe hypertension (office systolic pressure, ≥160 mm Hg 24-hour systolic pressure, ≥135 mm Hg and ≥3 antihypertensive medication classes) was also included. The analysis included protocol-defined safety events. Six-month outcomes for 998 patients, including 323 in the severe hypertension cohort, are reported. Mean baseline office systolic BP was 163.5±24.0 mm Hg for all patients and 179.3±16.5 mm Hg for the severe cohort the corresponding baseline 24-hour mean systolic BPs were 151.5±17.0 and 159.0±15.6 mm Hg. At 6 months, the changes in office and 24-hour systolic BPs were −11.6±25.3 and −6.6±18.0 mm Hg for all patients ( P .001 for both) and −20.3±22.8 and −8.9±16.9 mm Hg for those with severe hypertension ( P .001 for both). Renal denervation was associated with low rates of adverse events. After the procedure through 6 months, there was 1 new renal artery stenosis % and 5 cases of hospitalization for a hypertensive emergency. In clinical practice, renal denervation resulted in significant reductions in office and 24-hour BPs with a favorable safety profile. Greater BP-lowering effects occurred in patients with higher baseline pressures. URL: www.clinicaltrials.gov . Unique identifier: NCT01534299
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2023
DOI: 10.1161/HYPERTENSIONAHA.122.19693
Abstract: Accurate blood pressure (BP) measurement is critical for optimal cardiovascular risk management. Age-related trajectories for cuff-measured BP accelerate faster in women compared with men, but whether cuff BP represents the intraarterial (invasive) aortic BP is unknown. This study aimed to determine the sex differences between cuff BP, invasive aortic BP, and the difference between the 2 measurements. Upper-arm cuff BP and invasive aortic BP were measured during coronary angiography in 1615 subjects from the Invasive Blood Pressure Consortium Database. This analysis comprised 22 different cuff BP devices from 28 studies. Subjects were 64±11 years (range 40–89) and 32% women. For the same cuff systolic BP (SBP), invasive aortic SBP was 4.4 mm Hg higher in women compared with men. Cuff and invasive aortic SBP were higher in women compared with men, but the sex difference was more pronounced from invasive aortic SBP, was the lowest in younger ages, and the highest in older ages. Cuff diastolic blood pressure overestimated invasive diastolic blood pressure in both sexes. For cuff and invasive diastolic blood pressure separately, there were sex*age interactions in which diastolic blood pressure was higher in younger men and lower in older men, compared with women. Cuff pulse pressure underestimated invasive aortic pulse pressure in excess of 10 mm Hg for both sexes in older age. For the same cuff SBP, invasive aortic SBP was higher in women compared with men. How this translates to cardiovascular risk prediction needs to be determined, but women may be at higher BP-related risk than estimated by cuff measurements.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Bryan Williams.