ORCID Profile
0000-0003-4493-9901
Current Organisations
University of Oxford
,
Newcastle University Population Health Sciences Institute
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Publisher: Elsevier BV
Date: 07-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-02-2022
Publisher: Public Library of Science (PLoS)
Date: 17-06-2021
DOI: 10.1371/JOURNAL.PMED.1003674
Abstract: Our knowledge of how to better manage elevated blood pressure (BP) in the presence of comorbidities is limited, in part due to exclusion or underrepresentation of patients with multiple chronic conditions from major clinical trials. We aimed to investigate the burden and types of comorbidities in patients with hypertension and to assess how such comorbidities and other variables affect BP levels over time. In this multiple landmark cohort study, we used linked electronic health records from the United Kingdom Clinical Practice Research Datalink (CPRD) to compare systolic blood pressure (SBP) levels in 295,487 patients (51% women) aged 61.5 (SD = 13.1) years with first recorded diagnosis of hypertension between 2000 and 2014, by type and numbers of major comorbidities, from at least 5 years before and up to 10 years after hypertension diagnosis. Time-updated multivariable linear regression analyses showed that the presence of more comorbidities was associated with lower SBP during follow-up. In hypertensive patients without comorbidities, mean SBP at diagnosis and at 10 years were 162.3 mm Hg (95% confidence interval [CI] 162.0 to 162.6) and 140.5 mm Hg (95% CI 140.4 to 140.6), respectively in hypertensive patients with ≥5 comorbidities, these were 157.3 mm Hg (95% CI 156.9 to 157.6) and 136.8 mm Hg (95% 136.4 to 137.3), respectively. This inverse association between numbers of comorbidities and SBP was not specific to particular types of comorbidities, although associations were stronger in those with preexisting cardiovascular disease. Retrospective analysis of recorded SBP showed that the difference in mean SBP 5 years before diagnosis between those without and with ≥5 comorbidities was −9 mm Hg (95% CI −9.7 to −8.3), suggesting that mean recorded SBP already differed according to the presence of comorbidity before baseline. Within 1 year after the diagnosis, SBP substantially declined, but subsequent SBP changes across comorbidity status were modest, with no evidence of a more rapid decline in those with more or specific types of comorbidities. We identified factors, such as prescriptions of antihypertensive drugs and frequency of healthcare visits, that can explain SBP differences according to numbers or types of comorbidities, but these factors only partly explained the recorded SBP differences. Nevertheless, some limitations have to be considered including the possibility that diagnosis of some conditions may not have been recorded, varying degrees of missing data inherent in analytical datasets extracted from routine health records, and greater measurement errors in clinical measurements taken in routine practices than those taken in well-controlled clinical study settings. BP levels at which patients were diagnosed with hypertension varied substantially according to the presence of comorbidities and were lowest in patients with multi-morbidity. Our findings suggest that this early selection bias of hypertension diagnosis at different BP levels was a key determinant of long-term differences in BP by comorbidity status. The lack of a more rapid decline in SBP in those with multi-morbidity provides some reassurance for BP treatment in these high-risk in iduals.
Publisher: BMJ
Date: 20-01-2022
DOI: 10.1136/HEARTJNL-2021-320171
Abstract: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics. We conducted an in idual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists’ Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up. There were 363 684 participants (42% women), with baseline mean age=65 years and mean systolic/diastolic BP=152/87 mm Hg, and among whom 19% were current smokers, 49% had cardiovascular disease, 28% had diabetes and 69% were taking antihypertensive treatment at baseline. Drugs were effective in lowering BP showing maximal effect after 12 months and gradually attenuating towards later years. Based on measures taken ≥12 months postrandomisation, mean systolic/diastolic BP difference (95% CI) between more and less intense BP-lowering treatment was −11.1 (−11.3 to −10.8)/−5.6 (−5.7 to −5.4) mm Hg between active treatment and placebo was −5.1 (−5.3 to −5.0)/−2.3 (−2.4 to −2.2) mm Hg and between active and control arms for drug comparison trials was −1.4 (−1.5 to −1.3)/−0.6 (−0.7 to −0.6) mm Hg. BP reductions were observed across different baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes and prior antihypertensive treatment use. These findings suggest that BP-lowering pharmacotherapy is effective in lowering BP, up to 4 years on average, in people with different characteristics. Appropriate treatment strategies are needed to sustain substantive long-term BP reductions.
Publisher: Public Library of Science (PLoS)
Date: 06-2021
DOI: 10.1371/JOURNAL.PMED.1003599
Abstract: Randomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline. The study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC), in which in idual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens. For this study, only trials that had collected information on AF status at baseline were included. The effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline were estimated using fixed-effect one-stage IPD meta-analyses based on Cox proportional hazards models stratified by trial. Furthermore, to assess whether the associations between the intensity of BP reduction and cardiovascular outcomes are similar in those with and without AF at baseline, we used a meta-regression. From the full BPLTTC database, 28 trials (145,653 participants) were excluded because AF status at baseline was uncertain or unavailable. A total of 22 trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Risk of bias assessment showed that 20 trials were at low risk of bias and 2 trials at moderate risk. Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering in patients with and without AF at baseline. Over 4.5 years of median follow-up, a 5-mm Hg systolic BP (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.83 to 1.00) and in patients without AF at baseline (HR 0.91, 95% CI 0.88 to 0.93), with no difference between subgroups. There was no evidence for heterogeneity of treatment effects by baseline SBP or drug class in patients with AF at baseline. The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF. In this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events similarly in in iduals with and without AF. Pharmacological BP lowering for prevention of cardiovascular events should be recommended in patients with AF.
Publisher: Oxford University Press (OUP)
Date: 30-05-2013
Abstract: High body mass index (BMI) and large waist circumference are separately associated with increased coronary heart disease (CHD) risk but these measures are highly correlated. Their separate associations with incident CHD, cross-classifying one variable by the other, are less investigated in large-scale studies. We examined these associations in a large UK cohort (the Million Women Study), which is a prospective population-based study. We followed 496,225 women (mean age 60 years) with both waist circumference and BMI measurements who had no vascular disease or cancer. Adjusted relative risk and 20-year cumulative CHD incidence (first coronary hospitalization or death) from age 55 to 74 years were calculated using Cox regression. Plasma apolipoproteins were assayed in 6295 randomly selected participants. There were 10,998 incident coronary events after mean follow up of 5.1 years. Within each BMI category (<25, 25-29.9, ≥30 kg/m(2)), CHD risk increased with increasing waist circumference within each waist circumference category (<70, 70-79.9, ≥79 cm), CHD risk increased with increasing BMI. The cumulative CHD incidence was lowest in women with BMI <25 kg/m(2) and waist circumference <70 cm, with 1 in 14 (95% confidence interval 1 in 12 to 16) women developing CHD in the 20 years from age 55 to 74 years, and highest in women with BMI ≥30 kg/m(2) and waist circumference ≥80 cm, with 1 in 8 (95% confidence interval 1 in 7 to 9) women developing CHD over the same period. Similar associations for apolipoprotein B to A1 ratio across adiposity categories were observed, particularly in non-obese women. Our conclusions were that both waist circumference and BMI are independently associated with incident CHD.
Publisher: Elsevier BV
Date: 09-2022
Publisher: Springer Science and Business Media LLC
Date: 23-10-2012
Publisher: BMJ
Date: 05-2019
DOI: 10.1136/BMJOPEN-2018-028698
Abstract: Previous research from the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) and others has shown that pharmacological blood pressure (BP)- lowering substantially reduces the risk of major cardiovascular events, including ischaemic heart disease, heart failure and stroke. In this new phase, the aim is to conduct in idual patient-level data (IPD) meta-analyses involving eligible BP-lowering randomised controlled trials (RCTs) to address uncertainties relating to efficacy and safety of BP-lowering treatment. RCTs investigating the effect of pharmacological BP-lowering, with a minimum of 1000 patient-years of follow-up in each trial arm, are eligible. Our systematic review identified 100 potentially eligible trials. We requested their investigators/sponsors to contribute baseline, follow-up and outcomes data. As of June 2018, the collaboration has obtained data from 49 trials (n=315 046 participants), with additional data currently in the process of being transferred from four RCTs (n=34 642 participants). In addition, data harmonisation has commenced. Scientific activities of the collaboration are overseen by the Steering Committee with input from all collaborators. Detailed protocols for in idual meta-analyses will be developed and registered on public platforms. Ethics approval has been obtained for this new and extended phase of the BPLTTC, the largest collaboration of de-identified IPD from RCTs. It offers an efficient and ethical manner of re-purposing existing data to answer clinically important questions relating to BP treatment as well as methodological questions relating to IPD meta-analyses. Among the immediate impacts will include reliable quantification of effects of treatment modifiers, such as baseline BP, age and prior disease, on both vascular and non-vascular outcomes. Analyses will further assess the impact of BP-lowering on important, but less well understood, outcomes, such as new-onset diabetes and renal disease. Findings will be published in peer-reviewed medical journals on behalf of the collaboration.
Publisher: Elsevier BV
Date: 04-2022
Publisher: Frontiers Media SA
Date: 15-10-2020
Publisher: Springer Science and Business Media LLC
Date: 02-04-2013
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.IJCARD.2016.07.170
Abstract: Many studies investigating long-term vascular disease risk associated with hypertensive pregnancies examined risks in relatively young women among whom vascular disease is uncommon. We examined the prospective relation between a history of hypertension during pregnancy and coronary heart disease (CHD) and stroke in middle-aged UK women. In 1996-2001, 1.1 million parous women (mean age=56years) without vascular disease at baseline reported their history of hypertension during pregnancy and other factors. They were followed for incident CHD and stroke (hospitalisation or death). Adjusted relative risks (RRs) were calculated using Cox regression. Twenty-six percent (290,008/1.1 million) reported having had a hypertensive pregnancy 27% (79,163/290,008) of women with hypertensive pregnancy, but only 10% (82,145/815,560) of those without hypertensive pregnancy, reported being treated for hypertension at baseline. Mean follow-up was 11.6years (mean ages at diagnosis/N of events: CHD=65years/N=68,161, ischaemic stroke=67years/N=8365, haemorrhagic stroke=64years/N=5702). Overall, the RRs (95% confidence interval [CI]) of incident disease in women with hypertensive pregnancy versus those without such history were: CHD=1.29 (1.27-1.31), ischaemic stroke=1.29 (1.23-1.35), and haemorrhagic stroke=1.14 (1.07-1.21). However, among women with hypertensive pregnancy who were not taking hypertension treatment at baseline, their RRs (95% CI) were only modestly increased: CHD=1.17 (1.14-1.19), ischaemic stroke=1.18 (1.11-1.25), and haemorrhagic stroke=1.09 (1.02-1.18). Hypertension during pregnancy was associated with increased CHD and stroke incidence in middle age, largely because such women also had hypertension in their 50s and 60s, which has a substantially greater effect on vascular disease risk than hypertension during pregnancy without hypertension later in life.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 11-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2023
DOI: 10.1161/HYPERTENSIONAHA.123.21496
Abstract: Whether the relative effects of blood pressure (BP)–lowering treatment on cardiovascular outcomes differ by sex, particularly when BP is not substantially elevated, has been uncertain. We conducted an in idual participant-level data meta-analysis of randomized controlled trials of pharmacological BP lowering. We pooled the data and categorized participants by sex, systolic BP categories in 10-mm Hg increments from to ≥170 mm Hg, and age categories spanning from to ≥85 years. We used fixed-effect 1-stage in idual participant-level data meta-analyses and applied Cox proportional hazard models, stratified by trial, to analyze the data. We included data from 51 randomized controlled trials involving 358 635 (42% women) participants. Over 4.2 years of median follow-up, a 5-mm Hg reduction in systolic BP decreased the risk of major cardiovascular events both in women and men (hazard ratio [95% CI], 0.92 [0.89–0.95] for women and 0.90 [0.88–0.93] for men P for interaction, 1). There was no evidence for heterogeneity of relative treatment effects by sex for the major cardiovascular disease, its components, or across the different baseline BP categories (all P for interaction, ≥0.57). The effects in women and men were consistent across age categories and the types of antihypertensive medications (all P for interaction, ≥0.14). The effects of BP reduction were similar in women and men across all BP and age categories at randomization and with no evidence to suggest that drug classes had differing effects by sex. This study does not substantiate sex-based differences in BP-lowering treatment.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2019
Publisher: Cold Spring Harbor Laboratory
Date: 23-02-2021
DOI: 10.1101/2021.02.19.21252066
Abstract: Evidence from randomised trials on long-term blood pressure (BP) reduction from pharmacologic treatment is limited. To investigate the effects of antihypertensive drugs on long-term BP change and examine its variation over time and among people with different clinical characteristics In idual participant-level data meta-analysis The Blood Pressure Lowering Treatment Trialists’ Collaboration involving 51 large-scale long-term randomised clinical trials 352,744 people (42% women) with mean age of 65 years and mean baseline systolic/diastolic BP of 152/87 mmHg, of whom 18% were current smokers, 50% had cardiovascular disease, 29% had diabetes, and 72% were taking antihypertensive treatment at baseline Pharmacological BP-lowering treatment Difference in longitudinal changes in systolic and diastolic BP between randomised treatment arms over an average follow-up of four years Drugs were effective in lowering BP, with the maximum effect becoming apparent after 12-month follow-up and with gradual attenuation towards later years. Based on measures taken ≥12 months post-randomisation, more intense BP-lowering treatment reduced systolic/diastolic BP (95% confidence interval) by −11.2 (−11.4 to −11.0)/−5.6 (−5.8 to −5.5) mmHg than less intense treatment active treatment by −5.1 (−5.3 to −5.0)/−2.3 (−2.4 to −2.2) mmHg lower than placebo, and active arm by −1.4 (−1.5 to −1.3)/−0.6 (−0.7 to −0.6) mmHg lower than the control arm for drug class comparison trials. BP reductions were consistently observed across a wide range of baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes, and prior antihypertensive treatment use. Pharmacological agents were effective in lowering long-term BP among in iduals with a wide range of characteristics, but the net between-group reductions were modest, which is partly attributable to the intended trial goals.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Springer Science and Business Media LLC
Date: 12-03-2014
Publisher: Elsevier BV
Date: 05-2021
Publisher: Springer Science and Business Media LLC
Date: 08-10-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-01-2015
DOI: 10.1161/CIRCULATIONAHA.114.010070
Abstract: Early menarche has been associated with increased risk of coronary heart disease (CHD), but most studies were relatively small and could not assess risk across a wide range of menarcheal ages few have examined associations with other vascular diseases. We examined CHD, cerebrovascular disease, and hypertensive disease risks by age at menarche in a large prospective study of UK women. In 1.2 million women (mean±SD age, 56±5 years) without previous heart disease, stroke, or cancer, menarcheal age was reported to be 13 years by 25%, ≤10 years by 4%, and ≥17 years by 1%. After 11.6 years of follow-up, 73 378 women had first hospitalization for or death from CHD, 25 426 from cerebrovascular disease, and 249 426 from hypertensive disease. Using Cox regression, we calculated relative risks for each vascular outcome by single year of menarcheal age. The relationship was U-shaped for CHD. Compared with women with menarche at 13 years, the adjusted relative risk for CHD for menarche at ≤10 years of age was 1.27 (95% confidence interval, 1.22–1.31 P .0001) and for menarche at ≥17 years of age was 1.23 (95% confidence interval, 1.16–1.30 P .0001). U-shaped relationships were also seen for cerebrovascular and hypertensive disease, although the magnitudes of these risks for early and late menarche were smaller than those for CHD. In this cohort, the relation of age at menarche to vascular disease risk was U shaped, with both early and late menarche being associated with increased risk. Associations were weaker for cerebrovascular and hypertensive disease than for CHD.
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
No related grants have been discovered for Dexter Canoy.