Sex-Specific Effects of Blood Pressure Lowering Pharmacotherapy for the Prevention of Cardiovascular Disease: An Individual Participant-Level Data Meta-Analysis.

BACKGROUND: 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. METHODS: We conducted an individual 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 <120 to ≥170 mm Hg, and age categories spanning from <55 to ≥85 years. We used fixed-effect one-stage individual participant-level data meta-analyses and applied Cox proportional hazard models, stratified by trial, to analyze the data. RESULTS: We included data from 51 randomized controlled trials involving 358 636 (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). CONCLUSIONS: 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

Speed of processing training results in lower risk of dementia

• A randomized trial examined the efficacy of three cognitive training programs. • Speed of processing cognitive training significantly reduced dementia risk. • Each session of speed training completed was associated with reduced dementia risk

Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis

BACKGROUND: Controversy exists as to whether the threshold for blood pressure-lowering treatment should differ between people with and without type 2 diabetes. We aimed to investigate the effects of blood pressure-lowering treatment on the risk of major cardiovascular events by type 2 diabetes status, as well as by baseline levels of systolic blood pressure. METHODS: We conducted a one-stage individual participant-level data meta-analysis of major randomised controlled trials using the Blood Pressure Lowering Treatment Trialists' Collaboration dataset. Trials with information on type 2 diabetes status at baseline were eligible if they compared blood pressure-lowering medications versus placebo or other classes of blood pressure-lowering medications, or an intensive versus a standard blood pressure-lowering strategy, and reported at least 1000 persons-years of follow-up in each group. Trials exclusively on participants with heart failure or with short-term therapies and acute myocardial infarction or other acute settings were excluded. We expressed treatment effect per 5 mm Hg reduction in systolic blood pressure on the risk of developing a major cardiovascular event as the primary outcome, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal ischaemic heart disease, or heart failure causing death or requiring hospitalisation. Cox proportional hazard models, stratified by trial, were used to estimate hazard ratios (HRs) separately by type 2 diabetes status at baseline, with further stratification by baseline categories of systolic blood pressure (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg). To estimate absolute risk reductions, we used a Poisson regression model over the follow-up duration. The effect of each of the five major blood pressure-lowering drug classes, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β blockers, calcium channel blockers, and thiazide diuretics, was estimated using a network meta-analysis framework. This study is registered with PROSPERO, CRD42018099283. FINDINGS: We included data from 51 randomised clinical trials published between 1981 and 2014 involving 358 533 participants (58% men), among whom 103 325 (29%) had known type 2 diabetes at baseline. The baseline mean systolic/diastolic blood pressure of those with and without type 2 diabetes was 149/84 mm Hg (SD 19/11) and 153/88 mm Hg (SD 21/12), respectively. Over 4·2 years median follow-up (IQR 3·0-5·0), a 5 mm Hg reduction in systolic blood pressure decreased the risk of major cardiovascular events in both groups, but with a weaker relative treatment effect in participants with type 2 diabetes (HR 0·94 [95% CI 0·91-0·98]) compared with those without type 2 diabetes (0·89 [0·87-0·92]; pinteraction=0·0013). However, absolute risk reductions did not differ substantially between people with and without type 2 diabetes because of the higher absolute cardiovascular risk among participants with type 2 diabetes. We found no reliable evidence for heterogeneity of treatment effects by baseline systolic blood pressure in either group. In keeping with the primary findings, analysis using stratified network meta-analysis showed no evidence that relative treatment effects differed substantially between participants with type 2 diabetes and those without for any of the drug classes investigated. INTERPRETATION: Although the relative beneficial effects of blood pressure reduction on major cardiovascular events were weaker in participants with type 2 diabetes than in those without, absolute effects were similar. The difference in relative risk reduction was not related to the baseline blood pressure or allocation to different drug classes. Therefore, the adoption of differential blood pressure thresholds, intensities of blood pressure lowering, or drug classes used in people with and without type 2 diabetes is not warranted. FUNDING: British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School

Low utilization of health care services following screening for hypertension in Dar es Salaam (Tanzania): a prospective population-based study

Drug therapy in high-risk individuals has been advocated as an important strategy to reduce cardiovascular disease in low income countries. We determined, in a low-income urban population, the proportion of persons who utilized health services after having been diagnosed as hypertensive and advised to seek health care for further hypertension management. A population-based survey of 9254 persons aged 25-64 years was conducted in Dar es Salaam. Among the 540 persons with high blood pressure (defined here as BP >or= 160/95 mmHg) at the initial contact, 253 (47%) had high BP on a 4th visit 45 days later. Among them, 208 were untreated and advised to attend health care in a health center of their choice for further management of their hypertension. One year later, 161 were seen again and asked about their use of health services during the interval. Among the 161 hypertensive persons advised to seek health care, 34% reported to have attended a formal health care provider during the 12-month interval (63% public facility; 30% private; 7% both). Antihypertensive treatment was taken by 34% at some point of time (suggesting poor uptake of health services) and 3% at the end of the 12-month follow-up (suggesting poor long-term compliance). Health services utilization tended to be associated with older age, previous history of high BP, being overweight and non-smoking, but not with education or wealth. Lack of symptoms and cost of treatment were the reasons reported most often for not attending health care. Low utilization of health services after hypertension screening suggests a small impact of a patient-centered screen-and-treat strategy in this low-income population. These findings emphasize the need to identify and address barriers to health care utilization for non-communicable diseases in this setting and, indirectly, the importance of public health measures for primary prevention of these diseases

An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial

Background: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin ± aspirin) for prescription when appropriate; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification. Methods: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed. Discussion: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN1261600023342

Aspirin for Primary Prevention of Cardiovascular Events in People With Diabetes: A position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation

The burden of cardiovascular disease (CVD) among patients with diabetes is substantial. Individuals with diabetes are at two- to fourfold increased risk of cardiovascular events compared with age- and sex-matched individuals without diabetes. In diabetic patients over the age of 65 years, 68% of deaths are from coronary heart disease (CHD) and 16% are from stroke (1). A number of mechanisms for the increased cardiovascular risk with diabetes have been proposed, including increased tendency toward intracoronary thrombus formation (2), increased platelet reactivity (3), and worsened endothelial dysfunction (4). The increased risk for cardiovascular events and mortality in patients with diabetes has led to considerable interest in identifying effective means for cardiovascular risk reduction. Aspirin has been shown to be effective in reducing cardiovascular morbidity and mortality in high-risk patients with myocardial infarction (MI) or stroke (secondary prevention) (5). The Food and Drug Administration has not approved aspirin for use in primary prevention, and its net benefit among patients with no previous cardiovascular events is more controversial, for both patients with and without a history of diabetes (5). The U.S. Preventive Services Task Force recently updated its recommendation about aspirin use for primary prevention. The Task Force recommended encouraging aspirin use in men age 45–79 years and women age 55–79 years and not encouraging aspirin use in younger adults. They did not differentiate their recommendations based on the presence or absence of diabetes (6,7). In 2007, the American Diabetes Association (ADA) and the American Heart Association (AHA) jointly recommended that aspirin therapy (75–162 mg/day) be used as a primary prevention strategy in those with diabetes at increased cardiovascular risk, including those who are over 40 years of age or who have additional risk factors (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria) (8). These recommendations were

Investigating the stratified efficacy and safety of pharmacological blood pressure-lowering: an overall protocol for individual patient-level data meta-analyses of over 300 000 randomised participants in the new phase of the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC)

Introduction 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 individual 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. Methods and analysis 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 individual meta-analyses will be developed and registered on public platforms. Ethics and dissemination 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

Different distribution of cardiovascular risk factors according to ethnicity: A study in a high risk population

This study compares the distribution of cardiovascular risk factors in different ethnic groups at high risk of developing cardiovascular diseases within general practices. A total of 430 patients (179 Dutch, 126 Turks, 50 Surinamese, 23 Moroccans, 23 Antilleans and 29 from other ethnic groups) were included in the study. Data collection consisted of questionnaires and physical and clinical examinations. 54% was female. The mean age was 53.1 (sd 9.9) years. There were important ethnic differences in the distribution of cardiovascular risk factors. Compared to the Dutch, ethnic minorities had significantly greater odds of being diabetic (OR = 3.2-19.4); but were less likely to smoke (OR = 0.10-0.53). Turkish individuals had a lower prevalence of hypercholesterolemia but were 2.4 times more likely to be obese than the Dutch. Hypertension was very common in all ethnic groups and no significant ethnic differences were found. These findings provide additional evidence of the need for tailored interventions for different ethnic groups in general practices