Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy.: The PROGRESS MRI Substudy.

International audienceBACKGROUND: The prevalence of white matter hyperintensities (WMHs) detected on cerebral MRI is associated with hypertension, but it is not known whether blood pressure lowering can arrest their progression. We report here the results of an MRI substudy of PROGRESS (Perindopril Protection Against Recurrent Stroke Study), a randomized trial of blood pressure lowering in subjects with cerebrovascular disease. METHODS AND RESULTS: The substudy comprised 192 participants who had a cerebral MRI both at baseline and after a mean follow-up time of 36 months (SD=6.0 months). At the first MRI, WMHs were graded with a visual rating scale from A (no WMH) to D (severe WMH). Participants were assigned to a combination of perindopril plus indapamide (or their placebos; 58%) or to single therapy with perindopril (or placebo). At the time of the second MRI, the blood pressure reduction in the active arm compared with the placebo arm was 11.2 mm Hg for systolic blood pressure and 4.3 mm Hg for diastolic blood pressure. Twenty-four subjects (12.5%) developed new WMHs at follow-up. The risk of new WMH was reduced by 43% (95% CI -7% to 89%) in the active treatment group compared with the placebo group (P=0.17). The mean total volume of new WMHs was significantly reduced in the active treatment group (0.4 mm3 [SE=0.8]) compared with the placebo group (2.0 mm3 [SE=0.7]; P=0.012). This difference was greatest for patients with severe WMH at entry, 0.0 mm3 (SE=0) in the active treatment group versus 7.6 mm3 (SE=1.0) in the placebo group (P<0.0001). CONCLUSIONS: These results indicate that an active blood pressure-lowering regimen stopped or delayed the progression of WMHs in patients with cerebrovascular disease

The consistency of the treatment effect of an ACE-inhibitor based treatment regimen in patients with vascular disease or high risk of vascular disease: A combined analysis of individual data of ADVANCE, EUROPA, and PROGRESS trials

AimsAngiotensin-converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk in different groups of patients. Whether these effects can be generalized to the broad group of patients with vascular disease is unknown. Therefore, we undertook a combined analysis using individual data from ADVANCE, EUROPA, and PROGRESS to determine the consistency of the treatment effect of perindopril-based regimen in patients with vascular disease or at high risk of vascular disease.Methods and resultsWe studied all-cause mortality and major cardiovascular outcomes during a follow-up of about 4 years in the 29 463 patients randomly assigned a perindopril-based treatment regimen or placebo. The perindopril-based regimens were associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.89; 95 confidence interval (CI) 0.82-0.96; P = 0.006], cardiovascular mortality (HR 0.85; 95 CI 0.76-0.95; P = 0.004), non-fatal myocardial infarction (HR 0.80; 95 CI 0.71-0.90; P < 0.001), stroke (HR 0.82; 95 CI 0.74-0.92; P = 0.002), and heart failure (HR 0.84; 95 CI 0.72-0.96; P = 0.015). Results were consistent in subgroups with different clinical characteristics, concomitant medication use, and across all strata of baseline blood pressure.ConclusionThis study provides strong evidence for a consistent cardiovascular protection with an ACE-inhibitor treatment regimen (perindopril-indapamide) by improving survival and reducing the risk of major cardiovascular events across a broad spectrum of patients with vascular disease

Obesity as a risk factor for COVID-19 mortality in women and men in the UK biobank: Comparisons with influenza/pneumonia and coronary heart disease

Obesity is associated with severe COVID-19 outcomes, yet, it is unclear whether the risk of COVID-19 mortality associated with obesity is similar between the sexes. We used data from the UK Biobank to assess the risk of COVID-19 mortality associated with various anthropometric measures in women and men. To put these results in context, we also compared these estimates with those for mortality from influenza/pneumonia and coronary heart disease (CHD). The analyses included 502 493 individuals (54% women), of whom 410 (36% women) died from COVID-19, 549 (36% women) died from influenza/pneumonia and 3355 (19% women) died from CHD. A higher body mass index (BMI), waist circumference, waist-to-hip ratio and waist-to-height ratio were each associated with a greater risk of death from COVID-19, influenza/pneumonia and CHD in both sexes, with the exception of the association between higher BMI and the risk of influenza/pneumonia death in men. A higher BMI was associated with a stronger risk of COVID-19 mortality in women than men; the women-to-men ratio of hazard ratios was 1.20 (95% confidence interval 1.00; 1.43). This study demonstrates the role of obesity in COVID-19 mortality and shows that the relative effects of a higher BMI on COVID-19 mortality may be stronger in women than men

SMARThealth India: A stepped-wedge, cluster randomised controlled trial of a community health worker managed mobile health intervention for people assessed at high cardiovascular disease risk in rural India

BACKGROUND:Cardiovascular diseases (CVD) are rising in India resulting in major health system challenges. METHODS:Eighteen primary health centre (PHC) clusters in rural Andhra Pradesh were randomised over three, 6-month steps to an intervention comprising: (1) household CVD risk assessments by village-based community health workers (CHWs) using a mobile tablet device; (2) electronic referral and clinical decision support for PHC doctors; and (3) a tracking system for follow-up care. Independent data collectors screened people aged ≥ 40 years in 54 villages serviced by the PHCs to create a high CVD risk cohort (based on WHO risk charts and blood pressure thresholds). Randomly selected, independent samples, comprising 15% of this cohort, were reviewed at each 6-month step. The primary outcome was the proportion meeting systolic blood pressure (SBP) targets (<140mmHg). FINDINGS:Eight-four percent of the eligible population (n = 62,254) were assessed at baseline (18.4% at high CVD risk). Of those at high risk, 75.3% were followed up over two years. CHWs screened 85.9% of the baseline cohort and doctors followed up 70.0% of all high risk referrals. There was no difference in the proportion of people achieving SBP targets (41.2% vs 39.2%; adjusted odds ratio (OR) 1.01 95% CI 0.76-1.35) or receiving BP-lowering medications in the intervention vs control periods respectively. There was a high discordance in risk scores generated by independent data collectors and CHWs, resulting in only 37.2% of the evaluation cohort exposed to the intervention. This discordance was mainly driven by fluctuating BP values (both normal variability and marked seasonal variations). In the pre-specified high risk concordant subgroup, there was greater use of BP-lowering medications in the intervention period (54.3% vs 47.9%, OR 1.22, 95% CI 1.03-1.44) but no impact on BP control. CONCLUSIONS:The strategy was well implemented with increased treatment rates among high risk individuals assessed by CHWs, however effects on BP were not demonstrated. Use of guideline-recommended BP thresholds for identifying high risk individuals substantially affected the reproducibility of risk assessment, and thus the ability to reliably evaluate the effectiveness of the intervention. In addition, unanticipated seasonal variation in BP in the context of a stepped-wedge trial highlights the inherent risks of this study design. TRIAL REGISTRATION:Clinical Trials Registry of India CTRI/2013/06/ 003753

Elevated blood pressure and risk of aortic valve disease: a cohort analysis of 5.4 million UK adults

Aims To test two related hypotheses that elevated blood pressure (BP) is a risk factor for aortic valve stenosis (AS) or regurgitation (AR). Methods and results In this cohort study of 5.4 million UK patients with no known cardiovascular disease or aortic valve disease at baseline, we investigated the relationship between BP and risk of incident AS and AR using multivariable-adjusted Cox regression models. Over a median follow-up of 9.2 years, 20 680 patients (0.38%) were diagnosed with AS and 6440 (0.12%) patients with AR. Systolic BP (SBP) was continuously related to the risk of AS and AR with no evidence of a nadir down to 115 mmHg. Each 20 mmHg increment in SBP was associated with a 41% higher risk of AS (hazard ratio 1.41, 95% confidence interval 1.38–1.45) and a 38% higher risk of AR (1.38, 1.31–1.45). Associations were stronger in younger patients but with no strong evidence for interaction by gender or body mass index. Each 10 mmHg increment in diastolic BP was associated with a 24% higher risk of AS (1.24, 1.19–1.29) but not AR (1.04, 0.97–1.11). Each 15 mmHg increment in pulse pressure was associated with a 46% greater risk of AS (1.46, 1.42–1.50) and a 53% higher risk of AR (1.53, 1.45–1.62). Conclusion Long-term exposure to elevated BP across its whole spectrum was associated with increased risk of AS and AR. The possible causal nature of the observed associations warrants further investigation

Risk prediction in patients with heart failure: A systematic review and analysis

Objectives This study sought to review the literature for risk prediction models in patients with heart failure and to identify the most consistently reported independent predictors of risk across models. Background Risk assessment provides information about patient prognosis, guides decision making about the type and intensity of care, and enables better understanding of provider performance. Methods MEDLINE and EMBASE were searched from January 1995 to March 2013, followed by hand searches of the retrieved reference lists. Studies were eligible if they reported at least 1 multivariable model for risk prediction of death, hospitalization, or both in patients with heart failure and reported model performance. We ranked reported individual risk predictors by their strength of association with the outcome and assessed the association of model performance with study characteristics. Results Sixty-four main models and 50 modifications from 48 studies met the inclusion criteria. Of the 64 main models, 43 models predicted death, 10 hospitalization, and 11 death or hospitalization. The discriminatory ability of the models for prediction of death appeared to be higher than that for prediction of death or hospitalization or prediction of hospitalization alone (p = 0.0003). A wide variation between studies in clinical settings, population characteristics, sample size, and variables used for model development was observed, but these features were not significantly associated with the discriminatory performance of the models. A few strong predictors emerged for prediction of death; the most consistently reported predictors were age, renal function, blood pressure, blood sodium level, left ventricular ejection fraction, sex, brain natriuretic peptide level, New York Heart Association functional class, diabetes, weight or body mass index, and exercise capacity. Conclusions There are several clinically useful and well-validated death prediction models in patients with heart failure. Although the studies differed in many respects, the models largely included a few common markers of risk

Clustering of risk factors and the risk of incident cardiovascular disease in Asian and Caucasian populations: results from the Asia Pacific Cohort Studies Collaboration

To assess the relationship between risk factor clusters and cardiovascular disease (CVD) incidence in Asian and Caucasian populations and to estimate the burden of CVD attributable to each cluster.Asia Pacific Cohort Studies Collaboration.Individual participant data from 34 population-based cohorts, involving 314 024 participants without a history of CVD at baseline.Clusters were 11 possible combinations of four individual risk factors (current smoking, overweight, blood pressure (BP) and total cholesterol). Cox regression models were used to obtain adjusted HRs and 95% CIs for CVD associated with individual risk factors and risk factor clusters. Population-attributable fractions (PAFs) were calculated.During a mean follow-up of 7 years, 6203 CVD events were recorded. The ranking of HRs and PAFs was similar for Australia and New Zealand (ANZ) and Asia; clusters including BP consistently showed the highest HRs and PAFs. The BP-smoking cluster had the highest HR for people with two risk factors: 4.13 (3.56 to 4.80) for Asia and 3.07 (2.23 to 4.23) for ANZ. Corresponding PAFs were 24% and 11%, respectively. For individuals with three risk factors, the BP-smoking-cholesterol cluster had the highest HR (4.67 (3.92 to 5.57) for Asia and 3.49 (2.69 to 4.53) for ANZ). Corresponding PAFs were 13% and 10%.Risk factor clusters act similarly on CVD risk in Asian and Caucasian populations. Clusters including elevated BP were associated with the highest excess risk of CVD

The Report of the Ecological Society of America Committee on the Scientific Basis for Ecosystem Management

Ecosystem management is management driven by explicit goals, executed by policies, protocols, and practices, and made adaptable by monitoring and research based on our best understanding of the ecological interactions and processes necessary to sustain ecosystem composition, structure, and function

Sex differences in risk factors for cognitive decline and dementia, including death as a competing risk, in individuals with diabetes: Results from the ADVANCE trial

Aims: The association between diabetes and cognitive decline (CD) and dementia has been well-documented. This study estimated the associations between risk factors and CD/dementia, and the sex differences in these risk factors in individuals with type 2 diabetes, while accounting for the competing risk of death. Materials and methods: The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial of 11,140 individuals with type 2 diabetes was used to estimate the odds of CD/dementia using multinomial logistic regression. Results: During a median five-year follow-up, 1,827 participants (43.2% women) had CD/dementia (1,718 with CD only; 21 with dementia only; 88 with CD and dementia), and 929 (31.0% women) died without CD/dementia. Women had a lower odds of CD/dementia than men (Odds Ratio (OR) (95% confidence interval), 0.88 (0.77, 1.00)); older age, higher total cholesterol, HbA1c , waist circumference, waist-to-height ratio, moderately increased ACR (Albumin-Creatinine Ratio), stroke/transient ischemic attack and retinal disease were each associated with greater odds of CD/dementia; higher years at education completion, baseline cognitive function, taller stature and current alcohol use were inversely associated. Higher waist circumference (women-to-men Ratio of Odds Ratios (ROR), 1.05 (1.00, 1.10) per 5 cm) and presence of anxiety/depression (ROR, 1.28 (1.01, 1.63)) were associated with greater OR for CD/dementia in women than men. Conclusions: Several risk factors were associated with CD/dementia. Higher waist circumference and mental health symptoms were more strongly associated with CD/dementia in women than men. Further studies should examine the mechanisms which underlie these sex differences. This article is protected by copyright. All rights reserved

Cardiovascular disease risk and comparison of different strategies for blood pressure management in rural India.

BACKGROUND: Non-optimal blood pressure (BP) levels are a major cause of disease burden globally. We describe current BP and treatment patterns in rural India and compare different approaches to BP lowering in this setting. METHODS: All individuals aged ≥40 years from 54 villages in a South Indian district were invited and 62,194 individuals (84%) participated in a cross-sectional study. Individual 10-year absolute cardiovascular disease (CVD) risk was estimated using WHO/ISH charts. Using known effects of treatment, proportions of events that would be averted under different paradigms of BP lowering therapy were estimated. RESULTS: After imputation of pre-treatment BP levels for participants on existing treatment, 76·9% (95% confidence interval, 75.7-78.0%), 5·3% (4.9-5.6%), and 17·8% (16.9-18.8%) of individuals had a 10-year CVD risk defined as low ( 160/100 mmHg), respectively. Compared to the 19.6% (18.4-20.9%) of adults treated with current practice, a slightly higher or similar proportion would be treated using an intermediate (23·2% (22.0-24.3%)) or high (17·9% (16.9-18.8%) risk threshold for instituting BP lowering therapy and this would avert 87·2% (85.8-88.5%) and 62·7% (60.7-64.6%) more CVD events over ten years, respectively. These strategies were highly cost-effective relative to the current practice. CONCLUSION: In a rural Indian community, a substantial proportion of the population has elevated CVD risk. The more efficient and cost-effective clinical approach to BP lowering is to base treatment decisions on an estimate of an individual's short-term absolute CVD risk rather than with BP based strategy. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/2013/06/003753 , 14 June 2013