Summary Background The benefits of blood pressure lowering treatment for prevention of cardiovascular disease are well established. However, the extent to which these effects differ by baseline blood ...pressure, presence of comorbidities, or drug class is less clear. We therefore performed a systematic review and meta-analysis to clarify these differences. Method For this systematic review and meta-analysis, we searched MEDLINE for large-scale blood pressure lowering trials, published between Jan 1, 1966, and July 7, 2015, and we searched the medical literature to identify trials up to Nov 9, 2015. All randomised controlled trials of blood pressure lowering treatment were eligible for inclusion if they included a minimum of 1000 patient-years of follow-up in each study arm. No trials were excluded because of presence of baseline comorbidities, and trials of antihypertensive drugs for indications other than hypertension were eligible. We extracted summary-level data about study characteristics and the outcomes of major cardiovascular disease events, coronary heart disease, stroke, heart failure, renal failure, and all-cause mortality. We used inverse variance weighted fixed-effects meta-analyses to pool the estimates. Results We identified 123 studies with 613 815 participants for the tabular meta-analysis. Meta-regression analyses showed relative risk reductions proportional to the magnitude of the blood pressure reductions achieved. Every 10 mm Hg reduction in systolic blood pressure significantly reduced the risk of major cardiovascular disease events (relative risk RR 0·80, 95% CI 0·77–0·83), coronary heart disease (0·83, 0·78–0·88), stroke (0·73, 0·68–0·77), and heart failure (0·72, 0·67–0·78), which, in the populations studied, led to a significant 13% reduction in all-cause mortality (0·87, 0·84–0·91). However, the effect on renal failure was not significant (0·95, 0·84–1·07). Similar proportional risk reductions (per 10 mm Hg lower systolic blood pressure) were noted in trials with higher mean baseline systolic blood pressure and trials with lower mean baseline systolic blood pressure (all ptrend >0·05). There was no clear evidence that proportional risk reductions in major cardiovascular disease differed by baseline disease history, except for diabetes and chronic kidney disease, for which smaller, but significant, risk reductions were detected. β blockers were inferior to other drugs for the prevention of major cardiovascular disease events, stroke, and renal failure. Calcium channel blockers were superior to other drugs for the prevention of stroke. For the prevention of heart failure, calcium channel blockers were inferior and diuretics were superior to other drug classes. Risk of bias was judged to be low for 113 trials and unclear for 10 trials. Heterogeneity for outcomes was low to moderate; the I2 statistic for heterogeneity for major cardiovascular disease events was 41%, for coronary heart disease 25%, for stroke 26%, for heart failure 37%, for renal failure 28%, and for all-cause mortality 35%. Interpretation Blood pressure lowering significantly reduces vascular risk across various baseline blood pressure levels and comorbidities. Our results provide strong support for lowering blood pressure to systolic blood pressures less than 130 mm Hg and providing blood pressure lowering treatment to individuals with a history of cardiovascular disease, coronary heart disease, stroke, diabetes, heart failure, and chronic kidney disease. Funding National Institute for Health Research and Oxford Martin School.
Mendelian Randomization Emdin, Connor A; Khera, Amit V; Kathiresan, Sekar
JAMA : the journal of the American Medical Association,
11/2017, Letnik:
318, Številka:
19
Journal Article
Recenzirano
Mendelian randomization uses genetic variants to determine whether an observational association between a risk factor and an outcome is consistent with a causal effect. Mendelian randomization relies ...on the natural, random assortment of genetic variants during meiosis yielding a random distribution of genetic variants in a population. Individuals are naturally assigned at birth to inherit a genetic variant that affects a risk factor or not inherit such a variant. Individuals who carry the variant and those who do not are then followed up for the development of an outcome of interest. Because these genetic variants are typically unassociated with confounders, differences in the outcome between those who carry the variant and those who do not can be attributed to the difference in the risk factor. Here, Emdin et al discuss the principles of mendelian randomization.
Using a polygenic score of DNA sequence polymorphisms, the authors of this study quantified genetic risk and assessed four healthy lifestyle factors. Among participants at high genetic risk, a ...healthy lifestyle was associated with a reduced risk of coronary disease.
Both genetic and lifestyle factors are key drivers of coronary artery disease, a complex disorder that is the leading cause of death worldwide.
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A familial pattern in the risk of coronary artery disease was first described in 1938 and was subsequently confirmed in large studies involving twins and prospective cohorts.
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Since 2007, genomewide association analyses have identified more than 50 independent loci associated with the risk of coronary artery disease.
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These risk alleles, when aggregated into a polygenic risk score, are predictive of incident coronary events and provide a continuous and quantitative measure of genetic susceptibility.
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IMPORTANCE: Lowering blood pressure (BP) is widely used to reduce vascular risk in individuals with diabetes. OBJECTIVE: To determine the associations between BP–lowering treatment and vascular ...disease in type 2 diabetes. DATA SOURCES AND STUDY SELECTION: We searched MEDLINE for large-scale randomized controlled trials of BP–lowering treatment including patients with diabetes, published between January 1966 and October 2014. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted study characteristics and vascular outcome data. Estimates were stratified by baseline BP and achieved BP, and pooled using fixed-effects meta-analysis. MAIN OUTCOMES AND MEASURES: All-cause mortality, cardiovascular events, coronary heart disease events, stroke, heart failure, retinopathy, new or worsening albuminuria, and renal failure. RESULTS: Forty trials judged to be of low risk of bias (100 354 participants) were included. Each 10–mm Hg lower systolic BP was associated with a significantly lower risk of mortality (relative risk RR, 0.87; 95% CI, 0.78-0.96); absolute risk reduction (ARR) in events per 1000 patient-years (3.16; 95% CI, 0.90-5.22), cardiovascular events (RR, 0.89 95% CI, 0.83-0.95; ARR, 3.90 95% CI, 1.57-6.06), coronary heart disease (RR, 0.88 95% CI, 0.80-0.98; ARR, 1.81 95% CI, 0.35-3.11), stroke (RR, 0.73 95% CI, 0.64-0.83; ARR, 4.06 95% CI, 2.53-5.40), albuminuria (RR, 0.83 95% CI, 0.79-0.87; ARR, 9.33 95% CI, 7.13-11.37), and retinopathy (RR, 0.87 95% CI, 0.76-0.99; ARR, 2.23 95% CI, 0.15-4.04). When trials were stratified by mean baseline systolic BP at greater than or less than 140 mm Hg, RRs for outcomes other than stroke, retinopathy, and renal failure were lower in studies with greater baseline systolic BP (P interaction <0.1). The associations between BP-lowering treatments and outcomes were not significantly different, irrespective of drug class, except for stroke and heart failure. Estimates were similar when all trials, regardless of risk of bias, were included. CONCLUSIONS AND RELEVANCE: Among patients with type 2 diabetes, BP lowering was associated with improved mortality and other clinical outcomes with lower RRs observed among those with baseline BP of 140 mm Hg and greater. These findings support the use of medications for BP lowering in these patients.
Despite the vast amount of evidence on the benefits of blood pressure lowering accumulated to date, elevated blood pressure is still the leading risk factor for disease and disability worldwide. The ...purpose of this review is to summarize the epidemiological evidence underpinning the association between blood pressure and a range of conditions. This review focuses on the association between systolic and diastolic blood pressures and the risk of cardiovascular and renal disease. Evidence for and against the existence of a J-shaped curve association between blood pressure and cardiovascular risk, and differences in the predictive power of systolic, diastolic, and pulse pressure, are described. In addition, global and regional trends in blood pressure levels and management of hypertension are reviewed.
To quantify the association between atrial fibrillation and cardiovascular disease, renal disease, and death.
Systematic review and meta-analysis.
Medline and Embase.
Cohort studies examining the ...association between atrial fibrillation and cardiovascular disease, renal disease, and death. Two reviewers independently extracted study characteristics and the relative risk of outcomes associated with atrial fibrillation: specifically, all cause mortality, cardiovascular mortality, major cardiovascular events, any stroke, ischaemic stroke, haemorrhagic stroke, ischaemic heart disease, sudden cardiac death, congestive heart failure, chronic kidney disease, and peripheral arterial disease. Estimates were pooled with inverse variance weighted random effects meta-analysis.
104 eligible cohort studies involving 9 686 513 participants (587 867 with atrial fibrillation) were identified. Atrial fibrillation was associated with an increased risk of all cause mortality (relative risk 1.46, 95% confidence interval 1.39 to 1.54), cardiovascular mortality (2.03, 1.79 to 2.30), major cardiovascular events (1.96, 1.53 to 2.51), stroke (2.42, 2.17 to 2.71), ischaemic stroke (2.33, 1.84 to 2.94), ischaemic heart disease (1.61, 1.38 to 1.87), sudden cardiac death (1.88, 1.36 to 2.60), heart failure (4.99, 3.04 to 8.22), chronic kidney disease (1.64, 1.41 to 1.91), and peripheral arterial disease (1.31, 1.19 to 1.45) but not haemorrhagic stroke (2.00, 0.67 to 5.96). Among the outcomes examined, the highest absolute risk increase was for heart failure. Associations between atrial fibrillation and included outcomes were broadly consistent across subgroups and in sensitivity analyses.
Atrial fibrillation is associated with an increased risk of death and an increased risk of cardiovascular and renal disease. Interventions aimed at reducing outcomes beyond stroke are warranted in patients with atrial fibrillation.
Whether anxiety is a risk factor for a range of cardiovascular diseases is unclear. We aimed to determine the association between anxiety and a range of cardiovascular diseases. MEDLINE and EMBASE ...were searched for cohort studies that included participants with and without anxiety, including subjects with anxiety, worry, posttraumatic stress disorder, phobic anxiety, and panic disorder. We examined the association of anxiety with cardiovascular mortality, major cardiovascular events (defined as the composite of cardiovascular death, stroke, coronary heart disease, and heart failure), stroke, coronary heart disease, heart failure, and atrial fibrillation. We identified 46 cohort studies containing 2,017,276 participants and 222,253 subjects with anxiety. Anxiety was associated with a significantly elevated risk of cardiovascular mortality (relative risk RR 1.41, CI 1.13 to 1.76), coronary heart disease (RR 1.41, CI 1.23 to 1.61), stroke (RR 1.71, CI 1.18 to 2.50), and heart failure (RR 1.35, CI 1.11 to 1.64). Anxiety was not significantly associated with major cardiovascular events or atrial fibrillation although CIs were wide. Phobic anxiety was associated with a higher risk of coronary heart disease than other anxiety disorders, and posttraumatic stress disorder was associated with a higher risk of stroke. Results were broadly consistent in sensitivity analyses. Anxiety disorders are associated with an elevated risk of a range of different cardiovascular events, including stroke, coronary heart disease, heart failure, and cardiovascular death. Whether these associations are causal is unclear.
AKI associates with increased long-term risk of mortality, but the prognostic significance of AKI in terms of long-term cardiovascular disease remains unconfirmed. We conducted a systematic review ...and meta-analysis to assess whether AKI associates with long-term cardiovascular disease. We included cohort studies that examined adults with and without AKI and reported a multivariable-adjusted relative risk (RR) for the association between AKI and cardiovascular mortality, major cardiovascular events, and disease-specific events: congestive heart failure, acute myocardial infarction, and stroke. Twenty-five studies involving 254,408 adults (55,150 with AKI) were included. AKI associated with an 86% and a 38% increased risk of cardiovascular mortality and major cardiovascular events, respectively (RR 1.86; 95% confidence interval (95% CI), 1.72 to 2.01 and RR 1.38; 95% CI, 1.23 to 1.55, respectively). For disease-specific events, AKI associated with a 58% increased risk of heart failure (RR 1.58; 95% CI, 1.46 to 1.72) and a 40% increased risk of acute myocardial infarction (RR 1.40; 95% CI, 1.23 to 1.59). The elevated risk of heart failure and acute myocardial infarction persisted in subgroup analyses on the basis of AKI severity and the proportion of adults with baseline ischemic heart disease. Finally, AKI was associated with a 15% increased risk of stroke (RR 1.15; 95% CI, 1.03 to 1.28). In conclusion, AKI associates with an elevated risk of cardiovascular mortality and major cardiovascular events, particularly heart failure and acute myocardial infarction.
Reliable quantification of the association between blood pressure (BP) and risk of type 2 diabetes is lacking.
This study sought to determine the association between usual BP and risk of diabetes, ...overall and by participant characteristics.
A cohort of 4.1 million adults, free of diabetes and cardiovascular disease, was identified using validated linked electronic health records. Analyses were complemented by a meta-analysis of prospective studies that reported relative risks of new-onset diabetes per unit of systolic blood pressure (SBP).
Among the overall cohort, 20 mm Hg higher SBP and 10 mm Hg higher diastolic BP were associated with a 58% and a 52% higher risk of new-onset diabetes (hazard ratio: 1.58; 95% confidence interval CI: 1.56 to 1.59; and hazard ratio: 1.52; 95% confidence interval: 1.51 to 1.54), respectively. There was no evidence of a nadir to a baseline BP of 110/70 mm Hg. The strength of the association per 20 mm Hg higher SBP declined with age and with increasing body mass index. Estimates were similar even after excluding individuals prescribed antihypertensive or lipid-lowering therapies. Systematic review identified 30 studies with 285,664 participants and 17,388 incident diabetes events. The pooled relative risk of diabetes for a 20 mm Hg higher usual SBP across these studies was 1.77 (1.53 to 2.05).
People with elevated BP are at increased risk of diabetes. The strength of the association declined with increasing body mass index and age. Further research should determine if the observed risk is modifiable.
The Million Veteran Program (MVP) was established in 2011 as a national research initiative to determine how genetic variation influences the health of US military veterans. Here we genotyped 312,571 ...MVP participants using a custom biobank array and linked the genetic data to laboratory and clinical phenotypes extracted from electronic health records covering a median of 10.0 years of follow-up. Among 297,626 veterans with at least one blood lipid measurement, including 57,332 black and 24,743 Hispanic participants, we tested up to around 32 million variants for association with lipid levels and identified 118 novel genome-wide significant loci after meta-analysis with data from the Global Lipids Genetics Consortium (total n > 600,000). Through a focus on mutations predicted to result in a loss of gene function and a phenome-wide association study, we propose novel indications for pharmaceutical inhibitors targeting PCSK9 (abdominal aortic aneurysm), ANGPTL4 (type 2 diabetes) and PDE3B (triglycerides and coronary disease).
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