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Genetically Predicted Blood Pressure and Risk of Atrial Fibrillation.

ABSTRACT: Observational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF. To address this question, this study explored the relationship between genetic predictors of blood pressure and risk of AF. We secondarily explored the relationship between genetically proxied use of antihypertensive drugs and risk of AF. Two-sample Mendelian randomization was performed using an inverse-variance weighted meta-analysis with weighted median Mendelian randomization and Egger intercept tests performed as sensitivity analyses. Summary statistics for systolic blood pressure, diastolic blood pressure, and pulse pressure were obtained from the International Consortium of Blood Pressure and the UK Biobank discovery analysis and AF from the 2018 Atrial Fibrillation Genetics Consortium multiethnic genome-wide association studies. Increases in genetically proxied systolic blood pressure, diastolic blood pressure, or pulse pressure by 10 mm?Hg were associated with increased odds of AF (systolic blood pressure: odds ratio [OR], 1.17 [95% CI, 1.11-1.22]; P=1×10^-11; diastolic blood pressure: OR, 1.25 [95% CI, 1.16-1.35]; P=3×10^-8; pulse pressure: OR, 1.1 [95% CI, 1.0-1.2]; P=0.05). Decreases in systolic blood pressure by 10 mm?Hg estimated by genetic proxies of antihypertensive medications showed calcium channel blockers (OR, 0.66 [95% CI, 0.57-0.76]; P=8×10^-9) and ?-blockers (OR, 0.61 [95% CI, 0.46-0.81]; P=6×10^-4) decreased the risk of AF. Blood pressure-increasing genetic variants were associated with increased risk of AF, consistent with a causal relationship between blood pressure and AF. These data support the concept that blood pressure reduction with calcium channel blockade or ?-blockade could reduce the risk of AF.

SUBMITTER: Hyman MC

PROVIDER: S-EPMC7803440 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Genetically Predicted Blood Pressure and Risk of Atrial Fibrillation.

Hyman Matthew C MC Levin Michael G MG Gill Dipender D Walker Venexia M VM Georgakis Marios K MK Davies Neil M NM Marchlinski Francis E FE Damrauer Scott M SM

Hypertension (Dallas, Tex. : 1979) 20210104 2

Observational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF. To address this question, this study explored the relationship between genetic predictors of blood pressure and risk of AF. We secondarily explored the relationship between genetically proxied use of antihypertensive drugs and risk of AF. ...[more]

PMID: 33390040

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Project description:BackgroundWhether elevated blood pressure (BP) is a modifiable risk factor for atrial fibrillation (AF) is not established. We tested (1) whether the association between BP and risk of AF is causal, (2) whether it varies according to individual's genetic susceptibility for AF, and (3) the extent to which specific BP-lowering drugs are expected to reduce this risk.MethodsFirst, causality of association was assessed through two-sample Mendelian randomization, using data from two independent genome-wide association studies that included a population of one million Europeans in total. Second, the UK Biobank data of 329,237 participants at baseline was used to study the effect of BP on AF according to genetic susceptibility of developing AF. Third, a possible treatment effect with major BP-lowering drug classes on AF risk was predicted through genetic variants in genes encode the therapeutic targets of each drug class. Estimated drug effects were compared with effects on incident coronary heart disease, for which direct trial evidence exists.ResultsThe two-sample Mendelian randomization analysis indicated that, on average, exposure to a higher systolic BP increased the risk of AF by 19% (odds ratio per each 10-mmHg [OR] 1.19 [1.12 to 1.27]). This association was replicated in the UK biobank using individual participant data. However, in a further genetic risk-stratified analysis, there was evidence for a linear gradient in the relative effects of systolic BP on AF; while there was no conclusive evidence of an effect in those with low genetic risk, a strong effect was observed among those with high genetic susceptibility for AF. The comparison of predicted treatment effects using genetic proxies for three main drug classes (angiotensin-converting enzyme inhibitors, beta-blockers, and calcium channel blockers) suggested similar average effects for the prevention of atrial fibrillation and coronary heart disease.ConclusionsThe effect of elevated BP on the risk of AF is likely to be causal, suggesting that BP-lowering treatment may be effective in AF prevention. However, average effects masked clinically important variations, with a more pronounced effect in individuals with high genetic susceptibility risk for AF.

Project description:The association of blood pressure (BP) and hypertension with the presence of different types of brain lesions in patients with atrial fibrillation is unclear. BP values were obtained in a multicenter cohort of patients with atrial fibrillation. Systolic and diastolic BP was categorized in predefined groups. All patients underwent brain magnetic resonance imaging and neurocognitive testing. Brain lesions were classified as large noncortical or cortical infarcts, small noncortical infarcts, microbleeds, or white matter lesions. White matter lesions were graded according to the Fazekas scale. Overall, 1738 patients with atrial fibrillation were enrolled in this cross-sectional analysis (mean age, 73 years, 73% males). Mean BP was 135/79 mm?Hg, and 67% of participants were taking BP-lowering treatment. White matter lesions Fazekas ?2 were found in 54%, large noncortical or cortical infarcts in 22%, small noncortical infarcts in 21%, and microbleeds in 22% of patients, respectively. Compared with patients with systolic BP <120 mm?Hg, the adjusted odds ratios (95% CI) for Fazekas?2 was 1.25 (0.94-1.66), 1.41 (1.03-1.93), and 2.54 (1.65-3.95) among patients with systolic BP of 120 to 140, 140 to 160, and ?160 mm?Hg (P for linear trend<0.001). Per 5 mm?Hg increase in systolic and diastolic BP, the adjusted ?-coefficient (95% CI) for log-transformed white matter lesions was 0.04 (0.02-0.05), P<0.001 and 0.04 (0.01-0.06), P=0.004. Systolic BP was associated with small noncortical infarcts (odds ratios [95% CI] per 5 mm?Hg 1.05 [1.01-1.08], P=0.006), microbleeds were associated with hypertension, but large noncortical or cortical infarcts were not associated with BP or hypertension. After multivariable adjustment, BP and hypertension were not associated with neurocognitive function. Among patients with atrial fibrillation, BP is strongly associated with the presence and extent of white matter lesions, but there is no association with large noncortical or cortical infarcts. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.

Project description:The influence of systolic and diastolic blood pressure (BP) on incident atrial fibrillation (AF) is not well studied among initially healthy, middle-aged women.A total of 34,221 women participating in the Women's Health Study were prospectively followed up for incident AF. The risk of AF across categories of systolic and diastolic BP was compared by use of Cox proportional-hazards models. During 12.4 years of follow-up, 644 incident AF events occurred. Using BP measurements at baseline, we discovered that the long-term risk of AF was significantly increased across categories of systolic and diastolic BP. Multivariable-adjusted hazard ratios for systolic BP categories (<120, 120 to 129, 130 to 139, 140 to 159, and > or =160 mm Hg) were 1.0, 1.00 (95% CI, 0.78 to 1.28), 1.28 (95% CI, 1.00 to 1.63), 1.56 (95% CI, 1.22 to 2.01), and 2.74 (95% CI, 1.77 to 4.22) (P for trend <0.0001). Adjusted hazard ratios across baseline diastolic BP categories (<65, 65 to 74, 75 to 84, 85 to 89, 90 to 94, and > or =95 mm Hg) were 1.0, 1.17 (95% CI, 0.81 to 1.69), 1.18 (95% CI, 0.84 to 1.65), 1.53 (95% CI, 1.05 to 2.23), 1.35 (95% CI, 0.82 to 2.22), and 2.15 (95% CI, 1.21 to 3.84) (P for trend=0.004). When BP changes over time were accounted for in updated models, multivariable-adjusted hazard ratios were 1.0, 1.14 (95% CI, 0.89 to 1.46), 1.37 (95% CI, 1.07 to 1.76), 1.71 (95% CI, 1.33 to 2.21), and 2.21 (95% CI, 1.45 to 3.36) (P for trend <0.0001) for systolic BP categories and 1.0, 1.12 (95% CI, 0.82 to 1.52), 1.13 (95% CI, 0.83 to 1.52), 1.30 (95% CI, 0.89 to 1.88), 1.50 (95% CI, 1.01 to 1.88), and 1.54 (95% CI, 0.75 to 3.14) (P for trend=0.026) for diastolic BP categories.In this large cohort of initially healthy women, BP was strongly associated with incident AF, and systolic BP was a better predictor than diastolic BP. Systolic BP levels within the nonhypertensive range were independently associated with incident AF even after BP changes over time were taken into account.

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Genetically Predicted Blood Pressure and Risk of Atrial Fibrillation.

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Genetically Predicted Blood Pressure and Risk of Atrial Fibrillation.

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