BLOOD PRESSURE AND RISK OF VALVULAR HEART DISEASE

Abstract

Objective: In the absence of randomized clinical trials (RCTs) of blood pressure (BP) lowering treatment on risk of incident valvular heart disease, we aimed to test the hypothesis that systolic BP is causally associated with the risk of aortic stenosis, aortic regurgitation and mitral regurgitation, using a Mendelian randomisation study design. This gene-based approach takes advantage of the naturally occurring randomized exposure of individuals to genetic variants that are highly associated with lifetime systolic BP. It is similar to random allocation of intervention in RCTs and it can thus overcome the problems of reverse causation and confounding that are typical of non-randomized observational studies. Design and method: 337,335 participants in the UK Biobank study, aged 40 to 96 years, with valid genetic data and blood pressure measurements were included. 130 genetic variants associated with systolic BP in a genome-wide association meta-analysis were used. Instrumental variable analysis was performed using an adjusted two-stage predictor substitution method to assess the effect of systolic BP on incident aortic stenosis, aortic regurgitation and mitral regurgitation, individually and as a composite outcome. Results: Among 3570 (1.08 %) patients with valvular heart disease in the study cohort, 1491 had aortic stenosis, 634 had aortic regurgitation and 1736 had mitral regurgitation. Each genetically-determined 20 mmHg increment in systolic BP almost tripled the odds ratio (OR) of the composite valvular heart disease (OR 2.85; 95% CI 1.72 to 4.72). This association was consistent for individual valvular conditions (p for heterogeneity =0.89), although statistical power was limited for aortic regurgitation when considered individually (aortic stenosis OR 3.26; 95% CI 1.50 to 7.10, aortic regurgitation OR 2.59; 95% CI 0.75 to 8.92, and mitral regurgitation OR 2.19; 95% CI 1.07 to 4.47). Sensitivity analysis confirmed the robustness of the association.Conclusions: The present study showed that lifetime exposure to higher systolic BP substantially and causally increased the risk of major valvular heart disease, with stronger evidence for aortic stenosis in particular, therefore suggesting that BP-lowering treatment may be an effective strategy for prevention of valvular heart disease.