Systolic Blood Pressure and Risk of Valvular Heart Disease: A Mendelian Randomization Study

Key PointsQuestionIs elevated systolic blood pressure a risk factor for major valvular heart disease? FindingsIn this mendelian randomization study of 329237 individuals, genetically associated 20-mm Hg increments of elevated systolic blood pressure appeared to be associated with a higher risk of aortic stenosis, aortic regurgitation, and mitral regurgitation. MeaningLifetime exposure to elevated systolic blood pressure may be associated with an increased risk of major valvular heart disease, suggesting that blood pressure lowering might be a useful strategy for prevention of this condition. ImportanceModifiable risk factors for valvular heart disease remain largely unknown, which limits prevention and treatment. ObjectiveTo assess the association between systolic blood pressure (BP) and major valvular heart disease. Design, Setting, and ParticipantsA UK Biobank population-based cohort of 502602 men and women aged 40 to 96 years at baseline was evaluated through mendelian randomization using individual participant data. Inclusion criteria were valid genetic data and BP measurements. The participants were recruited between 2006 and 2010; data analysis was performed from June 2018 to January 2019. ExposuresSystolic BP was measured during clinical assessment and instruments for the genetic effect of high BP were identified from variants that were independently (linkage disequilibrium threshold of r(2)<0.1) associated with systolic BP with minor allele frequency greater than 0.01. A total of 130 single-nucleotide polymorphisms that have been shown to be associated with systolic BP in a genome-wide association meta-analysis involving 1 million participants of European ancestry were selected. Main Outcomes and MeasuresIncident aortic stenosis, aortic regurgitation, and mitral regurgitation, individually and combined. Cases were largely based on hospital records linked to the UK Biobank with International Classification of Diseases and Health Related Problems, Tenth Revision codes. ResultsOf the 502602 individuals screened, 329237 participants (177 741 [53.99%] women; mean [SD] age, 56.93 [7.99] years) had valid genetic data and BP measurements; of this cohort, 3570 individuals (1.08%) had a diagnosis of valvular heart disease (aortic stenosis, 1491 [0.45%]; aortic regurgitation, 634 [0.19%]; and mitral regurgitation, 1736 [0.53%]). Each genetically associated 20-mm Hg increment in systolic BP was associated with an increased risk of aortic stenosis (odds ratio [OR], 3.26; 95% CI, 1.50-7.10), aortic regurgitation (OR, 2.59; 95% CI, 0.75-8.92), and mitral regurgitation (OR, 2.19; 95% CI, 1.07-4.47), with no evidence for heterogeneity by type of valvular heart disease (P=.90). Sensitivity analyses confirmed the robustness of the association. Conclusions and RelevanceLifetime exposure to elevated systolic BP appears to be associated with an increased risk of major valvular heart disease. This population-based study uses mendelian randomization to evaluate whether there is an association between elevated systolic blood pressure and valvular heart disease.