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Original Investigation
July 10, 2019

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

Author Affiliations
  • 1The George Institute for Global Health, University of Oxford, Oxford, United Kingdom
  • 2Deep Medicine, Oxford Martin School, University of Oxford, Oxford, United Kingdom
  • 3Collaboration Center of Meta-analysis Research, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
  • 4National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals National Health Service Foundation Trust, Oxford, United Kingdom
  • 5Faculty of Medicine, University of New South Wales, Sydney, Australia
  • 6Division of Cardiology, University of Washington, Seattle
JAMA Cardiol. 2019;4(8):788-795. doi:10.1001/jamacardio.2019.2202
Key Points

Question  Is elevated systolic blood pressure a risk factor for major valvular heart disease?

Findings  In this mendelian randomization study of 329 237 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.

Meaning  Lifetime 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.


Importance  Modifiable risk factors for valvular heart disease remain largely unknown, which limits prevention and treatment.

Objective  To assess the association between systolic blood pressure (BP) and major valvular heart disease.

Design, Setting, and Participants  A UK Biobank population-based cohort of 502 602 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.

Exposures  Systolic 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 r2<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 Measures  Incident 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.

Results  Of the 502 602 individuals screened, 329 237 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 Relevance  Lifetime exposure to elevated systolic BP appears to be associated with an increased risk of major valvular heart disease.