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. 2019 Aug 1;4(8):788-795.
doi: 10.1001/jamacardio.2019.2202.

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

Milad Nazarzadeh  1   2   3 , Ana-Catarina Pinho-Gomes  1   2 , Karl Smith Byrne  1 , Dexter Canoy  1   2   4   5 , Francesca Raimondi  1   2 , Jose Roberto Ayala Solares  1   2 , Catherine M Otto  6 , Kazem Rahimi  1   2   4
Affiliations

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

Milad Nazarzadeh et al. JAMA Cardiol. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Canoy reported grants from the British Heart Foundation during the conduct of the study and support from the NIHR Oxford Biomedical Research Centre. Dr Solares receives support from the National Institute for Health Research (NIHR). Dr Rahimi reported grants from the NIHR Oxford Biomedical Research Centre, the British Heart Foundation, the Economic and Social Research Council, Research Councils UK grant ES/P011055/1, and the Oxford Martin School, University of Oxford, during the conduct of the study, and personal fees from PLoS Medicine and BMJ Heart outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Observational Hazard Ratio Derived From Previous Large-Scale Cohort Studies vs Odds Ratio Derived From the Present 1-Sample Mendelian Randomization for the Association Between Systolic Blood Pressure per 20–mm Hg and Valvular Heart Disease Outcomes
Mendelian randomization was adjusted for age, sex, body mass index, UK Biobank assessment center, genotype measurement batch, alcohol intake frequency, smoking status, genetic kinship to other participants, and 10 genetic principal components. Dark blue circles represent point estimation and vertical lines represent 95% CIs. Odds ratio indicates hazard ratio in observational cohort studies and odds ratio in mendelian randomization estimation.
Figure 2.
Figure 2.. Mendelian Randomization Estimates for the Association Between Systolic Blood Pressure per 20-mm Hg and Stroke, Heart Failure, and Coronary Heart Disease (CHD) as Positive Controls and Chronic Obstructive Pulmonary Disease (COPD) as Negative Outcome
The control analyses showed that the instrumental variable is valid.
Figure 3.
Figure 3.. Sensitivity Analysis With Exclusion of Patients With Coronary Heart Disease (CHD) or Heart Failure (HF) as Possible Mediators of Valvular Disease
Main estimation included all cases; with CHD and HF exclusions, all types were excluded from the analysis.
See this image and copyright information in PMC

Comment in

References

    1. Watkins DA, Johnson CO, Colquhoun SM, et al. . Global, regional, and national burden of rheumatic heart disease, 1990-2015. N Engl J Med. 2017;377(8):713-722. doi:10.1056/NEJMoa1603693 - DOI - PubMed
    1. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet. 2006;368(9540):1005-1011. doi:10.1016/S0140-6736(06)69208-8 - DOI - PubMed
    1. Baumgartner H, Falk V, Bax JJ, et al. ; ESC Scientific Document Group . 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J. 2017;38(36):2739-2791. doi:10.1093/eurheartj/ehx391 - DOI - PubMed
    1. Smith CR, Leon MB, Mack MJ, et al. ; PARTNER Trial Investigators . Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-2198. doi:10.1056/NEJMoa1103510 - DOI - PubMed
    1. Otto CM, Prendergast B. Aortic-valve stenosis—from patients at risk to severe valve obstruction. N Engl J Med. 2014;371(8):744-756. doi:10.1056/NEJMra1313875 - DOI - PubMed

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