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Systolic Blood Pressure and Risk of Valvular Heart Disease: A Mendelian Randomization Study
Milad Nazarzadeh1,2,3, Ana-Catarina Pinho-Gomes1,2, Karl Smith Byrne1
1The George Institute for Global Health, University of Oxford, Oxford, United Kingdom.
Insights
Elevated systolic blood pressure (BP) is linked to a higher risk of valvular heart disease. This finding highlights the importance of managing BP for cardiovascular health and preventing valve conditions.
Area of Science:
- Cardiology
- Genetics
- Epidemiology
Background:
- Modifiable risk factors for valvular heart disease are not well understood, hindering prevention efforts.
- Systolic blood pressure (BP) is a common cardiovascular risk factor, but its specific role in valvular heart disease requires further investigation.
Purpose of the Study:
- To investigate the association between genetically predicted systolic BP and the risk of developing major valvular heart diseases.
- To determine if elevated systolic BP contributes to the development of aortic stenosis, aortic regurgitation, and mitral regurgitation.
Main Methods:
- Mendelian randomization analysis was performed on a large UK Biobank cohort (over 329,000 participants).
- Genetic variants associated with systolic BP were identified from a genome-wide association meta-analysis of 1 million individuals.
- Incident cases of aortic stenosis, aortic regurgitation, and mitral regurgitation were identified through linked hospital records.
Main Results:
- Each genetically predicted 20-mm Hg increase in systolic BP was associated with significantly increased odds of developing valvular heart disease.
- Specific associations were observed for aortic stenosis (OR, 3.26), aortic regurgitation (OR, 2.59), and mitral regurgitation (OR, 2.19).
- Sensitivity analyses confirmed the robustness of these associations, indicating a reliable link between systolic BP and valvular heart disease.
Conclusions:
- Lifetime exposure to elevated systolic blood pressure is associated with an increased risk of major valvular heart diseases.
- These findings suggest that managing systolic blood pressure may be a crucial strategy for preventing valvular heart disease.
- Further research into the mechanisms linking systolic BP and valve disease is warranted.
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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