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Association between myeloperoxidase and the risks of ischemic stroke, heart failure, and atrial fibrillation: A
Yinan Wang1, Yiming Jia1, Qingyun Xu1
1Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China.
Background And Aims:
The causality between myeloperoxidase (MPO) and cardiovascular disease still remains unclear. We performed a two-sample Mendelian randomization (MR) study to estimate the potential causal effect of MPO on the risks of ischemic stroke, ischemic stroke subtypes, heart failure (HF), and atrial fibrillation (AF).
Methods And Results:
Seventeen independent single-nucleotide polymorphisms associated with MPO levels were identified as instrumental variables from a European-descent genome-wide association study. Summary-level data on ischemic stroke originated from the Multiancestry Genome-wide Association Study of Stroke Consortium with 440 328 European individuals. We used the inverse-variance weighted method to assess the potential causality of plasma MPO with ischemic stroke and its subtypes in the main analysis. Genetically determined higher plasma MPO concentration was significantly associated with increased risks of ischemic stroke (odds ratio [OR] per standard deviation [SD] increase, 1.05; 95% confidence interval [CI], 1.02-1.09; P = 0.002) and cardioembolic stroke (CES) (OR per SD increase, 1.10; 95% CI, 1.03-1.18; P = 0.005), but was not associated with risks of large artery stroke or small vessel stroke. In the secondary analysis, MPO was associated with a high risk of HF (OR per SD increase, 1.05; 95% CI, 1.02-1.07; P = 0.001) and AF (OR per SD increase, 1.04; 95% CI, 1.01-1.07; P = 0.004). MR-Egger regression showed no directional pleiotropy for all associations, and the sensitivity analyses further confirmed these findings.
Conclusion:
High plasma MPO levels were potentially associated with increased risks of ischemic stroke, CES, HF, and AF, suggesting that MPO plays an important role in the development of cardiovascular disease.
Insights
Higher myeloperoxidase (MPO) levels are linked to increased risks of cardiovascular diseases, including ischemic stroke, heart failure, and atrial fibrillation. This suggests MPO plays a key role in cardiovascular disease development.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Epidemiology
Background:
- The precise causal relationship between myeloperoxidase (MPO) and cardiovascular disease (CVD) remains incompletely understood.
- Investigating this link is crucial for understanding CVD pathogenesis and developing targeted therapies.
Purpose of the Study:
- To employ a two-sample Mendelian randomization (MR) approach to evaluate the potential causal impact of MPO on the incidence of ischemic stroke, its subtypes, heart failure (HF), and atrial fibrillation (AF).
Main Methods:
- Utilized 17 independent single-nucleotide polymorphisms (SNPs) associated with MPO levels as instrumental variables.
- Employed summary-level data from large-scale genome-wide association studies (GWAS) for ischemic stroke and its subtypes.
- Applied the inverse-variance weighted (IVW) method for primary analysis, supplemented by MR-Egger regression and sensitivity analyses to assess pleiotropy and confirm findings.
Main Results:
- Genetically predicted higher plasma MPO concentrations were significantly associated with increased risks of overall ischemic stroke (OR 1.05, P=0.002) and cardioembolic stroke (CES) (OR 1.10, P=0.005).
- No significant association was found between MPO levels and large artery stroke or small vessel stroke.
- Elevated MPO levels also showed a significant association with increased risks of heart failure (HF) (OR 1.05, P=0.001) and atrial fibrillation (AF) (OR 1.04, P=0.004).
Conclusions:
- Elevated plasma MPO levels are potentially causally linked to an increased risk of developing ischemic stroke, CES, HF, and AF.
- These findings underscore the significant role of MPO in the pathophysiology of cardiovascular diseases.
- MPO may represent a viable therapeutic target for the prevention and management of cardiovascular conditions.
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