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Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study
Jinbo Hu1, Qinglian Zeng1, Xiangjun Chen1
1Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi St, Chongqing, 400016, China.
Cardiovascular Diabetology
|December 21, 2023
Summary
Primary aldosteronism (PA) is linked to increased risks of lower-extremity arterial disease (LEAD), particularly in diabetic patients. This genetic association suggests that managing aldosterone secretion could help prevent arterial disease progression.
Area of Science:
- Endocrinology
- Vascular Medicine
- Genetics
Background:
- Primary aldosteronism (PA) involves autonomous aldosterone secretion, contributing to arterial injury.
- The relationship between PA and lower-extremity arterial disease (LEAD) requires further investigation.
Purpose of the Study:
- To explore the causal association between primary aldosteronism and lower-extremity arterial disease.
- To investigate the role of genetic predisposition to PA in the development of LEAD, especially in individuals with and without diabetes.
Main Methods:
- Utilized UK Biobank data from 39,713 diabetic and 419,312 non-diabetic participants.
- Derived a polygenic risk score (PRS) for PA based on GWAS.
- Conducted two-sample Mendelian randomization analysis to assess causal relationships between PA genetic predictors and LEAD outcomes (including gangrene and amputation).
Main Results:
- Higher PA PRS correlated with increased LEAD risk in the general population.
- Diabetic patients with the highest PA PRS tertile showed significantly higher risks of LEAD (OR 1.24), gangrene (OR 2.09), and amputation (OR 1.72).
- Mendelian randomization confirmed a genetic link between PA and higher risks of LEAD (OR 1.20) and gangrene (OR 1.48), with no significant heterogeneity.
Conclusions:
- Primary aldosteronism demonstrates a genetic and causal association with increased risks of LEAD and gangrene.
- These risks are notably elevated in patients with diabetes.
- Interventions targeting autonomous aldosterone secretion may offer a strategy for preventing LEAD progression.
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