| Title: | Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study |
| Journal: | Cardiovascular Diabetology |
| Published: | 20 Dec 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38124109/ |
| DOI: | https://doi.org/10.1186/s12933-023-02086-x |
| URL: | https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-023-02086-x |
Publication 9138
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Background and AimsPrimary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD).MethodsWe included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship.ResultsIn whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03-1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27-3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10-2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08-1.34]) for LEAD, 1.48 [95% CI 1.28-1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy.ConclusionsPrimary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression.</p>
12 Authors
- Jinbo Hu
- Qinglian Zeng
- Xiangjun Chen
- Wenjin Luo
- Ziwei Tang
- Mei Mei
- Wenrui Zhao
- Zhipeng Du
- Zhiping Liu
- Qifu Li
- Qingfeng Cheng
- Shumin Yang
1 Application
| Application ID | Title |
|---|---|
| 66536 | Abdominal obesity and Diabetic Kidney Disease: A Mendelian Randomization Study |
Enabling scientific discoveries that improve human health