Author:
Hu Jinbo,Zeng Qinglian,Chen Xiangjun,Luo Wenjin,Tang Ziwei,Mei Mei,Zhao Wenrui,Du Zhipeng,Liu Zhiping,Li Qifu,Cheng Qingfeng,Yang Shumin
Abstract
Abstract
Background and Aims
Primary 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).
Methods
We 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.
Results
In 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.
Conclusions
Primary 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.
Funder
Joint Medical Research Project of Chongqing Science and Technology Commission & Chongqing Health and Family Planning Commission
The Chongqing Science and Health Joint Medical Research Project
The Innovative Funded Project of Chongqing Innovation and Retention Program
Youth Foundation of the National Natural Science Foundation
National Natural Science Foundation of China, Major Joint Project
National key research & development plan of China, major project of prevention and treatment for common diseases
National Natural Science Foundation of China
Science and Technology Research Project of Chongqing Education Commission
Chongqing Outstanding Youth Funds
Publisher
Springer Science and Business Media LLC
Subject
Cardiology and Cardiovascular Medicine,Endocrinology, Diabetes and Metabolism