Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study

作者全名："Hu, Jinbo; Zeng, Qinglian; Chen, Xiangjun; Luo, Wenjin; Tang, Ziwei; Mei, Mei; Zhao, Wenrui; Du, Zhipeng; Liu, Zhiping; Li, Qifu; Cheng, Qingfeng; Yang, Shumin"

作者地址："[Hu, Jinbo; Zeng, Qinglian; Chen, Xiangjun; Luo, Wenjin; Tang, Ziwei; Mei, Mei; Zhao, Wenrui; Du, Zhipeng; Liu, Zhiping; Li, Qifu; Cheng, Qingfeng; Yang, Shumin] Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 1, 1 Youyi St, Chongqing 400016, Peoples R China"

通信作者："Li, QF; Cheng, QF; Yang, SM (通讯作者)，Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 1, 1 Youyi St, Chongqing 400016, Peoples R China."

来源：CARDIOVASCULAR DIABETOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001128629600001

JCR分区：Q1

影响因子：9.3

年份：2023

卷号：22

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Primary aldosteronism; Lower-extremity arterial disease; Diabetes; Mendelian randomization; Causal relationship

摘要："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."

基金机构：Joint Medical Research Project of Chongqing Science and Technology Commission & Chongqing Health and Family Planning Commission; First Affiliated Hospital of Chongqing Medical University

基金资助正文："We thank the participants and staff of the UK Biobank. We thank Laboratory of Endocrine and Laboratory of Lipid and Glucose Metabolism, the First Affiliated Hospital of Chongqing Medical University as well."