Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi St, Chongqing, 400016, China.
Cardiovasc Diabetol. 2023 Dec 20;22(1):352. doi: 10.1186/s12933-023-02086-x.
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).
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.
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.
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.
原发性醛固酮增多症（PA）是一种自主醛固酮分泌的肾上腺疾病，可促进动脉损伤。我们旨在探讨 PA 是否与下肢动脉疾病（LEAD）有关。
我们纳入了英国生物库中 39713 例糖尿病患者和 419312 例无糖尿病患者。我们根据先前的全基因组关联研究（GWAS）得出了一个 PA 的多基因风险评分（PRS）。结局包括 LEAD 和 LEAD 相关的坏疽或截肢。我们进行了两样本孟德尔随机化分析，以探讨 PA 与结局之间的潜在因果关系。
在全人群中，PA PRS 较高的个体发生 LEAD 的风险增加。在糖尿病患者中，与 PA PRS 第一 tertile 的患者相比，第三 tertile 的患者 LEAD 的风险增加了 1.24 倍（OR 1.24，95%CI 1.03-1.49），坏疽的风险增加了 2.09 倍（OR 2.09，95%CI 1.27-3.44），截肢的风险增加了 1.72 倍（OR 1.72，95%CI 1.10-2.67）。在无糖尿病患者中，PA PRS 与 LEAD、坏疽或截肢之间无显著关联。两样本孟德尔随机化分析表明，PA 的遗传预测因子与 LEAD 和坏疽的风险增加显著相关（LEAD 的逆方差加权 OR 1.20 [95%CI 1.08-1.34]），坏疽的 OR 为 1.48 [95%CI 1.28-1.70]），且无显著异质性或方向性偏倚的证据。
PA 在遗传上和因果上与 LEAD 和坏疽的风险增加相关，尤其是在糖尿病患者中。针对自主醛固酮分泌的治疗可能有助于预防 LEAD 的进展。
