Levels of angiotensin-converting enzyme 2 (ACE2), the gateway for COVID-19 virus into the cells, have been implicated in worse COVID-19 outcomes associated with aging and cardiovascular disease (CVD). Data on age-associated differences in circulating ACE2 levels in humans and the role of CVD and medications is limited. We analyzed data from 967 participants of the InCHIANTI study, a community-dwelling cohort in the Chianti region, Italy. Relative abundance of ACE2 in plasma was assessed using a proteomics platform. CVD diagnoses, use of renin-angiotensin-aldosterone system (RAAS) antagonists: ACEi, ARBs, and aldosterone antagonists, were ascertained. Multiple linear analyses were performed to examine the independent association of ACE2 with age, CVD, and RAAS antagonist use. Age was independently associated with lower log (ACE2) in persons aged ≥ 55 years (STD β = − 0.12, p = 0.0002). ACEi treatment was also independently associated with significantly lower ACE2 levels, and ACE2 was inversely associated with weight, and positively associated with peripheral artery disease (PAD) status. There was a trend toward higher circulating ACE2 levels in hypertensive individuals, but it did not reach statistical significance. In a stratified analysis, the association between log (ACE2) and log (IL-6) was more evidenced in participants with PAD. Circulating ACE2 levels demonstrate curvilinear association with age, with older individuals beyond the sixth decade age having lower levels. ACEi was associated with greater circulating ACE2 levels. Interestingly, ACE2 was elevated in PAD and positively associated with inflammatory markers, suggesting compensatory upregulation in the setting of chronic inflammation. Further studies are needed to comprehensively characterize RAAS components with aging and disease, and assess its prognostic role in predicting COVID-19 outcomes.

血管紧张素转换酶 2 (ACE2) 是 COVID-19 病毒进入细胞的门户，其水平与衰老和心血管疾病 (CVD) 相关的 COVID-19 结局恶化有关。关于人类循环 ACE2 水平与年龄相关的差异以及 CVD 和药物的作用的数据有限。我们分析了 InCHIANTI 研究的 967 名参与者的数据，该研究是意大利基安蒂地区的社区居住队列。使用蛋白质组学平台评估血浆中 ACE2 的相对丰度。确定了 CVD 诊断、肾素-血管紧张素-醛固酮系统 (RAAS) 拮抗剂：ACEi、ARB 和醛固酮拮抗剂的使用。进行多重线性分析来检查 ACE2 与年龄、CVD 和 RAAS 拮抗剂使用的独立关联。年龄≥ 55 岁的人的年龄与较低的对数 (ACE2) 独立相关（STD β  = − 0.12，p  = 0.0002）。ACEi 治疗还与 ACE2 水平显着降低独立相关，ACE2 与体重呈负相关，与外周动脉疾病 (PAD) 状态呈正相关。高血压患者的循环 ACE2 水平有升高的趋势，但并未达到统计学显着性。在分层分析中，log (ACE2) 和 log (IL-6) 之间的关联在 PAD 参与者中更为明显。循环中的 ACE2 水平与年龄呈曲线关系，超过 60 岁的老年人的水平较低。ACEi 与较高的循环 ACE2 水平相关。有趣的是，ACE2 在 PAD 中升高，并且与炎症标志物呈正相关，表明慢性炎症中存在代偿性上调。需要进一步研究来全面描述 RAAS 组成部分与衰老和疾病的关系，并评估其在预测 COVID-19 结果中的预后作用。