血浆 ACE2 与死亡或心血管代谢疾病风险：病例队列分析。
Plasma ACE2 and risk of death or cardiometabolic diseases: a case-cohort analysis.
机构信息
Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
出版信息
Lancet. 2020 Oct 3;396(10256):968-976. doi: 10.1016/S0140-6736(20)31964-4.
BACKGROUND
Angiotensin-converting enzyme 2 (ACE2) is an endogenous counter-regulator of the renin-angiotensin hormonal cascade. We assessed whether plasma ACE2 concentrations were associated with greater risk of death or cardiovascular disease events.
METHODS
We used data from the Prospective Urban Rural Epidemiology (PURE) prospective study to conduct a case-cohort analysis within a subset of PURE participants (from 14 countries across five continents: Africa, Asia, Europe, North America, and South America). We measured plasma concentrations of ACE2 and assessed potential determinants of plasma ACE2 levels as well as the association of ACE2 with cardiovascular events.
FINDINGS
We included 10 753 PURE participants in our study. Increased concentration of plasma ACE2 was associated with increased risk of total deaths (hazard ratio [HR] 1·35 per 1 SD increase [95% CI 1·29-1·43]) with similar increases in cardiovascular and non-cardiovascular deaths. Plasma ACE2 concentration was also associated with higher risk of incident heart failure (HR 1·27 per 1 SD increase [1·10-1·46]), myocardial infarction (HR 1·23 per 1 SD increase [1·13-1·33]), stroke (HR 1·21 per 1 SD increase [1·10-1·32]) and diabetes (HR 1·44 per 1 SD increase [1·36-1·52]). These findings were independent of age, sex, ancestry, and traditional cardiac risk factors. With the exception of incident heart failure events, the independent relationship of ACE2 with the clinical endpoints, including death, remained robust after adjustment for BNP. The highest-ranked determinants of ACE2 concentrations were sex, geographic ancestry, and body-mass index (BMI). When compared with clinical risk factors (smoking, diabetes, blood pressure, lipids, and BMI), ACE2 was the highest ranked predictor of death, and superseded several risk factors as a predictor of heart failure, stroke, and myocardial infarction.
INTERPRETATION
Increased plasma ACE2 concentration was associated with increased risk of major cardiovascular events in a global study.
FUNDING
Canadian Institute of Health Research, Heart & Stroke Foundation of Canada, and Bayer.
背景
血管紧张素转换酶 2（ACE2）是肾素-血管紧张素激素级联的内源性反向调节剂。我们评估了血浆 ACE2 浓度是否与更高的死亡或心血管疾病事件风险相关。
方法
我们使用 Prospective Urban Rural Epidemiology（PURE）前瞻性研究的数据，在 PURE 参与者的一个亚组中进行病例对照分析（来自五个大洲的 14 个国家：非洲、亚洲、欧洲、北美洲和南美洲）。我们测量了血浆 ACE2 浓度，并评估了血浆 ACE2 水平的潜在决定因素以及 ACE2 与心血管事件的关联。
结果
我们的研究纳入了 10753 名 PURE 参与者。血浆 ACE2 浓度升高与全因死亡风险增加相关（每增加 1 个标准差的危险比[HR]为 1.35[95%CI 1.29-1.43]），心血管和非心血管死亡的风险也相似增加。血浆 ACE2 浓度也与心力衰竭（HR 1.27 每增加 1 个标准差[1.10-1.46]）、心肌梗死（HR 1.23 每增加 1 个标准差[1.13-1.33]）、中风（HR 1.21 每增加 1 个标准差[1.10-1.32]）和糖尿病（HR 1.44 每增加 1 个标准差[1.36-1.52]）的发生率风险升高相关。这些发现独立于年龄、性别、祖源和传统心脏危险因素。除了心力衰竭事件的发生率外，ACE2 与临床终点（包括死亡）的独立关系在调整 BNP 后仍然稳健。ACE2 浓度的最高决定因素是性别、地理祖源和体重指数（BMI）。与临床危险因素（吸烟、糖尿病、血压、血脂和 BMI）相比，ACE2 是死亡的最高预测因子，并取代了一些危险因素作为心力衰竭、中风和心肌梗死的预测因子。
解释
在一项全球研究中，增加的血浆 ACE2 浓度与主要心血管事件的风险增加相关。
资助
加拿大卫生研究院、加拿大心脏和中风基金会和拜耳公司。
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