Department of Internal Medicine IV, University Hospital of Ludwigs-Maximilians-University Munich, Munich, Germany.
German Center for Diabetes Research (DZD), Partner Munich-Neuherberg, Munich, Germany.
Vasc Health Risk Manag. 2022 May 3;18:335-346. doi: 10.2147/VHRM.S363814. eCollection 2022.
Endothelin-1 and its prohormone C-terminal pro-endothelin-1 (CT-proET-1) have been linked to metabolic alterations, inflammatory responses and cardiovascular events in selected study populations. We analyzed the association of CT-proET-1 with cardiovascular events and mortality, carotid intima-media-thickness as surrogate for early atherosclerotic lesions, biomarkers of subclinical inflammation and adipokines in a population-based study.
The cross-sectional and prospective analyses used data from the KORA F4 study with a median follow-up time of 9.1 (8.8-9.4) years. Data on CT-proET-1 and mortality were available for 1554 participants, data on the other outcomes in subgroups (n = 596-1554). The associations were estimated using multivariable linear regression and Cox proportional hazard models adjusted for sex, age, body mass index, estimated glomerular filtration rate, arterial hypertension, diabetes, low-density and high-density lipoprotein cholesterol, current and former smoking and physical activity. The Bonferroni method was used to correct for multiple testing.
In the fully adjusted model, CT-proET-1 was associated with cardiovascular (hazard ratio (HR) per standard deviation increase: 1.66; 95% confidence interval (CI): 1.10-2.51; p = 0.017) and all-cause mortality (HR: 2.03; 95% CI 1.55-2.67; p < 0.001), but not with cardiovascular events, and was inversely associated with the intima-media thickness (β: -0.09 ± 0.03; p = 0.001). CT-proET-1 was positively associated with five out of ten biomarkers of subclinical inflammation and with two out of five adipokines after correction for multiple testing. After inclusion of biomarkers of subclinical inflammation in the Cox proportional hazard model, the association of CT-proET-1 with all-cause mortality persisted (p < 0.001).
These results emphasize the complexity of endothelin-1 actions and/or indicator functions of CT-proET-1. CT-proET-1 is a risk marker for all-cause mortality, which is likely independent of vascular endothelin-1 actions, cardiovascular disease and inflammation.
内皮素-1 及其前体 C 端肽内皮素-1（CT-proET-1）已与某些研究人群中的代谢改变、炎症反应和心血管事件相关联。我们分析了 CT-proET-1 与心血管事件和死亡率、颈动脉内膜中层厚度（作为早期动脉粥样硬化病变的替代指标）、亚临床炎症生物标志物和脂肪因子的相关性，这些都是基于一项基于人群的研究。
横断面和前瞻性分析使用了 KORA F4 研究的数据，中位随访时间为 9.1（8.8-9.4）年。1554 名参与者提供了 CT-proET-1 和死亡率的数据，596-1554 名参与者提供了其他结果的数据。使用多变量线性回归和 Cox 比例风险模型估计相关性，调整因素为性别、年龄、体重指数、估计肾小球滤过率、动脉高血压、糖尿病、低密度和高密度脂蛋白胆固醇、当前和以前的吸烟和体力活动。使用 Bonferroni 方法进行多重检验校正。
在完全调整模型中，CT-proET-1 与心血管疾病（每标准差增加的风险比：1.66；95%置信区间：1.10-2.51；p = 0.017）和全因死亡率（HR：2.03；95%置信区间 1.55-2.67；p < 0.001）相关，但与心血管事件无关，与内膜中层厚度呈负相关（β：-0.09 ± 0.03；p = 0.001）。在进行多次检验校正后，CT-proET-1 与十个亚临床炎症生物标志物中的五个和五个脂肪因子中的两个呈正相关。在 Cox 比例风险模型中纳入亚临床炎症生物标志物后，CT-proET-1 与全因死亡率的相关性仍然存在（p < 0.001）。
这些结果强调了内皮素-1 作用的复杂性和/或 CT-proET-1 的指示功能。CT-proET-1 是全因死亡率的风险标志物，可能与血管内皮素-1 作用、心血管疾病和炎症无关。
