BACKGROUND Circulating levels of endothelin-1 (ET1) are elevated in heart failure and predict poor prognosis. However, it is not clear whether ET1 elevation is an adaptive response, maladaptive response, or an epiphenomenon of heart failure. In this study, we evaluated the relationships between ET1, cardiac morphology, and incident heart failure or cardiovascular death in participants with no evidence of clinical cardiovascular disease at the time ET1 was measured. METHODS AND RESULTS ET1 was measured in 1,361 participants in the Multi-Ethnic Study of Atherosclerosis Angiogenesis Sub-Study. As suggested by linear regression, participants with lower circulating ET1 levels tended to be older, non-white, more likely to have smoked heavily, and less likely to report intentional exercise. Participants with higher ET1 levels had smaller left ventricular end-diastolic volumes (8.9 ml smaller per log increase in ET1, 95% confidence interval 17.1-0.7, p = 0.03) with an increased left ventricular ejection fraction (2.8% per log increase in ET1, 95% confidence interval 0.5%-5.2%, p = 0.02). As suggested by Cox Proportional Hazards estimates, participants with higher ET1 levels had a lower risk for the composite outcome of heart failure or cardiovascular death in models that were unadjusted or had limited adjustment (p = 0.03 and p = 0.05, respectively). Lower risk for heart failure with higher ET1 levels could not be clearly shown in a model including health behaviors. CONCLUSIONS These results suggest, but do not confirm, that elevated levels of circulating ET1 are associated with a more favorable cardiac phenotype. The relationship between ET1 and outcomes was not fully independent of one or more covariates.

中文翻译：

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内皮素-1，心脏形态和心力衰竭：MESA血管生成研究。

背景在心力衰竭中，内皮素-1（ET1）的循环水平升高，并预示不良预后。但是，尚不清楚ET1升高是适应性反应，适应不良反应还是心力衰竭的现象。在这项研究中，我们评估了没有测量到ET1时临床心血管疾病证据的参与者中ET1，心脏形态和突发性心力衰竭或心血管死亡之间的关系。方法和结果在多族裔动脉粥样硬化血管生成子研究中对1,361名参与者进行了ET1测量。正如线性回归所表明的那样，循环ET1水平较低的参与者倾向于年龄较大，非白人，吸烟的可能性较大，而报告有意锻炼的可能性较小。ET1水平较高的参与者的左心室舒张末期容积较小（ET1每次日志增加8.9 ml，95％置信区间17.1-0.7，p = 0.03），左心室射血分数增加（ET1每个日志增加2.8％） ，95％置信区间0.5％-5.2％，p = 0.02）。正如Cox比例危害评估所建议的那样，在未经调整或调整有限的模型中，具有较高ET1水平的参与者发生心力衰竭或心血管死亡的复合结果的风险较低（分别为p = 0.03和p = 0.05）。在包括健康行为在内的模型中，ET1水平较高时发生心力衰竭的风险较低。结论这些结果提示，但不能证实，循环中ET1水平升高与更有利的心脏表型有关。