Masson Serge, Latini Roberto, Anand Inder S, Barlera Simona, Judd Dianne, Salio Monica, Perticone Francesco, Perini Giampaolo, Tognoni Gianni, Cohn Jay N
Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
J Card Fail. 2006 Jun;12(5):375-80. doi: 10.1016/j.cardfail.2006.02.013.
Endothelin is elevated in heart failure and contributes to neurohormonal activation, hemodynamic deterioration, and cardiovascular remodeling. Here, we examined its prognostic value in a large population of patients with chronic heart failure.
Big endothelin-1 (Big ET-1) and 4 other neurohormones were measured at study entry in 2359 patients enrolled in the Valsartan Heart Failure Trial (Val-HeFT) and their concentrations related to outcome over a median follow-up of 23 months. Baseline concentration of Big ET-1 (median 0.80 pmol/L) was proportional to severity of disease (New York Heart Association class, left ventricular structure and function). High circulating concentrations of brain natriuretic peptide (BNP), creatinine and bilirubin, advanced New York Heart Association class, elevated body mass index, and the presence of atrial fibrillation were independently associated to higher concentrations of Big ET-1. Big ET-1 (ranking second just behind BNP among neurohormonal factors) was an independent predictor of outcome defined as all-cause mortality (hazard ratio 1.49, 95% CI 1.20-1.84, P = .0003) or the combined endpoint of mortality and morbidity (hazard ratio 1.43, 95% CI 1.20-1.69, P < .0001) and provided incremental prognostic value compared with BNP.
In a large population of patients with symptomatic heart failure, the circulating concentration of Big ET-1, a precursor of the paracrine and bioactive peptide ET-1, was an independent marker of mortality and morbidity. In this setting, BNP remained the strongest neurohormonal prognostic factor.
心力衰竭患者体内内皮素水平升高，可导致神经激素激活、血流动力学恶化及心血管重塑。在此，我们研究了内皮素在大量慢性心力衰竭患者中的预后价值。
在缬沙坦心力衰竭试验（Val-HeFT）纳入的2359例患者入组时，检测大内皮素-1（Big ET-1）及其他4种神经激素，并在中位随访23个月期间将其浓度与预后相关联。Big ET-1的基线浓度（中位数为0.80 pmol/L）与疾病严重程度（纽约心脏协会分级、左心室结构和功能）成正比。脑钠肽（BNP）、肌酐和胆红素的循环浓度升高、纽约心脏协会分级较高、体重指数升高及存在心房颤动均与较高的Big ET-1浓度独立相关。Big ET-1（在神经激素因素中仅次于BNP排名第二）是全因死亡率（风险比1.49，95%可信区间1.20-1.84，P = 0.0003）或死亡和发病复合终点（风险比1.43，95%可信区间1.20-1.69，P < 0.0001）的独立预测因子，与BNP相比具有额外的预后价值。
在大量有症状心力衰竭患者中，旁分泌和生物活性肽ET-1的前体Big ET-1的循环浓度是死亡率和发病率的独立标志物。在此情况下，BNP仍然是最强的神经激素预后因子。
