收缩性心力衰竭患者高密度脂蛋白相关蛋白抗氧化活性降低。
Diminished antioxidant activity of high-density lipoprotein-associated proteins in systolic heart failure.
机构信息
Center for Cardiovascular Diagnostics and Prevention, Department of Cell Biology, Lerner Research Institute, the Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
出版信息
Circ Heart Fail. 2011 Jan;4(1):59-64. doi: 10.1161/CIRCHEARTFAILURE.110.958348. Epub 2010 Nov 9.
BACKGROUND
Diminished serum arylesterase activity, catalyzed by the high-density lipoprotein-associated paraoxonase-1, is associated with heightened systemic oxidative stress and atherosclerosis risk. In the present study, we sought to determine the prognostic role of serum arylesterase activity in subjects with systolic heart failure, particularly in relation to established cardiac biomarkers.
METHODS AND RESULTS
We measured serum arylesterase activity in 760 subjects with impaired left ventricular systolic function (left ventricular ejection fraction <50%), and prospectively followed major adverse cardiac events (including death, nonfatal myocardial infarction, and stroke) for 3 years. In our study cohort (mean age, 64±11 years; 74% men; median left ventricular ejection fraction, 35%; median creatinine clearance, 96 mg/dL), mean serum arylesterase activity (98±25 μmol/L/min/mL) was lower compared with that in healthy control subjects (mean, 115±26 μmol/L/min/mL, P<0.01) but higher compared with advanced decompensated heart failure subjects (mean, 69±22 μmol/L/min/mL, P<0.01). Within our cohort, there was modest correlation between serum arylesterase activity and high-density lipoprotein cholesterol (r=0.33, P<0.01) as well as B-type natriuretic peptide (r=-0.23, P<0.01). Lower serum arylesterase activity was a strong predictor of poorer outcomes (hazard ratio, 2.94; 95% confidence interval, 1.54, 5.62; P<0.001). After adjusting for traditional risk factors, medication use, B-type natriuretic peptide, and creatinine clearance, lower serum arylesterase still conferred an increased risk of major adverse cardiac events at 3 years (hazard ratio, 2.69; 95% confidence interval, 1.37 to 5.28; P=0.004).
CONCLUSIONS
In patients with systolic heart failure, decreased serum arylesterase activity, a measure of diminished antioxidant properties of high-density lipoprotein, predicts higher risk of incident long-term adverse cardiac event independent of established clinical and biochemical risk factors.
背景
高密度脂蛋白相关对氧磷酶-1 催化的血清芳酯酶活性降低与全身氧化应激增加和动脉粥样硬化风险相关。在本研究中，我们试图确定血清芳酯酶活性在收缩性心力衰竭患者中的预后作用，特别是与已建立的心脏生物标志物的关系。
方法和结果
我们测量了 760 名左心室收缩功能受损（左心室射血分数 <50%）患者的血清芳酯酶活性，并前瞻性随访了 3 年的主要不良心脏事件（包括死亡、非致死性心肌梗死和中风）。在我们的研究队列中（平均年龄 64±11 岁；74%为男性；中位左心室射血分数 35%；中位肌酐清除率 96mg/dL），与健康对照组相比（平均 115±26μmol/L/min/mL，P<0.01），血清芳酯酶活性（平均 98±25μmol/L/min/mL）较低，但与晚期失代偿性心力衰竭患者相比（平均 69±22μmol/L/min/mL，P<0.01）较高。在我们的队列中，血清芳酯酶活性与高密度脂蛋白胆固醇（r=0.33，P<0.01）和 B 型利钠肽（r=-0.23，P<0.01）之间存在适度相关性。较低的血清芳酯酶活性是预后较差的强预测因子（风险比，2.94；95%置信区间，1.54，5.62；P<0.001）。在校正传统危险因素、药物使用、B 型利钠肽和肌酐清除率后，较低的血清芳酯酶仍与 3 年内发生主要不良心脏事件的风险增加相关（风险比，2.69；95%置信区间，1.37 至 5.28；P=0.004）。
结论
在收缩性心力衰竭患者中，血清芳酯酶活性降低，反映了高密度脂蛋白抗氧化特性降低，可预测长期不良心脏事件的发生风险增加，独立于已建立的临床和生化危险因素。
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