Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-4, Cleveland, OH 44195, USA.
Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):634-40. doi: 10.1161/ATVBAHA.109.201210. Epub 2009 Dec 23.
The presence of subclinical myocardial necrosis as a prodrome to longer-term adverse cardiac event risk has been debated. The debate has focused predominantly within patients with acute coronary syndrome, and on issues of troponin assay variability and accuracy of detection, rather than on the clinical significance of the presence of subclinical myocardial necrosis (ie, "troponin leak") within stable cardiac patients. Herein, we examine the relationship between different degrees of subclinical myocardial necrosis and long-term adverse clinical outcomes within a stable cardiac patient population with essentially normal renal function.
Sequential consenting patients (N=3828; median creatinine clearance, 100 mL/min/1.73m(2)) undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction (<0.03 ng/mL) were evaluated. The relationship of subclinical myocardial necrosis with incident major adverse cardiovascular events (defined as any death, myocardial infarction, or stroke) over 3-year follow-up was examined. "Probable" (cTnI 0.001-0.008 ng/mL) and "definite" (cTnI 0.009-0.029 ng/mL) subclinical myocardial necrosis were observed frequently within the cohort (34% and 18%, respectively). A linear relationship was observed between the magnitude of subclinical myocardial necrosis and risk of 3-year incident major adverse cardiovascular events, particularly in those with cTnI 0.009 ng/mL or higher (hazard ratio, 3.00; 95% confidence interval, 2.4-3.8), even after adjustment for traditional risk factors, C-reactive protein, and creatinine clearance. The presence of subclinical myocardial necrosis was associated with elevations in acute phase proteins (C-reactive protein, ceruloplasmin; P<0.01 each) and reduction in systemic antioxidant enzyme activities (arylesterase; P<0.01) but showed no significant associations with multiple specific measures of oxidant stress, and showed borderline associations with myeloperoxidase, a marker of leukocyte activation.
In stable cardiology patients, prodromal subclinical myocardial necrosis is associated with substantially higher long-term risk for major adverse cardiovascular events. The underlying mechanisms contributing to this minimal troponin leak phenomenon warrants further investigation.
亚临床心肌坏死作为长期不良心脏事件风险的先兆一直存在争议。争论主要集中在急性冠状动脉综合征患者中，以及肌钙蛋白检测的变异性和检测准确性问题上，而不是稳定型心脏病患者亚临床心肌坏死（即“肌钙蛋白漏”）的临床意义上。在此，我们在肾功能基本正常的稳定型心脏病患者人群中，研究不同程度的亚临床心肌坏死与长期不良临床结局之间的关系。
连续同意的患者（N=3828；中位数肌酐清除率为 100mL/min/1.73m²）接受选择性诊断性冠状动脉造影术，肌钙蛋白 I（cTnI）水平低于定义心肌梗死的诊断截止值（<0.03ng/mL）。在 3 年随访期间，研究了亚临床心肌坏死与主要不良心血管事件（定义为任何死亡、心肌梗死或中风）的发生之间的关系。在队列中经常观察到“可能”（cTnI 0.001-0.008ng/mL）和“确定”（cTnI 0.009-0.029ng/mL）亚临床心肌坏死（分别为 34%和 18%）。在亚临床心肌坏死的程度与 3 年主要不良心血管事件发生率之间观察到线性关系，尤其是在 cTnI 0.009ng/mL 或更高的患者中（危险比，3.00；95%置信区间，2.4-3.8），即使在调整了传统危险因素、C 反应蛋白和肌酐清除率后也是如此。亚临床心肌坏死与急性期蛋白（C 反应蛋白、铜蓝蛋白；P<0.01）升高和系统性抗氧化酶活性（芳基酯酶；P<0.01）降低有关，但与多种特定氧化应激指标无显著相关性，与白细胞活化标志物髓过氧化物酶呈边缘相关。
在稳定型心脏病患者中，前驱亚临床心肌坏死与主要不良心血管事件的长期风险显著增加相关。导致这种微量肌钙蛋白漏现象的潜在机制需要进一步研究。
