Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study.
Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study.
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DOI：
10.1161/circulationaha.112.129437
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发表时间：
2012-09-25
期刊：
影响因子：
37.8
通讯作者：
Januzzi JL
中科院分区：
文献类型：
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作者：
Wang TJ;Wollert KC;Larson MG;Coglianese E;McCabe EL;Cheng S;Ho JE;Fradley MG;Ghorbani A;Xanthakis V;Kempf T;Benjamin EJ;Levy D;Vasan RS;Januzzi JL
在以社区为基础的人群中预测心血管事件的生物标志物并没有一致地将信息添加到标准危险因素中。许多以前研究的生物标志物的局限性是它们缺乏心血管特异性。为了确定心血管应激诱导的3种新生物标志物的预后价值，我们在Framingham心脏研究中对3428名参与者(平均年龄59岁，其中53%是女性)进行了可溶性ST2、生长分化因子-15和高敏肌钙蛋白I的检测。我们采用多变量调整比例风险模型来评估生物标记物预测不良结果的个体和组合能力。我们还构建了一个由3个生物标记物以及B型利钠肽和高敏C反应蛋白组成的“多标记物”评分。在平均11.3年的随访中，有488例死亡，336例主要心血管事件，162例心力衰竭事件和142例冠状动脉事件。在多变量调整的模型中，除冠状动脉事件外，这3个新的生物标志物与每个终点(P<；0.001)相关。多标记物得分在最高四分位数的个体有3倍的死亡风险(调整后的风险比，3.2，95%可信区间，2.2-4.7；p<；0.001)，6倍的心力衰竭风险(6.2，95%可信区间，2.6-14.8；p<；0.001)和2倍的心血管事件风险(1.9，95%可信区间，1.3-2.7；p=0.001)。将多标记物评分添加到临床变量中，导致c统计量(p=0.007或更低)和净重新分类改善(p=0.001或更低)显著增加。心血管应激的多个生物标志物可在活动个体中检测到，并为预测死亡、总体心血管事件和心力衰竭的标准危险因素增加预后价值。
Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3,428 participants (mean age 59, 53% women) in the Framingham Heart Study. We performed multivariable-adjusted proportional hazards models to assess the individual and combined ability of the biomarkers to predict adverse outcomes. We also constructed a “multimarker” score composed of the 3 biomarkers, in addition to B-type natriuretic peptide and high-sensitivity C-reactive protein. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the 3 new biomarkers were associated with each endpoint (p<0.001) except for coronary events. Individuals with multimarker scores in the highest quartile had a 3-fold risk of death (adjusted hazard ratio, 3.2, 95% CI, 2.2–4.7; p<0.001), 6-fold risk of heart failure (6.2, 95% CI, 2.6–14.8; p<0.001), and 2-fold risk of cardiovascular events (1.9, 95% CI, 1.3–2.7; p=0.001). Addition of the multimarker score to clinical variables led to significant increases in the c-statistic (p=0.007 or lower) and net reclassification improvement (p=0.001 or lower). Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals, and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure.