TIMI Study Group Brigham and Women's HospitalHarvard Medical School Boston MA.
Department of Medicine Beth Israel Deaconess Medical CenterHarvard Medical School Boston MA.
J Am Heart Assoc. 2021 May 4;10(9):e018673. doi: 10.1161/JAHA.120.018673. Epub 2021 Apr 22.
Background Patients with stable atherothrombotic disease vary in their risk of developing heart failure (HF). Circulating cardiovascular biomarkers may improve HF risk assessment and identify patients who may benefit from emerging HF preventive therapies. Methods and Results We measured high-sensitivity cardiac troponin I and BNP (B-type natriuretic peptide) in 15 833 patients with prior myocardial infarction, ischemic stroke, or peripheral artery disease from the TRA 2°P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50) trial, excluding patients with recent myocardial infarction (<30 days). Biomarkers were categorized using a priori cut points. Hospitalization for HF (HHF) end points were adjudicated with blinded structured review of serious adverse events. Associations between biomarkers and HHF outcomes were adjusted for sex and independent clinical risk predictors of HHF in our cohort (age ≥75, prior HF, type 2 diabetes mellitus, polyvascular disease, body mass index, anemia, chronic kidney disease, hypertension). Baseline high-sensitivity cardiac troponin I and BNP each identified a significant graded risk of HHF independent of clinical risk predictors, including in the subgroups of patients with and without type 2 diabetes mellitus and with and without prior HF. Patients with both high-sensitivity cardiac troponin I ≥5 ng/L and BNP ≥100 pg/mL had the highest HHF event rates. When added to a multivariable Cox regression model with clinical risk predictors (C-index 0.88; 95% CI, 0.85-0.90), BNP (C -index 0.92; 95% CI, 0.90-0.93), and high-sensitivity cardiac troponin I (C-index 0.90; 95% CI, 0.88-0.92) each significantly improved the prognostic performance of the model (both <0.001). Conclusions Biomarkers of myocardial injury and hemodynamic stress are independent predictors of HHF risk in patients with stable atherothrombotic disease, with and without prior HF and/or type 2 diabetes mellitus. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00526474.
患有稳定动脉粥样硬化血栓形成疾病的患者发生心力衰竭（HF）的风险存在差异。循环心血管生物标志物可能改善 HF 风险评估，并确定可能从新兴 HF 预防治疗中获益的患者。
我们在来自 TRA 2°P-TIMI 50（二次预防动脉粥样硬化血栓形成事件的凝血酶受体拮抗剂-心肌梗死溶栓治疗 50）试验的 15833 例既往有心肌梗死、缺血性卒中和外周动脉疾病的患者中测量了高敏心肌肌钙蛋白 I 和 BNP（B 型利钠肽），排除了近期心肌梗死（<30 天）的患者。使用事先确定的切点对生物标志物进行分类。HF 住院（HHF）终点通过对严重不良事件进行盲法结构审查进行裁决。在我们的队列中，使用性别和 HHF 的独立临床风险预测因素（年龄≥75 岁、既往 HF、2 型糖尿病、多血管疾病、体重指数、贫血、慢性肾脏病、高血压）调整生物标志物与 HHF 结果之间的关联。高敏心肌肌钙蛋白 I 和 BNP 基线水平均独立于临床风险预测因素（包括有和没有 2 型糖尿病和有和没有既往 HF 的患者亚组）确定 HHF 的显著分级风险。同时具有高敏心肌肌钙蛋白 I≥5ng/L 和 BNP≥100pg/mL 的患者 HHF 事件发生率最高。当添加到包含临床风险预测因素的多变量 Cox 回归模型中时（C 指数 0.88；95%CI，0.85-0.90），BNP（C 指数 0.92；95%CI，0.90-0.93）和高敏心肌肌钙蛋白 I（C 指数 0.90；95%CI，0.88-0.92）均显著改善了模型的预后性能（均<0.001）。
心肌损伤和血流动力学应激的生物标志物是稳定动脉粥样硬化血栓形成疾病患者 HF 风险的独立预测因素，无论是否有既往 HF 和/或 2 型糖尿病。
