ImportanceIdentification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies.ObjectiveTo evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors.Design, Setting, and ParticipantsIndividual-level analysis including data on cardiovascular biomarkers from 28 general population–based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years.ExposureMeasurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein.Main Outcomes and MeasuresThe primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses.ResultsThe analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people.Conclusions and RelevanceCardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

中文翻译：

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心血管生物标志物在人群中的预后价值

重要性识别人群中动脉粥样硬化性心血管疾病高风险个体对于一级预防策略非常重要。目的评估常规心血管生物标志物添加到已确定的风险因素中的预后价值。设计、设置和参与者个体水平分析，包括以下数据：来自 12 个国家和 4 大洲 28 个普通人群的心血管生物标志物，并按参与者年龄进行评估。中位随访时间为 11.8 年。暴露测量高敏心肌肌钙蛋白 I、高敏心肌肌钙蛋白 T、N 端 B 型利钠肽前体、B 型利钠肽或高敏 C 反应蛋白主要结果和措施主要结果是动脉粥样硬化性心血管疾病的发生率，其中包括所有致命和非致命事件。次要结局是全因死亡率、心力衰竭、缺血性中风和心肌梗死。在调整已确定的风险因素后，计算生物标志物和结果关联的次分布风险比（HR）。使用 C 统计和重新分类分析评估生物标志物的额外预测价值。结果分析包括 164 054 名个体（中位年龄 53.1 岁 [IQR，42.7-62.9 岁]，52.4% 为女性）。共有 17 211 起动脉粥样硬化性心血管疾病事件。所有生物标志物均与动脉粥样硬化性心血管疾病发生显着相关（每 1-SD 变化的子分布 HR，高敏心肌肌钙蛋白 I 为 1.13 [95% CI，1.11-1.16]；高敏心肌肌钙蛋白 I 为 1.18 [95% CI，1.12-1.23]。心肌肌钙蛋白 T 敏感性；N 端 B 型利钠肽为 1.21 [95% CI，1.18-1.24]；B 型利钠肽为 1.14 [95% CI，1.08-1.22]； ，1.12-1.16] 对于高敏 C 反应蛋白）和所有次要结果。将每个单一生物标志物添加到包含已确定风险因素的模型中可以改善 C 统计量。对于年轻人（年龄<65岁）10年发生的动脉粥样硬化性心血管疾病，高敏心肌肌钙蛋白I、N端B型利尿钠肽前体和高敏C反应蛋白的组合导致 C 统计量从 0.812 (95% CI, 0.8021-0.8208) 提高到 0.8194 (95% CI, 0.8089-0.8277)。与传统模型相比，这些生物标志物的组合也改善了重新分类。风险预测的改善在心力衰竭和全因死亡率的次要结局中最为明显。与年轻人相比，65 岁或以上人群的生物标志物增量值更大。结论和相关性心血管生物标志物与致命和非致命心血管事件和死亡率密切相关。在已确定的风险因素中添加生物标志物仅导致动脉粥样硬化性心血管疾病的风险预测指标略有改善，但更有利于心力衰竭和死亡率。