Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Center for Population Health Innovation, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
JAMA. 2024 Jun 11;331(22):1898-1909. doi: 10.1001/jama.2024.5596.
Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies.
To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors.
DESIGN, SETTING, AND PARTICIPANTS: Individual-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.
Measurement 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.
The 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.
The 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.
Cardiovascular 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.
重要性：在人群中识别出发生动脉粥样硬化性心血管疾病风险较高的个体对于告知一级预防策略非常重要。
目的：评估常规心血管生物标志物在既定危险因素基础上的预后价值。
设计、地点和参与者：个体水平分析，包括来自 12 个国家和 4 个大陆的 28 个基于一般人群的队列中的心血管生物标志物数据，评估对象按年龄分组。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、氨基末端 B 型利钠肽前体、B 型利钠肽或高敏 C 反应蛋白。
主要结局和测量：主要结局是动脉粥样硬化性心血管疾病的发生，包括所有致命和非致命事件。次要结局为全因死亡率、心力衰竭、缺血性卒中和心肌梗死。在调整既定危险因素后，计算生物标志物与结局之间的亚分布危险比（HR）。使用 C 统计量和再分类分析评估生物标志物的额外预测价值。
结果：分析包括 164054 名个体（中位年龄 53.1 岁[四分位距（IQR），42.7-62.9 岁]，52.4%为女性）。发生了 17211 例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的发生显著相关（每个 SD 变化的亚分布 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 T 为 1.18[95%CI，1.12-1.23]；氨基末端 B 型利钠肽前体为 1.21[95%CI，1.18-1.24]；B 型利钠肽为 1.14[95%CI，1.08-1.22]；高敏 C 反应蛋白为 1.14[95%CI，1.12-1.16]）和所有次要结局。在包含既定危险因素的模型中添加每个单一生物标志物均能提高 C 统计量。对于年龄较轻（<65 岁）的 10 年动脉粥样硬化性心血管疾病发生风险，高敏心肌肌钙蛋白 I、氨基末端 B 型利钠肽前体和高敏 C 反应蛋白联合使用可将 C 统计量从 0.812（95%CI，0.8021-0.8208）提高至 0.8194（95%CI，0.8089-0.8277）。与传统模型相比，这种组合还能改善再分类。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。生物标志物的增量价值在 65 岁及以上人群中比在年轻人群中更大。
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以及死亡率密切相关。在既定危险因素的基础上增加生物标志物只能使动脉粥样硬化性心血管疾病的风险预测指标略有改善，但对心力衰竭和死亡率的改善更为有利。
