Ridker Paul M, Moorthy M Vinayaga, Cook Nancy R, Rifai Nader, Lee I-Min, Buring Julie E
From the Divisions of Preventive Medicine (P.M.R., M.V.M., N.R.C., I.-M.L., J.E.B.) and Cardiovascular Diseases (P.M.R.), Brigham and Women's Hospital, the Department of Epidemiology, Harvard T.H. Chan School of Public Health (P.M.R., N.R.C., I.-M.L., J.E.B.), and the Department of Laboratory Medicine, Boston Children's Hospital (N.R.) - all in Boston; and the Faculty of Medicine, University of Porto, Porto, Portugal (N.R.).
N Engl J Med. 2024 Dec 5;391(22):2087-2097. doi: 10.1056/NEJMoa2405182. Epub 2024 Aug 31.
High-sensitivity C-reactive protein (CRP), low-density lipoprotein (LDL) cholesterol, and lipoprotein(a) levels contribute to 5-year and 10-year predictions of cardiovascular risk and represent distinct pathways for pharmacologic intervention. More information about the usefulness of these biomarkers for predicting cardiovascular risk over longer periods of time in women is needed because early-life intervention represents an important risk-reduction method.
We measured high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) levels at baseline in 27,939 initially healthy U.S. women who were subsequently followed for 30 years. The primary end point was a first major adverse cardiovascular event, which was a composite of myocardial infarction, coronary revascularization, stroke, or death from cardiovascular causes. We calculated the adjusted hazard ratios and 95% confidence intervals across quintiles of each biomarker, along with 30-year cumulative incidence curves adjusted for age and competing risks.
The mean age of the participants at baseline was 54.7 years. During the 30-year follow-up, 3662 first major cardiovascular events occurred. Quintiles of increasing baseline levels of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) all predicted 30-year risks. Covariable-adjusted hazard ratios for the primary end point in a comparison of the top with the bottom quintile were 1.70 (95% confidence interval [CI], 1.52 to 1.90) for high-sensitivity CRP, 1.36 (95% CI, 1.23 to 1.52) for LDL cholesterol, and 1.33 (95% CI, 1.21 to 1.47) for lipoprotein(a). Findings for coronary heart disease and stroke appeared to be consistent with those for the primary end point. Each biomarker showed independent contributions to overall risk. The greatest spread for risk was obtained in models that incorporated all three biomarkers.
A single combined measure of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) levels among initially healthy U.S. women was predictive of incident cardiovascular events during a 30-year period. These data support efforts to extend strategies for the primary prevention of atherosclerotic events beyond traditional 10-year estimates of risk. (Funded by the National Institutes of Health; Women's Health Study ClinicalTrials.gov number, NCT00000479.).
高敏C反应蛋白（CRP）、低密度脂蛋白（LDL）胆固醇和脂蛋白（a）水平有助于预测5年和10年心血管风险，并且代表了不同的药物干预途径。由于早期干预是一种重要的风险降低方法，因此需要更多关于这些生物标志物在预测女性更长时间心血管风险方面有用性的信息。
我们在27939名最初健康的美国女性基线时测量了高敏CRP、LDL胆固醇和脂蛋白（a）水平，随后对她们进行了30年的随访。主要终点是首次发生的重大心血管不良事件，该事件是心肌梗死、冠状动脉血运重建、中风或心血管原因死亡的综合结果。我们计算了每个生物标志物五分位数的校正风险比和95%置信区间，以及根据年龄和竞争风险调整后的30年累积发病率曲线。
参与者基线时的平均年龄为54.7岁。在30年的随访期间，发生了3662例首次重大心血管事件。高敏CRP、LDL胆固醇和脂蛋白（a）基线水平升高的五分位数均能预测30年风险。在最高五分位数与最低五分位数的比较中，主要终点的协变量校正风险比，高敏CRP为1.70（95%置信区间[CI]，1.52至1.90），LDL胆固醇为1.36（95%CI，1.23至1.52），脂蛋白（a）为1.33（95%CI，1.21至1.47）。冠心病和中风的结果似乎与主要终点的结果一致。每个生物标志物对总体风险都有独立贡献。在纳入所有三种生物标志物的模型中，风险差异最大。
对最初健康的美国女性进行高敏CRP、LDL胆固醇和脂蛋白（a）水平的单一综合测量，可预测30年内发生的心血管事件。这些数据支持将动脉粥样硬化事件一级预防策略扩展至超过传统10年风险估计的努力。（由美国国立卫生研究院资助；妇女健康研究ClinicalTrials.gov编号，NCT00000479。）
