Kraaijenhof Jordan M, Nurmohamed Nick S, Nordestgaard Ask T, Reeskamp Laurens F, Stroes Erik S G, Hovingh G Kees, Boekholdt S Matthijs, Ridker Paul M
Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Eur Heart J. 2025 Apr 1. doi: 10.1093/eurheartj/ehaf209.
Recent data from a large American cohort of women strongly support universal one-time screening for LDL cholesterol, high-sensitivity C-reactive protein (hsCRP), and lipoprotein(a) [Lp(a)] in primary prevention. This study addresses the validity and generalizability of this novel primary prevention strategy in a large prospective European cohort of initially healthy men and women.
Plasma levels of LDL cholesterol, hsCRP, and Lp(a) were measured at study entry in 17 087 participants from the EPIC-Norfolk study who were subsequently followed over a period of 20 years for major adverse cardiovascular events (MACEs). Competing risk- and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MACE across quintiles of each biomarker and sought evidence of independent as well as additive effects over time were calculated.
During the 20-year follow-up, a total of 3249 MACEs occurred. Increasing quintiles of baseline LDL cholesterol, hsCRP, and Lp(a) all predicted 20-year risks; the multivariable-adjusted HRs in a comparison of the top to bottom quintile were 1.78 (95% CI: 1.57-2.00) for LDL cholesterol, 1.55 (95% CI: 1.37-1.74) for hsCRP, and 1.19 (95% CI: 1.07-1.33) for Lp(a). Compared with individuals with no biomarker elevations, the multivariable-adjusted HRs for incident MACE were 1.33, 1.68, and 2.41 for those with one, two, or three biomarkers in the top quintile, respectively (all P < .001). Each biomarker demonstrated independent contributions to overall risk and findings were consistent in analyses stratified by sex.
A single combined measure of LDL cholesterol, hsCRP, and Lp(a) among initially healthy European men and women was predictive of incident MACE during a 20-year period. These data replicate findings from a recent American cohort and strongly support universal screening for all three biomarkers in primary prevention.
来自美国一个大型女性队列的最新数据有力地支持了在一级预防中对低密度脂蛋白胆固醇、高敏C反应蛋白（hsCRP）和脂蛋白(a) [Lp(a)]进行普遍一次性筛查。本研究探讨了这一新型一级预防策略在一个大型欧洲前瞻性队列的初始健康男性和女性中的有效性和普遍性。
在EPIC-诺福克研究的17087名参与者入组时测量其血浆低密度脂蛋白胆固醇、hsCRP和Lp(a)水平，随后对他们进行为期20年的随访，观察主要不良心血管事件（MACE）。计算每个生物标志物五分位数组中发生MACE的竞争风险和多变量调整风险比（HR）及95%置信区间（CI），并寻找随时间的独立及相加效应的证据。
在20年随访期间共发生3249例MACE。基线低密度脂蛋白胆固醇、hsCRP和Lp(a)五分位数升高均预测了20年风险；在最高与最低五分位数比较中，多变量调整后的HR分别为：低密度脂蛋白胆固醇为1.78（95%CI：1.57 - 2.00），hsCRP为1.55（95%CI：1.37 - 1.74），Lp(a)为1.19（95%CI：1.07 - 1.33）。与生物标志物无升高的个体相比，最高五分位数中有1个、2个或3个生物标志物的个体发生MACE的多变量调整后HR分别为1.33、1.68和2.41（均P < .001）。每个生物标志物对总体风险均有独立贡献，且按性别分层分析的结果一致。
在初始健康的欧洲男性和女性中，单一联合检测低密度脂蛋白胆固醇、hsCRP和Lp(a)可预测20年内发生的MACE。这些数据重复了最近美国队列的研究结果，并有力支持在一级预防中对所有这三种生物标志物进行普遍筛查。
