Inflammation
BiomarCaRE project of 71,678 people finds Lp(a) predicts recurrent coronary events only in those with residual inflammatory risk (Eur Heart J 2024)
Original title: C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project
Using pooled data from eight European cohorts totalling 71 678 participants (65 661 without and 6017 with established coronary heart disease (CHD) at baseline), this BiomarCaRE project analysis tested whether high-sensitivity C-reactive protein (hsCRP) modifies Lp(a)'s association with CHD. Among CHD-free individuals, elevated Lp(a) predicted incident CHD regardless of hsCRP level, with fully adjusted hazard ratios of 1.45 below and 1.48 at or above 2 mg/L hsCRP (highest vs. lowest fifth), no interaction found (P = 0.82). Among those with established CHD, Lp(a) predicted recurrent events only when hsCRP was at or above 2 mg/L (hazard ratio 1.34), not below it (hazard ratio 1.29, P for interaction = 0.024). Lp(a) predicts first CHD events regardless of inflammatory status, but recurrent events specifically in patients with residual inflammatory risk, a distinction that could guide patient selection for future Lp(a)-targeting therapies.
Original abstract
Background And Aims: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population.
Methods: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L).
Results: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024).
Conclusions: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.