Epidemiology
High Lp(a) raises coronary heart disease risk just as much in people with zero or one traditional risk factor as in those with two or more, 66,495-person European pooled cohort finds (Eur J Prev Cardiol 2025)
Original title: Lipoprotein (a) and Incident Coronary Heart Disease in the Community: Impact of Traditional Cardiovascular Risk Factors
This study pooled 66,495 coronary-heart-disease-free individuals from eight European prospective population-based cohorts, stratified into low cardiovascular risk (0 or 1 of hypertension, diabetes, hypercholesterolaemia, smoking; n = 41,770) and increased risk (2 or more; n = 24,725), to test whether traditional risk factor burden modifies Lp(a)'s association with incident coronary heart disease (CHD). Over a median 9.7-year follow-up, 3,467 incident CHD events occurred. Despite their very low absolute risk on traditional factors, individuals with 0 or 1 risk factor showed a strong association between Lp(a) at or above the 90th percentile (43.2 mg/dL) and future CHD, comparable in magnitude to that seen in the higher-risk group (adjusted sub-distribution HR 1.38, 95% CI 1.12-1.71, versus 1.27, 95% CI 1.10-1.46, P for interaction = 0.50). The authors conclude high Lp(a) drives adverse CHD risk even in people who otherwise look low-risk by conventional factors, posing a substantial challenge for mitigating Lp(a)-associated risk in populations not flagged by traditional screening.
Original abstract
Aims: Deleterious effects Lipoprotein (a) (Lp(a)) might be mitigated by overall cardiovascular (CV) risk reduction. However, data on the relationship between increased Lp(a) and incident coronary heart disease (CHD) according to the distribution of modifiable CV risk factors (CVRF) at baseline are still scarce. We investigated the association between high Lp(a) and incident CHD in the general population, depending on the presence/absence of four major CVRFs (hypertension, diabetes, hypercholesterolemia, smoking) at baseline.
Methods: Overall 66,495 CHD-free individuals from eight European prospective population-based cohorts were included. The cohort was stratified according to CVRF burden at baseline in "0/1 CVRF" (low risk; n= 41,770) and"≥2 CVRFs" (increased risk; n=24,725). Fine and Gray competing risk-adjusted models were calculated for the association between Lp(a) mass (<90th versus ≥90th percentile (pctl.); cut-off 43.2 mg/dL) and future CHD events.
Results: During a median follow-up of 9.7 years, 3,467 incident CHD events occurred. Despite being at very low absolute risk based on traditional CVRF, individuals with 0/1CVRF demonstrated a strong association between increased Lp(a) mass (≥90th pctl.) and future CHD events, which was comparable to the association observed among individuals with ≥2 CVRFs. The fully-adjusted sub-distribution Hazard Ratios [sHRs] for elevated Lp(a) were 1.38 (95% CI, 1.12-1.71) versus 1.27 (95% CI, 1.10-1.46) in those having 0/1 versus ≥2 CVRFs at baseline (Pinteraction0.50).
Conclusion: Among CHD-free subjects, high Lp(a) was related to adverse outcome even in individuals with no or only one CVRF at baseline, thereby generating substantial challenges in mitigating Lp(a)-associated CHD risk in very low risk populations.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.