Lp(a) and its gene variants predict coronary disease severity but not mortality once heart disease is established, a study of 3313 LURIC patients validated in over 106 000 (Lancet Diabetes Endocrinol 2017)

Original title: Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Lancet Diabetes Endocrinol · 26 May 2017 · 8

Zewinger S, Kleber ME, Tragante V, McCubrey RO, Schmidt AF, Direk K, Laufs U, Werner C, Koenig W, Rothenbacher D, Mons U, Breitling LP et al.

This molecular and genetic association study examined whether Lp(a) concentration or LPA variants (rs10455872, rs3798220) predict long-term mortality in 3313 patients with established coronary heart disease from the LURIC study, with plasma Lp(a) findings validated in 10 195 patients from five independent studies and genetic findings replicated in the GENIUS-CHD consortium (106 353 patients, 19 332 deaths, 22 studies). Over a median 9·9-year follow-up, higher coronary heart disease severity was associated with the highest Lp(a) tertile (hazard ratio 1·44) and with either LPA SNP (hazard ratio 1·88). However, neither Lp(a) concentration (hazard ratio 0·95) nor the LPA SNPs (hazard ratio 1·10) were associated with all-cause mortality, nor with cardiovascular mortality, in LURIC or the validation studies. The findings show Lp(a) and its genetic variants predict coronary disease severity but are not useful for predicting mortality once coronary heart disease is already established.

Original abstract

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.

Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.

Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14-1·83) and the presence of either LPA SNP (1·88, 1·40-2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81-1·11 and either LPA SNP 1·10, 0·92-1·31) or cardiovascular mortality (0·99, 0·81-1·2 and 1·13, 0·90-1·40, respectively) or in the validation studies.

Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.

Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.