Genetics
LPA gene variants explain 28% of Lp(a) variability but not coronary anatomy in chronic coronary syndrome, 390-patient study (J Clin Lipidol 2026)
Original title: Lipoprotein(a) levels and common LPA gene variants in patients with chronic coronary syndrome: Genetic determinants and clinical associations
Study of 390 patients with chronic coronary syndrome (CCS) undergoing genetic evaluation for suspected inherited dyslipidaemia, testing associations of the LPA polymorphisms rs10455872 and rs3798220 with Lp(a) concentration and coronary anatomy. Both polymorphisms were robustly and independently associated with higher Lp(a) under dominant and additive models (p<0.001), and combined LPA genetic burden explained about 28% of Lp(a) variability; extreme Lp(a) phenotypes were more frequent among risk-allele carriers. However, neither Lp(a) levels, extreme phenotypes, nor LPA genetic burden were independently associated with coronary events, multivessel disease or the number of stents after adjustment. The authors conclude LPA variants strongly determine Lp(a) concentration but not the established anatomical extent of coronary disease, suggesting Lp(a)'s role is greatest in early disease stages.
Original abstract
Background: Despite optimal lipoprotein cholesterol control, patients with chronic coronary syndrome (CCS) exhibit substantial residual cardiovascular risk. Lipoprotein(a) (Lp[a]) is an independent cardiovascular risk factor, primarily determined by genetic variation within the LPA gene.
Objective: To evaluate the association between the LPA polymorphisms rs10455872 and rs3798220, plasma Lp(a) concentrations-including extreme phenotypes-and clinical and coronary anatomical characteristics in patients with CCS.
Methods: A total of 390 patients with CCS undergoing genetic evaluation for suspected inherited dyslipidemia were included. Lp(a) concentrations were measured using standardized assays, and the LPA polymorphisms rs10455872 and rs3798220 were genotyped. Associations with Lp(a) levels, clinical events, and coronary anatomical complexity were assessed using linear, logistic, ordinal, and negative binomial regression models.
Results: Both polymorphisms were robustly and independently associated with higher Lp(a) concentrations under dominant and additive genetic models (P < 0.001). The combined LPA genetic burden explained approximately 28% of the variability in Lp(a) levels. Extreme Lp(a) phenotypes were significantly more frequent among risk allele carriers. However, neither Lp(a) levels, extreme phenotypes, nor LPA genetic burden were independently associated with coronary events, multivessel disease, or coronary anatomical complexity (number of stents) after multivariable adjustment. Negative binomial models incorporating disease duration confirmed the lack of association with recurrent ischemic events.
Conclusion: In patients with CCS, common LPA gene variants strongly determine plasma Lp(a) concentrations, including extreme phenotypes, but are not associated with the anatomical extent of coronary artery disease. These findings suggest that Lp(a) plays a predominant role in early disease stages rather than in established coronary anatomy.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.