Soluble low-density lipoprotein receptor-related protein 1 as a biomarker of coronary risk: Predictive capacity and association with clinical events. (August 2019) - de Gonzalo-Calvo, David
Abstract: Background and aims: We aimed to determine whether circulating sLRP1 levels are associated with future coronary events and improve the predictive capacity of the REGICOR (Registre Gironí del Cor) risk function. Methods: We conducted a case-cohort study based on the follow-up of the REGICOR population-based cohort. Of the 5, 404 participants aged between 35 and 74 years, without previous history of cardiovascular disease, 117 subjects with angina or fatal or non-fatal myocardial infarction were included, and 512 individuals were randomly selected as a subcohort (including 14 patients who presented coronary events). sLRP1 levels were measured in basal plasma samples by commercial ELISA. Hazard ratio (HR) was estimated with Cox models adjusted for potential confounding factors. Discrimination and reclassification were analyzed with the c-index and the net reclassification index (NRI), respectively. A Mendelian randomization approach was used to explore the causality of the association between sLRP1 and coronary artery disease (CAD). Results: The group of participants who presented a CAD event showed higher levels of sLRP1 than the subcohort (2.45 [0.43; 8.31] vs. 2.07 [0.40; 6.65] μg/mL, p < 0.001). sLRP1 was significantly associated with CAD events even after adjustment for confounding factors (adjusted HR per standard deviation = 1.30, 95% CI: 1.01–1.67, p = 0.039). sLRP1 did not increase the predictive capacity or improve cardiovascular risk stratification of the REGICOR function. The LRP1 genetic variants associated with CAD risk were not related to sLRP1 concentration. Conclusions: Plasma sLRP1 is independently associated with the incidence of coronary events, but it does not improve the predictive capacity of the REGICOR risk function. Graphical abstract: Image 1 Highlights: Plasma sLRP1 is independently associated with the incidence of coronary events. Plasma sLRP1 does not improve risk prediction when added to the REGICOR function. The LRP1 variants tested are associated with coronary artery disease. The LRP1 variants tested are not associated with plasma sLRP1 concentration.