Association between lipoprotein(a), LPA genetic risk score, aortic valve disease, and subsequent major adverse cardiovascular events

Background Cohort studies have demonstrated associations between calcific aortic valve disease (CAVD) and Lp(a). As Lp(a) is almost entirely genetically determined, with the increasing clinical availability of genetic information, we aimed to determine if Lp(a), when predicted from genetic data, is associated with CAVD and major adverse cardiovascular events (MACE). Methods Patients undergoing coronary angiography were invited to participate in the study. Of 752 analysable participants, 446 had Lp(a) measured, and 703 had a calculable LPA genetic risk score (GRS). CAVD was categorized as absent/present and by severity. The primary outcomes were presence of CAVD at baseline, and MACE over seven years follow-up. Results The GRS explained 45% of the variation in Lp(a). After adjustment for cardiac risk factors and coronary artery disease, the odds of CAVD increased with Lp(a) (OR 1.039 per 10 unit increase, 95% C.I. 1.022 – 1.057, p<0.001) and GRS (OR 1.054 per 10-unit increase, 95% C.I. 1.024 – 1.086; p <0.001). Lp(a) and the GRS as continuous variables were not associated with subsequent MACE. Dichotomised GRS (>54) was associated with MACE, but this relationship became non-significant when coronary artery disease classification was added into the model (OR 1.333, 95% C.I. 0.927 – 1.912; p = 0.12). Conclusion An LPA GRS can explain 45% of the variation in Lp(a) levels, and both Lp(a) and the GRS are associated with CAVD. An elevated GRS is associated with future cardiac events in a secondary risk setting, but, if coronary artery disease status is known, it does not provide additional prognostic information.