Aortic stenosis
An LPA genetic risk score explaining 45% of Lp(a) variation predicts calcific aortic valve disease but adds little once coronary status is known (Eur J Prev Cardiol 2024)
Original title: Association between lipoprotein(a), LPA genetic risk score, aortic valve disease, and subsequent major adverse cardiovascular events
In 752 patients undergoing coronary angiography between 2012 and 2013 (446 with Lp(a) measured, 703 with a calculable LPA genetic risk score), the genetic risk score explained 45% of variation in Lp(a). After adjustment for cardiac risk factors and coronary artery disease, both Lp(a) (odds ratio 1.039 per 10-unit increase, 95% CI 1.022-1.057, P < 0.001) and the genetic risk score (odds ratio 1.054 per 10-unit increase, 95% CI 1.024-1.086, P < 0.001) were associated with baseline calcific aortic valve disease. Neither Lp(a) nor the genetic risk score, as continuous variables, predicted subsequent major adverse cardiovascular events over 7-year follow-up. A dichotomised high genetic risk score was associated with events, but this became non-significant once coronary artery disease classification was added to the model (odds ratio 1.333, 95% CI 0.927-1.912, P = 0.12). An LPA genetic risk score tracks with aortic valve disease as well as measured Lp(a), but offers no additional prognostic information once a patient's coronary disease status is already known.
Original abstract
Aims: Cohort studies have demonstrated associations between calcific aortic valve disease (CAVD) and Lp(a). As Lp(a) is almost entirely genetically determined, in this study, we aim to determine whether Lp(a), when predicted from genetic data, is associated with CAVD and major adverse cardiovascular events (MACEs).
Methods And Results: Patients undergoing coronary angiography between January 2012 and May 2013 were invited to participate in the study. Of 752 analysable participants, 446 had their Lp(a) measured and 703 had a calculable LPA genetic risk score (GRS). The primary outcomes were the presence of CAVD at baseline and MACE over a 7-year follow-up. The GRS explained 45% of variation in Lp(a). After adjustment for cardiac risk factors and coronary artery disease (CAD), the odds of CAVD increased with increasing Lp(a) [odds ratio (OR) 1.039 per 10-unit increase, 95% confidence interval (CI) 1.022-1.057, P < 0.001] and GRS (OR 1.054 per 10-unit increase, 95% CI 1.024-1.086; P < 0.001). Lipoprotein(a) and the GRS as continuous variables were not associated with subsequent MACEs. A dichotomized GRS (>54) was associated with MACE, but this relationship became non-significant when CAD classification was added into the model (OR 1.333, 95% CI 0.927-1.912; P = 0.12).
Conclusion: An LPA GRS can explain 45% of 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 the CAD status is known, it does not provide additional prognostic information.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.