This presentation Clinical Utility of LPA Genetic Characterization for Primary Prevention of Atherosclerotic Cardiovascular Disease by Mark Trinder (University of British Columbia, Canada) is available to view on demand.
A genetic risk score comprising 43 variants of the LPA gene has comparable risk prediction for incident atherosclerotic cardiovascular disease (ASCVD) as direct lipoprotein(a) measurement according to this study reported at the second Late Breaker Session. The study was published in JAMA Cardiology (1).
Elevated Lp(a) is causal for ASCVD and affects as many as one in five people in Europe (2). As LPA variants contribute about 60% of the variability in Lp(a) levels among European populations, a genetic risk score may have clinical value in risk prediction for ASCVD (3,4).
Researchers used data from the UK Biobank, a prospective observational study including about half a million adults aged 40 to 69 years recruited across the UK between 2006 and 2010. Lp(a) was measured at study entry using an immunoturbidimetric method which is isoform insensitive. The LPA GRS comprised 43 single-nucleotide variants that were conditionally and significantly associated with Lp(a) levels. By definition, an LPA GRS of at least 120 nmol/L (about 50 mg/dL) was considered elevated.
The LPA GRS was calculated for 374,099 subjects (mean age 57.6 years, 55% female). The utility of Lp(a) measurement and the LPA GRS in ASCVD risk assessment was investigated using the QRISK3 and Pooled Cohort Equations in individuals with borderline (n=113,703) to intermediate risk (n=44,350).
Over a median follow-up of 11.1 years, 15,444 (5.1%) individuals developed an incident ASCVD event. Each 120 nmol/L increase in Lp(a) level was associated with a 26% increase in incident ASCVD risk (hazard ratio 1.26; 95% CI 1.23-1.28). This compared with a 29% increase in risk based on the LPA GRS (hazard ratio 1.29; 95%CI 1.26-1.33). Thus, the LPA GRS did not provide additional prognostic information beyond measured Lp(a) levels on the incidence of ASCVD. Adding either to QRISK3 modestly improved discrimination of risk of incident ASCVD events.
The take home message from this study is that the use of an LPA GRS performs equal to a single Lp(a) measurement in predicting the increased risk of ASCVD.
- Trinder M, Uddin M, Finneran P, Aragam KG, Natarajan P. Clinical Utility of Lipoprotein(a) and LPA Genetic Risk Score in Risk Prediction of Incident Atherosclerotic Cardiovascular Disease. JAMA Cardiol doi:10.1001/jamacardio.2020.5398
- Nordestgaard BG, et al; European Atherosclerosis Society Consensus Panel. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J 2010;31:2844-2853.
- Verbeek R, et al. Population and assay thresholds for the predictive value of lipoprotein (a) for coronary artery disease: the EPIC-Norfolk Prospective Population Study. J Lipid Res 2016;57:697-705.
- Burgess S, et al. Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: a Mendelian randomization analysis. JAMA Cardiol. 2018;3:619-627.