Physicians' Academy for Cardiovascular Education

Measured Lp(a) levels and LPA GRS similarly associated with ASCVD risk in primary prevention setting

News - Oct. 7, 2020

Clinical utility of LPA genetic characterization for primary prevention of atherosclerotic cardiovascular disease

Presented at the virtual EAS 2020 by Mark Trinder (Broad Institute, Boston, MA, USA)

Introduction and methods

Variants in the LPA gene, which encodes lipoprotein(a), predominately determine Lp(a) levels in plasma. Mendelian randomization analyses have suggested that elevated Lp(a) levels are a causal risk factor of ASCVD. Conclusive testing of this association between Lp(a) and CV risk is currently in progress. However, recommendations for testing of Lp(a) levels in regard to primary prevention for ASCVD remain contentious.

This study assessed whether measurement of Lp(a) levels and/or LPA genetic risk score (GRS) have clinical utility in risk prediction of ASCVD in the primary setting.

Firstly, 374,099 individuals from the UK biobank cohort that had an Lp(a) measurement, genotyping info and had less than third degree relatedness were selected. LPA genetic risk score was determined using 43 LPA variants. Subjects were grouped into different ethnic groups (South Asian (SAS), European/white (EUR), East Asian (EAS), African (AFR) descent, and admixed or unknown) and their LPA GRS was tested for association with measured Lp(a) levels.

Secondly, 283,540 individuals from EUR descent from this cohort were tested for association of the LPA GRS and Lp(a) with incident ASCVD. Individuals using cholesterol-lowering medication were excluded.

Thirdly, individuals within this cohort that had no prior history of diabetes, <190 mg/dL LDL-c concentration and were classified as borderline to intermediate 10-year risk (5-20%) by Pooled Cohort Equations (n=113,703) or QRISK3 (n=144,350) were selected. This analysis assessed whether the addition of continuous levels of measured Lp(a) or LPA GRS improved risk prediction.

Main results


An LPA genetic risk score is, relative to Lp(a) levels, a comparable prediction marker for incident ASCVD. LPA genetic risk score and measured Lp(a) or combined improve risk assessment in borderline to intermediate risk groups for primary prevention and point to Lp(a) as an risk enhancer.

-Our reporting is based upon the information provided at the EAS 2020 congress-

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