Clinical Utility of Lipoprotein(a) and LPA Genetic Risk Score in Risk Prediction of Incident Atherosclerotic Cardiovascular Disease.

ABSTRACT:

Importance

Lipoprotein(a) is a highly heritable biomarker independently associated with atherosclerotic cardiovascular disease (ASCVD). It is unclear whether measured lipoprotein(a) or genetic factors associated with lipoprotein(a) can provide comparable or additional prognostic information for primary prevention.

Objective

To determine whether a genetic risk score (GRS) comprising 43 variants at the LPA gene, which encodes apolipoprotein(a), has clinical utility in assessing ASCVD risk compared with and in addition to lipoprotein(a) measurement.

Design, setting, and participants

The UK Biobank is a prospective observational study of approximately 500?000 volunteers aged 40 to 69 years who were recruited from 22 sites across the United Kingdom between 2006 and 2010. Using externally derived weights, an LPA GRS was calculated for 374?099 unrelated individuals with array-derived genotypes and lipoprotein(a) measures. Data were analyzed from April 2020 to March 2020.

Exposures

Measured lipoprotein(a) and LPA GRS.

Main outcomes and measures

We estimated the associations between measured lipoprotein(a) and LPA GRS with the incidence of ASCVD (peripheral arterial disease, coronary artery disease, myocardial infarction, ischemic stroke, and cardiovascular mortality) using Cox proportional hazards models. To determine the utility of using measured lipoprotein(a) and LPA GRS as risk enhancers for ASCVD, we assessed the potential improvement in ASCVD risk discrimination by QRISK3 and Pooled Cohort Equations among individuals with borderline to intermediate risk (n?=?113?703 and 144?350, respectively).

Results

The mean age of the overall study population was 57.6 years, and 204 355 individuals were female (54.6%). During a median follow-up of 11.1 years (interquartile range, 1.4 years), 15?444 individuals developed an incident ASCVD event (5.1%). The LPA GRS explained approximately 60% of the variation in measured lipoprotein(a) for White/European individuals. Independently, both lipoprotein(a) and LPA GRS were associated with incident, composite ASCVD (hazard ratio per 120 nmol/L increase, 1.26; 95% CI, 1.23-1.28 vs hazard ratio, 1.29; 95% CI, 1.26-1.33; P?Conclusions and relevanceWhen indicated, cardiovascular risk assessment with lipoprotein(a) at middle-age may include direct measurement or an LPA GRS.

SUBMITTER: Trinder M 

PROVIDER: S-EPMC7539232 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature