Genetic Risk Scoring of Lipoprotein(A) can Predict Risk of A
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Elevated levels of a little-known lipoprotein in the blood that may put people at high risk of cardiovascular disease can be as accurately detected by genetic testing as by conventional laboratory measurement, researchers at Massachusetts General Hospital (MGH) have found.

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.

This study aimed 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.

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.

Researchers 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, they assessed the potential improvement in ASCVD risk discrimination by QRISK3 and Pooled Cohort Equations among individuals with borderline to intermediate risk.

Key findings:
-- The mean age of the overall study population was 57.6 years, and 204355 individuals were female.
-- During a median follow-up of 11.1 years, 15?444 individuals developed an incident ASCVD event.
-- 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.
-- The association between LPA GRS and ASCVD was substantially attenuated after adjusting for measured lipoprotein(a).
-- Adding measured lipoprotein(a) or LPA GRS to QRISK3 provided modest improvements to the risk discrimination of incident ASCVD events.

When indicated, cardiovascular risk assessment with lipoprotein(a) at middle-age may include direct measurement or an LPA GRS, they concluded.