Genetic testing can accurately detect lipoprotein(a) to assess high CVD risk: JAMA
Genetic risk assessment with lipoprotein(a) at middle-age can be done with direct measurement or an LPA GRS (genetic risk score).
UK: Lipoprotein(a) can be accurately detected by genetic testing as efficiently as from conventional laboratory measurement, a recent study in the journal JAMA Cardiology has found. Elevated levels of the little known lipoprotein(a) in the blood put people at high risk of cardiovascular disease (CVD). This may help physicians to identify candidates for treatment (such as statin) or for ongoing trials of new medicines.
The findings are particularly important for expanding genetic research biobanks and for millions of people who use direct-to-consumer genetic testing kits.
Lipoprotein(a) is a highly heritable biomarker independently associated with atherosclerotic cardiovascular disease (ASCVD). It is not clear whether genetic factors associated with lipoprotein(a) or measured lipoprotein(a) can provide comparable or additional prognostic information for primary prevention. Mark Trinder, The University of British Columbia, Vancouver, British Columbia, Canada, and colleagues determined whether a 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 comprising approx 500 000 volunteers (aged 40 to 69 years). They were recruited from 22 sites across the United Kingdom between 2006 and 2010. An LPA GRS was calculated for 374 099 unrelated individuals with array-derived genotypes and lipoprotein(a) measures using externally derived weights. Data were analyzed from April 2020 to March 2020.
The mean age of the overall study population was 57.6 years, and 204 355 individuals were female (54.6%).
The researchers estimated the associations between measured lipoprotein(a) and LPA GRS with the ASCVD (peripheral arterial disease, coronary artery disease, myocardial infarction, ischemic stroke, and cardiovascular mortality) incidence using Cox proportional hazards models. To determine the utility of using measured lipoprotein(a) and LPA GRS as risk enhancers for ASCVD, the researchers 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).
Key findings of the study include:
- 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 vs hazard ratio, 1.29).
- 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 (area under the receiver operating curve, 0.640 vs 0.64).
"When indicated, cardiovascular risk assessment with lipoprotein(a) at middle-age may include direct measurement or an LPA GRS," concluded the authors.
The study, "Clinical Utility of Lipoprotein(a) and LPA Genetic Risk Score in Risk Prediction of Incident Atherosclerotic Cardiovascular Disease," is published in the journal JAMA Cardiology.
DOI: https://jamanetwork.com/journals/jamacardiology/fullarticle/2771455
