LPA genetic risk score may be similar to Lp(a) measurements at predicting ASCVD
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An LPA genetic risk score with 43 single nucleotide variants provided similar risk prediction for atherosclerotic CVD compared with measuring lipoprotein(a), researchers found.
“Our work demonstrates that genetic risk scoring of lipoprotein(a) offers risk prediction of atherosclerotic cardiovascular disease that’s comparable to directly measured lipoprotein(a),” Pradeep Natarajan, MD, MMSc, director of preventive cardiology at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, said in a press release. “We learned that genetic determinants of elevated lipoprotein(a) may help identify the most effective medication regimen for cardiovascular disease prevention.”
In this study published in JAMA Cardiology, Mark Trinder, MSc, visiting medical student from the Centre for Heart Lung Innovation at the University of British Columbia, and colleagues analyzed data from approximately 500,000 participants from the UK Biobank aged 40 to 69 years. Using genotyping array data and Lp(a) levels, researchers calculated LPA genetic risk scores for 374,099 unrelated participants (mean age, 58 years; 55% women).
Outcomes of interest included CAD, MI, peripheral artery disease, ischemic stroke, CV mortality and a composite of the individual outcomes. The LPA genetic risk score was compared with QRISK3 and Pooled Cohort Equations in participants with borderline (n = 113,703) to intermediate risk (n = 144,350) for ASCVD.
An incident ASCVD event was observed in 5.1% of participants during a median follow-up of 11.1 years. For white/European participants, the LPA genetic risk score explained approximately 60% of the variation in Lp(a) measurements.
Lp(a) (HR per 120 nmol/L increase = 1.26; 95% CI, 1.23-1.28) and the LPA genetic risk score (HR = 1.29; 95% CI, 1.26-1.33) were independently associated with incident, composite ASCVD. After adjusting for measured Lp(a), the association between the LPA genetic risk score and ASCVD was substantially attenuated.
Adding continuous Lp(a) levels and the LPA genetic risk score to QRISK3 improved its area under the receiver operative curve from 0.64 (95% CI, 0.633-0.647; P = .005) to 0.642 (95% CI; 0.635-0.649; P = .01). Results were similar when Lp(a) measurements were added to Pooled Cohort Equations.
“Measured lipoprotein(a) and the LPA [genetic risk score] both provided modest improvement in risk discrimination beyond guideline-supported risk scores, which supports the role of lipoprotein(a) as a risk-enhancing factor,” Trinder and colleagues wrote.
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