Coronary artery calcium (CAC) screening holds up for cardiovascular riskprediction in a population with high lipoprotein(a) (Lp[a]), with the two serving as independent risk factors, an observational study showed.

“These findings strengthen the case for CAC as a pragmatic gatekeeper in deciding when to initiate or escalate preventive therapy in middle- to older-age individuals with elevated Lp(a), particularly in primary prevention settings where overtreatment is a concern,” Parveen K. Garg, MD, MPH, of the University of Southern California Keck School of Medicine in Los Angeles, and his colleagues wrote in an editorial accompanying the study.

The findings mesh with the updated lipid management guideline released last week from the American College of Cardiology, American Heart Association, and other medical societies. The new guideline recommends universal Lp(a) testing at least once for adults, and CAC scoring in men aged at least 40 years and women aged at least 45 years as risk enhancing factors to guide treatment.

“We’re going to see a lot more people identified, especially people before having a first event,” said Harpreet S. Bhatia, MD, MAS, of the University of California San Diego. “This study helps us understand how a coronary calcium score, when appropriately used, can help…divide up that potentially 2 billion-person group of people with elevated Lp(a) into risk groups.”

Bhatia’s group reported the study findings in the Journal of the American College of Cardiology ahead of presentation at American College of Cardiology (ACC) Scientific Session 2026 in New Orleans.

Study Rationale

While genetic, epidemiologic, and mechanistic data have firmly established Lp(a) as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD), when to start and how intensively to target cardioprotective therapies in patients with high levels but without established ASCVD or traditional high-risk features has been unclear, as Garg and colleagues wrote in their editorial.

Whether CAC could meaningfully discriminate ASCVD risk in the setting of elevated Lp(a) was unclear, “particularly given Lp(a)’s known association with noncalcified and high-risk plaque phenotypes,” Garg’s group wrote.

Study Findings

Bhatia’s study pooled data from 11,319 largely middle-aged adults (mean age, 56 years; 54% women) in four US prospective cohorts: Multi-Ethnic Study of Atherosclerosis (MESA), Coronary Artery Risk Development in Young Adults Study, the Framingham Offspring Study, and Jackson Heart Study. These individuals initially free of baseline ASCVD were followed for a mean of 14.8 years, during which 1569 myocardial infarction, stroke, and coronary revascularization events occurred.

ASCVD risk correlated with both elevated Lp(a), defined as > 50 mg/dL (hazard ratio [HR], 1.24; 95% CI, 1.09-1.41) and a CAC score > 0 (HR, 2.44; 95% CI, 2.14-2.77), but the two were independent risk factors (P for interaction = .80).

“But the key is in the absolute event rates,” Bhatia told Medscape Medical News.

While ASCVD risk was higher with elevated Lp(a) and a zero CAC score than without elevated Lp(a), the absolute risk was low in both scenarios (4.9 vs 3.8 events per 1000 person-years; HR, 1.28; 95% CI, 1.01-1.60).

The risk rose with CAC to a peak 6.12-fold elevation in risk with a CAC score of at least 300 and Lp(a) over 50 mg/dL (HR, 6.12; 95% CI, 4.80-7.81).

Although results were consistent across age and sex subgroups, there was greater absolute risk past 50 years of age and in men. “These findings should not be interpreted as diminishing the relevance of elevated Lp(a), particularly in younger individuals and especially women,” Garg’s group cautioned. Absence of coronary calcification in younger adults may simply reflect insufficient time for calcific remodeling, they wrote.

Next Steps

While there are as yet no recommended risk prediction models that incorporate Lp(a) into a clinical algorithm, Bhatia said the study has shifted his practice to using CAC testing to move patients toward a more aggressive LDL cholesterolmanagement vs continued monitoring over time if they fit a certain profile: “someone 40 years of age or above, an appropriate candidate for calcium scoring, has a high Lp(a), maybe doesn’t have a lot of other cardiovascular risk factors, and we kind of want to understand more what their personal risk is.”

His group is now working on an observational study to identify the timeframe for repeat calcium scoring in this population, he said.

And the field may well move into using Lp(a) to guide other therapies as well, with antisense oligonucleotide and small interfering RNA therapies targeting Lp(a) advance through late-phase clinical trials.

“Trials evaluating cardiovascular risk reduction with these agents, on top of guideline-directed preventive therapy, may be especially informative when focused on individuals with both elevated Lp(a) and evidence of subclinical atherosclerosis, such as abnormal CAC scores,” Garg and colleagues noted.

This study was supported by UC San Diego BEACON. MESA was supported by the National Heart, Lung, and Blood Institute as well as by grants from the National Center for Advancing Translational Sciences. Bhatia reported being supported by a National Institutes of Health grant and serving as a consultant or advisor for Bayer, Abbott, Arrowhead, Kaneka, Novartis, and New Amsterdam. Garg’s group reported having no relevant conflicts of interest.

Crystal Phend is an award-winning medical journalist with decades of experience reporting on clinical research and healthcare developments across specialties. When not walking the halls at a medical conference, she can be found at a keyboard in upstate New York.