Association of Lp(a) and CAC score with ASCVD incidence

In a pooled cohort analysis among individuals with no known ASCVD, the Lp(a) level and coronary artery calcium (CAC) score were independently associated with ASCVD risk during 15-year follow-up, with the greatest risk observed when both Lp(a) levels and CAC score were elevated.

This summary is based on the publication of Bhatia HS, Fan Y, Dharmavaram G, et al. - Use of Coronary Artery Calcium Scoring in Individuals With Elevated Lipoprotein(a): A Multicohort Study. J Am Coll Cardiol. 2026 Mar 16:S0735-1097(26)05437-9 [Online ahead of print]. doi: 10.1016/j.jacc.2026.02.5067

Introduction and methods

Background

The coronary artery calcium (CAC) score, assessed with cardiac-gated CT imaging, can predict ASCVD risk in asymptomatic individuals [1]. Studies investigating the association between the CAC score and elevated Lp(a) levels—another known ASCVD risk factor—have shown mixed results [2-4]. Observational cohort data indicated the 2 parameters are in fact independently associated with ASCVD risk [5], but further understanding of the use of CAC scoring in individuals with elevated Lp(a) level is needed.

Aim of the study

The authors evaluated the interaction between Lp(a) levels and CAC score and the association of Lp(a) levels with ASCVD risk stratified by the CAC score among individuals with no known clinical CVD.

Methods

For this analysis, data of 11,319 participants with no known ASCVD were pooled from 4 US-based prospective observational cohort studies: MESA (Multi-Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults), FHS-OS (Framingham Offspring Study), and JHS (Jackson Heart Study) [6-9]. The authors used baseline Lp(a) measurements, CAC scores, information on CVD risk factors, and CV event follow-up data. Mean ± SD follow-up time was 14.8 ± 5.4 years.

Outcomes

The primary endpoints were the incidences of adjudicated CHD (fatal and nonfatal MI or coronary revascularization) and ASCVD (CHD plus fatal and nonfatal stroke).

Main results

Interaction between Lp(a) levels and CAC score

• In Cox proportional hazards regression analysis adjusted for possible confounders, both Lp(a) >50 mg/dL (adjusted HR: 1.24; 95%CI: 1.09–1.41) and CAC score >0 Agatston units (AU) (adjusted HR: 2.44; 95%CI: 2.14–2.77) were associated with incident ASCVD events, but there was no significant interaction between them (P for interaction=0.80).

Joint association of Lp(a) levels and CAC score with incident ASCVD events

• Among individuals with a CAC score of 0 AU, the incidence rate of ASCVD events was overall low but higher for those with Lp(a) >50 mg/dL compared with Lp(a) ≤50 mg/dL (4.88 vs. 3.83 per 1000 person-years; adjusted HR: 1.28; 95%CI: 1.01–1.61).
• In the group with CAC score >0 AU, participants with Lp(a) >50 mg/dL also had a higher ASCVD risk than those with Lp(a) ≤50 mg/dL (21.23 vs. 18.15 per 1000 person-years; adjusted HR: 3.03; 95%CI: 2.52–3.64).
• Similar results were found when the CAC score was further stratified into categories of 0, 1–99, 100–299, ≥300 AU, with the greatest risk seen for the combination of CAC score ≥300 AU and Lp(a) >50 mg/dL compared with CAC score =0 AU and Lp(a) ≤50 mg/dL (45.24 vs. 3.83 per 1000 person-years; adjusted HR: 6.12; 95%CI: 4.80–7.81).
• Subgroup analysis showed consistent results across subgroups stratified by age or sex, with greater absolute risk in individuals ≥55 years of age and men.

Conclusion

In this pooled cohort analysis among >11,000 individuals with no known ASCVD in the US, the Lp(a) level and CAC score were independently associated with ASCVD risk during 15-year follow-up. Elevated Lp(a) levels (>50 mg/dL) were associated with a higher relative risk of ASCVD across CAC score strata, including a CAC score of 0 AU. Among participants with a CAC score of 0 AU, absolute event rates were low even when Lp(a) levels were elevated. The greatest risk was observed when both Lp(a) levels and CAC score were elevated. The authors conclude their “findings suggest that CAC scoring remains useful for risk assessment in individuals with elevated Lp(a) and informs opportunities for ASCVD risk reduction.”

Find this article online at J Am Coll Cardiol.

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