The role of coronary artery calcium (CAC) scoring in individuals with elevated lipoprotein(a) (Lp[a]) remains uncertain due to the association of Lp(a) with noncalcified plaque. This pooled analysis published in the Journal of American College of Cardiology included participants without established atherosclerotic cardiovascular disease (ASCVD) from four U.S.-based prospective cohort studies with available baseline Lp(a) and CAC measurements. 

Individuals with prior ASCVD were excluded. The study assessed the relationship between elevated Lp(a) levels (>50 mg/dL), CAC strata, and incident ASCVD outcomes, including myocardial infarction (MI), stroke, and coronary revascularization, using multivariable Cox regression models.

A total of 11,319 participants (mean age 56 years; 54% women) were followed for a mean duration of 14.8 years, during which 1,569 ASCVD events occurred. Elevated Lp(a) (hazard ratio [HR] 1.24; 95% CI, 1.09–1.41) and CAC >0 (HR 2.44; 95% CI, 2.14–2.77) were independently associated with increased ASCVD risk, with no significant interaction observed (P interaction=0.80). Among individuals with CAC=0, overall ASCVD event rates were low but higher in those with elevated Lp(a) compared with lower levels (4.9 vs 3.8 per 1,000 person-years; HR 1.28; 95% CI, 1.01–1.60). 

In participants with CAC >0, elevated Lp(a) was associated with higher event rates (21.2 vs 18.2 per 1,000 person-years; HR 3.03; 95% CI, 2.52–3.64). The highest risk was observed in those with CAC ≥300 and elevated Lp(a) (HR 6.12; 95% CI, 4.80–7.81).

These findings demonstrate consistent associations of Lp(a) and CAC with ASCVD risk across strata. Absolute event rates remained low in individuals with CAC=0 despite elevated Lp(a).