Elevated Lp(a) plus a coronary calcium score of 100+ carries a 4.7-fold higher cardiovascular risk than either alone, in MESA and Dallas Heart Study participants (J Am Coll Cardiol 2022)

Original title: Independent Association of Lipoprotein(a) and Coronary Artery Calcification With Atherosclerotic Cardiovascular Risk

J Am Coll Cardiol · 1 March 2022 · 7

Mehta A, Vasquez N, Ayers CR, Patel J, Hooda A, Khera A, Blumenthal RS, Shapiro MD, Rodriguez CJ, Tsai MY, Sperling LS, Virani SS et al.

In asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis (MESA, n=4,512) and the Dallas Heart Study (DHS, n=2,078), Lp(a) (highest race-specific quintile) and coronary artery calcium (CAC) score were both independently associated with atherosclerotic cardiovascular disease (ASCVD) risk, with no significant Lp(a)-by-CAC interaction. In MESA (mean age 61.9 years, 52.5% women), 476 incident ASCVD events occurred over 13.2 years; hazard ratios were 1.29 (95% CI 1.04-1.61) for elevated Lp(a) alone, 1.68 (95% CI 1.30-2.16) for CAC 1-99, and 2.66 (95% CI 2.07-3.43) for CAC >=100. Compared with nonelevated Lp(a) and CAC=0, those with elevated Lp(a) and CAC>=100 had the highest risk (HR 4.71, 95% CI 3.01-7.40), while elevated Lp(a) with CAC=0 carried similar risk to the reference group (HR 1.31, 95% CI 0.73-2.35). Findings were replicated in DHS. The results support using Lp(a) and CAC together to guide primary prevention decisions.

Original abstract

Background: Elevated lipoprotein(a) [Lp(a)] and coronary artery calcium (CAC) score are individually associated with increased atherosclerotic cardiovascular disease (ASCVD) risk but have not been studied in combination.

Objectives: This study sought to investigate the independent and joint association of Lp(a) and CAC with ASCVD risk.

Methods: Plasma Lp(a) and CAC were measured at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 4,512) and DHS (Dallas Heart Study) (n = 2,078) cohorts. Elevated Lp(a) was defined as the highest race-specific quintile, and 3 CAC score categories were studied (0, 1-99, and ≥100). Associations of Lp(a) and CAC with ASCVD risk were evaluated using risk factor-adjusted Cox regression models.

Results: Among MESA participants (61.9 years of age, 52.5% women, 36.8% White, 29.3% Black, 22.2% Hispanic, and 11.7% Chinese), 476 incident ASCVD events were observed during 13.2 years of follow-up. Elevated Lp(a) and CAC score (1-99 and ≥100) were independently associated with ASCVD risk (HR: 1.29; 95% CI: 1.04-1.61; HR: 1.68; 95% CI: 1.30-2.16; and HR: 2.66; 95% CI: 2.07-3.43, respectively), and Lp(a)-by-CAC interaction was not noted. Compared with participants with nonelevated Lp(a) and CAC = 0, those with elevated Lp(a) and CAC ≥100 were at the highest risk (HR: 4.71; 95% CI: 3.01-7.40), and those with elevated Lp(a) and CAC = 0 were at a similar risk (HR: 1.31; 95% CI: 0.73-2.35). Similar findings were observed when guideline-recommended Lp(a) and CAC thresholds were considered, and findings were replicated in the DHS.

Conclusions: Lp(a) and CAC are independently associated with ASCVD risk and may be useful concurrently for guiding primary prevention therapy decisions.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.