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

J Am Coll Cardiol. 2022 Mar 1;79(8):757-768. doi: 10.1016/j.jacc.2021.11.058.


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.

Keywords: atherosclerotic cardiovascular disease; coronary artery calcium; lipoprotein(a); primary cardiovascular disease prevention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asymptomatic Diseases / epidemiology
  • Coronary Artery Disease* / epidemiology
  • Coronary Artery Disease* / prevention & control
  • Coronary Vessels / pathology*
  • Ethnicity
  • Female
  • Heart Disease Risk Factors
  • Humans
  • Lipoprotein(a) / blood*
  • Male
  • Middle Aged
  • Multidetector Computed Tomography / methods
  • Multidetector Computed Tomography / statistics & numerical data
  • Primary Prevention
  • Risk Factors
  • United States / epidemiology
  • Vascular Calcification* / blood
  • Vascular Calcification* / epidemiology
  • Vascular Calcification* / pathology


  • Lipoprotein(a)

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