Abstract

Introduction: Elevated plasma lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are established cardiovascular disease (CVD) risk factors that correlate with each other. In this study we hypothesized that other CVD risk factors could modify the relationship between baseline Lp(a) levels and CAC change over time. Methods: A total of 5975 participants from the Multi-Ethnic Study of Atherosclerosis were analyzed. All participants were 45-84 years old, free of apparent CVD at baseline and from one of four major ethnic groups (non-Hispanic white, African American, Hispanic American, and Chinese American). We tested for interactions of 24 study variables related to dyslipidemia, diabetes, insulin resistance, hypertension, inflammation and coagulation with baseline Lp(a) on change in CAC volume and density over 9.5 years. Results: Elevated Lp(a) was associated with larger annual absolute increase in CAC volume (3.21 and 4.45 mm 3 /year higher for Lp(a) ≥30 versus <30 mg/dL, and Lp(a) ≥50 versus <50 mg/dL, respectively, both P <0.05), but not in CAC density. The association of elevated Lp(a) with absolute change in CAC volume was more prominent in African Americans and Hispanic Americans, than other ethnic groups ( P for interaction <0.05). After multiple testing correction of 24 study variables, the association of elevated Lp(a) (≥30 mg/dL) with annual absolute change in CAC volume was greater in participants with higher levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor receptor 1 and fibrinogen (change = 15.33, 11.81 and 7.02 mm 3 /year in quartile 4, compared to -3.44, -0.59 and 1.91 mm 3 /year in quartile 1, respectively). A similar trend was seen when expressing Lp(a) ≥50 mg/dL as elevated levels. There were no associations for ln-transformed Lp(a) as a continuous variable, or when assessing the annual relative change in CAC volume and density. Conclusions: Elevated Lp(a) was associated with the progression of CAC volume, especially in participants with higher levels of selected markers of inflammation and coagulation. This study suggests that inflammation and coagulation may modify the relation between Lp(a) and CAC.

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