Differentiating Risk Factors for Coronary Artery Calcium Volume and Density: The Multi-Ethnic Study of Atherosclerosis”

Introduction: Coronary artery calcium (CAC) is a prognostic marker for incident cardiovascular disease (CVD), but its calculation involves measures of both CAC volume and density. Whereas CAC volume is directly associated with incident CVD, CAC density is inversely associated with incident CVD yet higher CAC density increases the CAC score. We compare the relative strength of association of markers of mineral metabolism and kidney fuction with CAC volume vs. density in a large population of community-living individuals free of CVD. Methods: The Multi-Ethnic Study of Atheroschlerosis (MESA) is an observational cohort study of 6814 adults free from CVD at baseline. Among the subset with detectable CAC (N=3398) we used multivariate analysis to determine association between markers of mineral metabolism and kidney function with CAC volume and density. Models evaluating CAC volume were adjusted for density, and vice versa, to understand the independent association of risk factors with each component of the CAC score. Standardized beta coefficients (beta symbol) were calculated to facilitate comparison of strengths of association. Results: Higher serum phosphorus ([beta]=0.032, 95% CI [0.009, 0.055]), 25-hydroxyvitamin D )[beta]=0.024 95% CI[[0.002, 0.047]), and bicarbonate ([beta]=0.025 95% CI [0.004, 0.046]) concentrations were directly associated with CAC density independently of CAC volume. Higher eGFR ([beta]=0.084 95% CI [0.034, 0.133]), urinary albumin to creatinine ratio ([beta]=0.71 95% CI [0.021, 0.120]) and fibroblast growth factor-23 ([beta]=0.054, 95% CI [0.007, 0.101]) were directly associated with CAC volume independently of density, while parathyroid hormone ([beta]=-0.052, CI 95% [-0.101, -0.002]), and bicarbonate ([beta]=-0.060, 95% CI [-0.105, -0.015]) were inversely associated with CAC volume independently of density. Conclusion: Factors known to promote mineralization including phosphate, vitamin D, and higher serum bicarbonate are more strongly associated with the density of CAC than with its volume. These findings support the hypothesis that these factors promote calcium deposition, but may not promote atherosclerotic plaque progression per se