Associations of Immune Cell Subsets With Coronary Artery Calcium Incidence and Progression in the Multi-Ethnic Study of Atherosclerosis

BACKGROUND: Limited data exist on associations of immune cell subsets with longitudinal changes in subclinical coronary artery disease. METHODS: In the MESA (Multi-Ethnic Study of Atherosclerosis) study, we used a case-cohort approach to explore associations of 28 immune cell subsets measured at baseline (2000-2002) with longitudinal changes in coronary artery calcium (CAC). We examined incident CAC from examination 2 (2002-2004) through examination 5 (2010-2012) in participants with 0 CAC at baseline using multivariable-adjusted Cox regression. In participants with CAC >0 at baseline, we analyzed changes in CAC through examination 5 using multivariable-adjusted linear mixed models. Because no studies have investigated immune cells and longitudinal CAC changes, analyses were considered exploratory, with P<0.05 as the threshold for possible significance. RESULTS: Of 975 participants with immune cells subsets and CAC measurements at baseline, 378 had CAC 0 at baseline (mean age, 58.4; 37.0% men) and 597 had CAC >0 at baseline (mean age, 65.7; 57.6% men). Natural killer cells were associated with higher incident CAC (hazard ratio [HR], 1.26 per SD higher natural killer cell proportion; P=0.03), whereas T helper type cells were associated with lower incident CAC (HR, 0.81; P=0.04). B cells were associated with CAC progression (β=53.1 Agatston units per SD higher B-cell proportion, P=0.04), whereas CD14+CD16+ monocytes (β=-71.6; P=0.03) and T regulatory cells (β=-61.9; P=0.03) were associated with lower CAC progression. CONCLUSIONS: Natural killer cells may be associated with incident CAC and T regulatory cells may be associated with attenuated CAC progression, among other findings. These warrant replication and experimental investigation.