Abstract P201: Prospective Associations of Innate and Adaptive Immune Cell Subsets in Peripheral Blood With Incident Myocardial Infarction

Abstract

Introduction: Activation of cell-mediated immunity promotes atherogenesis in animal models and correlates with advanced atherosclerosis and coronary syndromes in humans. Whether innate and adaptive immune cell subsets are risk factors for clinical cardiovascular disease (CVD) events is unknown. Hypothesis: Circulating proportions of pro-inflammatory (Th1, Th17), anti-inflammatory (Th2, T regulatory), and differentiated (naive, memory, and senescent) CD4 + T cells are risk factors for myocardial infarction (MI) and angina. We explored other cell types in secondary analyses. Methods: We performed a case-cohort study within the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS) (n=2,162). Case outcomes were incident MI and incident angina (n=869 total cases) compared to a cohort random sample (n=1,293). Immune cell phenotypes (n=34, including monocytes, T cells, and B cells) were measured by flow cytometry using cell samples cryopreserved at the MESA baseline and CHS Year 11 exams. Associations of immune cell phenotypes with MI and a composite outcome of incident MI or incident angina (MI-angina) were evaluated using Cox proportional hazards models, with sampling weights and CVD risk factor adjustment, over a median follow-up time of 9.3 years. We analyzed results separately in each cohort and in a combined-cohort meta-analysis. Based on previous findings, we specified seven CD4 + T cell populations as primary hypotheses (stated above). In Bonferroni-adjusted secondary analyses, we investigated associations of 27 additional cell phenotypes measured in the study. Results: In our primary hypotheses, the associations of Th1, Th2, T regulatory, naive, memory, and senescent CD4 + cells with incident MI were moderate and not statistically significant in either cohort individually or in combined-cohort analyses (hazards ratios ranging from 0.88 for naive cells (95% confidence interval (CI): 0.73, 1.06) to 1.15 for Th2 cells (95 CI: 0.96,1.38); all P-values >0.05). Associations of these cells with the composite endpoint of incident MI-angina were also null (hazards ratios ranging from 0.90 (Th1 cells; 95% CI: 0.74, 1.11) to 1.11 (Th17 cells; 95% CI: 0.91, 1.37); all P-values >0.10). In exploratory secondary analyses that investigated subsets of CD14 + monocytes, CD8 + T cells, and CD19 + B cells, no significant relationships with incident MI or MI-angina were observed. Conclusions: In a study of modest sample size, these results suggest that variation in the proportions of several lymphocyte and monocyte subsets measured in peripheral blood are only weakly, if at all, associated with incident MI or incident angina. Given the literature on the roles of cellular immunity in atherosclerosis, large prospective studies evaluating the relationships of immune cell subsets with the progression of atherosclerosis are warranted.