Abstract 4141868: Circulating immune cells, inflammatory risk, and atherosclerotic cardiovascular disease: an analysis across 5 cohorts of 17,971 diverse adults

Introduction: Inflammation is pivotal in initiating and accelerating atherosclerotic cardiovascular disease (ASCVD). Inflammatory responses result from coordinated actions of circulating molecular mediators and circulating immune cells (CIC). The complete blood count (CBC) is the standard approach to profile CIC. In an analysis across 5 cohorts, we sought to define the relationships between CBC features and ASCVD. Hypothesis: We hypothesized that CBC features are associated with ASCVD endpoints, including stroke, myocardial infarction (MI), revascularization, and mortality. Methods: We examined the relationships between CBC features, traditional risk factors, and mortality in NHANES (n=6162). We then examined individual CBC features and ASCVD endpoints using adjusted Cox proportional hazards models to compute hazard ratios (HR) standardized in each cohort and combined with random effects meta-analysis across four longitudinal cohorts (n=11,809 subjects from Framingham Offspring, Framingham 3 rd Gen, MESA, and CARDIA cohorts). Results: We first examined the prognostic value of CBC features compared with laboratory assessments (lipid panel, HbA1c, hs-CRP, and basic metabolic panel) in NHANES and found that CBC features were significantly associated with all-cause and CV mortality (data not shown). Next, we validated and extended these findings in a meta-analysis across four additional longitudinal cohorts, evaluating the association of individual CBC features with ASCVD endpoints. In the fully adjusted and fully adjusted + hs-CRP models, CBC features (e.g., neutrophils, monocytes, and lymphocytes) were associated with ASCVD endpoints ( Figure 1A ). The meta-analyzed standardized hazard ratio of WBC for MACE3 (stroke, MI, all-cause mortality) was 1.07 (1.01 - 1.14; p=0.02) ( Figure 1B ). Conclusions: To our knowledge, this is the first study to examine the association of CIC features with ASCVD across a large, diverse sample of adults. CIC features are associated with ASCVD endpoints and mortality even after adjustment for traditional risk factors and laboratory values, including hs-CRP. Taken together, our data reveal unexpected insights into the interplay of CIC, inflammatory risk, and ASCVD.