The complete blood count (CBC) is one of the most commonly performed laboratory studies. Although studies have found associations between the CBC and cardiovascular disease (CVD), there is limited contemporary information regarding the relationship between the CBC and traditional risk factors and their joint association with CVD endpoints. We sought to define the relationships between the CBC and traditional CVD risk factors and their joint association with CVD endpoints in diverse adult populations. We first examined the relationships between the CBC variables (directly and their principal components), traditional CVD risk factors, and mortality in NHANES (n=7843). Next, we validated and extended these findings to more refined CVD endpoints in five additional cohorts (n=15,527). We first examined the variance accounted for by common laboratory studies (lipid panel, HbA1c, hs-CRP, and basic metabolic panel) by traditional risk factors in NHANES. With the exception of hemoglobin (Hb)-related components, we found that traditional risk factors accounted for less than 20% of the variance in CBC values, similar to that of lipid parameters. Additionally, in the clinically adjusted model, the CBC was more strongly associated with all-cause mortality than the lipid panel or CRP (p<0.0001). Next, we validated and extended these findings across five additional longitudinal cohorts with a mean follow-up of 16 years to evaluate the association of individual CBC parameters and their principal components with refined CVD endpoints. In the fully adjusted meta-analyses across the five cohorts, several CBC components including the white blood cell (WBC) count, neutrophil (PMN) count, hemoglobin (Hb) level, and an integrated immune cell score, were associated with individual CVD endpoints and a composite CV endpoint (MACE3: incident stroke, MI, and revascularization) with standardized hazard ratios of 1.13 (p=0.002), 1.15 (p=0.0006), 0.82 (p<0.0001), and 2.16 (p<0.0001) respectively. This study represents the first systematic examination of the relationship between CBC features and established risk factors, as well as numerous CVD endpoints, in a diverse cohort of 23,370 adults. The findings of this study underscore the potential utility of integrating CBC features into CVD risk assessment and suggest important mechanistic insights into the association between individual CBC components and the genesis of CVD.
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