Abstract

BACKGROUND: The complete blood count (CBC) is one of the most performed laboratory studies. However, the CBC and its components are not commonly used to understand and quantify cardiovascular disease (CVD) risk. OBJECTIVE: We sought to define the relationships between the CBC, traditional CVD risk factors, and common CVD biomarkers and their joint association with all-cause mortality and CVD. METHODS: We examined the relationships between the CBC, traditional CVD risk factors, and mortality in NHANES (n=7843). We validated and extended these findings to more refined CVD endpoints in five additional cohorts (n=15,527). RESULTS: 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. Except for hemoglobin (Hb) components, we found that traditional risk factors accounted for less than 20% of the variance in the CBC, suggesting that the CBC provides unique information beyond traditional risk factors and CVD biomarkers. Additionally, the CBC was strongly associated with all-cause mortality (p<0.0001), even more than traditional CVD biomarkers (lipid panel, HbA1c, and CRP). We validated and extended these findings across five additional cohorts with a mean follow-up of 16 years and more refined CVD endpoints. In the fully adjusted analyses, several CBC components, including the white blood cell (WBC) count, neutrophil (PMN) count, Hb level, and an integrated immune cell score, were associated with individual CVD endpoints (incident stroke, MI, or revascularization) and a composite CV endpoint (MACE3) 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. CONCLUSION: This study represents the first systematic examination of the relationship between the CBC, all-cause mortality, and CVD in a diverse cohort of 23,370 adults. These findings underscore the added value of the CBC over traditional risk factors and common CVD biomarkers for CVD risk assessment. Future studies should explore the integration of CBC parameters into predictive models to enhance our understanding, early identification, and prevention strategies for CVD.