Abstract Body (Do not enter title and authors here): Background: Aging is a complex process that affects various organ systems, including the cardiovascular (CV) and immune systems. Chronologic age does not fully capture the heterogeneity in biological aging, and studies suggest that the immuno-hematologic (IH) systems play a critical role in the aging process and may contribute to CV disease. However, the relationship between IH aging and CV risk is not well characterized. Routine complete blood count with differential (CBC-diff) is a widely available test that assesses blood components. Its utility in capturing biological age and association with CV risk has not been explored.
Methods: Using data from adult participants in NHANES 1999-2018, we trained an XGBoost model to predict chronologic age using 20 variables obtained from CBC-diff. The model was trained on 50% of the data (n=26,677), and the remaining 50% (n=26,677) was used to predict age (IH_AGE). We calculated the difference between IH_AGE and chronologic age (ΔAge), and categorized it into 3 groups: proportionate IH aging (ΔAge -10 to 10 years), accelerated IH aging (ΔAge >10 years), and resilient IH aging (ΔAge <-10 years). We then examined the association between IH groups and CV mortality using Cox regression models (model 1 adjusted for chronologic age and model 2 additionally adjusted for sex, race, body mass index, blood pressure, history of diabetes, kidney disease, heart failure, coronary disease, myocardial infarction, stroke, smoking and serum cholesterol).
Results: A total of 10,621 (39.8%) had proportionate IH aging, 7,953 (29.8%) had resilient IH aging, and 8,103 (30.4%) had accelerated IH aging (figure). In model 1, accelerated IH aging was associated with near doubling of CVM risk (adjusted hazard ratio [aHR] 2.28, 95% CI [1.66-3.13], P<0.001), while IH resilience was associated with a near half the risk of CVM (aHR 0.54, 95% CI [0.47-0.62], P<0.001). In model 2, resilient aging was associated with 32% lower risk of CV mortality (aHR 0.68, 95% CI [0.58-0.80], P<0.001), while accelerated aging had a 75% higher risk of CV mortality (aHR 1.75, 95% CI [1.22-2.51], P<0.001), figure. The leading contributors to IH_AGE were RDW, MCV and Absolute Lymphocyte Count.
Conclusions: We introduce a new concept, IH_AGE, which captures IH biologic aging from CBC-diff. IH aging is independently associated with CV mortality, providing a novel tool for risk stratification and personalized prevention strategies in cardiovascular disease.