Abstract 106: Circulating Immune Cells as Predictive Markers of Cardiovascular Mortality in Ambulatory US Adults: Insights From NHANES

Introduction: While inflammation is associated with worse cardiovascular (CV) prognosis, the relative prognostic importance of circulating immune cell populations for predicting CV mortality is unknown.

Methods: We used data from 3 cycles of NHANES (1999-2000, 2001-2002, 2003-2004) to estimate the prognostic importance of total leukocyte count (TLC), and differential leukocyte counts in participants ≥20 years of age and TLC in normal clinical range (4,000-11,000 cells/μL). The cause of death was derived from the National Death Index. We estimated the relative importance of different immune cell markers, and compared the prognostic importance of the dominant immune cell marker with components of the Framingham Risk Score (FRS). We used partial χ2 and standardized domination statistic to estimate the relative importance of immune markers in predicting CV mortality.

Results: Among 10, 825 participants (49% women, 51% self-reported Non-Hispanic White) eligible for this analysis, the median age was 49 years (Interquartile Range [IQR] 35 to 66). Over a median follow-up of 13.2 years (IQR 11.4 to 14.8), there were 620 deaths due to CV causes. The hazard of CV mortality increased by 11% with every 1000 cells/uL increase in TLC after adjusting for co-morbidities (Hazard Ratio [HR] 1.11 95% CI 1.02, 1.21, p=0.011). Among the immune cell markers assessed, the monocyte-lymphocyte ratio had the highest domination to predict CV mortality (Figure Panel A). The hazard of CV mortality increased by 14% with every 1 unit increase in the monocyte-lymphocyte ratio in the fully adjusted model (HR 1.14 95% CI 1.07, 1.22, p<0.001). Among participants aged ≥30 years without prevalent CV disease, FRS was calculated in 8,190 participants (75.7% of total). As compared to the individual components of FRS, the monocyte-lymphocyte ratio had higher relative importance in predicting CV mortality than gender, smoking status, HDL, total cholesterol and treatment for hypertension (Figure Panel B).

Conclusion: In this study of a large representative adult US population with TLC within the clinically normal range, we found that readily available circulating immune markers are independently associated with CV mortality. The monocyte-lymphocyte ratio was the best predictor of CV mortality and outperformed 5 risk factors included in the FRS.