Abstract
BACKGROUND: Monocyte-to-HDL Ratio (MHR) biomarker reflects monocyte-driven inflammation and HDL's anti-inflammatory properties. MHR's reference ranges and prognostic utility remain undefined. We establish normal MHR reference ranges and examine its association with inflammatory diseases and mortality. METHODS: Using NHANES data (1999-2018, 2021-2023), two sets of sex-specific MHR reference ranges were generated using two healthy adult populations (monocyte count: 6,757; monocyte percentage: 6,817). Further analyses utilized MHR by monocyte count for more straightforward interpretation. Adjusted associations between MHR and inflammatory diseases were assessed in 49,929 adults, and disease-specific mortality in 35,781. RESULTS: The 2.5th-97.5th percentiles for MHR by monocyte count were 0.175 (90% CI: 0.167-0.184) to 0.709 (90% CI: 0.690-0.727) in males and 0.135 (90% CI: 0.130-0.140) to 0.511 (90% CI: 0.503-0.520) in females, with similar trends for MHR by monocyte percentage. High MHR was most strongly associated with diabetes (aOR = 1.76, p < 0.001) and cardiovascular disease (aOR = 1.69, p < 0.001), while mortality risk was highest for kidney disease (aHR = 3.13, p < 0.001) and diabetes (aHR = 2.26, p < 0.001). CONCLUSION: MHR is a feasible and accessible biomarker of inflammation and lipid dysregulation that can be derived from routine laboratory tests and shows strong associations with cardiometabolic diseases and disease-related mortality.