Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and high-sensitivity C-reactive protein in US adults: Results from NHANES 2015-2018.

The non-high-density lipoprotein to high-density lipoprotein cholesterol ratio (NHHR) is an emerging lipid index linked to cardiovascular and metabolic risk. High-sensitivity C-reactive protein (hs-CRP) serves as a well-established marker of systemic inflammation. However, the association between NHHR and hs-CRP in the general population remains unclear. This study aimed to investigate their relationship using nationally representative US data. We analyzed data from 5994 adults aged ≥20 years from the 2015 to 2018 National Health and Nutrition Examination Survey (NHANES). NHHR was calculated as (total cholesterol - high-density lipoprotein cholesterol HDL-C)/high-density lipoprotein cholesterol. Survey-weighted multivariable linear regression models were used to evaluate the association between NHHR (both continuous and quartiles) and hs-CRP levels. Restricted cubic spline analysis assessed nonlinear patterns. Subgroup and interaction analyses were conducted by age, sex, body mass index, diabetes, and hypertension. After full adjustment, NHHR was positively associated with hs-CRP (β = 0.91, 95% CI: 0.42-1.40, P = .002). Participants in Q3 and Q4 had significantly higher hs-CRP levels than those in Q1. Restricted cubic spline analysis revealed a significant nonlinear (inverted U-shaped) relationship (P for nonlinearity < .001). Subgroup analyses showed stronger associations in women and individuals with hypertension (P for interaction < .05). In this exploratory, cross-sectional analysis, our findings suggest that NHHR may be independently associated with hs-CRP and may exhibit a nonlinear relationship in US adults, suggesting its potential utility as an accessible marker of low-grade systemic inflammation; however, longitudinal cohort studies are needed to confirm these associations and to evaluate its potential predictive value and clinical applicability.