High-density lipoprotein cholesterol refines phenotyping and risk stratification in combined hyperlipidemia: a nationwide cross-sectional study
L Wang, L Zhang, Z Liu, Y Sun, L Dong, X Liu, F Fan, J Jia, S Zhou, Y Zhang, J LiAbstract
Background
Combined hyperlipidemia (CHL) is common in clinical practice, yet operational definitions vary and current threshold-based approaches seldom incorporate high-density lipoprotein cholesterol (HDL-C) for phenotypic risk refinement.
Purpose
To evaluate whether HDL-C stratification can improve risk-oriented characterization within threshold-defined CHL in a nationwide cross-sectional dyslipidemia survey in China.
Methods
We analyzed adults with dyslipidemia enrolled from 2,750 participating sites across 28 provinces (September 2022–November 2024). CHL was defined as LDL-C ≥3.40 mmol/L and triglycerides (TG) ≥1.70 mmol/L; low HDL-C as HDL-C <1.00 mmol/L. We compared cardiometabolic profiles, comorbidity burden, lifestyle factors, and guideline-based ASCVD risk categories between CHL subgroups with versus without low HDL-C. Secondary analyses used multivariable logistic regression with highest-recorded lipid values to assess lipid–ASCVD associations and compared LDL-C versus non–HDL-C performance using AUC.
Results
Among 604,250 participants with dyslipidemia, 185,444 met CHL criteria and 22.2% had low HDL-C. The low–HDL-C phenotype was more prevalent in men (69% vs 48%) and was characterized by greater adiposity, higher cardiometabolic comorbidity, and more prevalent ASCVD, with a marked upward shift in ASCVD risk categories (high risk 61% vs 45%; very high risk 19% vs 7.4%). Low–HDL-C CHL also showed higher non–HDL-C (highest-recorded median 5.60 [IQR 4.80–6.71] vs 5.18 [4.48–6.41] mmol/L; P<0.001). In overall CHL, 48.6% were untreated and lipid-target attainment was poor in higher-risk strata. HDL-C was inversely associated with prevalent ASCVD (adjusted OR per 1-SD increase, 0.31; 95% CI 0.29–0.33), whereas LDL-C and non–HDL-C were positively associated. Non–HDL-C provided only a small incremental gain over LDL-C for ASCVD history (AUC 0.708 vs 0.703; ΔAUC=0.005).
Conclusions
HDL-C stratification identifies a higher-risk CHL phenotype and offers a pragmatic approach to refine CHL phenotyping using routine lipid panels. Low–HDL-C CHL also tended to show a higher non–HDL-C burden, suggesting a combined atherogenic burden in the setting of elevated TG.Figure 1Figure 2