Atherosclerosis · Oct 30, 2026

Non-HDL cholesterol as a lipid control target in severe hypercholesterolemia in primary care: a sex-stratified analysis

By Gijón-Conde T

Background and aims Non-HDL cholesterol (non-HDL-C) is recognized as a co-primary lipid target by the 2019 ESC/EAS guidelines, yet its attainment in patients with severe hypercholesterolemia (SH) in primary care remains poorly characterized. We aimed to assess non-HDL-C goal attainment in SH, examine LDL-C/non-HDL-C discordance, and evaluate sex differences in treatment and lipid control. Methods Cross-sectional, multicenter study using electronic health records from 156,082 adults attending 69 primary care centers in Madrid (2018–2021). SH was defined as total cholesterol ≥300 mg/dL or LDL-C ≥220 mg/dL. Non-HDL-C goal was <100 mg/dL per ESC/EAS 2019. Discordance was defined as LDL-C <70 mg/dL with non-HDL-C ≥100 mg/dL. Sex-stratified multivariable logistic regression identified independent predictors of goal attainment. Results Of 6,071 patients with SH, only 228 (3.8%) achieved non-HDL-C <100 mg/dL. Men received high/very high intensity lipid-lowering therapy (LLT) more often than women (34.1% vs 26.0%; p<0.001), yet non-HDL-C levels were higher in men across all treatment categories except very high intensity. Among patients with established ASCVD, men achieved the target more often than women at both the <100 mg/dL (13.9% vs 6.1%; p=0.001) and <85 mg/dL thresholds (7.8% vs 2.6%; p=0.022). LDL-C/non-HDL-C discordance was identified in 21.3% of patients with LDL-C <70 mg/dL, more frequently in men (31.8% vs 13.8%; p=0.006), and increased with triglyceride levels. LLT intensity was not independently associated with goal attainment; diabetes, age, obesity, and ASCVD were the main predictors. Conclusions Non-HDL-C goal attainment is critically low in SH patients in primary care, independently of treatment intensity. Sex disparities were significant, particularly in secondary prevention. Systematic non-HDL-C monitoring via electronic records and greater use of combination LLT are needed.

doi.org/10.1016/j.atherosclerosis.2026.121941PubMed 42971903Populations