Non-HDL cholesterol

Non-HDL cholesterol (non-HDL-C) equals total cholesterol minus HDL and captures the cholesterol in all atherogenic lipoproteins — LDL, VLDL, IDL, chylomicron remnants, and Lp(a). Because each carries apolipoprotein B (ApoB), non-HDL-C serves as a surrogate for total ApoB particle burden without a direct ApoB assay, and — unlike calculated LDL-C — is reliable in a non-fasting state. It is especially informative in elevated triglycerides, insulin resistance, or type 2 diabetes, where VLDL and remnant particles drive atherogenic risk yet are invisible to LDL-C. A 2012 JAMA meta-analysis by Boekholdt et al. pooled data from 8 statin trials (62,154 participants; 38,153 statin-treated) and found on-treatment non-HDL-C more strongly associated with cardiovascular events than on-treatment LDL-C. Patients reaching LDL-C below 100 mg/dL but non-HDL-C above 130 mg/dL retained significantly elevated residual risk. The 2019 ESC/EAS dyslipidaemia guidelines set non-HDL-C as a secondary target — below 85 mg/dL in very-high-risk and below 100 mg/dL in high-risk patients — 30 mg/dL above corresponding LDL-C goals, reflecting average VLDL cholesterol in the general population. Evidence is observational and from secondary analyses of intervention trials; causal direction is supported by Mendelian randomization and ApoB genetics, though whether targeting non-HDL-C over LDL-C yields incremental benefit in primary prevention remains open.