ApoB and Non‐HDL Cholesterol Versus LDL Cholesterol for Ischemic Stroke Risk

OBJECTIVE: Conflicting results have been reported on the association between lipids and risk of ischemic stroke. We tested the hypothesis that the burden of ischemic stroke attributable to either elevated apolipoprotein B (apoB) or non‐high‐density lipoprotein (non‐HDL) cholesterol is higher than that attributable to elevated low‐density lipoprotein (LDL) cholesterol. METHODS: We included 104,618 individuals from an ongoing cohort study, the Copenhagen General Population Study. The associations of quintiles of apoB, non‐HDL cholesterol, and LDL cholesterol with risk of ischemic stroke were estimated by Cox proportional hazards regressions with 95% confidence intervals. With 1(st) quintile as reference, the proportion of ischemic stroke attributable to the 2(nd), 3(rd), 4(th), and 5(th) quintiles of apoB, non‐HDL cholesterol, and LDL cholesterol were estimated by population attributable fractions. RESULTS: Higher quintiles of apoB and non‐HDL cholesterol were associated with increased risk of ischemic stroke (both trends: p < 0.0001), whereas for LDL cholesterol this association was somewhat attenuated (trend: p = 0.0005). A similar pattern was seen for population attributable fraction values. Compared to individuals in the 1(st) quintile, the combined proportion of ischemic stroke attributable to individuals in the 2(nd) to 5(th) quintiles was 16.3% for apoB (levels >82 mg/dL), 14.7% for non‐HDL cholesterol (>3.0 mmol/L; >117 mg/dL), and 6.8% for LDL cholesterol (>2.4 mmol/L; >94 mg/dL). INTERPRETATION: The proportion of ischemic stroke attributable to either elevated apoB or non‐HDL cholesterol was double that attributable to elevated LDL cholesterol. ANN NEUROL 2022;92:379–389