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.