Association of Non-LDL Indices with Recurrent Stroke Risk while on Lipid-Modifying Therapy

Aims: Low-density lipoprotein (LDL)-lowering statin therapy is an established secondary stroke prevention strategy. However, the differential impact of key non-LDL levels on recurrent stroke risk, while on lipid-modifying therapy (LT), remains unclear. Methods: We analyzed the dataset of a multicenter trial involving 3640 recent (< 4 months) noncardioembolic stroke patients followed for 2 years. Participants were categorized into four groups of presumed improving lipid profile: level 0, no LT prescribed; level I, LT use with low high-density lipoprotein cholesterol (HDL-C) (< 40 mg/dL for men; < 50 mg/dL for women); level II, LT use with high HDL-C (≥ 40 mg/dL and ≥ 50 mg/dL, respectively); and level III, level II with low triglycerides (< 150 mg/dL). Independent associations of LT category with stroke, major vascular events (MVEs; stroke/coronary heart disease/vascular death), and all-cause death were assessed. Results: LTs were mostly statins (> 95%). The unadjusted recurrent stroke rate declined with LT category level (9.2% for level 0; 8.4% for level I; 7.5% for level II; and 5.7% for level III). Compared with level 0, the adjusted hazard ratio of stroke for level I was 0.78 (95% confidence interval (CI), 0.59–1.03), level II 0.80 (0.54–1.18), and level III 0.63 (0.43–0.91). Multivariable analyses of MVEs and all-cause death followed a similar pattern of declining risk with higher LT category level. Conclusions: Compared with the nonuse of LT, there may be a hierarchy of residual vascular risk after stroke by non-LDL type and target, while on LT. Particularly, stroke patients with low HDL-C levels on LT may benefit from additional therapeutic strategies to improve their outcomes.