Low Cholesterol Levels Increase Symptomatic Intracranial Hemorrhage Rates After Intravenous Thrombolysis: A Multicenter Cohort Validation Study

Aim: Although a lower level of non-high-density lipoprotein cholesterol (HDL-C) was reported to be inversely associated with spontaneous intracranial hemorrhage (ICH), no enough evidence has verified whether lipid profiles modify hemorrhagic transformation and functional outcomes in patients with acute ischemic treated with thrombolysis. Methods: This multicenter cohort study included 2373 patients with acute ischemic stroke treated with intravenous thrombolysis between December 2004 and December 2016. Of these, 1845 patients were categorized into either the hyperlipidemia or non-hyperlipidemia group. Symptomatic ICH (SICH) rates within 24–36 h of thrombolytic onset and functional outcomes at 30 and 90 days were longitudinally surveyed. Models of predicting hemorrhagic transformation were used to validate our findings. Results: For enrolled 1845 patients, SICH rates were ≥ 2-fold reduced for the hyperlipidemia group by the NINDS (adjusted RR: 0.488 [0.281–0.846], p = 0.0106), the ECASS II (adjusted RR: 0.318 [0.130–0.776], p = 0.0119), and SITS-MOST standards (adjusted RR: 0.214 [0.048–0.957], p = 0.0437). The favorable functional rates between the two groups were not significantly different. Lower levels of LDL-C were showed in robust association with SICH. With a cut-off LDL-C value of < 130 mg/dL, new models are more robust and significant in predicting hemorrhagic transformation within 24–36 h. Conclusions: This study supports the strong association between reduced LDL-C and increased SICH, but not for functional outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. LDL-C level of < 130 mg/dL is supposed to a candidate marker for predicting SICH within 24–36 h.