Abstract
BACKGROUND: The association between low-density lipoprotein cholesterol (LDL-C) levels and the risk of hemorrhagic stroke (HS) detected through different blood pressure statuses remains unclear. Hence, we systematically evaluated the association between LDL-C and HS in populations with and without hypertension. METHODS: We searched PubMed, Cochrane Library, and Embase databases for articles written in English. Only prospective design or randomized controlled trials (RCTs) reporting effect estimates with 95% confidence intervals (CIs) for the relationship between LDL-C and HS were included. We pooled risk ratios (RRs) stratified by blood pressure status and dose-response analyses with a two-stage generalized least squares for trend estimation (GLST) model. Finally, we compared the lower and optimal groups to find the effect of very low LDL-C levels on the risk of HS. RESULTS: We included seven randomized controlled trials and 9 prospective cohort studies involving 304,763 participants with 2125 (0.70%) HS events. The non-linear trend suggested that LDL-C levels of approximately 80 mg/dL among hypertensive patients and 115 mg/dL among non-hypertensive patients had the lowest risk of HS. Meanwhile, continually lowering LDL-C levels under the optimal (80 mg/dL for hypertensive patients and 115 mg/dL for non- hypertensive patients) LDL-C level would increase the risk of HS in the hypertensive population (RR = 1.84, 95% CI: 1.36-2.50) but not in the non-hypertensive population (RR = 1.15, 95% CI: 0.97-1.36). CONCLUSIONS: The risk of HS can be effectively reduced by controlling LDL-C levels to 60-80 mg/dL in the hypertensive population and 115 mg/dL in the non-hypertensive population. The safety range of controlling LDL-C levels to protect against HS among hypertensive patients is narrower than that among the non-hypertensive population. Additionally, controlling blood pressure might play a positive role in safeguarding against HS by lowering LDL-C levels.