Cholesterol Levels and Risk of Hemorrhagic Stroke: A Systematic Review and Meta-Analysis

BACKGROUND AND PURPOSE—Cholesterol levels are inconsistently associated with the risk of hemorrhagic stroke. The purpose of this study is to assess their relationships using a meta-analytic approach. METHODS—We searched PubMed and Embase for pertinent articles published in English. Only prospective studies that reported effect estimates with 95% confidential intervals (CIs) of hemorrhagic stroke for ≥3 categories of cholesterol levels, for high and low comparison, or for per 1 mmol/L increment of cholesterol concentrations were included. We used the random-effects model to pool the study-specific results. RESULTS—Twenty-three prospective studies were included, totaling 1 430 141 participants with 7960 (5.6%) hemorrhagic strokes. In high versus low analysis, the summary relative risk of hemorrhagic stroke was 0.69 (95% CI, 0.59–0.81) for total cholesterol, 0.98 (95% CI, 0.80–1.19) for high-density lipoprotein cholesterol, and 0.62 (95% CI, 0.41–0.92) for low-density lipoprotein cholesterol. In dose–response analysis, the summary relative risk of hemorrhagic stroke for 1 mmol/L increment of total cholesterol was 0.85 (95% CI, 0.80–0.91), for high-density lipoprotein cholesterol was 1.11 (95% CI, 0.99–1.25), and for low-density lipoprotein cholesterol was 0.90 (95% CI, 0.77–1.05). The pooled relative risk for intracerebral hemorrhage was 1.17 (95% CI, 1.02–1.35) for high-density lipoprotein cholesterol. CONCLUSIONS—Total cholesterol level is inversely associated with risk of hemorrhagic stroke. Higher level of low-density lipoprotein cholesterol seems to be associated with lower risk of hemorrhagic stroke. High-density lipoprotein cholesterol level seems to be positively associated with risk of intracerebral hemorrhage.