LAUSR

Objectives To prospectively examine the association between low density lipoprotein cholesterol (LDL-C) concentrations and intracerebral hemorrhage (ICH) risk, and test the association in a meta-analysis combining the present data with previous studies. Methods The current cohort study included 96,043 participants (mean age 51.3 y), free of stroke, myocardial infarction, and cancer at baseline (2006). Serum LDL-C concentrations were assessed in 2006, 2008, 2010 and 2012. Cumulative average LDL-C concentrations were calculated from all available LDL-C data during that period. Incident ICH was confirmed by review of medical records. Results We identified 753 incident ICH cases during 9 years of follow-up. The ICH risk was similar among participants with LDL concentrations of 70-99 mg/dL and those with LDL-C concentrations ≥100 mg/dL. In contrast, participants with LDL-C concentrations less than 70 mg/dL had a significantly higher risk of developing ICH than those with LDL-C concentrations of 70-99 mg/dL -adjusted HR 1.65 (95%CI, 1.32 to 2.05) for LDL-C concentrations of 50-69 mg/dL and 2.69 (95%CI, 2.03 to 3.57) for LDL-C concentrations of <50 mg/dL. In the meta-analysis of 11 prospective studies, the pooled HRs of hemorrhagic stroke for per 10 mg/dL decrement in LDL-C was 1.03 (95% CI, 1.01 to 1.06). Conclusions We observed a significant association between lower LDL-C and higher risk of ICH when LDL-C concentrations <70 mg/dL, and the risk decreased to a non-significance level and stabilized when LDL-C ≥70 mg/dL. These data can help determination of ideal LDL range in patients who are at increased risk of both atherosclerotic disease and hemorrhagic stroke and also guide planning of future lipid lowering studies. Funding Sources Supported by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. Supporting Tables Images and/or Graphs