Low-density lipoprotein cholesterol and risk of intracerebral hemorrhage: A prospective study

Abstract

Objective: To prospectively examine the association between low-density lipoprotein (LDL) cholesterol (LDL-C) concentrations and intracerebral hemorrhage (ICH) risk.

Methods: The current cohort study included 96,043 participants (mean age 51.3 years) who were 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 to 99 mg/dL and those with LDL-C concentrations ≥100 mg/dL. In contrast, participants with LDL-C concentrations <70 mg/dL had a significantly higher risk of developing ICH than those with LDL-C concentrations of 70 to 99 mg/dL; adjusted hazard ratios were 1.65 (95% confidence interval [CI] 1.32-2.05) for LDL-C concentrations of 50 to 69 mg/dL and 2.69 (95% CI 2.03-3.57) for LDL-C concentrations <50 mg/dL.

Conclusions: We observed a significant association between lower LDL-C and higher risk of ICH when LDL-C was <70 mg/dL, and the association became nonsignificant when LDL-C ≥70 mg/dL. These data can help determination of the ideal LDL range in patients who are at increased risk of both atherosclerotic disease and hemorrhagic stroke and guide planning of future lipid-lowering studies.

Figure. Hazard ratios for intracerebral hemorrhage according to updated cumulative average blood LDL cholesterol from 2006 to 2012 among 96,043 Kailuan participants

Model was adjusted for age; sex; smoking (current, past or never); alcohol intake (never, past, light, moderate, or heavy); education (illiteracy or elementary school, middle school, or college/university); physical activity (never, sometimes, or active); average monthly income of each family member (<500, 500–2,999, or ≥3,000 ¥); salt intake (≥10.0, 6.0–9.9 or <6.0 g/d); updated diabetes status (no, prediabetes, or diabetes mellitus); use of antihypertensive, lipid-lowering agents, aspirin, and anticoagulants (yes/no for each); updated cumulative average body mass index (≥30.0, 25.0–29.9, or <25.0 kg/m²); triglycerides (<150, 150–199, 200–240, or ≥240 mg/dL), high-density lipoprotein cholesterol (≥60, 40–59, or <40 mg/L), and high-sensitivity C-reactive protein (<1.00, 1.00–2.99, or ≥3.00 mg/mL) concentrations; alanine aminotransferase (for men <47 or ≥47 U/L; for women <36 or ≥36 U/L); systolic blood pressure (quintile); diastolic blood pressure (quintile); and estimated glomerular filtration rate (quintile). Data were fitted by a restricted cubic spline Cox proportional hazards model. The 95% confidence intervals are indicated by the dashed lines. LDL = low-density lipoprotein.