Association of low levels of low-density lipoprotein cholesterol and initial onset of intracerebral hemorrhage-an electronic health records database study in Japan

Background/Objectives Low-density lipoprotein cholesterol (LDL-C) levels are inconsistently associated with intracerebral hemorrhage (ICH) risk. We assessed the relationship between LDL-C levels and ICH onset using a database of Japanese electronic health records. Methods This retrospective observational study used data from patients hospitalized between April 1, 2001 and March 31, 2015. Patients with two consecutive LDL-C measurements were classified into four LDL-C level groups: Very low, <50 mg/dL; low, ≥50 < 100 mg/dL; moderate, ≥100 < 140 mg/dL; and high, ≥140 mg/dL. ICH onset and patient characteristics were compared between groups. Additionally, the association of LDL-C and other risk factors with ICH onset were investigated by adjusting for the effects of covariates. Results 44,029 patients were investigated, 739 (1.7%) with very low LDL-C, 32,206 (73.1 %) with low LDL-C, 9346 (21.2%) with moderate LDL-C, and 1738 (3.9%) with high LDL-C. Median follow-up was 3.3 person-years. The very low group included a higher proportion of patients with hypertension, cardiovascular disease, diabetes and aged ≥75 years. Risk factors with the highest hazard ratios (HRs) for ICH onset were age ≥75 years and non-hemor-rhagic stroke; HRs (95% confidence interval) men ≥75 years, 2.145 (1.683, 2.735); women ≥75 years, 2.384,(1.836, 3.094) [both vs. males aged <75 years]; non-hemorrhagic stroke, 2.032 (1.637, 2.522). No statistically significant associations were found between ICH onset and LDL-C level. Conclusions LDL-C levels, including very low levels, were not significantly associated with ICH onset. Males and females aged ≥75 years, and patients with non-hemorrhagic stroke were at the highest risks of developing ICH.