Intracerebral Hemorrhage Risk Decreased With Increasing Cholesterol, Statin Use

An inverse relationship was discovered between rising cholesterol levels and decreased risk for intracerebral hemorrhage in new statin users.

A study published in Neurology demonstrated an inverse relationship between increasing cholesterol levels and a decreased risk for intracerebral hemorrhage (ICH). Despite these findings, the use of statin therapy for hypercholesterolemia was also found to reduce the risk for ICH.

Data on new statin users between 2005 and 2010 from an electronic database in Israel were retrospectively analyzed (N=345,531). Patients included in the analysis had cholesterol level data recorded within 1 year prior to their first filled statin prescription (ie, index date) and had ≥1-year follow-up data from their index date. Statin exposure was defined by the mean atorvastatin equivalent daily dose (AAEDD), which was calculated based on statin type, dosage, and number of filled prescriptions during follow-up. Based on the ICD-9 code 431, investigators identified the association between ICH incidence and statin therapy as the primary outcome of interest. The median follow-up time was 9.5 years.

A total of 1304 patients had received a diagnosis of ICH 3,110,593 person-years of follow-up, which translated to an ICH crude incidence rate of 41.9 per 100,000 person-years. An AAEDD <10 mg/d, 0 to 19.9 mg/d, and ≥20 mg/d was recorded in 75.3%, 19.0%, and 5.7% of patients, respectively. In the unadjusted analysis, the rate of ICH decreased in a dose-response manner with statins and with increasing AAEDD to 46.1/100,000 person-years (AAEDD <10 mg/d), 31.1/100,000 person-years (AAEDD 10 to 19.9 mg/d), and 27.3/100,000 person-years (AAEDD ≥20 mg/d).

The study investigators calculated an adjusted hazard ratio (HR) for ICH of 0.68 (95% CI, 0.58-0.79) in patients with an AAEDD 10 to 19.9 mg/d compared with patients with an AAEDD <10 mg/d. In addition, the HR in patients with an AAEDD ≥20 mg/d relative to patients with AAEDD <10 mg/d was 0.62 (95% CI, 0.47-0.81).

The unadjusted rate of ICH also decreased with increasing baseline total cholesterol levels, including 64.4/100,000 person-years (lowest quartile), 41.8/100,000 person-years (second quartile), 31.2/100,000 person-years (third quartile), and 31.6/100,000 person-years (highest quartile). In the second, third, and highest cholesterol quartiles, the HRs were 0.71 (95% CI, 0.62-0.82), 0.55 (95% CI, 0.47-0.64), and 0.57 (95% CI, 0.49-0.67), respectively, compared with the lowest total cholesterol quartile at baseline.

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Limitations of the analysis included the relatively high anticoagulant use in the lowest AAEDD category as well as ICH misclassification, which may have potentially occurred during the study.

The researchers argued that the fear of an ICH diagnosis “should not discourage prescription of statins for primary and secondary prevention,” despite the findings suggesting an inverse association between rising cholesterol and lower ICH risk.


Saliba W, Rennert HS, Barnett-Griness O, et al. Association of statin use with spontaneous intracerebral hemorrhage: A cohort study [published online July 3, 2018]. Neurology. doi:10.1212/WNL.0000000000005907