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(Circulation. 2009;119:2136-2145.)
© 2009 American Heart Association, Inc.

Epidemiology

Low-Density Lipoprotein Cholesterol Concentrations and Death Due to Intraparenchymal Hemorrhage

The Ibaraki Prefectural Health Study

Hiroyuki Noda, MD; Hiroyasu Iso, MD; Fujiko Irie, MD; Toshimi Sairenchi, PhD; Emiko Ohtaka; Mikio Doi, MD; Yoko Izumi, MD; Hitoshi Ohta, MD

From Public Health (H.N., H.I.), Department of Social and Environmental Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan; Harvard Center for Population and Development Studies (H.N.), Harvard School of Public Health, Cambridge, Mass; Department of Health and Social Services (F.I., M.D., Y.I.), Ibaraki Prefectural Office, Ibaraki, Japan; Department of Public Health (T.S.), Dokkyo Medical University School of Medicine, Tochigi, Japan; and Ibaraki Prefectural Health Plaza (T.S., E.O., H.O.), Ibaraki Health Service Association, Ibaraki, Japan. Dr Izumi is currently with the Office for Health Hazards Caused by Asbestos, Ministry of Environment, Tokyo, Japan.

Reprint requests to Professor Hiroyasu Iso, MD, Public Health, Department of Social and Environmental Medicine, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Shuita-shi, Osaka 565-0871 Japan. E-mail iso{at}pbhel.med.osaka-u.ac.jp

Received May 31, 2008; accepted February 5, 2009.

Background— Few studies have examined the association between low levels of low-density lipoprotein (LDL) cholesterol and risk of intraparenchymal hemorrhage.

Methods and Results— A total of 30 802 men and 60 417 women, 40 to 79 years of age with no history of stroke or coronary heart disease, completed a baseline risk factor survey in 1993 under the auspices of the Ibaraki Prefectural Health Study. Systematic mortality surveillance was performed through 2003, and 264 intraparenchymal hemorrhage deaths were identified. LDL cholesterol levels were calculated with the Friedewald formula. Persons with LDL cholesterol 140 mg/dL had half the sex- and age-adjusted risk of death due to intraparenchymal hemorrhage of those with LDL cholesterol <80 mg/dL. After adjustment for cardiovascular risk factors, the multivariable hazard ratio compared with persons with LDL cholesterol <80 mg/dL was 0.65 (95% CI 0.44 to 0.96) for those with LDL cholesterol 80 to 99 mg/dL, 0.48 (0.32 to 0.71) for 100 to 119 mg/dL, 0.50 (0.33 to 0.75) for 120 to 139 mg/dL, and 0.45 (0.30 to 0.69) for 140 mg/dL. These inverse associations were not altered substantially after the exclusion of persons with hypertriglyceridemia, after analysis with a Cox proportional hazard model with time-dependent covariates, or in sensitivity analysis for the potential effect of competing risks.

Conclusions— Low LDL cholesterol levels are associated with elevated risk of death due to intraparenchymal hemorrhage.

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CLINICAL PERSPECTIVE

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