title: A pooled analysis of the association of isolated low levels of high-density lipoprotein cholesterol with cardiovascular mortality in Japan.
abstract: Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40-89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.
authors.affiliation: Center for Supercentenarian Medical Research, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. t-hirata@keio.jp.
authors.forename: Takumi
authors.identifier: 0000-0003-2899-6762
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
authors.affiliation: Department of Epidemiology and Public Health, Kanazawa Medical University, Uchinada, Japan.
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Nagasawa
authors.affiliation: Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Nursing, Sapporo Medical University School of Health Sciences, Sapporo, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Research Institute of Strategy for Prevention, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Okayama
authors.affiliation: Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Iso
authors.affiliation: Department of Health and Welfare, Ibaraki Prefectural Office, Mito, Japan.
authors.forename: Fujiko
authors.initials: F
authors.lastname: Irie
authors.affiliation: Department of Public Health, Dokkyo Medical University School of Medicine, Mibu, Japan.
authors.forename: Toshimi
authors.initials: T
authors.lastname: Sairenchi
authors.affiliation: Department of Preventive Medicine and Epidemiologic Informatics, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Center for Community Medicine, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Shizukiyo
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Department of Public Health, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miura
authors.affiliation: Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ueshima
authors.affiliation: Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Okamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D003327:Coronary Disease / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000401:mortality
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL
keywords: Cardiovascular diseases; Epidemiology; High-density lipoprotein cholesterol; Mortality