title: Combined effect of blood pressure and total cholesterol levels on long-term risks of subtypes of cardiovascular death: Evidence for Cardiovascular Prevention from Observational Cohorts in Japan.
abstract: No large-scale, longitudinal studies have examined the combined effects of blood pressure (BP) and total cholesterol levels on long-term risks for subtypes of cardiovascular death in an Asian population. To investigate these relationships, a meta-analysis of individual participant data, which included 73 916 Japanese subjects (age, 57.7 years; men, 41.1%) from 11 cohorts, was conducted. During a mean follow-up of 15.0 years, deaths from coronary heart disease, ischemic stroke, and intraparenchymal hemorrhage occurred in 770, 724, and 345 cases, respectively. Cohort-stratified Cox proportional hazard models were used. After stratifying the participants by 4 systolic BP ×4 total cholesterol categories, the group with systolic BP ≥160 mm Hg with total cholesterol ≥5.7 mmol/L had the greatest risk for coronary heart disease death (adjusted hazard ratio, 4.39; P<0.0001 versus group with systolic BP <120 mm Hg and total cholesterol <4.7 mmol/L). The adjusted hazard ratios of systolic BP (per 20 mm Hg) increased with increases in total cholesterol categories (hazard ratio, 1.52; P<0.0001 in group with total cholesterol ≥5.7 mmol/L). Similarly, the adjusted hazard ratios of total cholesterol increased with increases in systolic BP categories (P for interaction ≤0.04). Systolic BP was positively associated with ischemic stroke and intraparenchymal hemorrhage death, and total cholesterol was inversely associated with intraparenchymal hemorrhage, but no significant interactions between BP and total cholesterol were observed for stroke. High BP and high total cholesterol can synergistically increase the risk for coronary heart disease death but not for stroke in the Asian population.
authors.affiliation: From the Department of Pharmacy, Tohoku University Hospital, Sendai, Japan (M. Satoh); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T. Ohkubo, K.A.); Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan (K.A., Y.I.); Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan (Y.M.); Department of Epidemiology and Public Health, Kanazawa Medical University, Ishikawa, Japan (M. Sakurai, H.N.); Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (H.I.); Research Institute of Strategy for Prevention, Tokyo, Japan (A.O.); Department of Public Health, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); and Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan (T. Okamura).
authors.forename: Michihiro
authors.initials: M
authors.lastname: Satoh
authors.affiliation: From the Department of Pharmacy, Tohoku University Hospital, Sendai, Japan (M. Satoh); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T. Ohkubo, K.A.); Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan (K.A., Y.I.); Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan (Y.M.); Department of Epidemiology and Public Health, Kanazawa Medical University, Ishikawa, Japan (M. Sakurai, H.N.); Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (H.I.); Research Institute of Strategy for Prevention, Tokyo, Japan (A.O.); Department of Public Health, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); and Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan (T. Okamura).
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohkubo
authors.affiliation: From the Department of Pharmacy, Tohoku University Hospital, Sendai, Japan (M. Satoh); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T. Ohkubo, K.A.); Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan (K.A., Y.I.); Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan (Y.M.); Department of Epidemiology and Public Health, Kanazawa Medical University, Ishikawa, Japan (M. Sakurai, H.N.); Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (H.I.); Research Institute of Strategy for Prevention, Tokyo, Japan (A.O.); Department of Public Health, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); and Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan (T. Okamura).
authors.forename: Kei
authors.initials: K
authors.lastname: Asayama
authors.affiliation: From the Department of Pharmacy, Tohoku University Hospital, Sendai, Japan (M. Satoh); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T. Ohkubo, K.A.); Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan (K.A., Y.I.); Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan (Y.M.); Department of Epidemiology and Public Health, Kanazawa Medical University, Ishikawa, Japan (M. Sakurai, H.N.); Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (H.I.); Research Institute of Strategy for Prevention, Tokyo, Japan (A.O.); Department of Public Health, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); and Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan (T. Okamura).
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: From the Department of Pharmacy, Tohoku University Hospital, Sendai, Japan (M. Satoh); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T. Ohkubo, K.A.); Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan (K.A., Y.I.); Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan (Y.M.); Department of Epidemiology and Public Health, Kanazawa Medical University, Ishikawa, Japan (M. Sakurai, H.N.); Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (H.I.); Research Institute of Strategy for Prevention, Tokyo, Japan (A.O.); Department of Public Health, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); and Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan (T. Okamura).
authors.forename: Masaru
authors.initials: M
authors.lastname: Sakurai
authors.affiliation: From the Department of Pharmacy, Tohoku University Hospital, Sendai, Japan (M. Satoh); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T. Ohkubo, K.A.); Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan (K.A., Y.I.); Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan (Y.M.); Department of Epidemiology and Public Health, Kanazawa Medical University, Ishikawa, Japan (M. Sakurai, H.N.); Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (H.I.); Research Institute of Strategy for Prevention, Tokyo, Japan (A.O.); Department of Public Health, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); and Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan (T. Okamura).
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: From the Department of Pharmacy, Tohoku University Hospital, Sendai, Japan (M. Satoh); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T. Ohkubo, K.A.); Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan (K.A., Y.I.); Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan (Y.M.); Department of Epidemiology and Public Health, Kanazawa Medical University, Ishikawa, Japan (M. Sakurai, H.N.); Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (H.I.); Research Institute of Strategy for Prevention, Tokyo, Japan (A.O.); Department of Public Health, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); and Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan (T. Okamura).
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Iso
authors.affiliation: From the Department of Pharmacy, Tohoku University Hospital, Sendai, Japan (M. Satoh); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T. Ohkubo, K.A.); Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan (K.A., Y.I.); Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan (Y.M.); Department of Epidemiology and Public Health, Kanazawa Medical University, Ishikawa, Japan (M. Sakurai, H.N.); Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (H.I.); Research Institute of Strategy for Prevention, Tokyo, Japan (A.O.); Department of Public Health, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); and Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan (T. Okamura).
authors.forename: Akira
authors.initials: A
authors.lastname: Okayama
authors.affiliation: From the Department of Pharmacy, Tohoku University Hospital, Sendai, Japan (M. Satoh); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T. Ohkubo, K.A.); Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan (K.A., Y.I.); Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan (Y.M.); Department of Epidemiology and Public Health, Kanazawa Medical University, Ishikawa, Japan (M. Sakurai, H.N.); Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (H.I.); Research Institute of Strategy for Prevention, Tokyo, Japan (A.O.); Department of Public Health, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); and Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan (T. Okamura).
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miura
authors.affiliation: From the Department of Pharmacy, Tohoku University Hospital, Sendai, Japan (M. Satoh); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T. Ohkubo, K.A.); Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan (K.A., Y.I.); Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan (Y.M.); Department of Epidemiology and Public Health, Kanazawa Medical University, Ishikawa, Japan (M. Sakurai, H.N.); Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (H.I.); Research Institute of Strategy for Prevention, Tokyo, Japan (A.O.); Department of Public Health, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); and Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan (T. Okamura).
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imai
authors.affiliation: From the Department of Pharmacy, Tohoku University Hospital, Sendai, Japan (M. Satoh); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T. Ohkubo, K.A.); Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan (K.A., Y.I.); Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan (Y.M.); Department of Epidemiology and Public Health, Kanazawa Medical University, Ishikawa, Japan (M. Sakurai, H.N.); Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (H.I.); Research Institute of Strategy for Prevention, Tokyo, Japan (A.O.); Department of Public Health, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); and Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan (T. Okamura).
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ueshima
authors.affiliation: From the Department of Pharmacy, Tohoku University Hospital, Sendai, Japan (M. Satoh); Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T. Ohkubo, K.A.); Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan (K.A., Y.I.); Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan (Y.M.); Department of Epidemiology and Public Health, Kanazawa Medical University, Ishikawa, Japan (M. Sakurai, H.N.); Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan (H.I.); Research Institute of Strategy for Prevention, Tokyo, Japan (A.O.); Department of Public Health, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan (K.M., H.U.); and Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan (T. Okamura).
authors.forename: Tomonori
authors.initials: T
authors.lastname: Okamura
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality*; D002784:Cholesterol / Q000097:blood*; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D007564:Japan / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000401:mortality; D015996:Survival Rate
chemical_list: D002784:Cholesterol
keywords: Asia; coronary disease; epidemiology; hypercholesterolemia; hypertension; meta-analysis; stroke