title: Efficacy of HMG-CoA reductase inhibitors in the prevention of cerebrovascular attack in 1016 patients older than 75 years among 4014 type 2 diabetic individuals.
abstract: OBJECTIVE
  HMG-CoA reductase inhibitors (statins) reduce ischemic heart disease (IHD) in middle-aged diabetic individuals, and LDL-cholesterol (LDL-C) is a risk factor. However, their preventive effects on cerebrovascular attack (CVA) have not been identified in elderly, especially in elderly ≥ 75 years (late elderly), who account for approximately 30% of diabetic individuals in Japan. Randomized controlled studies of statins for late elderly are difficult to carry out, because many co-morbidities in elderly disrupt randomized controlled conditions.
  
  
  METHODS
  We performed a prospective cohort study (Japan Cholesterol and Diabetes Mellitus Study) with 5.5 years of follow-up since 2004. A total of 4014 type 2 diabetic patients without previous IHD or CVA (n=1936 women; age = 67.4 ± 9.5 years; ≥ 75 years: n = 1016) were enrolled, while 405 patients were registered as sub-cohort patients. We recorded detailed information on medications and laboratory data after every change in medication in patients of sub-cohort and suffered from IHD or CVA. We subdivided statin-users into prevalent, new and non-users.
  
  
  RESULTS
  A total of 104 CVAs occurred during 5.5-years. Plasma HDL-C level was inversely correlated with CVA in patients ≥ 65 years. In case-control study, among patients who were not prescribed statins, CVA increased in age-dependent manner. CVA incidence was lower in prevalent and new statin-users than in non-users (hazard ratio [HR]:0.46, 0.523), especially in late elderly (HR: 0.51, 0.21). Statins reduced CVAs mainly due to a direct effect and partially due to the effects of HDL-C and glucose metabolism. No significant differences were observed between statins.
  
  
  CONCLUSIONS
  Statins prevented CVA in middle-aged, elderly and late elderly diabetic patients via a direct effect. This study is the first to demonstrate the usefulness of observational studies for statistically analyzing agents' effects on late elderly.
authors.affiliation: Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: hayashi@med.nagoya-u.ac.jp.
authors.forename: Toshio
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Pharmacoepidemiology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Osaka Saiseikai Nakatsu Hospital, Osaka, Japan.
authors.forename: Seinosuke
authors.initials: S
authors.lastname: Kawashima
authors.affiliation: Department of Internal Medicine, Endocrinology and Metabolism, Niigata Graduate School of Medicine, Niigata, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Sone
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohrui
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Chiba University Hospital, Chiba, Japan.
authors.forename: Koutaro
authors.initials: K
authors.lastname: Yokote
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Chiba University Hospital, Chiba, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Takemoto
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Araki
authors.affiliation: Department of Diabetes and Metabolic Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Noda
authors.affiliation: Department of Diabetes and Metabolic Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Noto
authors.affiliation: Cardiovascular Medicine, Hokko Memorial Clinic, Sapporo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.affiliation: Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Yoshizumi
authors.affiliation: Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ina
authors.affiliation: Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Geriatrics, Aichi Nonami Clinic, Nagoya, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nomura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000037:antagonists & inhibitors / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000453:epidemiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Cerebrovascular attack; High-density lipoprotein; Late elderly (older than 75years); Pleiotropic effect; Statin (HMG-CoA reductase inhibitor); Type 2 diabetes