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

Toshio Hayashi, Kiyoshi Kubota, Seinosuke Kawashima, Hirohito Sone, Hiroshi Watanabe, Takashi Ohrui, Koutaro Yokote, Minoru Takemoto, Atsushi Araki, Mitsuhiko Noda, Hiroshi Noto, Ichiro Sakuma, Masao Yoshizumi, Koichiro Ina, Hideki Nomura

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    1 Citation (Scopus)


    Background/objectives 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. Conclusion 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.

    Original languageEnglish
    Pages (from-to)860-866
    Number of pages7
    JournalInternational Journal of Cardiology
    Issue number3
    Publication statusPublished - 2014 Dec 20


    • Cerebrovascular attack
    • High-density lipoprotein
    • Late elderly (older than 75 years)
    • Pleiotropic effect
    • Statin (HMG-CoA reductase inhibitor)
    • Type 2 diabetes

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine


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