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Primary Cardiovascular Events and Serum Lipid Levels in Elderly Japanese with Hypercholesterolemia Undergoing 6-Year Simvastatin Treatment: A Subanalysis of the Japan Lipid Intervention Trial

Authors

  • Hisanori Horiuchi MD,

    1. From the *Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Molecular Genetics and Cardiovascular Disorders, Kanazawa University Graduate School of Medicine, Kanazawa, JapanDepartment of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan§Sumitomo Hospital, Osaka, JapanNakaya Clinic, Tokyo, JapanThird Department of Internal Medicine, Nippon Medical School, Tokyo, Japan#Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan**International University Graduate School of Health and Welfare, Fukuoka, Japan††Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan‡‡Ibaraki Christian University, Ibaraki, Japan.
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  • Toru Kita MD,

    1. From the *Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Molecular Genetics and Cardiovascular Disorders, Kanazawa University Graduate School of Medicine, Kanazawa, JapanDepartment of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan§Sumitomo Hospital, Osaka, JapanNakaya Clinic, Tokyo, JapanThird Department of Internal Medicine, Nippon Medical School, Tokyo, Japan#Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan**International University Graduate School of Health and Welfare, Fukuoka, Japan††Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan‡‡Ibaraki Christian University, Ibaraki, Japan.
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  • Hiroshi Mabuchi MD,

    1. From the *Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Molecular Genetics and Cardiovascular Disorders, Kanazawa University Graduate School of Medicine, Kanazawa, JapanDepartment of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan§Sumitomo Hospital, Osaka, JapanNakaya Clinic, Tokyo, JapanThird Department of Internal Medicine, Nippon Medical School, Tokyo, Japan#Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan**International University Graduate School of Health and Welfare, Fukuoka, Japan††Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan‡‡Ibaraki Christian University, Ibaraki, Japan.
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  • Masunori Matsuzaki MD,

    1. From the *Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Molecular Genetics and Cardiovascular Disorders, Kanazawa University Graduate School of Medicine, Kanazawa, JapanDepartment of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan§Sumitomo Hospital, Osaka, JapanNakaya Clinic, Tokyo, JapanThird Department of Internal Medicine, Nippon Medical School, Tokyo, Japan#Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan**International University Graduate School of Health and Welfare, Fukuoka, Japan††Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan‡‡Ibaraki Christian University, Ibaraki, Japan.
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  • Yuji Matsuzawa MD,

    1. From the *Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Molecular Genetics and Cardiovascular Disorders, Kanazawa University Graduate School of Medicine, Kanazawa, JapanDepartment of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan§Sumitomo Hospital, Osaka, JapanNakaya Clinic, Tokyo, JapanThird Department of Internal Medicine, Nippon Medical School, Tokyo, Japan#Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan**International University Graduate School of Health and Welfare, Fukuoka, Japan††Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan‡‡Ibaraki Christian University, Ibaraki, Japan.
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  • Noriaki Nakaya MD,

    1. From the *Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Molecular Genetics and Cardiovascular Disorders, Kanazawa University Graduate School of Medicine, Kanazawa, JapanDepartment of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan§Sumitomo Hospital, Osaka, JapanNakaya Clinic, Tokyo, JapanThird Department of Internal Medicine, Nippon Medical School, Tokyo, Japan#Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan**International University Graduate School of Health and Welfare, Fukuoka, Japan††Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan‡‡Ibaraki Christian University, Ibaraki, Japan.
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  • Shinichi Oikawa MD,

    1. From the *Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Molecular Genetics and Cardiovascular Disorders, Kanazawa University Graduate School of Medicine, Kanazawa, JapanDepartment of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan§Sumitomo Hospital, Osaka, JapanNakaya Clinic, Tokyo, JapanThird Department of Internal Medicine, Nippon Medical School, Tokyo, Japan#Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan**International University Graduate School of Health and Welfare, Fukuoka, Japan††Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan‡‡Ibaraki Christian University, Ibaraki, Japan.
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  • Yasushi Saito MD,

    1. From the *Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Molecular Genetics and Cardiovascular Disorders, Kanazawa University Graduate School of Medicine, Kanazawa, JapanDepartment of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan§Sumitomo Hospital, Osaka, JapanNakaya Clinic, Tokyo, JapanThird Department of Internal Medicine, Nippon Medical School, Tokyo, Japan#Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan**International University Graduate School of Health and Welfare, Fukuoka, Japan††Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan‡‡Ibaraki Christian University, Ibaraki, Japan.
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  • Jun Sasaki MD,

    1. From the *Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Molecular Genetics and Cardiovascular Disorders, Kanazawa University Graduate School of Medicine, Kanazawa, JapanDepartment of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan§Sumitomo Hospital, Osaka, JapanNakaya Clinic, Tokyo, JapanThird Department of Internal Medicine, Nippon Medical School, Tokyo, Japan#Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan**International University Graduate School of Health and Welfare, Fukuoka, Japan††Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan‡‡Ibaraki Christian University, Ibaraki, Japan.
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  • Kazuaki Shimamoto MD,

    1. From the *Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Molecular Genetics and Cardiovascular Disorders, Kanazawa University Graduate School of Medicine, Kanazawa, JapanDepartment of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan§Sumitomo Hospital, Osaka, JapanNakaya Clinic, Tokyo, JapanThird Department of Internal Medicine, Nippon Medical School, Tokyo, Japan#Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan**International University Graduate School of Health and Welfare, Fukuoka, Japan††Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan‡‡Ibaraki Christian University, Ibaraki, Japan.
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  • Hiroshige Itakura MD,

    1. From the *Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Molecular Genetics and Cardiovascular Disorders, Kanazawa University Graduate School of Medicine, Kanazawa, JapanDepartment of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan§Sumitomo Hospital, Osaka, JapanNakaya Clinic, Tokyo, JapanThird Department of Internal Medicine, Nippon Medical School, Tokyo, Japan#Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan**International University Graduate School of Health and Welfare, Fukuoka, Japan††Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan‡‡Ibaraki Christian University, Ibaraki, Japan.
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  • the J-LIT Study Group

    1. From the *Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Molecular Genetics and Cardiovascular Disorders, Kanazawa University Graduate School of Medicine, Kanazawa, JapanDepartment of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan§Sumitomo Hospital, Osaka, JapanNakaya Clinic, Tokyo, JapanThird Department of Internal Medicine, Nippon Medical School, Tokyo, Japan#Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan**International University Graduate School of Health and Welfare, Fukuoka, Japan††Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan‡‡Ibaraki Christian University, Ibaraki, Japan.
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  • This study was supported in part by a grant from Banyu Pharmaceutical Co. Ltd, Tokyo, Japan.

Toru Kita, MD, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto 606–8507, Japan. E-mail: tkita@kuhp.kyoto-u.ac.jp

Abstract

Objectives: To determine the relationship between serum lipid levels and the incidence of coronary events in older Japanese hypercholesterolemic patients without prior coronary heart disease (CHD).

Design: Post hoc subanalysis of the results in the Japan Lipid Intervention Trial.

Setting: A large-scale cohort observational study conducted throughout Japan.

Participants: Men aged 35 to 70 and postmenopausal women younger than 70 with serum total cholesterol (TC) level of 220 mg/dL or greater treated for 6 years with low-dose simvastatin (52,421 total patients). After exclusion of 5,127 patients because of prior CHD and 4,934 patients because of incomplete data, 42,360 patients were divided into an older (9,860 patients, aged 65–70, mean age 67.1) and younger (32,500 patients, younger than 65, mean age 54.9) group and analyzed.

Measurements: Fasting serum lipid levels were measured every 6 months. Major coronary events, including fatal or nonfatal myocardial infarction, and sudden cardiac death as the primary endpoint and other cardiovascular diseases, including onset of angina pectoris, cerebrovascular events, and any causes of death, as the secondary endpoints were monitored.

Results: Simvastatin treatment in older patients was as safe and effective as in younger patients. Incident rates of major coronary events were 1.30 per 1,000 patient-years in the older group and 0.80 per 1,000 patient-years in the younger group. The incidence of a major coronary event was correlated to serum TC and low-density lipoprotein cholesterol (LDL-C) levels in both groups. The absolute risk of major coronary events in the older group was higher than in the younger group at any level of LDL-C, whereas the relative risk increased by 1.7% with an elevation of each 1 mg/dL LDL-C level in both groups. In the older group, the risk of major coronary events also increased as triglyceride level increased, whereas the risk decreased as high-density lipoprotein cholesterol level increased above 60 md/dL.

Conclusion: The LDL-C level-dependent increase of relative risk of CHD was similar in elderly and younger patients, whereas the absolute risk at any LDL-C level in elderly patients was higher than in younger patients.

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