title: Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia.
abstract: Hyperlipidemia is a well-established risk factor for primary coronary heart disease (CHD). Although simvastatin is known to lower serum lipid concentrations, the protective effect of such lipid-lowering therapy against primary CHD has not been established in Japanese patients with hypercholesterolemia. The Japan Lipid Intervention Trial was a 6-year, nationwide cohort study of 47,294 patients treated with open-labeled simvastatin (5-10 mg/day) and monitored by physicians under standard clinical conditions. The aim of the study was to determine the relationship between the occurrence of CHD and the serum lipid concentrations during low-dose simvastatin treatment. Simvastatin reduced serum concentrations of total cholesterol (TC), low-density lipoprotein- cholesterol (LDL-C) and triglyceride (TG), by 18.4%, 26.8% and 16.1% on average, respectively, during the treatment period. The risk of coronary events was higher when the average TC concentration was > or =240 mg/dl and the average LDL-C concentration was > or =160 mg/dl. The incidence of coronary events increased in the patients with TG concentration > or =300 mg/dl compared with patients with TG concentration <150 mg/dl. The high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of coronary events. The J-curve association was observed between average TC or LDL-C concentrations and total mortality. Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC and LDL-C concentrations with low-dose statin. A reasonable strategy to prevent coronary events in Japanese hypercholesterolemic patients without prior CHD under low-dose statin treatment might be regulating the serum lipid concentrations to at least <240 mg/dl for TC, <160 mg/dl for LDL-C, <300 mg/dl for TG, and >40 mg/dl for HDL-C.
authors.affiliation: Yamaguchi University Graduate School of Medicine, Ube, Japan. masunori@yamaguchi-u.ac.jp
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mabuchi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nakaya
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oikawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Jun
authors.initials: J
authors.lastname: Sasaki
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Itakura
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002784:Cholesterol / Q000097:blood*; D015331:Cohort Studies; D003327:Coronary Disease / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D015994:Incidence; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012307:Risk Factors; D012449:Safety; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000924:Anticholesteremic Agents; D008055:Lipids; D002784:Cholesterol; D019821:Simvastatin