title: The Combination of Elevated Triglycerides and Abnormal Fasting Glucose Increases Risk of Cerebral Infarction in Patients With Mild to Moderate Hypercholesterolemia: A Post Hoc Analysis of the MEGA Study.
abstract: BACKGROUND
  While triglycerides (TGs) and diabetes increase the risk of cardiovascular disease (CVD), their combined effects have not been quantified. We explored the combined effect of elevated TGs and glucose on CVD in a post hoc analysis of the large-scale Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study.
  
  
  METHODS
  In the MEGA Study, 8214 patients with mild to moderate hypercholesterolemia were randomly allocated to the diet alone group or diet plus pravastatin group and followed for 5 years. Of those, 7832 patients included in the intention-to-treat analysis were stratified into 4 groups: abnormal fasting glucose (AFG) plus high TGs, high TGs alone, AFG alone, and normal fasting glucose plus normal TGs (reference). Cox proportional hazard models were used to compare the incidence of and mortality from CVD in the 4 groups.
  
  
  RESULTS
  Incidence of CVD and coronary heart disease was significantly higher in the groups with AFG alone (hazard ratio [HR], 2.02 and 3.38; P < .01, respectively) and AFG plus high TGs (HR, 2.87 and 3.87; P < .01, respectively) than the reference group. A similar relation was found in models adjusting for high-density lipoprotein cholesterol (HDL-C). Although the incidence of cerebral infarction was significantly higher only in the group with AFG plus high TGs (HR, 2.16; P = .01), it was marginally significantly higher than the reference group after adjustment for HDL-C (HR, 1.86; P = .06). Diet plus pravastatin treatment reduced the risk of cerebral infarction by 66% in the group with AFG plus high TGs (P = .03).
  
  
  CONCLUSIONS
  Our findings contribute to the formulation of the hypothesis that patients with hypercholesterolemia having AFG plus high TGs have an increased risk of cerebral infarction. These are compatible with the result from the main study that patients with hypercholesterolemia randomized to diet plus pravastatin had a reduced risk of cerebral infarction.
authors.affiliation: Diabetes Center, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan nakagami@dmc.twmu.ac.jp.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nakagami
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
authors.forename: Rimei
authors.initials: R
authors.lastname: Nishimura
authors.affiliation: Department of Internal Medicine, Niigata University Faculty of Medicine, Chuo-ku, Niigata, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Sone
authors.affiliation: Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Tajima
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D002544:Cerebral Infarction / Q000209:etiology*; D008076:Cholesterol, HDL / Q000097:blood; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D014280:Triglycerides / Q000097:blood*
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D014280:Triglycerides
keywords: cerebral infarction; clinical trial; glucose; hypercholesterolemia; statin; triglycerides