title: Sex differences in diabetes and risk of incident coronary artery disease in healthy young and middle-aged adults.
abstract: OBJECTIVE
  Controversy exists about the coronary artery disease (CAD) risk conveyed by diabetes in young and middle-aged women. We investigated sex differences in CAD by diabetes status among healthy individuals with different underlying risks of heart disease.
  
  
  METHODS
  We examined subjects aged <60 years without CAD at enrollment in the high-risk GeneSTAR Study (n = 1,448; follow-up ∼12 years), Multi-Ethnic Study of Atherosclerosis (MESA; n = 3,072; follow-up ∼7 years), and National Health and Nutrition Examination Survey III (NHANES III) Mortality Follow-up Study (n = 6,997; follow-up ∼15 years). Diabetes was defined by report, hypoglycemic use, and/or fasting glucose ≥126 mg/dL. The outcome was any CAD event during follow-up (fatal CAD in NHANES).
  
  
  RESULTS
  In the absence of diabetes, CAD rates were lower among women in GeneSTAR, MESA, and NHANES (4.27, 1.66, and 0.40/1,000 person-years, respectively) versus men (11.22, 5.64, and 0.88/1,000 person-years); log-rank P < 0.001 (GeneSTAR/MESA) and P = 0.07 (NHANES). In the presence of diabetes, CAD event rates were similar among women (17.65, 7.34, and 2.37/1,000 person-years) versus men (12.86, 9.71, and 1.83/1,000 person-years); all log-rank P values > 0.05. Adjusting for demographics, diabetes was associated with a significant four- to fivefold higher CAD rate among women in each cohort, without differences in men. In meta-analyses of three cohorts, additionally adjusted for BMI, smoking, hypertension, HDL, and non-HDL cholesterol, antihypertensive and cholesterol-lowering medication use, the hazard ratio of CAD in men versus women among nondiabetes was 2.43 (1.76-3.35) and diabetes was 0.89 (0.43-1.83); P = 0.013 interaction by diabetes status.
  
  
  CONCLUSIONS
  Though young and middle-aged women are less likely to develop CAD in the absence of diabetes, the presence of diabetes equalizes the risk by sex. Our findings support aggressive CAD prevention strategies in women with diabetes and at similar levels to those that exist in men.
authors.affiliation: Corresponding author: Rita Rastogi Kalyani, rrastogi@jhmi.edu.
authors.forename: Rita Rastogi
authors.initials: RR
authors.lastname: Kalyani
authors.forename: Mariana
authors.initials: M
authors.lastname: Lazo
authors.forename: Pamela
authors.initials: P
authors.lastname: Ouyang
authors.forename: Evrim
authors.initials: E
authors.lastname: Turkbey
authors.forename: Karinne
authors.initials: K
authors.lastname: Chevalier
authors.forename: Frederick
authors.initials: F
authors.lastname: Brancati
authors.forename: Diane
authors.initials: D
authors.lastname: Becker
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Vaidya
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003324:Coronary Artery Disease / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult