title: Hemoglobin a1c is associated with increased risk of incident coronary heart disease among apparently healthy, nondiabetic men and women.
abstract: BACKGROUND
  Hemoglobin A1c (HbA1c), a time-integrated marker of glycemic control, predicts risk of coronary heart disease (CHD) among diabetics. Few studies have examined HbA1c and risk of CHD among women and men without clinically elevated levels or previously diagnosed diabetes.
  
  
  RESULTS
  We conducted parallel nested case-control studies among women (Nurses' Health Study) and men (Health Professionals Follow-up Study). During 14 and 10 years of follow-up, 468 women and 454 men developed incident nonfatal myocardial infarction (MI) and fatal CHD. Controls were matched 2:1 based on age, smoking, and date of blood draw. For these analyses, participants with a history of diabetes or HbA1c levels ≥6.5% at baseline were excluded. Compared with HbA1c of 5.0% to <5.5%, those with an HbA1c of 6.0% to <6.5% had a multivariable-adjusted relative risk (RR) of CHD of 1.90 (95% CI 1.11 to 3.25) in women and 1.81 (95% CI 1.09 to 3.03) in men. The pooled RR of CHD was 1.29 (95% CI 1.11 to 1.50) for every 0.5%-increment increase in HbA1c levels and 1.67 (95% CI 1.23 to 2.25) for every 1%-increment increase, with the risk plateauing around 5.0%. Furthermore, participants with HbA1c levels between 6.0% and <6.5% and C-reactive protein levels >3.0 mg/L had a 2.5-fold higher risk of CHD compared with participants in the lowest categories of both biomarkers.
  
  
  CONCLUSIONS
  Our findings suggest that HbA1c is associated with CHD risk among apparently healthy, nondiabetic women and men and may be an important early clinical marker of disease risk.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Pai
authors.forename: Leah E
authors.initials: LE
authors.lastname: Cahill
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Rexrode
authors.forename: Joann E
authors.initials: JE
authors.lastname: Manson
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
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