title: Haemoglobin A1c even within non-diabetic level is a predictor of cardiovascular disease in a general Japanese population: the Hisayama Study.
abstract: BACKGROUND
  There is little information about predictive ability of haemoglobin A1c (HbA1c) for cardiovascular disease (CVD) in Asians. To investigate the discriminatory ability of HbA1c to identify subjects who are at greater risk of developing CVD in a prospective study of a defined community-dwelling Japanese population.
  
  
  METHODS
  A total of 2,851 subjects aged 40-79 years were stratified into five groups (HbA1c levels with ≤ 5.0, 5.1-5.4, 5.5-6.4, and ≥ 6.5% and a group with antidiabetic medication) and followed up prospectively for 7 years (2002-2009).
  
  
  RESULTS
  During the follow-up, 119 subjects developed CVD. The multivariable-adjusted risk of CVD was significantly increased in subjects with HbA1c levels of 5.5-6.4 and ≥ 6.5% and diabetic medication compared to HbA1c level with ≤ 5.0% (hazard ratio, 2.26 [95% confidence interval, 1.29-3.95] for the 5.5-6.4%; 4.43 [2.09-9.37] for the ≥ 6.5%; and 5.15 [2.65-10.0] for the antidiabetic medication group). With regard to CVD subtype, the positive associations between HbA1c levels and the risk of coronary heart disease (CHD) and ischaemic stroke were also significant, but no such associations were seen for haemorrhagic stroke. The C statistic for developing CVD was significantly increased by adding HbA1c values to the model including other risk factors (0.789 vs. 0762, p = 0.006), and the net reclassification improvement was 0.105 (p = 0.004).
  
  
  CONCLUSIONS
  Our findings suggest that elevated HbA1c levels are an independent risk factor for CVD, especially CHD and ischaemic stroke, and that the addition of HbA1c to the model with traditional risk factors significantly improves the predictive ability of CVD.
authors.affiliation: Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, Japan. fumikeda@envmed.med.kyushu-u.ac.jp.
authors.forename: Fumie
authors.initials: F
authors.lastname: Ikeda
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Doi
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hirakawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Mukai
authors.forename: Jun
authors.initials: J
authors.lastname: Hata
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shikata
authors.forename: Daigo
authors.initials: D
authors.lastname: Yoshida
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kiyohara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000378:metabolism; D003327:Coronary Disease / Q000453:epidemiology / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000453:epidemiology* / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000453:epidemiology* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007564:Japan / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000378:metabolism
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; C517652:hemoglobin A1c protein, human