title: Synergistic association of combined glycemic and blood pressure level with risk of complications in US veterans with diabetes.
abstract: OBJECTIVE
  Hemoglobin A1c levels less than 7.0% and systolic blood pressure (SBP) less than 140 mmHg are each associated with lower risk of vascular complications in patients with diabetes mellitus. Associations between combined A1c level and SBP categories and risk of mortality and morbidity in diabetic patients are not well characterized.
  
  
  METHODS
  We examined 891 670 US diabetic veterans with baseline estimated glomerular filtration rates more than 60 ml/min per 1.73 m (mean age 67 ± 11 years, 97% men, 17% African-Americans). The associations of mutually exclusive combined categories of A1c (<6.5, 6.5-6.9, 7.0-7.9, 8.0-8.9, 9.0-9.9, and ≥10%) and SBP (<100, 100-119, 120-139, 140-159, 160-179, and ≥180 mmHg) with the risk of all-cause mortality and incident chronic kidney disease (CKD), coronary heart disease, and stroke were examined in Cox models adjusted for baseline characteristics using patients with concomitant A1c 6.5-6.9% and SBP of 120-139 mmHg as the referent group.
  
  
  RESULTS
  A total of 221 529 (25%) patients died, and 178 588 (20%), 43 373 (5%) and 36 935 (4%) developed CKD, coronary heart disease and stroke, respectively, during a median follow-up of 7.4 years. SBP displayed a J-shaped association with each outcome except CKD risk that was linearly associated with SBP across all A1c categories. A1c above 7.0% was associated with monotonically worse outcomes for all end points in all SBP categories. Patients with the combined highest A1c and SBP levels experienced the worst outcomes.
  
  
  CONCLUSIONS
  SBP greater than 120-139 mmHg and A1c greater than 7.0% are associated with higher mortality and vascular complications in diabetic patients, independent of each other. Combined efforts to improve both glycemic and blood pressure control may synergistically improve outcomes in patients with normal kidney function.
authors.affiliation: aDivision of Endocrinology, Diabetes, and Metabolism bDivision of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee cDivision of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, CA dNephrology Section, Memphis Veterans Affairs Medical Center, Memphis, Tennessee, USA *Current affiliation: Endocrinology Section, Stratton VA Medical Center, Albany, New York, USA.
authors.forename: Aidar R
authors.initials: AR
authors.lastname: Gosmanov
authors.forename: Jun L
authors.initials: JL
authors.lastname: Lu
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sumida
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Potukuchi
authors.forename: Connie M
authors.initials: CM
authors.lastname: Rhee
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
authors.forename: Miklos Z
authors.initials: MZ
authors.lastname: Molnar
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D003920:Diabetes Mellitus / Q000097:blood*; D005006:Ethnicity; D005260:Female; D006442:Glycated Hemoglobin; D038321:Glycemic Index; D006801:Humans; D006973:Hypertension / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000401:mortality*; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000150:complications; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014728:Veterans / Q000706:statistics & numerical data*
chemical_list: D006442:Glycated Hemoglobin