title: Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension: the ALLHAT Diabetes Extension Study.
abstract: BACKGROUND
  Thiazide-type diuretics are associated with an increased incidence of diabetes compared with other antihypertensive medications. In this study, we determined the long-term cardiovascular disease (CVD) consequences of incident diuretic-associated diabetes compared with the effects of incident diabetes associated with calcium channel blocker and angiotensin-converting enzyme inhibitor use.
  
  
  RESULTS
  A total of 22 418 participants from the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with baseline diabetes, incident diabetes (7.5% with chlorthalidone, 5.6% with amlodipine, and 4.3% with lisinopril), or no diabetes at 2 years of in-trial follow-up were followed for a mean total of 6.9 years (2.9 years in-trial and 4 additional years posttrial) through the use of national databases. The primary outcome was CVD mortality (death from coronary heart disease [CHD], stroke, heart failure, or other CVD). Among other outcomes were all-cause mortality, non-CVD mortality, and CHD (nonfatal myocardial infarction or fatal CHD). Participants on chlorthalidone with incident diabetes versus no diabetes had consistently lower, nonsignificant risk for CVD mortality (hazard ratio [HR], 1.04; 95% CI, 0.74-1.47), all-cause mortality (HR, 1.04; 95% CI, 0.82-1.30), and non-CVD mortality (HR, 1.05; 95% CI, 0.77-1.42) than participants on amlodipine or lisinopril with incident diabetes (HR range, 1.22-1.53). Participants with incident diabetes had elevated CHD risk compared with those with no diabetes (HR, 1.46; 95% CI, 1.09-1.96), but those on chlorthalidone had significantly lower risk than those on lisinopril (HR, 1.18 versus 2.57; P=0.04 for interaction).
  
  
  CONCLUSIONS
  The findings suggest that thiazide-related incident diabetes has less adverse long-term CVD impact than incident diabetes that develops while on other antihypertensive medications.
authors.affiliation: Kaiser Permanente of Georgia and Emory University School of Medicine, Atlanta, GA.
authors.forename: Joshua I
authors.initials: JI
authors.lastname: Barzilay
authors.forename: Barry R
authors.initials: BR
authors.lastname: Davis
authors.forename: Sara L
authors.initials: SL
authors.lastname: Pressel
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cutler
authors.forename: Paula T
authors.initials: PT
authors.lastname: Einhorn
authors.forename: Henry R
authors.initials: HR
authors.lastname: Black
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.forename: Charles E
authors.initials: CE
authors.lastname: Ford
authors.forename: Karen L
authors.initials: KL
authors.lastname: Margolis
authors.forename: Jamaluddin
authors.initials: J
authors.lastname: Moloo
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.forename: Linda B
authors.initials: LB
authors.lastname: Piller
authors.forename: Debra L
authors.initials: DL
authors.lastname: Simmons
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Sweeney
authors.forename: Paul K
authors.initials: PK
authors.lastname: Whelton
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Wong
authors.forename: Jackson T
authors.initials: JT
authors.lastname: Wright
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects; D002121:Calcium Channel Blockers / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000401:mortality*; D002752:Chlorthalidone / Q000009:adverse effects; D003327:Coronary Disease / Q000401:mortality; D003920:Diabetes Mellitus / Q000139:chemically induced*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D049993:Sodium Chloride Symporter Inhibitors; D002752:Chlorthalidone