Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension the ALLHAT diabetes extension study

Joshua I. Barzilay, Barry R. Davis, Sara L. Pressel, Jeffrey A. Cutler, Paula T. Einhorn, Henry R. Black, William Cushman, Charles E. Ford, Karen L. Margolis, Jamaluddin Moloo, Suzanne Oparil, Linda B. Piller, Debra L. Simmons, Mary Ellen Sweeney, Paul K. Whelton, Nathan D. Wong, Jackson T. Wright

Research output: Contribution to journalArticle

44 Citations (Scopus)

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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)153-162
Number of pages10
JournalCirculation: Cardiovascular Quality and Outcomes
Volume5
Issue number2
DOIs
StatePublished - Mar 1 2012

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Diabetes Mellitus
Chlorthalidone
Hypertension
Lisinopril
Cardiovascular Diseases
Coronary Disease
Mortality
Antihypertensive Agents
Amlodipine
Myocardial Infarction
Thiazides
Sodium Chloride Symporter Inhibitors
Calcium Channel Blockers
Angiotensin-Converting Enzyme Inhibitors
Diuretics
Heart Failure
Stroke
Databases
Lipids
Incidence

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension the ALLHAT diabetes extension study. / Barzilay, Joshua I.; Davis, Barry R.; Pressel, Sara L.; Cutler, Jeffrey A.; Einhorn, Paula T.; Black, Henry R.; Cushman, William; Ford, Charles E.; Margolis, Karen L.; Moloo, Jamaluddin; Oparil, Suzanne; Piller, Linda B.; Simmons, Debra L.; Sweeney, Mary Ellen; Whelton, Paul K.; Wong, Nathan D.; Wright, Jackson T.

In: Circulation: Cardiovascular Quality and Outcomes, Vol. 5, No. 2, 01.03.2012, p. 153-162.

Research output: Contribution to journalArticle

Barzilay, JI, Davis, BR, Pressel, SL, Cutler, JA, Einhorn, PT, Black, HR, Cushman, W, Ford, CE, Margolis, KL, Moloo, J, Oparil, S, Piller, LB, Simmons, DL, Sweeney, ME, Whelton, PK, Wong, ND & Wright, JT 2012, 'Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension the ALLHAT diabetes extension study', Circulation: Cardiovascular Quality and Outcomes, vol. 5, no. 2, pp. 153-162. https://doi.org/10.1161/CIRCOUTCOMES.111.962522
Barzilay, Joshua I. ; Davis, Barry R. ; Pressel, Sara L. ; Cutler, Jeffrey A. ; Einhorn, Paula T. ; Black, Henry R. ; Cushman, William ; Ford, Charles E. ; Margolis, Karen L. ; Moloo, Jamaluddin ; Oparil, Suzanne ; Piller, Linda B. ; Simmons, Debra L. ; Sweeney, Mary Ellen ; Whelton, Paul K. ; Wong, Nathan D. ; Wright, Jackson T. / Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension the ALLHAT diabetes extension study. In: Circulation: Cardiovascular Quality and Outcomes. 2012 ; Vol. 5, No. 2. pp. 153-162.
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AU - Barzilay, Joshua I.

AU - Davis, Barry R.

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AU - Cutler, Jeffrey A.

AU - Einhorn, Paula T.

AU - Black, Henry R.

AU - Cushman, William

AU - Ford, Charles E.

AU - Margolis, Karen L.

AU - Moloo, Jamaluddin

AU - Oparil, Suzanne

AU - Piller, Linda B.

AU - Simmons, Debra L.

AU - Sweeney, Mary Ellen

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AU - Wong, Nathan D.

AU - Wright, Jackson T.

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N2 - 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. Methods and 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.

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