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Author Notes:

Steven M. Smith (steven.smith@ucdenver.edu).

We acknowledge and thank the valuable contributions of the study participants, support staff, and study physicians: Drs George Baramidze, Carmen Bray, R. Whit Curry, Karen Hall, Frederic Rabari-Oskoui, Dan Rubin, and Seigfried Schmidt.

The authors declared no conflict of interest.


Research Funding:

This work is supported by a grant from the National Institutes of Health (Bethesda, MD), grant # U01 GM074492, funded as part of the Pharmacogenetics Research Network.

Additional support for this work includes: K23 grants HL091120 (A.L.B.) and HL086558 (R.M.C.-D); CTSA grants UL1-RR029890 (University of Florida), UL1-RR025008 (Emory University), and UL1-RR024150 (Mayo Clinic); and funds from the Mayo Foundation.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Peripheral Vascular Disease
  • Cardiovascular System & Cardiology
  • thiazide diuretics
  • atenolol
  • beta-blockers
  • blood pressure
  • hydrochlorothiazide
  • hypertension
  • metabolic effects

Blood Pressure Responses and Metabolic Effects of Hydrochlorothiazide and Atenolol


Journal Title:

American Journal of Hypertension


Volume 25, Number 3


, Pages 359-365

Type of Work:

Article | Post-print: After Peer Review


Background: Thiazides and Β-blockers cause adverse metabolic effects (AMEs), but whether these effects share predictors with blood pressure (BP) response is unknown. We aimed to determine whether AMEs are correlated with BP response in uncomplicated hypertensives. Methods: In a multicenter, open-label, parallel-group trial, we enrolled 569 persons, aged 17-65, with random assignment to 9 weeks of daily hydrochlorothiazide (HCTZ) or atenolol monotherapy, followed by 9 weeks of add-on therapy with the alternate agent. Measurements included home BP, averaged over 1 week, weight and fasting levels of serum glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and uric acid (UA) before and after monotherapy and after add-on therapy. Results: Increases in UA correlated with reductions in systolic BP (SBP) (r = 0.18; P = 0.003) and diastolic BP (DBP) (r = 0.20; P = 0.001) following HCTZ monotherapy and add-on therapy (r = 0.27 and r = 0.21, respectively; both P< 0.001). After adjustment for age, race, gender, and baseline body mass index (BMI), only the correlation between UA and DBP response became nonsignificant. Reductions in HDL correlated with systolic response following atenolol monotherapy (r = 0.18; P = 0.002) and with systolic and diastolic response following add-on therapy (r = 0.30 and r = 0.24, respectively; both P< 0.0001). These correlations remained significant after covariate adjustment. BP responses were not correlated with changes in glucose, LDL, triglycerides, or weight following either therapy. Conclusions: BP response correlated with changes in UA following HCTZ therapy and HDL following atenolol therapy. No other significant correlations were observed between BP response and AMEs, suggesting that these effects generally do not share predictors. Patients should be monitored for AMEs, regardless of BP response.

Copyright information:

© 2012 American Journal of Hypertension, Ltd.

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