Blood Pressure Responses and Metabolic Effects of Hydrochlorothiazide and Atenolol

• Authors: Steven M. Smith, University of Colorado; Yan Gong, University of Florida; Stephen T. Turner, Mayo Clinic; Rhonda M. Cooper-DeHoff, University of Florida; Amber L. Beitelshees, University of Maryland; Arlene B Chapman, Emory University; Eric Boerwinkle, University of Texas Houston; Kent Bailey, Mayo Clinic; Julie A. Johnson, University of Florida; John G. Gums, University of Florida
• Journal Title: American Journal of Hypertension
• Volume: Volume 25, Number 3
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option D | 2012-03-01, Pages 359-365
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/ajh.2011.215
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, Pharmacology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Peripheral Vascular Disease; Cardiovascular System & Cardiology; thiazide diuretics; atenolol; beta-blockers; blood pressure; hydrochlorothiazide; hypertension; metabolic effects; DIABETES-MELLITUS; HYPERTENSIVE PATIENTS; GLUCOSE; CARVEDILOL; DIURETICS; THERAPIES; INSULIN; TRIAL; HEART; URATE

Abstract

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.