Blood Pressure Responses and Metabolic Effects of Hydrochlorothiazide and Atenolol

• Published in: American journal of hypertension 2012-03, Vol.25 (3), p.359-365
• Main Authors: Smith, Steven M., Gong, Yan, Turner, Stephen T., Cooper-DeHoff, Rhonda M., Beitelshees, Amber L., Chapman, Arlene B., Boerwinkle, Eric, Bailey, Kent, Johnson, Julie A., Gums, John G.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Arterial hypertension. Arterial hypotension; Atenolol - pharmacology; Atenolol - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Blood Glucose - drug effects; Blood Pressure - drug effects; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide - pharmacology; Hydrochlorothiazide - therapeutic use; Hypertension - drug therapy; Lipoproteins, HDL - blood; Lipoproteins, HDL - drug effects; Lipoproteins, LDL - blood; Lipoproteins, LDL - drug effects; Male; Medical sciences; Middle Aged; Triglycerides - blood; Uric Acid - blood
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1038/ajh.2011.215

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.