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Impact of Abdominal Obesity on Incidence of Adverse Metabolic Effects Associated With Antihypertensive Medications — Cooper-DeHoff et al. 55 (1): 61 — Hypertension

Impact of Abdominal Obesity on Incidence of Adverse Metabolic Effects Associated With Antihypertensive Medications — Cooper-DeHoff et al. 55 (1): 61 — Hypertension

Impact of Abdominal Obesity on Incidence of Adverse Metabolic Effects Associated With Antihypertensive Medications
Rhonda M. Cooper-DeHoff; Sheron Wen; Amber L. Beitelshees; Issam Zineh; John G. Gums; Stephen T. Turner; Yan Gong; Karen Hall; Vishal Parekh; Arlene B. Chapman; Eric Boerwinkle; Julie A. Johnson

From the Colleges of Pharmacy (R.M.C.-D., S.W., J.G.G., Y.G., J.A.J.) and Medicine (R.M.C.-D., J.G.G., K.H., J.A.J.) and Center for Pharmacogenomics (R.M.C.-D., S.W., J.G.G., Y.G., J.A.J.), University of Florida, Gainesville, Fla; School of Medicine (A.L.B.), University of Maryland, Baltimore, Md; US Food and Drug Administration (I.Z.), Silver Spring, Md; Mayo Clinic College of Medicine (S.T.T.), Rochester, Minn; Morehouse School of Medicine (V.P.), Atlanta, Ga; School of Medicine (A.B.C.), Emory University, Atlanta, Ga; Human Genetics Center and Institute of Molecular Medicine (E.B.), University of Texas at Houston, Houston, Tex.

Correspondence to Rhonda M. Cooper-DeHoff, Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, 1600 SW Archer Rd, Box 100486, Gainesville, FL 32610-0486. E-mail [email protected]

We assessed adverse metabolic effects of atenolol and hydrochlorothiazide among hypertensive patients with and without abdominal obesity using data from a randomized, open-label study of hypertensive patients without evidence of cardiovascular disease or diabetes mellitus. Intervention included randomization to 25 mg of hydrochlorothiazide or 100 mg of atenolol monotherapy followed by their combination. Fasting glucose, insulin, triglycerides, high-density lipoprotein cholesterol, and uric acid levels were measured at baseline and after monotherapy and combination therapy. Outcomes included new occurrence of and predictors for new cases of glucose ≥100 mg/dL (impaired fasting glucose), triglyceride ≥150 mg/dL, high-density lipoprotein ≤40 mg/dL for men or ≤50 mg/dL for women, or new-onset diabetes mellitus according to the presence or absence of abdominal obesity. Abdominal obesity was present in 167 (58%) of 395 patients. Regardless of strategy, in those with abdominal obesity, 20% had impaired fasting glucose at baseline compared with 40% at the end of study (P<0.0001). Proportion with triglycerides ≥150 mg/dL increased from 33% at baseline to 46% at the end of study (P<0.01). New-onset diabetes mellitus occurred in 13 patients (6%) with and in 4 patients (2%) without abdominal obesity. Baseline levels of glucose, triglyceride, and high-density lipoprotein predicted adverse outcomes, and predictors for new-onset diabetes mellitus after monotherapy in those with abdominal obesity included hydrochlorothiazide strategy (odds ratio: 46.91 [95% CI: 2.55 to 862.40]), female sex (odds ratio: 31.37 [95% CI: 2.10 to 468.99]), and uric acid (odds ratio: 3.19 [95% CI: 1.35 to 7.52]). Development of adverse metabolic effect, including new-onset diabetes mellitus associated with short-term exposure to hydrochlorothiazide and atenolol was more common in those with abdominal obesity. Key Words: atenolol • hydrochlorothiazide • abdominal obesity • metabolic syndrome • new-onset diabetes mellitus • hypertension
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