Impact of Abdominal Obesity on Incidence of Adverse Metabolic Effects Associated With Antihypertensive Medications

Abstract

Abstract-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 Ն100 mg/dL (impaired fasting glucose), triglyceride Ն150 mg/dL, high-density lipoprotein Յ40 mg/dL for men or Յ50 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 (PϽ0.0001). Proportion with triglycerides Ն150 mg/dL increased from 33% at baseline to 46% at the end of study (PϽ0.01). New-onset diabetes mellitus occurred in 13 patients (6%) with and in 4 patients (2%) without abdominal obesity. Key Words: atenolol Ⅲ hydrochlorothiazide Ⅲ abdominal obesity Ⅲ metabolic syndrome Ⅲ new-onset diabetes mellitus Ⅲ hypertension I t is estimated that Ͼ72 million US adults are obese, affecting 33% of men and 35% of women. 1 This epidemic is associated with increased mortality, 2 primarily via metabolic and cardiovascular (CV) complications. Abdominal fat accumulation increases CV disease risk independent of overall adiposity. 3 The presence of abdominal obesity provides additional predictive information for the development of CV morbidity and mortality compared with increased body mass index alone. 4 Hypertension requiring treatment is highly prevalent in those with obesity and abdominal obesity, regardless of sex or ethnicity, and is poorly controlled. [5][6][7] Some antihypertensives are associated with adverse metabolic effects (AMEs), including hyperglycemia, hypertriglyceridemia, and hyperuricemia. 8 The predisposing factors for these AMEs are unknown, but preexisting abdominal obesity may contribute. Although there are many studies in older, high-risk populations indicating that thiazide diuretics and ␤-blockers increase the incidence of new-onset diabetes mellitus compared with other antihypertensive regimens, 9 our knowledge is incomplete with regard to the development of

Effects of a Fixed Combination of Losartan With Hydrochlorothiazide on Glucose Tolerance in Hypertensive Patients Uncontrolled with Angiotensin II Receptor Blockers Alone

“…It has been reported that low doses of HCTZ caused hypokalemia and glucose tolerance aggravation within three months, but we showed that ARB constrained the effect of HCTZ when we changed from a common dose of ARBs to ARB with HCTZ 27,28) . The significant improvement of the urine albumin/creatinine ratio might be due to the effect of adequate lowering of blood pressure 29) .…”

Stopping the cardiovascular disease continuum: Focus on prevention

“…There are several classes of antihypertensive drugs to choose from because they are all effective in lowering BP [63] , but individualization of treatment may be necessary. Diuretics, although effective in lowering BP, may not be a good choice for hypertensive subjects with diabetes or the metabolic syndrome, because they increase blood glucose, which is associated with high incidence of cardiovascular morbidity and mortality [64][65][66] . Drugs that block the RAS such as ACEIs, ARBs, and DRIs are preferable in such cases, because they interfere with the action of angiotensin II, which is responsible for cardiovascular remodeling, new-onset diabetes mellitus, and HF (Figure 2).…”

Effects on Insulin Action of Adding Low-Dose Thiazide to Angiotensin-Converting Enzyme Inhibitor in Essential Hypertension

“…4,6,10,23 Such an effect occurs after short-term exposure and is more common in those with abdominal obesity. 24 This has created a dilemma when choosing appropriate therapy. Although clinicians rely heavily on the results of long-term clinical outcome studies, inevitably these do not cover all situations where a decision about drug choice is required.…”