Metabolic manifestations of low-dose diuretics

Hypertension has been defined and treated as a disease of abnormal systolic and diastolic blood pressure. Recent data have, however, demonstrated that effective blood-pressure control has not resulted in the expected decrease in coronary artery disease. These findings are probably a result of hypertension being a complex inherited syndrome of cardiovascular risk factors, all of which are genetically linked and all of which contribute to the development of cardiovascular disease in these patients. Included in the hypertension syndrome are abnormalities of lipid profile, insulin resistance, changes in renal function, left ventricular hypertrophy and reduced arterial compliance. In many patients, high blood pressure is a late manifestation of this disease process. Since all cardiovascular risk factors contribute to heart disease in these patients, they should all be considered in the management of this disease process. Diuretics and β blockers, when used at high doses, negatively impact lipid metabolism and insulin sensitivity, while angiotensin converting enzyme (ACE) inhibitors and calcium antagonists tend to have a neutral effect on these metabolic risk factors. These findings have resulted in decreased use of diuretics and β blockers in favor of newer agents such as ACE inhibitors and calcium antagonists. However, recent data have demonstrated that when used at low doses (6.25 or 12.5 mg of hydrochlorothiazide), diuretics lack significant metabolic side effects while bringing about significant reductions in blood pressure. Thus, at these doses, hydrochlorothiazide is a useful drug in the treatment of hypertension, both as monotherapy and in combination therapy.