The effects of antihypertensive drugs on serum lipids and lipoproteins, I. Diuretics.

Potassium-losing diuretic drugs, when used in the treatment of hypertension, cause unfavourable short term alterations in blood lipid and lipoprotein concentrations. The disturbance is characterised by increases in total cholesterol of 4 to 13%, in low density lipoprotein (LDL) cholesterol of 7 to 29%, in very-low density lipoprotein (VLDL) cholesterol of 7 to 56%, and in total triglyceride of 14 to 37%. The disturbance is variable among patients and over time in individual patients; it is absent in some. In long term treatment the data are fragmentary, but total cholesterol and triglycerides usually return to baseline values or below. The variability of the lipid response to diuretics has several consequences: firstly, it necessitates a sizeable study population (minimum of 30 patients) in order to document convincingly its presence or absence; secondly, lipoprotein fractions must be examined to define the pattern of the disturbance; and thirdly, the subsidence of the diuretic-induced lipid effects in long term treatment may be more apparent than real because even larger decreases have been noted in untreated groups in the few studies that wisely included these important controls for comparison. While the cause of the lipid-lipoprotein aberration is unclear, existing data suggest that certain attributes of the study population influence the response, i.e. age, habitual diet, hormonal milieu (gender), baseline cholesterol concentrations, and induced glucose intolerance. The apparent absence of lipid alterations with indapamide needs to be substantiated and compared with low doses of a standard thiazide-type drug. The lipid-lipoprotein effects of diuretics seem inconsequentially small, but they may contribute to the disappointing failure of diuretic-based regimens to lower the incidence of coronary heart disease in hypertensive patients. Nevertheless, diuretic-based treatment remains the only therapeutic regimen of proven benefit to congestive heart failure in patients with hypertension, and it is superior to beta-blockade in preventing stroke. Hence, alternative antihypertensive drug regimens must be compared prospectively with diuretics in order to verify any theoretic superiority.