Diuretics and ß-Blockers: Is There a Risk for Dyslipidemia?

Matthew R. Weir, MD, Marvin Moser, MD, Division of Nephrology, University of Maryland School of Medicine, Baltimore, Md; Yale University School of Medicine, New Haven, Conn.

Am Heart J. 2000;139(1) 

In This Article

Proposed Mechanisms for Effects of Thiazide Diuretics on Lipids

There are several theories as to how diuretics may induce dyslipidemia. One theory suggests that a thiazide-induced reduction in insulin sensitivity may cause an associated increase in hepatic production of cholesterol.[37,44] However, this observation may be more related to the reduction in serum potassium that may occur with high dosages of thiazides. There also appear to be sex differences in lipoprotein responses with thiazide therapy. Among postmenopausal women, diuretics may induce a greater short-term increase in total cholesterol and LDL-C than they do among men.[45] No changes are observed among premenopausal women, suggesting that there may be a protective effect of estrogens.[44] Estrogen therapy also has been demonstrated to increase the number of hepatic LDL binding sites and to stimulate hepatic uptake of chylomicron remnants.[46]

In a review of data on lower doses of thiazide diuretics and their effect on lipid metabolism, one sees that most studies do not show any significant effect on lipid profile. Most of these studies have been conducted with 12.5 mg hydrochlorothiazide. As shown in Table I, minimal effects on lipids are seen with most antihypertensive drugs. In only one study conducted with postmenopausal women was there any evidence that 12.5 mg hydrochlorothiazide produced effects on lipids similar to those with higher doses used in earlier clinical trials.[45] This suggests that when one uses low doses of thiazides even the short-term negative effects on lipids are absent. This also may be related to the decreased likelihood of inducing hypokalemia and associated insulin resistance, which may have an impact on hepatic lipoprotein production.[47]