Effects of antihypertensive therapy on serum lipoproteins.

Abstract

Several drugs used for standard antihypertensive therapy may also interact with the lipoprotein metabolism. The following has been observed after 1 to 12 months of treatment. Various thiazide-type diuretics may significantly increase the potentially atherogenic serum low-density-lipoprotein cholesterol (LDL-C) and/or very-LDL-C-fractions, while the antiatherogenic high-density-lipoprotein cholesterol (HDL-C) is largely unchanged. Certain loop-diuretics also increase the LDL-C/HDL-C ratio and both types of diuretics elevated serum triglycerides (Tg) in some but not all studies. LDL-C was increased in diuretic-treated men and in chlorthalidone-treated postmenopausal women, but not in chlorthalidone-treated premenopausal women. The latter may be protected from this effect. Only two diuretics evaluated, namely indapamide and spironolactone, had no apparent influence on lipoproteins. Beta-blocker monotherapy may often increase Tg and slightly decrease HDL-C. The magnitude of these changes did not distinctly differ between highly cardioselective and nonselective beta-blockers, but it was less pronounced on beta-blockers than on those without intrinsic sympatholytic activity. Other sympatholytics such as reserpine, methyldopa, clonidine, debrisoquine, the alpha-beta-blocker labetalol, or the postsynaptic alpha-blocker, prazosin, did not affect or even slightly decrease Tg or total C, LDL-C, and very-LDL-C values. With combinations, a tendency for increased Tg and lower HDL-C was also apparent during thiazide-type diuretic-beta-blocker therapy. However, diuretic-induced increases in LDL-C were prevented or reversed by concomitant beta-blockade, but not by reserpine, methyldopa, or clonidine. Monotherapy with the potent direct vasodilator, carprazidil, improved blood pressure and significantly increased HDL-C. Prospective long-term studies are needed to clarify the course and the pathogenic and prognostic relevance of lipoprotein changes induced by certain diuretics or beta-blockers.

Plasma lipoprotein levels in treated and untreated hypertensive men and women. The National Heart Foundation of Australia Risk Factor Prevalence Study.

“…These results are consistent with the Lipid Research Clinics' observation of a lower HDL cholesterol level and a higher TG level in the small group of subjects receiving propranolol in comparison with matched controls from the same study population. 31 Our finding of similar levels of TC and LDL cholesterol in treated and untreated hypertensive subjects suggests that: 1) diuretics were most often prescribed in conjunction with beta-blockers, which prevent the increase in TC and LDL cholesterol normally associated with diuretic therapy; 16 or 2) the effects of diuretic monotherapy on TC and LDL cholesterol are not of sufficient magnitude or duration to significantly affect population lipid or lipoprotein levels.…”

“…10 " 15 When beta-blockers and diuretics are given concurrently, HDL cholesterol is decreased and TG is increased, but there is no increase in total cholesterol or LDL cholesterol. 16 Decreases in HDL cholesterol have also been reported 1718 after treatment with methyldopa. The changes in plasma lipid and lipoprotein levels associated with antihypertensive treatment have been shown 17 to significantly offset the reduction in the calculated risk of coronary artery disease (CAD) that results from blood pressure reduction.…”

Serum lipoproteins during treatment with the antihypertensive agent indapamide.

“…Also, HDL-C and, whenever measured, HDL's major apoproteins Al and A2 (apo Al and A2) were largely unchanged with thiazides. 12 This documents a frequent occurrence of elevated LDL-C/HDL-C and total C/HDL-C ratios in thiazidetreated men or postmenopausal women. Loop diuretics, such as furosemide, mefruside, and muzolimine, also increased these ratios due to mildly raised total or LDL-C and unchanged or even slightly decreased HDL-C values.…”

Serum lipoprotein levels during long-term treatment of hypertension with indapamide.

“…8 More recent studies 9 "" focused on impaired lipid metabolism due to long-term therapy with sulfonamide diuretics. Weidmann et al 12 showed that hydrochlorothiazides and chlorthalidone increase plasma triglycerides and total cholesterol in mildly hypertensive patients. Other investigations also demonstrated a tendency to increased triglyceride and/or total cholesterol levels in patients treated with thiazide diuretics.""…”

“…Whether or not elevation of serum LDL cholesterol levels during treatment with chlorthalidone or hydrochlorothiazide 13 or elevation of beta-lipoprotein fraction during furosemide therapy 12 will persist during long-term treatment and modify the coronary risk is presently unknown.…”