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

Abstract

SUMMARY The beneficial effect of antihypertensive pharmacotherapy in decreasing morbidity and mortality in hypertensive patients may be counteracted by metabolic and biochemical disturbances, such as hypokalemia, hyperglycemia, hyperuricemia, and hyperlipoproteinemia, that occur with the administration of thiazides and related diuretics. Antiatherogenk high-density lipoprotein cholesterol may be unchanged, whereas the potentially atherogenic low-density lipoprotein cholesterol may be increased by long-term therapy with thiazide diuretics. Indapamide is a methylindoline antihypertensive diuretic with a considerable peripheral vasodilatory effect. At a low dose of 2.5 mg daily, it did not alter total circulating cholesterol, in contrast to chlorthalidone. High-density lipoprotein cholesterol levels increased significantly in 20 hypertensive men after 6 months of therapy with indapamide, resulting in a significant fall of the low-density lipoprotein/high-density lipoprotein ratio, an atherogenic risk factor, regardless of preexisting lipid disorders. (Hypertension 7 [Suppl IT]: II-170-H-174, 1985) KEY WORDS • total body potassium • high-density lipoprotein cholesterolM ULTICENTER trials 13 demonstrated the beneficial effect of antihypertensive pharmacotherapy in decreasing morbidity and mortality in patients with high blood pressure, including mild hypertension. Long-term antihypertensive therapy with thiazides and related diuretics has been associated with distinct biochemical side effects, including changes in total body potassium, 4 hypokalemia, 5 hyperglycemia, 6 and hyperuricemia, 7 and to a lesser degree, decreased glucose tolerance and worsening diabetes mellitus. 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."" 13 Significant increase of the potentially atherogenic serum low-density lipoprotein (LDL) cholesterol accom- panied by a possible increase of very low-density lipoprotein (VLDL) cholesterol fractions may be detected with long-term treatment with thiazide diuretics, whereas the level of antiatherogenic high-density lipoprotein (HDL) cholesterol remains unchanged. It is therefore of considerable importance to study lipoproteins, which are probably more important correlates of atherogenesis than lipid levels per se with any longterm diuretic and/or antihypertensive therapy.Miller et al. w were among the first to note an inverse correlation between HDL cholesterol and the prevalence of coronary heart disease (CHD). Data generated from the Framingham Study 13 showed that the cholesterol ratio (total cholesterol to HDL cholesterol) was higher among men and women with clinical evidence of CHD than among those with standard risk factor...

Optimizing cardiovascular risk reduction during antihypertensive therapy.

“…52 Indapamide has also been reported not to cause hypokalemia at doses of 2.5 mg/day or less in one study, 53 but in two other studies, a slight but statistically significant decrease was seen at the same dose. 54 - 55 Administration of copious amounts of supplemental potassium (60-120 meq/day) or potassium-sparing agents can prevent diuretic-induced hypokalemia. However, the expense and relative unpalatability of the former and the potential side effects and variable efficacy of the latter often make these approaches unsatisfactory.…”

“…Not only have the benzodiathiazide agents been implicated, but also chlorthalidone and loop diuretics such as furosemide, particularly when given at antihypertensive doses. 72 Indapamide at a dose of 25 mg/ day has been reported to have no adverse lipid effects, 54 -55 although one study reported an elevation in serum cholesterol with this agent. 73 The reformulation of metolazone with increased bioavailability (Mykrox) was found to raise cholesterol, triglycerides, and LDL when 0.5 mg was given, as was hydrochlorothiazide plus triamterene.…”

Efficacious Response with Low-Dose Indapamide Therapy in the Treatment of Type II Diabetic Patients with Normal Renal Function or Moderate Renal Insufficiency and Moderate Hypertension

“…Apart from a few cases where blood glucose levels have risen following indapamide therapy, the overall results of studies of up to 1 year's duration have shown that 2.5 mg indapamide/day does not adversely affect glucose tolerance in diabetic and nondiabetic hypertensive patients [4,5,11,14]. Similarly, this dose of indapamide did not cause a significant increment in total plasma cholesterol, triglycerides or low density and high density lipoproteins [13][14][15].…”

Radical Scavenging Properties of Indapamide and Renal Protection in Dahl Salt-Sensitive Rats.

“…These factors might be responsible for the lack of renal protection with thiazide treatment. Conversely, the favorable effects by indapamide may be attributable in part to the fact that untoward metabolic alterations are rarely reported in its clinical usage (27,28).…”