Rubino Mordasini

Increased serum low-density lipoprotein cholesterol in men treated short-term with the diuretic chlorthalidone☆☆☆

The effect of the diuretic chlorthalidone (100 mg/day for 6 weeks) on serum lipoproteins was evaluated in 37 subjects. In 19 men with essential hypertension (aged 41 +/- 3 yr), 8 normal men (26 +/- 3 yr), or all of these men considered together, chlorthalidone significantly increased serum low density lipoprotein--cholesterol (LDL-C) by 20% (p less than 0.05 to less than 0.01). There was also a tendency for increased LDL-C in seven postmenopausal women (+/- 15%) but not in three premenopausal women with essential hypertension. High density lipoprotein--cholesterol was not significantly changed in hypertensive women or normal men and decreased slightly (p less than 0.05) in hypertensive men. Apolipoproteins A-I, A-II, and B were not changed significantly in women or men. Diuretic-induced lipoprotein alterations were not associated with altered plasma volume and unrelated to variations in serum potassium, glucose, insulin levels, blood pressure, and body weight. Short-term diuretic therapy with chlorthalidone may increase serum LDL-C in young or middle-aged men with normal or high blood pressure.

Secondary type II hyperlipoproteinemia in patients with anorexia nervosa

In 18 patients with anorexia nervosa, plasma cholesterol and triglyceride concentral concentrations were repeatedly determined over a period of 14 mo. In 11 patients elevated cholesterol concentrations were found which were due to an increase of low-density lipoprotein cholesterol, whereas high-density lipoprotein and very low density lipoprotein cholesterol levels were in the normal range. The elevated cholesterol values did not correlate with clinical and laboratory parameters such as the degree of weight loss and thyroid function tests. In follow-up studies it could be shown that in patients who regained their original weight, elevated plasma cholesterol concentrations fell to normal levels parallel to weight increase. In patients who showed no change in weight, however, cholesterol levels remained high. The cause for this secondary type II hyperlipoproteinemia in anorexia nervosa is not known. Hepatic triglyceride lipase and lipoprotein lipase activities in post-heparin plasma were found to be low despite normal triglyceride concentrations.

Menopause-Dependent Plasma Lipoprotein Alterations in Diuretic-Treated Women

The effects of chlorthalidone, 100 mg/d given for 6 weeks, on serum lipids and lipoproteins were assessed in 22 premenopausal and 18 postmenopausal women. In the latter, chlorthalidone significantly increased total serum cholesterol (13%, p less than 0.001), low-density-lipoprotein (LDL) cholesterol (21%, p less than 0.001) and apoprotein B (16%, p less than 0.05). In contrast, these values were not altered in the premenopausal group. Levels of LDL cholesterol, high-density-lipoprotein cholesterol, total and very-low-density triglycerides, apoproteins A1 and A2, and plasma volume, plasma glucose, insulin, epinephrine, estradiol, and free fatty acids were unchanged in both groups. Chlorthalidone-induced changes in levels of LDL cholesterol did not correlate significantly with variations in blood pressure, plasma potassium, uric acid, renin, aldosterone, or norepinephrine levels. These findings indicate that the thiazide-like diuretic chlorthalidone increases serum LDL cholesterol in postmenopausal but not in premenopausal women.

Diuretic treatment and serum lipoproteins: Effects of tienilic acid and indapamide

SummaryTreatment with the commonly used diuretic, chlorthalidone, has previously been found to increase the serum low-density-lipoprotein cholesterol (LDL-C) fraction. Therefore, the effects of two new agents, tienilic acid (a combined diuretic-uricosuric) and indapamide on serum lipid and lipoprotein levels were assessed. Six weeks of treatment with tienilic acid, 250 mg/day, markedly decreased serum uric acid and significantly increased LDL-C and triglycerides in 16 men. In contrast, indapamide 2.5 mg/day, had no apparent influence on serum lipids or lipoproteins in 18 men.ZusammenfassungIn einer früheren Studie fanden wir, daß eine Kurzzeitbehandlung mit dem Diuretikum Chlorthalidon eine Erhöhung der Serum Low-Density-Lipoprotein-Cholesterin Fraktion (LDL-C) bewirkt. In der vorliegenden Arbeit wurde der Einfluß von zwei neueren Substanzen auf die Serum Lipidund Lipoprotein-Spiegel untersucht. Dabei handelte es sich um Tienilsäure, das gleichzeitig diuretische und uricosurische Wirksamkeit besitzt, sowie um Indapamid. Eine 6-wöchige Behandlung mit Tienilsäure in einer Dosis von 250 mg/Tag bewirkte bei 16 Männern eine deutliche Abnahme der Serum-Harnsäure und eine signifikante Zunahme von LDL-C und Serum-Triglyzeriden. Dagegen hatte eine gleichlange Behandlung mit Indapamid in einer Dosis von 2,5 mg/Tag bei 18 Männern keinen erkennbaren Einfluß auf Serum-Lipide oder -Lipoproteine.

Blood pressure and adipose tissue linoleic acid.

SummaryIn a natural, “free-living population” of 650 men, surveyed with the purpose of health assessment within an epidemiological design, a strongly significant negative correlation between the relative linoleic acid composition of adipose tissue and blood pressures was found (P<0.001). This correlation remained significant when age and weight were statistically controlled for. Thus, dietary, lipid-lowering linoleic acid seems to effect blood pressures as well in a favorable way.

Reversal of diuretic-induced increases in serum low-density-lipoprotein cholesterol by the betablocker pindolol

Seventeen patients with mild to moderate essential hypertension received during three consecutive 4 wk periods a matched placebo, the thiazide-like diuretic, clopamide in a low dosage of 5 mg/day, or this diuretic combined with the betablocker, pindolol in a low dosage of 10 mg/day. Compared to placebo conditions, clopamide monotherapy significantly increased serum low-density lipoprotein cholesterol (LDL-C) by 13% (p less than 0.025). Following addition of pindolol, serum LDL-C was restored to control values. These variations in serum LDL-C were unrelated to concomitant changes in blood pressure, plasma potassium, renin activity or aldosterone levels. Blood pressure in the supine position was reduced from 152/99 +/- 13/9 mm Hg (+ SD) to 141/93 +/- 15/7 mm Hg following diuretic-monotherapy and to 139/90 +/- 12/9 mm Hg following diuretic-betablocker combination treatment. These findings suggest that antihypertensive combination treatment with low doses of clopamide and pindolol is not only effective and well tolerated, but may also avoid the increase in serum LDL-C levels occurring when the thiazide-like diuretic is given alone.

Quantitation of the major apoproteins of human high density lipoproteins by solid phase radioimmunoassay

Serum high density lipoprotein (HDL) plays a major role in the transport and metabolism of cholesterol which is mediated through its interaction with the enzyme lecithin: cholesterol acyltransferase (LCAT) [l] . Evidence has also been presented that HDL facilitates the uptake of cholesterol from peripheral tissues and the clearance of cholesterol from arterial wall [2] . Furthermore, decreased HDL and HDL cholesterol levels were shown to be correlated to the incidence of coronary heart disease [3,4] . HDL contains two major apoprotein components which have been designated apoprotein A-I (apo A-I) and apoprotein A-II (apo A-II) [5-71. These two protein moieties account for 90% of the total protein content of HDL [8] , and are believed to be of central importance not only for the structural but also for the functional integrity of HDL. Apo A-I has been shown to activate LCAT in vitro [9] and to remove cholesterol from the aortic smooth muscle cells [lo] . Rapid and precise measurement of apo A-I and apo A-II would be valuable in elucidating their structural and physiological functions. To this end we have

Reduced LDL- and increased HDL-apoproteins in patients with hypercholesterolaemia under treatment with bezafibrate.

The effect of bezafibrate on serum lipids, lipoproteins and the apoproteins A-I, A-II and B was studied in 18 patients with primary hypercholesterolaemia. Total cholesterol was lowered by 20% (P less than 0.05), LDL-cholesterol by 24% (P less than 0.05), and apo B by 14% (P less than 0.05), which is comparable to the effect obtained with anion exchange resins but with far fewer side-effects. HDL increased significantly during bezafibrate treatment both by measurement of HDL-cholesterol (+54%, P less than 0.05) and by the determination of HDL-apoproteins A-I (+ 19%, P less than 0.05) and A-II (+ 23%, P less than 0.05). This increase of HDL and the decrease of triglycerides was maintained for 6 weeks of placebo treatment after cessation of bezafibrate, while serum total and LDL cholesterol as well as apo B returned to their baseline levels.

[Secondary hyperlipoproteinemia induced by diuretic therapy (author's transl)].

In order to study the degree and pathogenic aspects of the secondary hyperlipoproteinemia in patients under diuretic therapy we measured serum lipids, lipoproteins and the apoproteins A1, A2 and B in 12 adults after a 4 weeks placebo period and 6 weeks of treatment with chlorthalidon. There was a significant increase in atherogenic low density lipoproteins (LDL), (18%, P less than 0.05) whereas the high density lipoprotein-cholesterol Apo A1 and A2 levels were not significantly altered. The same was true for the total serum triglyceride- and the very low density lipoprotein- and LDL-triglyceride levels. The activity of lipoprotein lipase and hepatic triglyceride lipase was slightly but not significantly increased. A delayed LDL-catabolism seems to be the most probable pathogenic mechanism underlying the Chlorthalidon-induced hyperlipoproteinemia.SummaryIn order to study the degree and pathogenic aspects of the secondary hyperlipoproteinemia in patients under diuretic therapy we measured serum lipids, lipoproteins and the apoproteins A1, A2 and B in 12 adults after a 4 weeks placebo period and 6 weeks of treatment with chlorthalidon. There was a significant increase in atherogenic low density lipoproteins (LDL), (18%,P<0.05) whereas the high density lipoprotein-cholesterol, Apo A1 and A2 levels were not significantly altered. The same was true for the total serum triglyceride- and the very low density lipoprotein- and LDL-triglyceride levels. The activity of lipoprotein lipase and hepatic triglyceride lipase was slightly but not significantly increased.A delayed LDL-catabolism seems to be the most probable pathogenic mechanism underlying the Chlorthalidon-induced hyperlipoproteinemia.ZusammenfassungZur Abklärung von Ausmaß und Pathogenese der Diuretikainduzierten sekundären Hyperlipoproteinämie wurden bei 12 Probanden die Serumlipide und -lipoproteine, die Apoproteine A1, A2 und B sowie die lipolytischen Enzyme Lipoproteinlipase und hepatische Triglyzeridlipase nach einer vierwöchigen Placeboperiode und nach 6 Wochen Behandlung mit Chlorthalidon untersucht.Außer einem signifikanten Anstieg der atherogenen low density Lipoproteine (LDL), (der LDL-Cholesteringehalt nahm um 18% zu,P<0,05) waren keine signifikanten Lipoproteinveränderungen faßbar. Insbesondere blieb die high density Lipoprotein-Konzentration sowohl gemessen am HDL-Cholesteringehalt wie an den beiden Apoproteinen A1 und A2 nahezu unverändert. Der leichte statistisch nicht signifikante Anstieg der Serumtriglyzeride war begleitet von einer ebenso wenig signifikanten Zunahme der Aktivität der Lipoproteinlipase und der hepatischen Triglyzeridlipase. Pathogenetisch dürfte der sekundären Hyperlipoproteinämie unter Chlorthalidon am ehesten eine Abbaustörung der LDL zugrunde liegen.

REVERSAL OR PREVENTION OF DIURETIC-INDUCED ALTERATIONS IN SERUM LIPOPROTEINS WITH BETABLOCKERS

In 18 patients with essential hypertension serum low density lipoprotein cholesterol (LDL-C) was significantly (P less than 0.001) increased following short-term chlorthalidone therapy, but not during combination therapy with chlorthalidone and a betablocker. This tendency was similar in two subgroups which were studied with an inverse sequence of drug administration. In Group I (11 men), a 22% increase (P less than 0.01) in LDL-C during chlorthalidone monotherapy was restored to normal 6 weeks after addition to a betablocker to the diuretic; in Group II (5 men, 2 postmenopausal women) LDL-C levels were increased by 41% (P less than 0.05) 6 weeks after withdrawal of the betablocker from the combination therapy. No significant changes occurred during either the treatment phase in high density lipoprotein cholesterol or apoprotein B levels. It is concluded that combination therapy with a betablocker may prevent or reverse an increase in serum LDL-C associated with short-term chlorthalidone monotherapy.