Increased Serum Low-density Lipoprotein Research Articles

Serum Lipoproteins During Treatment with Antihypertensive Drugs

Several drugs used for antihypertensive therapy may modify the lipoprotein metabolism. Thiazides in high dosage and loop diuretics can increase serum low-density lipoprotein (LDL) cholesterol and/or very-LDL cholesterol and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio, while HDL cholesterol is largely unchanged; triglycerides (Tg) are also often elevated. Premenopausal women may be protected from this side effect. Whether diuretic-induced dyslipidemia is dose-dependent and low thiazide doses (i.e., hydrochlorothiazide < or = 12.5 mg daily) are interacting less, awaits clarification. beta-Blockers without intrinsic sympathomimetic activity increase serum triglycerides and tend to lower the potentially antiatherogenic HDL cholesterol. The diuretic-antihypertensive agent indapamide, given at a dose of 2.5 mg/day, is neutral with regard to serum lipoprotein and glucose metabolism. The potassium-sparing diuretic spironolactone, conventional sympatholytic agents, calcium-channel blockers, and probably the serotonin2-receptor antagonist ketanserin, exert no relevant effects on the lipoprotein profile. Angiotensin-converting enzyme inhibitors may slightly decrease serum triglycerides. alpha 1-Receptor blockers slightly decrease LDL cholesterol and Tg and increase HDL cholesterol. Drug-induced development or aggravation of dyslipidemia represents a potentially adverse influence. In the hypertensive population, effective blood pressure control with traditional drug therapy based on thiazide-type diuretics in high dosage led to a distinct decrease in cerebrovascular morbidity and mortality, but failed to satisfactorily reduce coronary complications. The prognostic relevance of drug-induced changes in serum lipoproteins, carbohydrate metabolism and other risk factors or correlates awaits further clarification.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary lipids and thrombosis. Relationships to atherosclerosis.

A high intake of saturated fatty acids and cholesterol is associated with a high incidence of occlusive arterial lesions involving both atherosclerosis and thrombosis. The evidence is based on epidemiological, experimental, and clinical studies. Such dietary habits increase serum low density lipoprotein cholesterol, a main risk factor for atherosclerosis. The mechanisms by which dietary saturated fatty acids are connected to arterial thrombogenesis are only partly known. Experimental and epidemiological studies also indicate an association between dietary saturated fatty acids and venous thrombosis; however, the chain of evidence lacks documentation from prospective clinical studies. When unsaturated fatty acids of the (n-9), (n-6), or (n-3) families replace saturated fatty acids in the diet, risk factors related to atherosclerosis may be reduced and the development of atherosclerosis, inhibited. This potential is related both to the reduction of saturated fatty acids and, in varying degrees, to the individual unsaturated fatty acids. The very long-chain fatty acids of the (n-3) family and probably also linoleic acid of the (n-6) family have the potential to inhibit thrombogenesis. In this respect, the effect of the individual fatty acids seems even more important. To obtain an optimal dietary lipid composition for the prevention of atherosclerosis and thrombosis, it is important to appreciate the metabolic and structural effects of the individual fatty acids. The interaction between the various dietary fatty acids and their effects on lipid biosynthesis is still only partly known. The present nutritional recommendations include a low intake of saturated fatty acids and cholesterol and a balanced content of the unsaturated fatty acids and represent a well-documented approach to the prevention of both processes.

Effect of taurine administration on serum lipid and biliary lipid composition in man.

The effect of oral administration of taurine (3.2 g/day, 2 weeks) on the metabolism of lipids and bile acids was studied with healthy humans. Four male subjects were fed taurine. Another five male subjects were administered 1 g of cholesterol daily for two weeks and, at intervals of two weeks, cholesterol and taurine simultaneously. Serum lipoprotein and duodenal bile were analyzed. Oral administration of taurine resulted in the increase of taurine-conjugated bile acids. However, neither serum lipid nor biliary lipid composition was altered. Addition of taurine with cholesterol administration showed elevation of both the serum low density lipoprotein cholesterol level and the lithogenic index in bile. The ratio of glycine-to taurine-conjugated bile acids was changed from 4.1 to 0.63. The ratio of cholic acid/chenodeoxycholic acid was augmented from 0.57 to 0.81. The percentage of taurocholic acid, taurochenodexycholic acid and taurodeoxycholic acid were increased about 4-fold, 2.5-fold and 3-fold, respectively. Our results suggested that taurine administration alone did not influence the serum lipid level although taurine-conjugated bile acids were increased. The taurine intake would increase serum low density lipoprotein cholesterol and biliary cholesterol levels when excessive cholesterol is administered simultaneously.

Bioled coffee increases serum low density lipoprotein concentration

The effects of boiled coffee, filtered coffee, and tea on serum lipoprotein lipids and apoproteins were compared in 42 middle-aged hypercholesterolemic subjects (21 men and 21 women). The subjects consumed the beverages, eight cups a day, in random order during successive 4-week periods with 2-week run-in intervals in a crossover design. The diet was kept unchanged. Statistically significant differences were found between the periods in serum total cholesterol ( P <.0001 ANOVA), LDL cholesterol ( P < .01), and apoprotein B ( P < .01) levels. All differences were due to significantly higher levels during boiled coffee as compared with filtered coffee and tea. No statistically significant differences were found between the filtered coffee and tea periods. There were no differences in serum VLDL cholesterol or triglyceride, HDL cholesterol, and apoprotein A-I concentrations between the periods. Consumption of boiled coffee thus increased the concentration of low density lipoprotein in the serum without affecting its lipid-protein composition. The effect seemed to be determined by the method of brewing.

Effect of biotin deficiency and supplementation on lipid metabolism in rats: cholesterol and lipoproteins

The effect of biotin deficiency and supplementation upon tissue cholesterol and serum lipoprotein profile in rats was investigated. Biotin-dependent carboxylases in liver of deficient animals were decreased to 12–27% of control activity. The brain carboxylase activities of deficient rats were reduced less than in liver. The total, free, and esterified cholesterol were decreased in the serum of deficient rats compared to those in control or supplemented rats. Deficient rats had increased serum low-density lipoprotein fractions and decreased very low-density lipoprotein fractions, but no change in the high-density lipoprotein fractions. No differences were found between groups in the cholesterol content of liver, cerebrum, or cerebellum. Pharmacologic doses of biotin had no effect on tissue cholesterol content or serum lipoprotein profile. These results suggest that the neurologic symptoms in biotin deficiency and in the inherited multiple carboxylase deficiencies are not due to alterations in the content of cholesterol or lipoproteins.

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 < 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.

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 < 0.05 to <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 < 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.