Screening of preformed oxidised low density lipoprotein isolated by a polyanion precipitation method. Its correlation with serum triglyceride levels.

For clinical and epidemiological screening a simple and sensitive methodology was developed for detection of preformed lipid peroxides (LPO) in low density lipoprotein (LDL). For this purpose, the iodometric assay of El-Saadani et al. (J Lipid Res 1989;30:627-30) was adapted to the fraction containing LDL isolated by polyanion precipitation avoiding ultracentrifugation. This fraction also includes intermediate density lipoprotein. Stratifying 53 individuals by their serum triglyceride levels (TG) the highest quartile showed a highly significant elevation of LDL-LPO compared with the lowest one (69.2 +/- 41.2 vs 22.9 +/- 10.0 nmol mg-1 LDL-apo B, P < 0.001). LDL-LPO concentration also showed a strong correlation with TG (r = 0.73, P < 0.00001) and significant inverse correlations with high density lipoprotein cholesterol (HDL-C) and HDL3-C subfraction (r = -0.37, P < 0.01 and r = -0.38, P = 0.01, respectively). The TG/HDL-C ratio, which is closely associated with insulin resistance, was strongly correlated with LDL-LPO (r = 0.83, P < 0.00001). Significant elevations of LPO were observed in phenotypic hyperlipoproteinemias (HLP) IIb and IV (P < 0.01 and P < 0.02, respectively) and when expressing LPO in mol/mol of LDL-apo B, two- and 2.5-fold higher values were found in types IIb and IV HLP, respectively, compared with normolipidemic subjects, suggesting a more oxidative environment for apo B in both phenotypes. No variations in LPO were found in type IIa HLP. This simple assay for in vivo detection of LDL-LPO, emphasises the possible atherogenic effect of TG through their oxidative capacity and suggests the integration of LPO to the cluster of associated risk factors: high TG, low HDL-C and insulin resistance.

Significant increase of high-density lipoprotein2-cholesterol under prolonged simvastatin treatment.

In a contribution to a prolonged multicenter study 15 patients with primary hypercholesterolemia were treated with simvastatin, a competitive inhibitor of HMG-CoA reductase. The first part of the study was done in a double-blind fashion comparing the effect of this new drug with that of gemfibrozil during 12 weeks, and after this period on open-label treatment was started with the administration to all the patients of simvastatin in doses ranging from 2.5 to 40 mg q.p.m. Persistent and significant reductions (P less than 0.001) were achieved for total serum cholesterol (TC), LDL-cholesterol (LDL-C), apo B and triglycerides: by 38, 49, 44 and 33%, respectively, after 40 weeks of the open-label extension. From week 12, LDL-C levels were maintained at a cut point less than or equal to 140 mg/dl in every patient throughout the study. At week 40, cholesterol values of HDL subfractions showed a significant increase in HDL2-C (28%, P less than 0.01) and a concomitant reduction in HDL3-C (12%, P less than 0.01) in spite of a nonsignificant elevation of total HDL-C (by 6%). The HDL2-C/HDL3-C ratio rose by 47% (P less than 0.001) and the TC/HDL-C ratio was significantly reduced by 43%: from 6.1 +/- 1.2 to 3.5 +/- 0.7 (mean +/- SD, P less than 0.001). No adverse effects were detected. Our results suggest a conversion of HDL3 into HDL2, which could imply a beneficial effect of simvastatin upon the so-called reverse cholesterol transport, in addition to the striking reduction in atherogenic lipoproteins.

Evaluation of the high density lipoprotein cholesterol protective effect against atherogenesis in rabbits fed cholesterol supplemented diets

El colesterol de las lipoproteínas de alta densidad (C-HDL) plasmático fue evaluado en 15 conejos alimentados con dietas suplementadas con colesterol respecto a su efecto protector en el proceso aterogénico. Partiendo de un nivel basal de C-HDL de 29 ñ 11 mg/dl (promedio ñ DS), sólo se logró como máximo duplicar dicho valor en tres conejos, mientras que el colesterol total (CT) aumentó hasta 20 veces. El índice plasmático CT/HDL aumentó 80 veces su valor basal (2,4 ñ 0,9) y fue el parámetro que detectó la mejor correlación con el colesterol acumulado en la aorta y con los scores de los estudios patológicos (r:0,956, p < 0,001 y r:0,805, p < 0,003, respectivamente). El contenido de CT aórtico aumentó 10 veces y la relación colesterol libre/colesterol esterificado disminuyó 20 veces. Los resultados patológico demostraron scores de lesiones aórticas que se elevaron desde 0 a 4. se concluye que las altas correlaciones obtendias cuando el índice CT/C-HDL fue graficado contra la acumulación del colesterol aórtico o contra los scores de las lesiones, avalan la teoría del transporte reverso del colesterol y la efectividad de dicho índice para predecir el grado del proceso aterogénico. Por otra parte, la escasa respuesta del C-HDL en este modelo experimental alienta a emprender futuras investigaciones con fármacos con el objeto de elevar este parámetro para normalizar el índice CT/C-HDL y evitar las lesiones

Evaluation of the high density lipoprotein cholesterol protective effect against atherogenesis in rabbits fed cholesterol supplemented diets

El colesterol de las lipoproteínas de alta densidad (C-HDL) plasmático fue evaluado en 15 conejos alimentados con dietas suplementadas con colesterol respecto a su efecto protector en el proceso aterogénico. Partiendo de un nivel basal de C-HDL de 29 ñ 11 mg/dl (promedio ñ DS), sólo se logró como máximo duplicar dicho valor en tres conejos, mientras que el colesterol total (CT) aumentó hasta 20 veces. El índice plasmático CT/HDL aumentó 80 veces su valor basal (2,4 ñ 0,9) y fue el parámetro que detectó la mejor correlación con el colesterol acumulado en la aorta y con los scores de los estudios patológicos (r:0,956, p < 0,001 y r:0,805, p < 0,003, respectivamente). El contenido de CT aórtico aumentó 10 veces y la relación colesterol libre/colesterol esterificado disminuyó 20 veces. Los resultados patológico demostraron scores de lesiones aórticas que se elevaron desde 0 a 4. se concluye que las altas correlaciones obtendias cuando el índice CT/C-HDL fue graficado contra la acumulación del colesterol aórtico o contra los scores de las lesiones, avalan la teoría del transporte reverso del colesterol y la efectividad de dicho índice para predecir el grado del proceso aterogénico. Por otra parte, la escasa respuesta del C-HDL en este modelo experimental alienta a emprender futuras investigaciones con fármacos con el objeto de elevar este parámetro para normalizar el índice CT/C-HDL y evitar las lesiones (AU)

Evaluation of the high density lipoprotein cholesterol protective effect against atherogenesis in rabbits fed cholesterol supplemented diets.

Plasma high density lipoprotein cholesterol (HDL-C) was evaluated in 15 rabbits fed cholesterol supplemented diets to assess its protective effect on the atherogenic process. From a baseline level of 29 +/- 11 mg/dl (mean +/- SD) the maximum attained for HDL-C was twofold in only three rabbits, whereas total cholesterol (TC) increased 20 fold. Plasma TC/HDL-C ratio rose 80 fold from the baseline (2.4 +/- 0.9) and it was the best parameter that correlated with aortic cholesterol accumulation and pathological scores. Aortic TC content increased 10 fold and free cholesterol/cholesterol esters ratio decreased 20 fold. Pathological studies showed that aortic lesion scores rose from 0 to 4. It can be concluded that the high correlations obtained when TC/HDL-C ratio was plotted against both aortic cholesterol deposition and lesion scores, support the theory of the reverse cholesterol transport and the effectiveness of this index to predict the degree of the atherogenic process. On the other hand, the poor response of HDL-C in this model encourages future research using drugs to increase this parameter in order to normalize TC/HDL-C ratio and avoid lesions.

Evaluation of the high density lipoprotein cholesterol protective effect against atherogenesis in rabbits fed cholesterol supplemented diets.

Plasma high density lipoprotein cholesterol (HDL-C) was evaluated in 15 rabbits fed cholesterol supplemented diets to assess its protective effect on the atherogenic process. From a baseline level of 29 +/- 11 mg/dl (mean +/- SD) the maximum attained for HDL-C was twofold in only three rabbits, whereas total cholesterol (TC) increased 20 fold. Plasma TC/HDL-C ratio rose 80 fold from the baseline (2.4 +/- 0.9) and it was the best parameter that correlated with aortic cholesterol accumulation and pathological scores. Aortic TC content increased 10 fold and free cholesterol/cholesterol esters ratio decreased 20 fold. Pathological studies showed that aortic lesion scores rose from 0 to 4. It can be concluded that the high correlations obtained when TC/HDL-C ratio was plotted against both aortic cholesterol deposition and lesion scores, support the theory of the reverse cholesterol transport and the effectiveness of this index to predict the degree of the atherogenic process. On the other hand, the poor response of HDL-C in this model encourages future research using drugs to increase this parameter in order to normalize TC/HDL-C ratio and avoid lesions.

Treatment of acute myocardial infarction with subcutaneous heparin at low doses.

Heparin has been used intensively in the treatment of acute myocardial infarction and preinfarction angina (PA) at full doses as a single drug by us. However, heparin may be used at smaller doses for similar purposes. These doses are not exactly anticoagulant, even though they reduce blood hypercoagulability, and act mainly in an antithrombotic capacity. We studied 529 patients with acute myocardial infarction, of whom 262 were treated with subcutaneous heparin at low doses (5000 IU every 12 h) and 267 received conventional therapy without antithrombotic drugs. Heparin used was Heparina (Abbott) and Liquemine (Roche), in vials with the equivalence 1 cm3 = 50 mg = 5000 IU. Blood rheologic factors (thromboelastography, platelet adhesiveness, total blood viscosity, and number of platelets) were determined in all patients, those treated with heparin at low doses and also the control group, before and after the 30-day treatment period. Diagnosis was based on clinical symptoms, laboratory studies, and electrocardiogram examination. In both the 262 patients treated with heparin at low doses and in the control group of 267 patients, baseline values of rheological factors were high. After 30 days (i.e., after study completion) these high values which are statistically significant compared with normal values, with p less than 0.0001 for both groups, remained constant in the control group who did not receive heparin. On the contrary, in the group treated with heparin at low doses, all these factors changed. Heparin provides protection against thrombosis by increasing the negative charge of the vessel wall and by other reactions at the endothelial surface. Heparin requires a plasmatic component called antithrombine III.(ABSTRACT TRUNCATED AT 250 WORDS)