Effects of pindolol on serum lipids, apolipoproteins, and lipoproteins in patients with mild to moderate essential hypertension

The effects of 12 weeks' administration of the beta-blocker pindolol (5 mg twice daily) on serum lipids, apolipoproteins (apo), and lipoproteins were studied in 20 normolipidemic patients with mild to moderate essential hypertension (WHO I-II). Pindolol significantly increased both high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), while very-low-density lipoprotein cholesterol (VLDL-C) was significantly decreased. Apo A-II levels were increased significantly and the apo B/apo A-I ratio, which is one of the atherogenic indexes, was decreased significantly after pindolol therapy. Total cholesterol, HDL subfraction cholesterols, the LDL-C/HDL-C ratio, triglycerides, apo A-I, apo B, apo C-II, apo C-III, and apo E did not change significantly.     

Effects of pindolol on serum lipoproteins and postheparin lipolytic activities in hypertensive patients

Thirty-four hyperlipoproteinemic, hypertensive patients received 5 mg of pindolol twice daily for 12 weeks. During pindolol administration, there were significant decreases in serum triglyceride levels and increases in high-density lipoprotein cholesterol (HDL-C) levels, while total cholesterol levels did not change. Serum levels of very-low-density lipoprotein (VLDL) triglyceride and VLDL cholesterol decreased over time as HDL-C increased. There was a significant increase in low-density lipoprotein cholesterol at week 12. Apolipoprotein (apo) A-I, A-II, and B levels did not change during pindolol administration, but apo C-II, C-III, and E levels decreased significantly. Lipoprotein lipase activity in heparin-treated plasma was significantly higher after pindolol administration. The results suggest that the reduction in triglyceride levels and increase in HDL-C after pindolol are partly a response to an increase in the hydrolysis of VLDL resulting from an increase in lipoprotein lipase activity.     

Fenofibrate for the treatment of type IV and V hyperlipoproteinemias: a double-blind, placebo-controlled multicenter US study

The results of a randomized, double-blind, placebo-controlled multicenter trial of fenofibrate in the treatment of type IV/V hyperlipoproteinemia are reported. Ten study centers in the United States recruited 147 adults with a history of type IV or V hyperlipoproteinemia. After a six- to 12-week dietary stabilization period and a four-week placebo period, patients whose 12-hour fasting total plasma triglyceride levels ranged from 350 to 1,500 mg/dl were continued in the study; 55 patients with levels of 350 to 499 mg/dl were placed in group A and 92 with levels of 500 to 1,500 mg/dl in group B. Patients in each group were randomly assigned to receive 100 mg of fenofibrate or placebo three times daily for eight weeks. In both groups A and B fenofibrate-treated patients showed statistically significant reductions in levels of total cholesterol, very-low-density lipoprotein cholesterol, total triglycerides, and very-low-density lipoprotein triglycerides, and significant increases in high-density lipoprotein cholesterol; patients in group B also showed a significant increase in low-density lipoprotein cholesterol levels. Sixteen of the 75 fenofibrate-treated patients and 11 of the 72 placebo patients reported adverse events that were potentially drug related; most of these were gastrointestinal and a few reported musculoskeletal and skin reactions. It is concluded that fenofibrate is an effective and safe agent in the treatment of type IV/V hyperlipoproteinemia.     

Ciprofibrate treatment decreases non-high density lipoprotein cholesterol and triglycerides and increases high density lipoprotein cholesterol in patients with Frederickson type IV dyslipidemia phenotype

OBJECTIVE: The combination of hypertriglyceridemia and low high density lipoprotein (HDL) cholesterol is one of the most common lipid abnormalities. Thus, the aim of this study was to determine the effects of ciprofibrate on lipid profile in patients with Frederickson's type IV dyslipidemia phenotype. RESEARCH DESIGN AND METHODS: Seventy-five patients with type IV dyslipidemia were assigned at random to 1 of 2 therapeutic options: group A (control), American Heart Association (AHA) Step II diet and physical activity; and group B, AHA diet, physical activity, and ciprofibrate 100 mg daily for 8 weeks. The lipid profile of all patients was determined at baseline and after therapeutic intervention. RESULTS: Patients in group B (treated with ciprofibrate) compared with group A (control) had significantly higher reductions in total cholesterol (downward arrow 14.2% vs. downward arrow 4.8%; P < 0.02), triglycerides (downward arrow 38.0% vs. downward arrow 21.6%; P < 0.007), very low density lipoprotein cholesterol (downward arrow 38.0% vs. downward arrow 21.6%; P < 0.007), non-HDL cholesterol (downward arrow 20.5% vs. downward arrow 7.1%; P < 0.007), and total cholesterol/high density cholesterol ratio (downward arrow 25.6% vs. downward arrow 9.4%; P < 0.01). The ciprofibrate group had a significantly higher increase in HDL cholesterol levels compared with the other group (upward arrow 25.0% vs. upward arrow 9.6%, P < 0.02). CONCLUSIONS: Ciprofibrate treatment effectively reduced triglyceride-rich particles and non-HDL cholesterol, and significantly increased HDL cholesterol, proving its effectiveness in patients with low HDL cholesterol and type IV Frederickson's hyperlipidemia.     

Effects of gamma-oryzanol on serum lipids and apolipoproteins in dyslipidemic schizophrenics receiving major tranquilizers

The subjects were 20 chronic schizophrenic patients with dyslipidemia (total cholesterol levels greater than or equal to 220 mg/dl, triglycerides greater than or equal to 150 mg/dl, or high-density lipoprotein cholesterol less than or equal to 40 mg/dl) who had been receiving neuroleptics for a mean of ten years. Each patient was given 100 mg of gamma-oryzanol three times daily for 16 weeks. Total cholesterol and low-density lipoprotein cholesterol levels, respectively, decreased significantly, from 204 and 124 mg/dl at baseline to 176 and 101 mg/dl at week 12. High-density lipoprotein cholesterol levels were 36.1 mg/dl at baseline and 35.9 mg/dl at week 12. Apolipoprotein (apo) B levels decreased significantly from 116 mg/dl to 101 mg/dl at week 16; apo A-II levels increased significantly from 31.7 mg/dl to 34.7 mg/dl; and the apo B/apo A-I ratio declined significantly from 0.99 to 0.84. No treatment side effects were recorded. It is concluded that gamma-oryzanol is safe and effective in the treatment of dyslipidemia.     

Detailed analysis of serum lipids and lipoproteins from Japanese type III hyperlipoproteinemia with apolipoprotein E2/2 phenotype

BACKGROUND: To clarify a detailed profile of serum lipids, lipoproteins and apolipoproteins (apo) in type III hyperlipoproteinemia (HLP) with apolipoprotein E (apo E) phenotype 2/2. METHODS: Nineteen consecutive Japanese type III HLP (9 men, 10 women) were studied. All had hypertriglyceridemia and 74% showed hypercholesterolemia. RESULTS: The degree of hyperlipidemia [total cholesterol (TC) 8.1 +/- 3.2 mmol/l, triglycerides (TG) 5.2 +/- 2.9 mmol/l] was milder than that in type III HLP in western countries. Lipoprotein fractions analyzed by ultracentrifugation showed that very low density lipoprotein cholesterol (VLDL-C) concentrations were considerably increased and that intermediate density lipoprotein cholesterol (IDL-C) concentrations were also increased, whereas low-density lipoprotein cholesterol (LDL-C) concentrations were low. Serum apo A-I, A-II and B concentrations were not increased, while apo C-II, C-III and E concentrations were considerably increased. However, the increase of apo E concentrations in the study subjects was far more pronounced than that of apo C-III, causing the ratio of apo E/C-III to be considerably higher than hyperlipidemia with other apo E phenotypes. CONCLUSION: By using this index apo E/C-III, it is possible to segregate type III HLP with apo E2/2 phenotype from other types of hyperlipidemia.     

肝脂酶基因-763A／G多态性与混合型高脂血症的关系

目的探讨混合型高脂血症（CHL）与肝脂酶（HL）基因启动子763A／G多态性的关系。方法运用聚合酶链反应一限制性内切酶片段长度多态性技术（RCR—RFLP）,对219名对照者和218例CHL患者的HL基因启动子763A／G多态性进行检测,并研究其对血脂水平的影响。结果总研究组的HL-763A／G多态性的AA、AG和GG基因型频率分别为0．3155、0．4936、0．1908;A、G等位基因频率分别为0．5623、0．4377。在CHL组中除年龄、高密度脂蛋白胆固醇（HDL—C）、载脂蛋白A—I（apoA—I）,AA型的低密度脂蛋白胆固醇（LDL—C）、载脂蛋白B（apoB）及GG型的apoA～I水平外,其余指标均与对照组同基因型之间差异有统计学意义（P〈0．05）;GG型的年龄明显低于AA型（P〈0．05）,apoA—I水平明显高于AA型（P〈0．05）,而apoA—I及apoA—I／apoB水平明显高于AG型（P〈0．05）。在CHL男性组中,除AA型HDL—C、GG型HDL—C、apoA—I水平外,其余血脂水平均高于对照男性组（P〈0．05）,同样,在CHL女性组中,除GG型的HDL—C、apoA—I、非高密度脂蛋白胆固醇（nonHDL—C）、apoB水平外,其余血脂水平均高于对照女性组（P〈0．05）。而CHL女性组GG型的apoA—I水平明显高于AA型（P〈0．05）。结论HL启动子763A／G多态性与CHL的发生相关,并可影响血浆的脂类代谢。     

Postprandial plasma lipoproteins in normal and hypertriglyceridaemic subjects and their in vitro effect on platelet activity: differences between saturated and polyunsaturated fats

The postprandial plasma lipoprotein pattern was studied in 10 normal and 10 hypertriglyceridaemic subjects after consumption of either a saturated or a polyunsaturated fat-rich meal. Plasma triglycerides increased in both groups 3 h after the meal, and this was followed after 5 h by a dramatic reduction in the normal subjects only; the reduction was less after the saturated fat meal than after the polyunsaturated fat meal. This plasma triglyceride pattern was a consequence of changes in the chylomicron and very-low-density lipoprotein (VLDL) fractions. No significant changes were found in high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol, triglycerides or protein concentration. Plasma cholesterol and apolipoproteins (apo) A-I and B were not significantly altered. The VLDL-apo C-III/apo C-II ratio increased 3 h after the saturated fat-rich meal, but decreased after the polyunsaturated fat-rich meal in normals, but not in the patient group. The effect of these postprandial lipoproteins on platelet function was studied by incubating normal washed platelets with the lipoprotein and then determining aggregation and [14C]serotonin release. All chylomicron fractions decreased platelet activity, whereas postprandial VLDL increased platelet activity. Five hours after the meals, the effect of VLDL on platelet activation was reduced in normal subjects only. The effect of postprandial LDL and HDL on platelet function differed little from that of the fasting lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreases in apolipoprotein(a) after renal transplantation: implications for lipoprotein(a) metabolism.

Serum concentrations of apolipoprotein(a) [apo(a)], the unique glycoprotein of lipoprotein(a), are increased in patients with end-stage renal failure. We prospectively studied serum apo(a) and other lipoproteins in 20 consecutive patients, ages 46 +/- 11 years, before and for six months after successful renal transplantation. All patients received cyclosporine, and no patient was treated for hyperlipidemia. The mean creatinine clearance increased from 7.5 mL/min before transplant surgery to 40.9 mL/min six months afterwards (P less than 0.001). Apo(a) decreased from a median of 403 units/L before transplantation to 184 units/L at one week (P less than 0.001) and was 170 units/L (P less than 0.001) at six months. For the assay used, 1 unit of apo(a) is equivalent to 1 mg of lipoprotein(a). In contrast, from baseline to six months, increases were found for low-density lipoprotein (LDL) cholesterol (P = 0.03), high-density lipoprotein cholesterol (P = 0.06), apo B (P = 0.07), and apo A-I (P = 0.01). The decrease in apo(a) in individual patients was significantly correlated with the increase in creatinine clearance (r = -0.48, P less than 0.001). The single patient who developed nephrotic syndrome after renal transplantation had marked increases in apo(a) (693-1595 units/L), apo B, and LDL cholesterol, which paralleled the degree of proteinuria. These findings suggest that abnormal renal function affects the regulation of lipoprotein(a) metabolism.     

Apolipoprotein E phenotypes, serum lipoproteins and apolipoproteins in angiographically assessed coronary heart disease

To determine the influence of the apolipoprotein E polymorphism on the occurrence of coronary artery disease (CAD) and on serum lipids, lipoproteins and apolipoproteins we studied 145 patients with angiographically defined CAD and compared them with 153 control subjects without history or complaints of vascular disease and with 35 subjects without significant stenosis on coronary arteriography. Subjects with hypertension, diabetes mellitus and endocrine or metabolic disorders were excluded. Covariance analysis and logistic regression analysis were performed with adjustment for age, sex, smoking habits and relative body weight. There were no significant differences for the apoE phenotypes on risk of cardiovascular disease. The CAD group had significantly higher mean values of serum cholesterol and triglycerides, very-low-density lipoprotein (VLDL)-cholesterol and VLDL-triglycerides, low-density lipoprotein (LDL)-cholesterol and apoprotein B; they had lower high-density lipoprotein (HDL)-cholesterol and apo A-I. The combination of LDL-cholesterol, apoA-I and VLDL-cholesterol was the best model in predicting cardiovascular disease. ApoE phenotype group E3/E2 had significantly lower values for serum cholesterol, LDL-cholesterol, and apoB and higher levels of apoE in comparison with the phenotype groups E3/E3 and E4/E3. The combination of LDL-cholesterol, cholesterol, apoE and VLDL-triglycerides was the best model in predicting the apoE phenotype. Thus, taking other risk factors into account, the apoE phenotype is not an independent risk factor for CAD; the apoE polymorphism influences lipoprotein levels and possibly, in that way, indirectly also the risk for CAD.     

Abnormal lipoprotein composition in normolipidemic diabetic patients

To see whether there are any lipoprotein abnormalities in diabetic patients without hyperlipidemia, lipoprotein composition was examined in 75 strictly normolipidemic diabetic patients. Their plasma cholesterol (chol) and triglyceride (TG) were limited to less than 6.0 and less than 1.7 mM, respectively. Body-weight- and age-adjusted normolipidemic healthy subjects served as the control group. Plasma total chol and TG and low-density lipoprotein (LDL-) and high-density lipoprotein (HDL-) chol were identical in the diabetic and control subjects. Total apolipoprotein B (apoB) in the plasma of the diabetic subjects was significantly elevated. The chol-apoB ratio in the TG-rich (very-low-density + intermediate-density) lipoprotein fraction (Sf12-400) of the diabetic subjects was significantly higher than the control value, whereas LDL-apoB levels were increased and chol-apoB ratio in the LDL fraction was significantly suppressed in the diabetic subjects. Because each LDL particle contains only one apoB molecule, apoB and chol-apoB ratio in this fraction can represent particle number and chol loading of the LDL particles, respectively. Thus, these data suggest that LDL particle number is increased, and the particles are chol depleted in diabetic subjects even if they are normolipidemic.     

Lipids, lipoproteins and apolipoproteins in the elderly

The lipoprotein components were studied in connection with a population study concerning the state of health and living habits of the elderly people in Turku, Finland. Serum levels of total cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1 (apo A1) and apolipoprotein B (apo B) of the 347 elderly people (aged 65 years or over) were measured and those of low density lipoprotein (LDL) cholesterol were calculated. The levels of total cholesterol, LDL cholesterol and apo B were significantly higher in females than in males, and the concentrations decreased with advancing age. The concentrations of HDL cholesterol and apo A1 were significantly higher in females than in males but age had no effect. Serum triglycerides behaved differently in males and females; in females age had a significant increasing effect whereas in males no age effect was observed. The apo A1/apo B ratio did not differ between males and females. Reference values of serum lipids, lipoproteins and apolipoproteins of the elderly are suggested.     

Effect of lovastatin on serum lipids in patients with nonfamilial primary hypercholesterolemia

The effect of lovastatin on serum lipids and its tolerability in patients with non-familial primary hypercholesterolemia (type II-A and type II-B) during a six-month period were evaluated in this open-label study. Thirty-eight patients were enrolled in the study; tolerability was assessed in all 38 patients. Thirty patients completed the study, and the effect of lovastatin on serum lipids in these patients was assessed. Some patients had been treated for hypercholesterolemia with long-term dietary and other non-pharmacologic means before entry into the study. All patients were unresponsive to a six-week program of intensive dietary therapy and other nonpharmacologic treatment to lower their blood cholesterol levels before receiving lovastatin. While maintaining intensive dietary therapy, administration of lovastatin was instituted at a dosage of 20 mg/day, which was increased by 20-mg increments monthly, as necessary, to a maximum of 80 mg/day. In an effort to achieve goal levels of low-density lipoprotein cholesterol (LDL-C), ten patients received a daily dosage of 20 mg, 12 patients received 40 mg, seven patients 60 mg, and one patient 80 mg. Twenty-nine of the 30 patients achieved significant lowering of serum levels of total cholesterol (TC), LDL-C, and apolipoprotein (apo) B-I; this was demonstrated after the first month of therapy with lovastatin and was maintained throughout the six-month treatment period. One patient failed to demonstrate lowering of these serum lipids, despite receiving the maximum recommended dosage of lovastatin of 80 mg/day. Comparative measurements of serum lipids during dietary therapy alone and after six months of diet plus lovastatin therapy were as follows: TC, 289 +/- 5 versus 216 +/- 9 mg/dl (P less than 0.0005); LDL-C, 206 +/- 4 versus 141 +/- 5 mg/dl (P less than 0.0005); and apo B-I, 112 +/- 3 versus 89 +/- 2 mg/dl (P less than 0.0005). Serum levels of very-low-density lipoprotein cholesterol (VLDL-C) and triglycerides decreased slightly during lovastatin therapy, but the changes were not statistically significant. There were slight but statistically insignificant increases in serum levels of high-density lipoprotein cholesterol (HDL-C), apo A-I, and apo A-II.(ABSTRACT TRUNCATED AT 400 WORDS)     

癌症与血脂水平的相关性初探

目的探讨癌症与血脂水平的相关性。方法采用1∶1病例对照研究的方法 ,病例组选自住院的癌症患者,对照组是社区中与病例性别和年龄匹配的健康人群。分析病例组与对照组的血脂水平比较。结果病例组血浆三酰甘油（TG）、极低密度脂蛋白胆固醇（VLDL）和低密度脂蛋白胆固醇/高密度脂蛋白胆固醇（LDL/HDL）水平均高于对照组,而血浆HDL水平低于对照组（P〈0.001）;TC和LDL则无差异（P〉0.05）。高TG患癌症的相对危险度为1.757（95%C I：1.020~3.025）;低HDL患癌症相对危险度为2.677（95%C I：1.266~5.662）;其余血脂异常指标的相对危险度无统计学意义。结论血脂水平与癌症发生有一定的相关性。其中高TG是癌症发生的可疑危险因素,而HDL是保护因素。     

Serum lipids and apolipoproteins in patients with psoriasis.

Psoriasis is characterized by defects in the normal cycle of epidermal development that lead to epidermal hyperproliferation, altered maturation of skin cells, vascular changes and inflammation. Also, psoriasis has been associated with an abnormal plasma lipid metabolism. Changes in plasma lipid and lipoprotein composition in patients with psoriasis may be the reason for the increased risk of atherosclerosis in these patients. We determined serum concentrations of lipids, lipoproteins and apolipoprotein Al and B (apo A1 and apo B) in 72 patients with psoriasis and 30 age matched controls. Serum lipoprotein (a) (Lp(a)), apo A1 and apo B were measured by immunoprecipitation assays, and the lipids and other biochemical parameters by enzymatic methods. Serum Lp(a) and triglyceride (TG) were significantly higher in patients with psoriasis than in healthy control subjects (p<0.01 for both). Apo B was also found to be higher in the patient group, but the difference was not significant. The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apo A1 did not differ significantly from those of the controls. These observations imply that serum Lp(a) and TG concentrations may play a role as risk factors for atherosclerotic disease in patients with psoriasis.     

Correlation between the ratio of serum low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with that of serum apolipoproteins B and A-I

Summary Phosphowolframate/magnesium chloride, a commonly used precipitation method for the determination of high-density lipoprotein cholesterol in human serum, yields a supernatant containing almost all of the lipoproteins apo A-I and apo A-II but no lipoprotein apo B. The correlation between high-density lipoprotein cholesterol and apo A-I was very high (r=0.94), as well as that between the precipitation method and ultracentrifugal analysis (r>0.95,P<0.001). In contrast, detergent precipitation (for the determination of low-density lipoprotein cholesterol in human serum) produced sediments which contained the major proportion of apo B and only minor amounts of apo A-I and apo A-II. The precipitation method for low-density lipoprotein cholesterol showed very good agreement with ultracentrifugal analysis (r=0.99). Yields of 80.2% were obtained for apo B with both methods. Results obtained using the precipitation methods showed excellent agreement with those obtained using the Friedewald formula (r>0.99). Results were also very similar when hypertriglyceridemic serum samples were briefly centrifuged before analysis of cholesterol, high-density lipoprotein cholesterol and triglyceride values. The present study shows highly significant correlations between cholesterol/high-density lipoprotein cholesterol or low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and apo B/apo A-I ratios (P<0.001). Apo B and apo A-I levels could be used in addition to low- and high-density lipoprotein cholesterol values when assessing the risk of cardiovascular disease, if the methods for determining serum apolipoproteins have been properly standardized.     

Apolipoproteins and lipoprotein particles in moroccan patients with previous myocardial infarction

We investigated for the first time in the Moroccan population the relationship between lipoprotein particles and the progression of coronary atherosclerosis. Plasma lipid variables, including total cholesterol, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, apolipoproteins AI and B, Lp AI, Lp AI:AII, and Lp(a) were measured in 40 Moroccan adults who suffered a verified myocardial infarction before the age of 50 years. The results were compared with a healthy control group. Plasma total cholesterol, triglyceride, and Lp AI : AII levels of patients did not differ significantly from control subjects. Patients had lower plasma high-density lipoprotein-cholesterol (P<0.05), apo AI (P<0.05), and Lp AI (P<0.001 ) than control subjects, suggesting that the cholesterol reverse transport system is altered in patients with previous myocardial infarction. However, patients had higher plasma low-density lipoproteincholesterol (P<0.001), apo B (P<0.001), and Lp(a) (P<0.001). In all patients the best predictor of cardiovascular risk was the independent risk factor Lp(a) plasma level, and the Lp AI plasma level. In this study, the increased coronary atherosclerosis risk with elevated plasma levels of apo B and Lp(a), and with reduced Lp AI, was substantially modified by smoking habits, but not by family history of myocardial infarction.     

Effects of short-term treatment with corticotropin on the serum apolipoprotein pattern

Treatment with adrenocorticotrophic hormone (ACTH) has a well-documented cholesterol-lowering effect. Increased uptake of low-density lipoprotein (LDL) by HepG2 cells in response to incubation with ACTH has been demonstrated but the precise cholesterol-lowering mechanism has resisted elucidation. Since apolipoproteins are important determinants of lipoprotein metabolism, we sought to extend the knowledge of the effect of ACTH treatment on the serum apolipoprotein (apo) pattern. Twelve healthy individuals and 14 dyslipoproteinemic hemodialysis patients were recruited. The two groups responded similarly to ACTH1-24 at the dose of 1 mg daily for four days. In accordance with previous results, serum concentrations of total cholesterol decreased by 18% and 17%, LDL cholesterol by 25% and 30%, and apo B by 20% and 19%, respectively, while there were no significant changes in the serum concentrations of triglycerides, high-density lipoprotein cholesterol and apo AI. Novel findings were that the serum concentrations of total apo E increased by 48% and 31%, and apo B-associated apo E by 69% and 46%, respectively. Moreover, in the healthy individuals, the serum concentrations of apo CIII did not change in response to ACTH, whereas in the hemodialysis patients, those of apo CIII not associated with apo B increased significantly by 44%. Since apo E binds strongly to the LDL receptor, the present results suggest that the cholesterol-lowering effect of ACTH may be mediated by facilitated hepatic uptake of apo E-enriched apo B-containing lipoproteins. Thus, the findings stimulate further research.     

A phenocopy of type III dysbetalipoproteinemia occurring in a candidate family for a putative apo E receptor defect.

On theoretical grounds, an apo E receptor defect should be manifested by the accumulation of lipoprotein remnants that are normally cleared by this receptor and cannot be processed by the normal apo B, E receptor (LDL-receptor). Furthermore, the defect should not be selective for a specific apo E phenotype since none of the isoforms would be cleared preferentially. Our search for such an occurrence led us to the discovery, in five members of a family of ten, of a unique dyslipoproteinemia mimicking type III. As in type III, plasma levels of cholesterol, triglycerides, VLDL-cholesterol, VLDL-triglycerides and apo E, as well as the VLDL-C/TG ratio, were high. LDL-cholesterol and HDL-cholesterol tended to be low. The clearance of plasma triglycerides after a fat load was impaired. Tubero-eruptive xanthomas, arcus corneae and manifestations of atherosclerosis were present in some individuals. In contrast to type III, the dyslipoproteinemia occurred in subjects bearing three different apo E phenotypes: E4/2, E4/3 and E3/2. VLDL-apo B levels were markedly increased, the VLDL-C/VLDL-B ratio was low and a double pre-beta band was present on lipoprotein electrophoresis. In spite of high apo E and borderline high apo CIII plasma levels, levels of the lipoprotein particles LpCIII:B and LpE:B, which characterize type III, were not raised. Rapid weight loss or treatment with a fibrate was observed to normalize the lipoprotein profile. It is surmised that the apo E-rich lipoprotein particles accumulating in this type III phenocopy with "hyperapoprebetalipoproteinemia" could be those that are normally cleared by an apo E receptor.     

Cerivastatin-a new synthetic 3-hydroxy-3-methylglutaryl (HMG) inhibitor: effect of 0,2 mg dose in patients with primary hyperlipidemias]

AIM: To elucidate efficacy, safety and tolerance of lipobay (cerivastatin), a new HMG-CoA-reductase inhibitor (0.2 mg/day) in patients with primary hyperlipidemia (PHL). MATERIALS AND METHODS: The trial enrolled 15 men aged 21-64 years with PHL of type 2a and 2b. After 1 and 3 months of treatment all the patients underwent a general clinical examination with measurements of blood lipids (total cholesterol, triglycerides, high density lipoprotein cholesterol--HDL-C), apolipoproteins (apo A-1 and apo B). RESULTS: After 3 months of treatment total cholesterol, LDL-C and apolipoprotein B decreased by 24.94 +/- 2.87%, 28.94 +/- 3.08%, 19.32 +/- 2.43% (p = 0.0001), respectively, while LDL-C levels were < 3.4 mmol/l in 4 patients. Triglycerides dropped by 17.84 +/- 6.41%, while HDL-C rose by 5.01 +/- 4.47%, but the changes were not significant. Lipobay in doses 0.2 mg/day was well tolerated. One patient stopped taking the drug because of severe abdominal pain. CONCLUSION: Lipobay is a novel, effective and well-tolerated drug for treatment of patients with primary hyperlipidemia of type 2a and 2b.