Estimation of cardiovascular risk: total cholesterol versus lipoprotein profile

Summary The complete lipoprotein profile is thought to give more information about the individual risk of coronary heart disease than total cholesterol alone. Although total cholesterol has a low sensitivity in the correct assessment of the risk of coronary heart disease, it may be of value in screening programs because of its low cost. In this study of 5,335 subjects, total cholesterol gave a different assessment of coronary heart disease risk (United States National Cholesterol Education Program guidelines) in 25% of subjects than the complete lipoprotein profile. Differences in risk assignment were mainly accounted for by high- and low-density lipoprotein-cholesterol (Friedewald equation). The calculated low-density lipoprotein-cholesterol was highly correlated with the value measured with a mixed ultracentrifugation and precipitation procedure. However, calculated values gave estimates of coronary heart disease risk which were 20% different from those from measure values. In 200 subjects in whom the lipoprotein profile was assessed three times in 1 year, the total cholesterol low-density lipoprotein-cholesterol varied by more than 30 mg/dl (0.78 mmol/l) in 52% and 50%, respectively, triglycerides by more than 30 mg/dl (0.34 mmol/l) in 75%, and high-density lipoprotein-cholesterol by more than 15 mg/dl (0.39 mmol/l) in 34%. Compared with the mean of the measurements, the single measurement of total cholesterol misclassified 48% of subjects, low-density lipoprotein-cholesterol 60%, high-density lipoprotein-cholesterol 12%, and 28%. We conclude that total cholesterol alone may be misleading in the assignment of coronary heart disease risk. Calculation of low-density lipoprotein-cholesterol, although less accurate than desirable, is the only way of evaluating this in clinical practice. Finally, repeated lipid measurements are required to assess coronary heart disease risk accurately.     

HDL and clinical and biochemical correlates in Italian non-smoker women.

High-density lipoprotein (HDL)-cholesterol levels, inversely related to the risk of myocardial infarction, are determined by genetic and environmental factors. The aim of this study was to evaluate the prevalence of low and high HDL plasma levels and the influence of environmental factors and lipid profile in an Italian non-smoker female population. HDL, apolipoprotein A-I, apolipoproteins, lipids and estrogen plasma levels were measured in a population of 1471 women with a mean age of 45 +/- 14 years. HDL values < or = 35 mg/dl were noted in 11.2% of the subjects, showing 2.4% coronary heart disease (CHD) prevalence. The 90th percentile was characterized by HDL levels > or = 66 mg/dl and the absence of coronary atherosclerosis. Total cholesterol, apolipoprotein B and triglycerides (r = -0.31, p < 0.0001) were the main determinants of HDL levels; apolipoprotein E, estrogen use, body mass index (BMI), alcohol consumption and age showed a weaker correlation. Apolipoprotein A-I concentration was influenced more notably by estrogen use, total cholesterol and apolipoprotein E; levels of triglycerides, apolipoprotein B, BMI, age and alcohol consumption are less important. The parameters considered here, taken together, explain HDL and apolipoprotein A-I variability of approximately 31% and 24%, respectively. A surprisingly high prevalence of very low (< or = 35 mg/dl) and high (> or = 66 mg/dl) HDL levels in Italian women further confirms the importance of studies on the HDL distribution in different population groups.     

Risk factors for cardiovascular disease in patients with subclinical hypothyroidism

INTRODUCTION: The relationship between subclinical hypothyroidism (SCH) and cardiovascular disease is not fully understood. We investigated risk factors for cardiovascular disease (lipid profile, lipoproteins, insulin resistance, C-reactive protein [CRP] homocysteine [Hcy] and fibrinogen levels) and their relationships with thyroid hormones in SCH patients and controls. METHODS: Thirty-eight SCH patients and 44 controls were enrolled in this study. No patients had any substantial confounding medical conditions (including diabetes mellitus or coronary heart disease) or were taking thyroid-related medication. RESULTS: Serum total cholesterol (P<0.05), low-density lipoprotein cholesterol (P<0.05) and triglycerides (P<0.001) were higher in patients with SCH than in controls. Serum lipoprotein(a) (Lp[a]) levels were higher in SCH subjects but this difference did not reach statistical significance (P=0.07). No significant differences were noted in CRP, Hcy, fibrinogen, high-density lipoprotein cholesterol, apolipoprotein A-1, apolipoprotein B (Apo B) or insulin resistance between patients with SCH and controls (in all cases, P>0.05). Free triiodothyronine (FT3) negatively correlated with Apo B (r=.0.46, P=0.005) and Lp(a) (r=.0.31, P=0.03) in patients with SCH and negatively correlated with Lp(a) (r=.0.30, P=0.04) in controls. All of these parameters were comparable between patients with thyroid-stimulating hormone (TSH) >10 microIU/ml and TSH <10 microIU/ml (in SCH patients, P>0.05). CONCLUSION: Our results suggest that SCH is associated with some lipid and lipoprotein abnormalities. Our results also suggest that this association does not depend on the subject's TSH level.     

Concentrations of lipids, lipoprotein, and apolipoproteins in serum of Zimbabwean Africans

The subjects in this study were volunteers from a Zimbabwean population: 794 men and 705 women, ages between 20 and 65 years. They were receiving no medication and had no disease that could influence lipid metabolism. For determination of high-density lipoprotein cholesterol and apolipoproteins, they were screened for the known risk factors for coronary heart disease, to exclude factors known to influence those analytes. The results showed a significant sex- and age-dependence. The means and ranges for cholesterol, apolipoprotein B, and triglycerides were lower than those found in European populations. The high-density lipoprotein cholesterol and apolipoprotein A concentrations, on the other hand, were higher than in the European populations. This study established the reference ranges of the analytes studied and suggests that the prevalence of coronary heart disease may be low in Zimbabwean Africans.     

Apolipoproteins and coronary artery disease

In this study, we compared the relative utility of plasma levels of cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoproteins in identifying men with angiographically significant coronary artery disease in a combined sample of consecutive male patients undergoing coronary angiography (N = 304) and healthy, normal male control subjects (N = 135). The plasma apolipoprotein levels were measured by using specific radioimmunoassays. We found that plasma levels of apolipoprotein A-I, followed by those of apolipoproteins A-II and B, were better discriminators than plasma cholesterol, triglycerides, or HDL cholesterol levels for identifying those with coronary artery disease. In confirmation of previous findings, the presence of coronary artery disease resulted in lower levels of apolipoproteins A-I and A-II and HDL cholesterol and higher levels of apolipoprotein B, cholesterol, and triglycerides. Linear and quadratic discriminant function analysis demonstrated that by using the age of the patients and apolipoprotein A-I, A-II, and B levels, one could correctly classify patients either as being normal or as having angiographically significant coronary artery disease in more than 75% of the cases. Thus, plasma apolipoprotein levels (especially A-I and A-II) may be considerably better markers for coronary artery disease than traditional lipid determinations.     

Lipoprotein predictors of cardiovascular events in statin-treated patients with coronary heart disease. Insights from the Incremental Decrease in End-points through Aggressive Lipid-lowering Trial (IDEAL)

Background. Few studies have looked into the ability of measurements of apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1) or apoB/apoA-1 to predict new coronary heart disease (CHD) events in patients with CHD on statin treatment.

Aims. In the IDEAL trial, to compare lipoprotein components to predict CHD events and to what degree differences in those parameters could explain the observed outcome.

Methods. We compared the ability of treatment with atorvastatin 80 mg/day to that of simvastatin 20–40 mg/day to prevent CHD events in patients with CHD and used Cox regression models to study the relationships between on-treatment levels of lipoprotein components to subsequent major coronary events (MCE).

Findings. Variables related to low-density lipoprotein cholesterol (LDL-C) carried more predictive information than those related to high-density lipoprotein cholesterol (HDL-C), but LDL-C was less predictive than both non-HDL-C and apoB. The ratio of apoB to apoA-1 was most strongly related to MCE. However, for estimating differences in relative risk reduction between the treatment groups, apoB and non-HDL-C were the strongest predictors.

Interpretation. The on-treatment level of apoB/apoA-1 was the strongest predictor of MCE in the pooled patient population, whereas apoB and non-HDL-C were best able to explain the difference in outcome between treatment groups. Measurements of apoB and apoA-1 should be more widely available for routine clinical assessments.     

Decrease of lipoprotein(a) with improved glycemic control in IDDM subjects.

OBJECTIVE: Recently, lipoprotein(a) [Lp(a)] has been identified as a major risk factor for coronary heart disease. There are few data available on the influence of metabolic control on plasma Lp(a) concentrations in subjects with insulin-dependent diabetes mellitus (IDDM), a group at high risk for coronary heart disease. RESEARCH DESIGN AND METHODS: We examined the effects of improved metabolic control on plasma lipid and lipoproteins and Lp(a) concentrations in 12 subjects before and after 21 days of tight metabolic control. RESULTS: Glycosylated hemoglobin declined from 8.4 to 6.9% (P less than 0.001), and Lp(a) declined from 29.7 to 27.1 mg/dl (P = 0.022). There were no significant differences in total, low-density lipoprotein, or high-density lipoprotein cholesterol, although the decline in triglyceride concentrations were borderline statistically significant. The distribution of apolipoprotein(a) isoforms in IDDM patients was not unusual, and the apolipoprotein(a) isoform phenotypes did not change with improved metabolic control. Lp(a) concentrations were also significantly higher than in a population-based control group of nondiabetic subjects from the San Antonio Heart Study. CONCLUSIONS: Although the number of subjects was small and the degree of improvement in metabolic control was modest, the results suggest that improved metabolic control may decrease the risk of coronary heart disease mediated by Lp(a) in IDDM.     

Common genetic variants that relate to disorders of lipid transport in Spanish subjects with premature coronary artery disease

Fifteen common polymorphic variants at six loci (apolipoproteins AI, B, CIII and E, hepatic lipase and lipoprotein lipase) involved in plasma lipid transport have been studied in 210 northern Spanish men, of whom 98 had proven coronary artery disease. The other 112 men were clinically free from coronary artery disease and acted as controls. The genotypes were investigated for relationships with plasma lipid and lipoprotein levels, as well as for the presence of coronary artery disease. As expected, the mean levels of plasma triacylglycerols (triglycerides) and lipoprotein (a) and the number of smokers were significantly higher in the disease group, and high-density lipoprotein (HDL)-cholesterol was significantly lower. Surprisingly, plasma cholesterol and low-density lipoprotein cholesterol were not different between the two groups. With regard to the common mutations, plasma triacylglycerol levels were related to the HindIII variants of lipoprotein lipase (P<0.05), to the apolipoprotein CIII variant (C3175G in exon 4) and to the apolipoprotein AI XmnI polymorphisms (P<0.05 and P<0.02 respectively). The apolipoprotein E variants were related to plasma cholesterol (P<0.05), HDL-cholesterol (P<0.02), plasma triacylglycerols (P<0.05) and the triacylglycerol/HDL ratio (P<0.01). Only the three-codon insertion/deletion variants of the apolipoprotein B signal peptide region discriminated between the two groups with or without arterial disease (P=0.02). The possible functional effects of these common mutations are discussed.     

Lipid and blood pressure treatment goals for type 1 diabetes: 10-year incidence data from the Pittsburgh Epidemiology of Diabetes Complications Study

OBJECTIVE--Subjects with type 1 diabetes are at high risk for many long-term complications, including early mortality and coronary artery disease (CAD). Few data are available on which to base goal levels for two major risk factors, namely blood pressure and lipid/lipoproteins. The objective of this study was to determine at which levels of LDL and HDL cholesterol, triglycerides, and blood pressure the relative risks of type 1 diabetic complications increase significantly. RESEARCH DESIGN AND METHODS--Observational prospective study of 589 patients with childhood-onset type 1 diabetes (<17 years) aged > or =18 years at baseline; 10-year incidence of mortality, CAD, lower-extremity arterial disease, proliferative retinopathy, distal symmetric polyneuropathy, and overt nephropathy. Relative risks were determined using traditional groupings of blood pressure and lipid/lipoproteins, measured at baseline, using the lowest groupings (<100 mg/dl [2.6 mmol/l] LDL cholesterol, <45 mg/dl [1.1 mmol/l] HDL cholesterol, <100 mg/dl [1.1 mmol/l] triglycerides, <110 mmHg systolic blood pressure, and <80 mmHg diastolic blood pressure) as reference. Adjustments for age, sex, and glycemic control were examined. RESULTS--Driven mainly by strong relationships (RR range 1.8-12.1) with mortality, CAD, and overt nephropathy, suggested goal levels are as follows: LDL cholesterol <100 mg/dl (2.6 mmol/l), HDL cholesterol >45 mg/dl (1.1 mmol/l), triglycerides <150 mg/dl (1.7 mmol/l), systolic blood pressure <120 mmHg, and diastolic blood pressure <80 mmHG: Age, sex, and glycemic control had little influence on these goals. CONCLUSIONS--Although observational in nature, these data strongly support the case for vigorous control of lipid levels and blood pressure in patients with type 1 diabetes.     

Variations in apolipoproteins B and A, during the course of myocardial infarction

The plasma apolipoproteins B and A1, and plasma lipids and lipoproteins, were studied in fifteen patients with acute myocardial infarction. In the days immediately after acute infarction there was a decrease in total cholesterol, low density lipoprotein-cholesterol, total apolipoprotein-B, low density lipoprotein apolipoprotein-B and high density lipoprotein apolipoprotein A1. High density lipoprotein-cholesterol remained unchanged. In the same period the total triglycerides, very low density lipoprotein-protein, very low density lipoprotein-cholesterol, very low density lipoprotein apolipoprotein-B and very low density lipoprotein apolipoprotein A1 were increased. A reduction of the apolipoprotein ratio CII/CIII occurred after the acute phase. After 25--30 days all these values regained their baseline values.     

Effect of Aerobic Exercise on Risk Factors of Cardiovascular Disease and the Apolipoprotein B / Apolipoprotein A-1 Ratio in Obese Woman

[Purpose] The objective of this study was to confirm whether consistent aerobic exercise has an effect on the apolipoprotein B/apolipoprotein A-1 ratio or reduces the risk of cardiovascular disease in obese women. [Subjects and Methods] The participants included 32 obese women between the ages of 40 and 49. Subjects were randomly divided into two groups (n = 16 in each group): the control group and the exercise group. The exercise program in this study corresponded to an intensity of 50 to 60% of the maximum volume of minute oxygen consumption and was performed three times per week over 12 weeks. Physical measurements, measurement of cardiorespiratory fitness and blood pressure, and blood collection were done before and after the 12 weeks of exercise at the same time and under the same conditions. [Results] Based on the results of this study, there were significant interaction effects in both time and group weight, for body mass index, percent body fat, maximum volume of minute oxygen consumption, high-density lipoprotein cholesterol, and the apolipoprotein B/apolipoprotein A-1 ratio. Moreover, waist circumference, total cholesterol, and the atherogenic index decreased significantly after 12 weeks of aerobic exercise. [Conclusion] Regular aerobic exercise effectively improved cardiovascular risk factors and decreased the obesity index in obese women.Key words: Aerobic exercise, Apolipoprotein, Cardiovascular disease     

男性冠心病心力衰竭患者性激素水平及意义

目的探讨男性冠心病心力衰竭患者性激素水平。方法用放射免疫法及ELISA法测定血清睾酮、雌二醇及脂蛋白(a)[Lp(a)]水平,用酶法及透射比浊法测定血胆固醇及载脂蛋白浓度。结果冠心病心力衰竭患者血清睾酮、高密度脂蛋白胆固醇(HDLC)、载脂蛋白AI及血清钠明显低于健康对照组(P<0.05或0.01),血清雌二醇/睾酮、Lp(a)、胆固醇及低密度脂蛋白胆固醇(LDLC)显著高于健康对照组(P<0.05或0.01);健康人血清睾酮与雌二醇呈正相关(r=0.372,P<0.05),心力衰竭患者血清睾酮与雌二醇无明显相关性(P>0.05),与血清钠及HDLC呈显著正相关(r=0.341和0.356,P<0.05),与血LDL-C呈负相关(r=-0.385,P<0.05),与左心室射血分数及其他血脂成分无明显相关性(P>0.05)。结论男性冠心病心力衰竭患者血清睾酮水平明显下降,适当应用睾酮可改善预后。     

Lipid and protein oxidation and antioxidant status in patients with angiographically proven coronary artery disease

OBJECTIVES: We aimed to evaluate the association of lipid peroxidation, protein oxidation and antioxidant system, and to assess an association with the severity of the disease, in patients with and without coronary artery disease (CAD) documented by coronary angiography. DESIGN AND METHODS: The population included 208 patients, undergoing clinically indicated coronary angiography. While the subjects with normal coronary angiograms (n=54) were evaluated as controls, the patients with CAD (n=154) were divided into three categories according to the number of diseased coronaries; one-vessel (n=50), two-vessels (n=51) and three-vessels (n=53). Lipid parameters were determined by routine laboratory methods. Plasma malondialdehyde and vitamin E concentrations were determined with the high-performance liquid chromatography. Other oxidant and antioxidant parameters were studied spectrophotometrically. RESULTS: While plasma malondialdehyde levels, the susceptibilities of erythrocyte and apolipoprotein B containing lipoproteins to in vitro induced oxidative stress, serum protein carbonyls, low density lipoprotein-cholesterol, triglyceride, apolipoprotein B and lipoprotein (a) levels had significantly increased, high-density lipoprotein-cholesterol and apolipoprotein AI levels, erythrocyte glutathione peroxidase, glutathione reductase, glucose 6 phosphate dehydrogenase, serum catalase, paraoxonase and arylesterase activities, plasma vitamin E and C and carotenoid levels had significantly decreased. The odds ratios for one-, two-, and three-vessel disease increased across especially higher tertiles of concentrations for oxidation parameters and lower tertiles of concentrations for antioxidant parameters. CONCLUSIONS: According to the results, we suggest that increased lipid and protein oxidation products and decreased antioxidant enzymes and vitamins contribute to increased oxidative stress which in turn is related to the severity of the disease.     

Biological variation of lipoprotein(a) in a diabetic population. Analysis of the causes and clinical implications.

The aims of the present study were to evaluate the biological variability of lipoprotein(a) (Lp(a)) in diabetic patients and to investigate the biological sources of this variability. Lp(a) was measured by ELISA in four serum specimens collected in 3-month intervals from 70 patients. The other parameters analyzed were: total cholesterol, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides, glucose, HbA and albumin excretion rate. The overall biological within-subject variance (CVb) was 31.7%, and it was inversely correlated with Lp(a) serum levels. According to the initial ranges of Lp(a) serum levels (< 15, 15-30 and > 30 mg/dl) the CVb were 42.3%, 24.1% and 23.7%, respectively. In multivariate analysis the total intra-individual coefficient of variation (CVt) of triglycerides and the CVt of the albumin excretion rate (AER) were independently associated with the CVb of Lp(a) (R2 = 0.54). The intra-individual biological variation of Lp(a) produced a misclassification of 20% of diabetic patients for cardiovascular risk attributable to this lipoprotein. In conclusion, the higher biological variability of Lp(a) observed in diabetic patients suggests that a single determination could be inaccurate to assess the cardiovascular risk associated with this lipoprotein, at least in those patients in whom serum levels are near the cut-off considered as risk for cardiovascular disease (> 30 mg/dl). Finally, triglycerides and AER are the main factors influencing Lp(a) serum levels in the diabetic population.     

Effects of glyburide treatment on serum lipoprotein and apolipoprotein concentrations and ratios in non-insulin-dependent diabetes mellitus

Lipoproteins and apolipoproteins were studied in 28 patients with newly detected non-insulin-dependent diabetes mellitus (NIDDM) before and after combined dietary and glyburide treatment. The patients, aged 33 to 67 years and without coronary or other atherosclerotic diseases, displayed fasting blood sugar levels of over 140 mg/dl after four weeks of dietary treatment. Overnight fasting blood samples were collected before the beginning of the trial, after four weeks of dietary treatment, and after four and eight weeks of combined dietary and glyburide treatment. The pretrial levels of total serum cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 and A2, and apolipoprotein B were similar to or even lower than those of nondiabetics; however, high-density lipoprotein cholesterol (HDL-C) levels and HDL-C% (the percentage of TC bound to HDL) were significantly lower in the diabetic patients. After combined dietary and glyburide treatment and normalization of blood sugar, apolipoprotein A1 and A2, HDL-C levels, and HDL-C% increased significantly. TC, TG, and LDL-C levels, although not exceeding the normal range, decreased significantly. HDL-C2 and HDL-C3 levels also increased, but the differences did not reach significance. Among the lipid, lipoprotein, and apolipoprotein ratios in the patients, only the ratios HDL-C:LDL-C, apolipoprotein A1:apolipoprotein B, and HDL-C: apolipoprotein B increased significantly as a result of the opposing responses of the protective lipoprotein HDL-C and apolipoprotein A1 and the atherogenic lipoprotein LDL-C and apolipoprotein B. The results demonstrate the favorable effects of combined dietary and sulphonylurea drug treatment on lipoproteins and apolipoproteins in NIDDM patients, thereby reducing coronary and atherosclerotic risks.     

Serum lipoprotein profile in patients with cancer. A comparison with non-cancer subjects

The association of cancer with low serum total cholesterol is well established. Less clear is the relationship of cancer with the cholesterol distribution among the different lipoprotein classes. Conflicting results have been reported on low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and serum triglyceride levels in different types of tumor. Total serum cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and serum triglycerides were analyzed in 530 patients with newly diagnosed cancer (97 with hematological malignancies, 92 with tumor of the lung, 108 of the upper digestive system, 103 of colon, 32 of breast, and 98 of the genitourinary system) and in 415 non-cancer subjects. Anthropometric (body mass index) and biochemical (serum albumin) indices of nutritional status were also determined in all subjects. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum albumin, and body mass index were significantly lower in cancer than in non cancer-subjects. The lowest values of total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were recorded in patients with hematological malignancies and the highest in patients with breast tumor. All the cancer groups, with the exception of women with breast cancer, showed significantly lower total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol than age- and sex-matched non-cancer subjects. Multiple regression analysis with low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides as dependent variables and sex, age, body mass index, albumin, and cancer (dummy variable) as independent variables, showed that cancer was independently associated with low levels of low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol and with high values of serum triglycerides. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum triglycerides, body mass index and serum albumin were significantly lower in patients with metastatic than in patients with non-metastatic solid tumor. The significant difference in low-density lipoprotein-cholesterol and serum triglycerides between patients with metastatic and non-metastatic cancer was lost when lipoprotein cholesterol and serum triglyceride levels were adjusted for nutritional variables. The lipid profile in cancer patients is characterized by low low-density lipoprotein-cholesterol, low high-density lipoprotein-cholesterol and relatively high serum triglycerides. The abnormality is a common feature of both hematological and solid tumors and is not entirely explained by poor nutrition.     

Apolipoprotein E polymorphism--a risk factor for metabolic syndrome.

BACKGROUND: Metabolic syndrome is closely related to several disturbances in lipid and lipoprotein metabolism. The aim of this study was to determine the association between apolipoprotein E (apoE) genotypes and the risk of metabolic syndrome and/or coronary heart disease complications. METHODS: The study included 279 subjects divided into three groups: 1) control subjects, 2) metabolic syndrome patients, and 3) obese patients with coronary heart disease. All subjects were characterized by body mass index, and plasma levels of glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). ApoE genotypes were identified by PCR-restriction fragment length polymorphism using genomic DNA. RESULTS: Statistical analysis of plasma parameters showed that subjects in groups 2 and 3 had higher levels of triglycerides and lower levels of HDL-C compared to group 1. The frequencies of apoE genotypes determined in this Romanian population (65% for E3/3, 19.6% for E4/3, 9.5% for E3/2, 4.1% for E2/2, 0.6% for E4/4, 1.3% for E4/2) were in agreement with those reported for other Caucasian populations. The distribution of apoE alleles indicated a higher frequency of epsilon4 in groups 2 and 3. There was a higher frequency of the apoE4/3 genotype in groups 2 and 3, which was significantly correlated with higher levels of triglycerides and lower levels of HDL-C. CONCLUSIONS: Correlations of apoE genotypes with these markers indicate that the epsilon4 allele is an independent risk factor for metabolic syndrome.     

Do mutations causing low HDL-C promote increased carotid intima-media thickness?

BACKGROUND: Although observational data support an inverse relationship between high-density lipoprotein (HDL) cholesterol and coronary heart disease (CHD), genetic HDL deficiency states often do not correlate with premature CHD. METHODS: Carotid intima-media thickness (cIMT) measurements were obtained in cases comprising 10 different mutations in LCAT, ABCA1 and APOA1 to further evaluate the relationship between low HDL resulting from genetic variation and early atherosclerosis. RESULTS: In a 1:2 case-control study of sex and age-related (+/-5 y) subjects (n=114), cIMT was nearly identical between cases (0.66+/-0.17 cm) and controls (0.65+/-0.18 cm) despite significantly lower HDL cholesterol (0.67 vs. 1.58 mmol/l) and apolipoprotein A-I levels (96.7 vs. 151.4 mg/dl) (P<0.05) CONCLUSIONS: Genetic variants identified in the present study may be insufficient to promote early carotid atherosclerosis.     

Efficacy and safety of cerivastatin 0.8 mg in patients with hypercholesterolaemia: the pivotal placebo-controlled clinical trial. Cerivastatin Study Group

This pivotal, multicentre, double-blind, parallel-group study evaluated the efficacy and safety of cerivastatin 0.8 mg. Patients with primary hypercholesterolaemia were randomized, after 10 weeks' dietary stabilization on an American Heart Association (AHA) Step I diet, to treatment with cerivastatin 0.8 mg (n = 776), cerivastatin 0.4 mg (n = 195) or placebo (n = 199) once daily for 8 weeks. Cerivastatin 0.8 mg reduced mean low density lipoprotein-cholesterol (LDL-C) by 41.8% compared with cerivastatin 0.4 mg (-35.6%, P < 0.0001) or placebo. In 90% of patients receiving cerivastatin 0.8 mg LDL-C was reduced by 23.9 -58.4% (6th - 95th percentile). Overall attainment of the National Cholesterol Education Program (NCEP) goal was achieved by 84% of patients receiving cerivastatin 0.8 mg and by 59% of those with coronary heart disease (CHD). In the sub-population meeting the NCEP criteria for pharmacological therapy for LDL-C reduction, 74.6% of patients, including the 59% with CHD, reached the goal with cerivastatin 0.8 mg. Cerivastatin 0.8 mg also reduced mean total cholesterol by 29.9%, apolipoprotein B by 33.2% and median triglycerides by 22.9% (all P < 0.0001). Mean high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 were elevated 8.7% (P < 0.0001) and 4.5% (P < 0.0001), respectively, by cerivastatin 0.8 mg. Reductions of triglyceride and elevation in HDL-C were dependent upon triglyceride baseline levels; in patients having baseline triglyceride levels 250 - 400 mg/dl, cerivastatin 0.8 mg reduced median triglycerides by 29.5% and elevated HDL-C by 13.2%. Cerivastatin 0.8 mg was well tolerated. The most commonly reported adverse events included headache, pharyngitis and rhinitis (4 - 6%). Symptomatic creatine kinase elevations > 10 times upper limit of normal occurred in 0%, 1% and 0.9% of patients receiving placebo, cerivastatin 0.4 mg or cerivastatin 0.8 mg, respectively. Cerivastatin 0.8 mg is an effective and safe treatment for patients with primary hypercholesterolaemia who need aggressive LDL-C lowering in order to achieve NCEP-recommended levels.     

纤维化标志物CTGF与冠心病的相关性

目的探讨血清结缔组织生长因子(CTGF)水平与冠心病的关系及其临床诊断价值。方法将102例行冠状动脉造影检查确诊的冠心病患者作为冠心病组,将年龄和性别与冠心病组严格匹配的冠状动脉造影检查正常的98例作为健康对照组;采用t检验分析冠心病组与健康对照组间临床基线资料、CTGF和人转化生长因子β1(TGF-β1)的差异,采用二元Logistic逐步回归方法探讨冠心病与CTGF等的相关性,评价其临床诊断价值。结果冠心病组三酰甘油、总胆固醇、载脂蛋白A1、高密度脂蛋白、脂蛋白a、低密度脂蛋白、TGF-β1和CTGF与健康对照组比较差异有统计学意义(P0.05)。经Spearman相关分析显示CTGF和TGF-β1呈正相关(r=0.773,P=0.002);检测CTGF可以在评价冠心病的危险分层方面起到积极的作用。结论年龄、吸烟、高血压、总胆固醇、载脂蛋白A1、高密度脂蛋白、低密度脂蛋白、脂蛋白a、CTGF、TGF-β1是冠心病的影响因素,临床工作中检测CTGF可以作为评估冠状动脉狭窄及严重程度的指标。