氨氯地平对阿托伐他汀调脂作用的影响

目的观察氨氯地平对高血压合并冠心病患者阿托伐他汀调脂作用的影响。方法选择高血压合并冠心病患者174例,根据用药情况将患者分为2组,A组86例,以氨氯地平为基础的降压方案+阿托伐他汀;B组88例,无氨氯地平的降压方案+阿托伐他汀。分别观察2组在治疗前,治疗后2、4、8周时血脂、肝功、肌酸激酶等变化及不良反应发生情况。结果 A组与B组患者治疗前血清TC、TG、LDL-C、HDL-C水平差异无统计学意义(P0.05)。与治疗前比较,A组和B组患者治疗后2、4、8周血清TC、LDL-C水平明显降低,差异有统计学意义(P0.05);A组患者治疗后4、8周血清HDL-C水平明显升高,8周血清TG水平明显降低,差异有统计学意义(P0.05);B组患者治疗后2、4、8周血清HDL-C水平虽有升高趋势,TG水平虽有下降趋势,但差异无统计学意义(P0.05)。与B组比较,A组患者治疗后4、8周血清TC、LDL-C水平明显下降;治疗后8周血清HDL-C水平明显升高,差异有统计学意义(P0.05)。结论氨氯地平可能加强高血压合并冠心病患者阿托伐他汀的调脂作用,合用无明显不良反应。     

Lipid peroxidation,antioxidants, lipid profile,and HbA1c in diabetic patients

Diabetes mellitus is characterized by hyperglycemia together with biochemical changes in glucose, lipid profile, lipid peroxidation, and antioxidants status. This study aims to assess lipid profile, lipid peroxidation, antioxidants, and glycated hemoglobin (HbA1c) in type 1 and type 2 diabetic subjects. Type 1 and type 2 diabetic patients were selected from the subjects attending OPD in Nepalgunj Medical College, Nepal, for medical checkup. Fasting blood sugar (FBS), lipid profile, lipid peroxidation (malondialdehyde), and antioxidants status (reduced glutathione and vitamin E) were estimated in both groups and were compared with healthy controls. Low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio was calculated to assess the cardiovascular risk factors. When type 1 diabetic patients were compared with type 2 diabetic patients, it showed statistically significant increase in the levels of HbA1c, triglycerides (TGs), and high-density lipoprotein cholesterol (HDL-C), whereas statistically significant decreased level was found in malondialdehyde (MDA). FBS, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), reduced glutathione (GSH), vitamin E, and HDL/LDL ratio were not significant. Early diagnosis of dyslipidemia and oxidative stress can be used as a preventive measure for the development of microvascular and macrovascular complications in type 1 and type 2 diabetes mellitus.     

血清胆红素和血脂的综合指数与冠心病的关系研究

目的探讨血清胆红素与血脂的综合指数与冠心病(CHD)的关系.方法将80名行冠状动脉造影术的患者分为2组:CHD组与对照组(冠状动脉正常).测定血清总胆红素水平(TBIL),总胆固醇(TC),高密度脂蛋白胆固醇(HDL-C),低密度脂蛋白胆固醇(LDL-C),计算出其综合指数:LDL-C/(HDL-C TBIL)和TC/(HDL-C TBIL),分析其与CHD之间的关系.结果CHD患者血清TBIL水平明显低于非冠心病患者(P＜0.05).CHD患者总胆固醇(TC),低密度脂蛋白胆固醇(LDL-C),LDL-C/(HDL-C TBIL)比值,TC/(HDL-C TBIL)比值水平明显高于冠状动脉正常组(P＜0.05).进行Logistic回归分析,TC,LDL-C,LDL-C/(HDL-C TBIL),TC/(HDL-C TBIL)可引入Logistic回归模型,它们为CHD的危险因素.结论CHD的发生与TBIL的降低有一定的相关性,综合考虑血脂、血清胆红素与血脂的综合指数有助于CHD的诊断.     

Effect of alpha-lipoic acid on lipid profile in rats fed a high-fructose diet

This study investigated the effect of administration of alpha-lipoic acid (LA) on lipid metabolism in high fructose-fed insulin-resistant rats. High-fructose feeding (60 g/100 g diet) to normal rats resulted in a significant increase in the concentrations of cholesterol, triglycerides (TGs), free fatty acids (FFAs), and phospholipids in plasma, liver, kidney, and skeletal muscle. Reduced activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) and increased activity of the lipogenic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase were observed in plasma and liver. High-density lipoprotein cholesterol (HDL-C) was significantly lowered and very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were significantly elevated. Treatment with LA (35 mg/kg body weight intraperitoneal) reduced the effects of fructose. The rats showed near-normal levels of lipid components on plasma and tissues. Activities of key enzymes of lipid metabolism were also restored to normal values. Cholesterol distribution in the plasma lipoproteins was normalized, resulting in a favorable lipid profile. This study demonstrates that LA can alter lipid metabolism in fructose-fed insulin-resistant rats and may have implications in the treatment of insulin resistance.     

The effects of oral anti-hyperglycaemic medications on serum lipid profiles in patients with type 2 diabetes

Aim:  Patients with type 2 diabetes often have dyslipidaemia, putting them at risk of cardiovascular disease, and are frequently treated with oral anti-hyperglycaemic medications (OAMs). This review compares the effects of OAMs on serum lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and free fatty acids (FFAs)] in patients with type 2 diabetes.
Methods:  medline was searched for entries indexed from January 1966 to November 2002; search terms included the names of OAMs and serum lipids, limited to English language and human subjects. We selected clinical studies in type 2 diabetes of OAM monotherapy that included serum lipid data, treated all patients in a treatment group with the same drug, used therapeutic OAM doses not higher than the maximum recommended in the USA, compared therapy with baseline or placebo and specified statistical tests used. One unblinded investigator selected studies for inclusion. Data reported include number of patients, study length, OAM dose, serum lipid data at baseline and endpoint, p-values and statistical tests.
Results:  Data on the serum lipid effects of sulphonylureas, repaglinide, nateglinide and miglitol were inconclusive. Acarbose increased HDL-C and decreased LDL-C and voglibose reduced TC. Metformin at higher doses reduced TC; data on its effects on other lipids were inconclusive. Rosiglitazone increased LDL-C, HDL-C and TC and reduced FFAs but had no effect on TGs. Pioglitazone increased HDL-C and reduced TGs and FFAs but did not affect LDL-C or TC.
Conclusions:  Lipid changes as a result of improved glycaemic control are not uniform findings associated with anti-diabetic therapy. Only metformin, acarbose, voglibose, rosiglitazone and pioglitazone had significant effects on the lipid profile. These effects should be considered when selecting OAMs for patients with type 2 diabetes.     

Cord blood lipoprotein-cholesterol: relationship birth weight and gestational age of newborns

Umbilical plasma levels of lipoproteins-cholesterol were measured in 60 premature (less than 37 weeks), 60 small for gestational age (SGA, greater than 37 weeks), and 60 full term newborns (greater than 37 weeks) to ascertain the relationship between gestational age, infant's weight and concentration of plasma lipoprotein cholesterol. Umbilical levels of total cholesterol (TC), unesterified cholesterol (UC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in premature newborns were significantly higher (P less than .001) than in term infants. The levels of TC, UC, HDL-C and very low density lipoprotein cholesterol (VLDL-C) were substantially higher (P less than .05) in umbilical cord plasma of SGA newborns than in cord plasma of full term newborns. Lecithin:cholesterol acyltransferase activity in cord plasma was indirectly assessed by measuring the ratio of esterified cholesterol to unesterified cholesterol (CE/UC). This ratio was significantly lower (P less than .01) in preterm and SGA than in full term newborns. In addition, plasma TC, UC, LDL-C and HDL-C levels were inversely correlated with gestational age of newborns. By contrast, CE/UC ratio had an inverse correlation with gestational age and HDL-C of the newborns. These findings suggest that the levels of TC in newborns are regulated by the uptake of LDL-C by the fetal adrenal and, additionally, by the lecithin:cholesterol acyltransferase (LCAT) activity of newborn plasma. Only by careful follow-up of hyperlipidemic neonates can the true incidence of familial hyperlipoproteinemia and the value of early diagnosis be assessed.     

冠状动脉病变与血脂代谢异常的相关性

目的　探讨冠状动脉病变与血脂代谢紊乱的关系。方法　将2 6 7例疑似冠心病的患者依据冠状动脉造影结果分为对照组(非冠心病组) 1 0 1例,冠心病组1 6 6例,其中单支病变组54例,双支病变组6 8例,三支病变组4 4例,同时测定并统计分析血脂各成分及其比值与冠状动脉病变之间的关系。结果　冠心病(CHD)组总胆固醇(TC)、低密度脂蛋白胆固醇(LDL- C)、甘油三脂(TG)水平明显高于对照组,高密度脂蛋白胆固醇(HDL C)水平明显低于对照组,差异有统计学意义。随着冠状动脉病变范围的增加,TC、LDL C、载脂蛋白B(ApoB)、TC HDL- C、LDL- C HDL- C升高,HDL- C降低,与对照组比较,差异有统计学意义。冠心病组血脂各组分和其比值与冠状动脉积分的相关分析表明,TC HDL- C、LDL -C HDL -C与冠状动脉病变的相关性最强。结论　血脂代谢紊乱的严重程度与冠状动脉病变的严重程度是一致的,通过异常的血脂代谢有可能初步预测冠状动脉病变,其中LDL- C HDL- C、TC- HDL C比值优于其他血脂指标。     

Managing diabetic dyslipidemia: Beyond statin therapy

Cardiovascular disease is a significant cause of morbidity and mortality in patients with diabetes mellitus. The lipid profile of type 2 diabetes mellitus is characterized by increased triglycerides (TGs), decreased high-density lipoprotein cholesterol (HDL-C), increased very low density lipoproteins (VLDLs), and small, dense low-density lipoprotein particles, the combination of which is highly atherogenic. In diabetic patients, current treatment guidelines target low-density lipoprotein cholesterol (LDL-C) ≤ 100 mg/dL with statins. In patients with elevated TGs, non-HDL-C is considered a secondary target of therapy. Despite the use of statin therapy in diabetes, a significant number of fatal and nonfatal coronary heart disease (CHD) events still occur, indicating the need to target other modifiable risk factors for CHD, including high TGs and low HDL-C.     

女性原发性高血压患者绝经前后脂蛋白(a)及血脂水平变化的研究

目的　观察女性原发性高血压患者绝经前后脂蛋白 (a) [L p(a) ]及血脂水平的变化 ,探讨其对女性冠心病发病情况可能存在的影响。方法　女性原发性高血压患者 12 1例 ,测定 L p(a)、总胆固醇 (TC)、三酰甘油 (TG)、低密度脂蛋白胆固醇 (L DL- C)和高密度脂蛋白胆固醇 (HDL- C)。对比绝经前后 L p(a)及血脂水平的变化 ,并与女性健康体检者 (对照组 )进行对比。结果　高血压组 L p(a)、TC、TG、L DL - C均显著高于对照组 ,而 HDL - C及 HDL - C/TC则明显低于对照组 ,在所有原发性高血压患者中 ,绝经后的患者 L p(a)、TC、TG、L DL - C显著高于绝经前患者 ,而 HDL - C/ TC则前者低于后者。结论　绝经后原发性高血压患者 L p(a)、TC、L DL - C均明显高于绝经前患者 ,而HDL- C/ TC则低于绝经前患者 ,提示绝经后女性原发性高血压患者 L p(a)及血脂水平增高与内源性雌激素水平下降有关 ,是绝经后冠心病发病率明显上升的重要原因。     

Avasimibe, an ACAT inhibitor, enhances the lipid lowering effect of atorvastatin in subjects with homozygous familial hypercholesterolemia

This study assessed the efficacy and safety of avasimibe (CI-1011), an inhibitor of acyl coenzyme A-cholesterol acyltransferase (ACAT) in subjects with homozygous familial hypercholesterolemia (HoFH). Twenty seven subjects were enrolled in a double-blind, randomized, 3-sequence crossover trial of atorvastatin 80 mg QD, avasimibe 750 mg QD, and the combined treatment of atorvastatin 80 mg QD and avasimibe 750 mg QD after a washout period of 4 weeks. Each treatment period was administered over 6 weeks for a total of 18 weeks. There were no significant lipid changes resulting from the administration of avasimibe monotherapy. Avasimibe in combination with atorvastatin resulted in a significantly better reduction of total cholesterol (TC) as compared to atorvastatin alone (-22% versus -18%) (P < 0.05). All other lipid changes were not statistically significant for combination therapy compared to atorvastatin monotherapy, however there were greater reductions in triglycerides (TG) (-24% versus -13%), low-density lipoprotein cholesterol (LDL-C) (-23% versus -19%), very low-density lipoprotein cholesterol (VLDL-C) (-24% versus -13%) and high-density lipoprotein cholesterol (HDL-C) (-11% versus -6%). Avasimibe may modestly enhance the lipid-reducing effect of atorvastatin by further inhibiting the production of intracellular cholesterol through mechanisms that appear to be compatible in this population.     

Experimental atherosclerosis and oxygen free radicals

Oxygen free radicals are known to produce cellular injury by peroxidation of phospholipids in the cell membrane. These free radicals might damage the endothelial cell and thus set the stage for atherosclerosis. The authors studied the effect of high-cholesterol diets on the genesis of atherosclerosis and lipid peroxidation products, malondialdehyde (MDA) in rabbits. The animals were divided into four groups each comprising 5 rabbits, on the basis of their diets. Group I, control diet; group II, cholesterol; group III, coconut oil; group IV, a mixture of cholesterol, coconut oil, and cholic acid. Rabbits were sacrificed five months after being on the respective diets. Blood samples were obtained for the measurements of total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglycerides, and MDA at the end of the protocol. The aortas were removed from different animals for the identification of atherosclerotic plaques. Plaques were detected in all the animals in group II and group IV. The serum total cholesterol, LDL-C, and VLDL-C were significantly higher in animals of group II and IV than in those of group I. The values for serum total cholesterol, HDL-C, LDL-C, and VLDL-C in group III were not significantly different from those in group I. The blood MDA and serum triglycerides were also higher in animals of group II and IV than in those of group I. There were, however, no significant differences in these parameters in group III as compared with those in group I.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum lipids in north Indian children treated for kawasaki disease

A prospective cross sectional analysis of serum lipids was carried out in 20 children aged between 1.3 and 16 years with Kawasaki disease (KD). The controls were siblings of other patients. The mean interval between diagnosis of the disease and time of assay was 2.6 years (range 0.41 to 6 years). Standard biochemical methods were employed for determination of various components of the lipid profiles. There were significant differences in high-density lipoprotein cholesterol (HDL-C) (40.37 +/- 12.0 mg/dL versus 53.49 +/- 4.31 mg/dL, P < 0.001) and low-density lipoprotein cholesterol (LDL-C) concentrations (77.76 +/- 26.25 mg/dL versus 57.7 +/- 23.2 mg/dL, P < 0.05) between the cases and controls. Lower HDL-C levels persisted at 1-3 and more than 3 years of disease duration. No significant differences were seen in the values of other parameters in the lipidogram, such as total cholesterol (TC), triglycerides (TG), and very low-density lipoprotein cholesterol (VLDL-C). Premature atherosclerosis that occurs in KD may be secondary to these lipid metabolism abnormalities.     

Lipid and lipoprotein abnormalities in young quadriplegic men.

To assess the effect of severe inactivity on the serum lipid and lipoprotein profile, 21 quadriplegic men between the ages of 24 and 47 were compared with 20 age-matched healthy control men. The group of quadriplegic men had significantly lower levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), HDL2-C and HDL3-C. The current recommendation for desirable TC is less than 200 mg/dl, whereas HDL-C of less than 35 mg/dl is considered a risk factor for coronary heart disease. Of the 50% (10/20) of the men in the normal control group who had a desirable TC, only 10% (1/10) had a low or undesirable HDL-C value. In comparison, although 81% (17/21) of the group of quadriplegic men had a desirable TC, 53% (9/17) of these individuals had a low HDL-C level. It is concluded that although the presence of lower TC could be beneficial in QM, the decreased values of HDL-C and HDL2-C and the increased ratio of TC/HDL-C suggest a higher risk of coronary heart disease. The findings are consistent with recent reports of an increased prevalence of coronary heart disease in spinal cord injury patients, which could be due to an abnormal lipoprotein profile related to diet, inactivity, changes in body composition, and life style. Moreover, the present data suggest that HDL-C should be measured in quadriplegic men with modifiable risk factors, even if they have desirable TC, to avoid missing an increased coronary heart disease risk status.     

Relationship of menopausal status and exercise level to HDL-cholesterol in women

The relationship between exercise habits, menopausal status and HDL cholesterol (HDL-C) was studied in 44 long-distance runners, 47 joggers, and 45 relatively inactive females. In each group, some women were post-menopausal (Post-M) and some pre-menopausal (Pre-M). HDL-C level was higher in runners (77.6 mg/dl) and joggers (70.4 mg/dl) than in the inactive group (62.1 mg/dl), but was not different Pre-M vs Post-M. Total cholesterol (TC) and LDL-C were higher in Post-M than in Pre-M subjects, but did not differ among exercise groups. Body weight and % fat were lower in Pre-M vs Post-M groups and were lower in the runners vs inactive subjects. The HDL-C/TC ratio was higher in the runners vs inactive subjects and there was a significant exercise-menopausal interaction indicating a beneficial exercise effect. Adjustment of lipoprotein values for possible confounding variables did not alter these results. Endurance exercise by Post-M females may help prevent adverse lipid and lipoprotein changes which might predispose them to coronary heart disease.     

Oxygen free radicals as a mechanism of hypercholesterolemic atherosclerosis: Effects of probucol

We investigated the effects of high cholesterol diet in the presence and absence of probucol on the genesis of atherosclerosis, the blood lipid profile, aortic tissue lipid peroxidation product malondialdehyde (MDA), and aortic tissue chemiluminescence (CL) a marker for antioxidant reserve in rabbits. Five groups each of 10 rabbits were studied: group I, regular rabbit chow; group II, as I + cholesterol (0.5%); group III, as I + cholesterol (0.5%) and probucol (0.5 gm/kg/day); group IV, as I + cholesterol (1%), and group V, as I + cholesterol (1%) and probucol (0.5 gm/kg/day). Blood concentrations of triglyceride (TG), total cholesterol (TC), high density lipoproteincholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) were measured at monthly intervals for 4 months. The aorta was removed at the end of the protocol for assessment of atherosclerotic changes (gross and microscopic), MDA concentration and CL. TC, LDL-C, LDL-C/HDL-C ratio increased in all the groups except group I, while VLDL-C increased in group II only. HDL-C decreased in groups III, IV and V but remained unchanged in groups I and II. There was a decrease in HDL-C and VLDL-C components and an increase in LDL-C components of total cholesterol in all the groups II, III, IV and V, the changes being greater in group IV than in group II. Probucol did not appreciably affect the changes in lipid profile except that it decreased HDL-C significantly. Aortic tissue MDA increased in groups II, IV and V to a similar extent. Aortic CL which was measured only in groups I, IV and V increased to similar extent in the latter two groups. Atherosclerotic changes were greater in group II than in group III but similar to that in groups IV and V. Histological changes were practically similar in groups II, III, IV and V. The increased levels of aortic MDA and CL, which were associated with development of atherosclerosis, suggest a role for oxygen free radicals in the pathogenesis of hypercholesterolemia-induced atherosclerosis. Protection afforded by probucol was associated with a decrease in aortic MDA in spite of hypercholesterolemia. Ineffectiveness of probucol in 1% cholesterolfed rabbits was associated with its inability to reduce MDA and increase antioxidant reserve. These findings further support for the hypothesis that oxygen free radicals are involved in the genesis and maintenance of hypercholesterolemic atherosclerosis.     

Lipid profile in congenital adrenal hyperplasia

Glucocorticoids have been reported to exert a marked effect on lipoprotein metabolism. Several studies have shown a potential risk of hyperlipidemia in patients under long-term glucocorticoid therapy. Current management of patients with congenital adrenal hyperplasia (CAH) includes the use of glucocorticoids to attenuate the increased production of undesirable adrenal hormones. A case-control study was designed to compare the serum lipid profiles of 14 patients with CAH under glucocorticoid therapy and 14 normal controls and to determine the characteristics of the profiles. A total of 9 patients (64.3%) had serum total cholesterol (TC) greater than 4.4 mmol/L (170 mg/dL), compared with 6 individuals in the control group (42.3%). Nine patients with CAH (64.3%) had serum triglycerides (TGs) more than 1.0 mmol/L (90 mg/dL), compared with only 2 in the control group (14.3%). Similarly, the mean serum TG was higher in the CAH group versus the controls, 1.33 mmol/L (118 mg/dL) versus 0.75 mmol/L (67 mg/dL), respectively. Serum low-density lipoprotein, (LDL-C) and high-density, lipoprotein (HDL-C) cholesterol were determined in 13 children with CAH and in the 14 controls. Nine CAH patients (69.2%) and 8 controls (57%) had LDL-C greater than 2.8 mmol/L (<110 mg/dL). For HDL-C, 2 children with CAH (15.4%) and 4 controls (28.6%) had levels less than 0.9 mmol/L (35 mg/dL). There were no significant differences for the cholesterol index, 0.24 for the controls and 0.22 for the CAH group. In the CAH group, the mean serum TG level and the percentage of individuals with TGs greater than 1.0 mmol/L were statistically significant compared with the controls. The mean serum TC and LDL-C, as well as the percentage of subjects with levels over the cutoff point, although slightly higher in the CAH group, were of no statistical significance. The results of this pilot study suggest that long-term glucocorticoid therapy in patients with CAH may induce abnormalities in the serum lipid profile characterized mainly by an increment in serum TGs.     

The ratio of plasma high-density lipoprotein cholesterol to total and low-density lipoprotein cholesterol: age-related changes and race and sex differences in selected North American populations. The Lipid Research Clinics Program Prevalence Study

The distribution of the ratios of plasma high-density lipoprotein cholesterol (HDL-C) to total cholesterol (TC) and of HDL-C to low-density lipoprotein cholesterol (LDL-C) are presented for 6900 white and 495 black examinees greater than 4 years old. Measurements were obtained during the visit 2 survey of the Lipid Research Clinics (LRC) Program Prevalence Study, and correspond to a 15% random sample of 60,502 participants screened during the LRC visit 1 survey. Age-specific means, medians, and selected percentiles are given by sex and by gonadal hormone use in white women. Apparent in these cross-sectional data was a consistent age-related decline in the ratio of HDL-C to TC for white male participants, from a mean of 0.360 in the age group 5 to 9 to a mean of 0.211 in the age group 50 to 54. Thereafter the mean ratio increased slightly. In white women not using gonadal hormones the age-related decline in the ratio was only evident starting at the age group 35 to 39, from which it declines from 0.329 to 0.258 in the age group 55 to 59. White women using gonadal hormones showed very minor age-related changes in the HDL-C/TC ratio, varying around a mean of 0.300. The number of blacks examined was low and thus the racial comparisons must be interpreted with caution. For each gender, age-related trends were similar in black and white study participants. Black men, however, had a higher percentage of TC carried as HDL-C than white men in all age groups examined. Black women had a higher percentage of TC in HDL-C than white women only below age 20; in the adult age range no appreciable differences were seen. Pearson correlation coefficients between the lipid, lipoprotein, and lipoprotein ratios are presented. The ratio HDL-C/TC correlated highly with the ratio HDL-C/LDL-C (greater than 0.92 for all groups) and the former may be a more conveniently determined surrogate for the latter. Although not exhaustive regarding the information it conveys about a lipid pattern, the ratio HDL-C/TC has the advantage of summarizing complex associations into a single numerical approximation.     

Efficacy and short-term safety of a new ACAT inhibitor, avasimibe, on lipids, lipoproteins, and apolipoproteins, in patients with combined hyperlipidemia.

Although acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors have been shown to reduce lipid levels in several animal models, the safety and lipid modifying activity of any single agent in this class has not been demonstrated in humans. The safety and efficacy of avasimibe (CI-1011), a new, unique, wholly synthetic ACAT inhibitor, was evaluated in the treatment of 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia (low levels of high-density lipoprotein cholesterol [HDL-C]). Following an 8-week placebo and dietary-controlled baseline period, patients were randomly assigned to double-blind treatment with placebo, 50, 125, 250, or 500 mg avasimibe administered as capsules once daily for 8 weeks. At all evaluated doses, avasimibe treatment resulted in prompt and significant reductions (P<0.05) in plasma levels of total triglycerides (TG) and very low-density lipoprotein cholesterol (VLDL-C) with mean reductions of up to 23% and 30% respectively, apparently independent of dose. No statistically significant changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C or apolipoprotein (apo) B were detected. ApoAI levels were also unchanged on all doses of avasimibe apart from the 500 mg dosage, which was associated with a significant decrease in plasma apoAI. The relevance of this latter finding in only one dosage group is not known. All doses of avasimibe were well tolerated with no resulting significant abnormalities of biochemical, hematological, or clinical parameters.     

炎症及免疫指标对类风湿关节炎患者血脂的影响分析

目的 探讨类风湿关节炎(RA)患者血脂情况以及炎症和免疫状态对血脂的影响.方法 选取2008年至2009年在我院住院的225例RA患者,检测入院第1天的血脂、血沉(ESR)、C反应蛋白(CRP)、类风湿因子(RF)、抗环瓜氨酸肽抗体(抗CCP)、抗角蛋白抗体(AKA)、抗核周因子抗体(APF)、补体(C),分析上述指标对血脂及致动脉粥样硬化指数(AIP)的影响.结果 (1)225例患者中,12.9％的患者总胆固醇(TC)升高,43.6％的患者高密度脂蛋白胆固醇(HDL-C)降低,10.2％的患者低密度脂蛋白胆固醇(LDL-C)升高,14.2％的患者TG升高.(2) TC升高组中C3高于TC正常组(P＜0.05),HDL-C降低组的ESR及CRP高于HDL-C正常组(P＜0.05),LDL-C升高组CRP、C3及C4高于LDL-C正常组(P＜0.05).(3)多因素逐步回归分析显示:C3与TC水平正相关(R2=0.067,P＜0.05),ESR、CRP与HDL-C水平负相关(R2=0.202,P＜0.05),CRP、抗CCP抗体与LDLC正相关(R2=0.129,P＜0.05),ESR、C4与AIP正相关(R2=0.046,P＜0.05).结论 类风湿关节炎患者的系统性炎症及异常免疫反应影响其血脂水平及血脂的致动脉粥样硬化作用.     

Association between plasma lipids, and apolipoproteins and coronary artery disease: a cross-sectional study in a low-risk Korean population

BACKGROUND: Due to the lower level of the traditional lipid profiles in Koreans than in the series of patients from the western countries, the need to investigate other lipid parameters to help identify the individuals at high risk of CAD has been emphasized. AIM AND METHODS: To investigate whether apolipoprotein B (apo B), apolipoprotein A-I (apo A-I) and their ratio give additional information to the traditional lipid risk factors for discriminating the individuals at high-risk for coronary artery disease (CAD), 544 subjects, who met the lipid criteria of total cholesterol (TC) <230 mg/dl, low-density lipoprotein cholesterol (LDL-C) <120 mg/dl and high-density lipoprotein cholesterol (HDL-C) >40 mg/dl were recruited. Patients were considered to be CAD(+) if they had > or =50% stenosis in at least one coronary artery. RESULTS: In men, TC and apo B/apo A-I ratio were significantly different between groups with and without CAD after adjusting for age and diabetes (P = 0.037 and 0.035), and in women, triglyceride (TG), HDL-C and apo B/apo A-I ratio were significantly different after adjusting for age, diabetes and smoking status (P = 0.006, 0.007 and 0.030, respectively). In the lowest quartile of TC, TG and LDL-C, and the highest quartile of HDL-C, only apo B/apo A-I ratio was associated with CAD in both men and women. The only variable showing a significant difference between patients with and without CAD was apo B/apo A-I ratio. In models assessing whether apolipoproteins give additional information to traditional lipid risk factors, HDL-C, LDL-C, apo B/apo A-I ratio and in women but not in men, TG and apo B were all independent markers for the presence of CAD. Among the nontraditional lipid factors, only apo B/apo A-I ratio showed its additional value for identifying the presence of CAD. CONCLUSION: Apo B/apo A-I ratio is the only variable that differentiates the patients with CAD from those without and, furthermore, gives additional information to that supplied by traditional lipid risk factors in a low-risk Korean population.