Relation between charge-based apolipoprotein B-containing lipoprotein subfractions and remnant-like particle cholesterol levels

OBJECTIVE: Both mildly modified LDL subfraction that carries a more-negative electric charge and remnant-like particles (RLP) are closely related to triglyceride (TG) levels. We examined the relation between the RLP-cholesterol (C) level and charge-based apolipoprotein (apo) B-containing lipoprotein subfractions as determined by capillary isotachophoresis (cITP) in patients with hypercholesterolemia. METHODS AND RESULTS: cITP apo B lipoprotein subfractions were identified by analyzing plasma depleted of the related lipoproteins. While fast-migrating triglyceride-rich lipoprotein (fTRL) subfraction contained both chylomicrons and VLDL fraction, slow TRL (sTRL) only contained VLDL. cITP fLDL also contained VLDL fraction, i.e., beta-VLDL. Levels of cITP fTRL and sTRL were significantly correlated with serum levels of TG, RLP-C, apo C-II, and C-III. Levels of cITP sTRL were also correlated with apo E. Levels of cITP fLDL were positively correlated with not only LDL-C levels but also levels of TG, RLP-C, apo C-II, C-III, and E. CONCLUSION: cITP fast LDL correlated with RLP-C levels and modified the relation between RLP-C and TG levels.     

冠心病患者血清脂蛋白残粒胆固醇、血脂水平检测及其相关性分析

目的研究脂蛋白残粒胆固醇（RLP-C）在冠心病发病中的作用。方法检测76例冠心病患者（冠心病组）和40例正常查体者（对照组）血清RLP-C、TC、HDL—C、LDL-C水平,并对冠心病组血清TC水平不同者RLP-C水平进行比较。结果冠心病组血清RLP-C水平显著高于对照组（P〈0．01）;冠心病组血清TC水平正常者血清RLP-C水平显著高于血清TC水平临界和升高者（P〈0．01）。结论血清RLP-C水平升高是冠心病重要的独立致病因子;对于血清TC正常者进行RLP-C检测有重要的临床意义。     

Doxazosin reduces prevalence of small dense low density lipoprotein and remnant-like particle cholesterol levels in nondiabetic and diabetic hypertensive patients

Small dense low density lipoprotein (LDL) and remnant lipoproteins are potent atherogenic lipoproteins, often elevated in the plasma of patients with type 2 diabetes. The α₁-blocker doxazosin has been reported to favorably affect the plasma lipid profile. We examined whether doxazosin could reduce these atherogenic lipoproteins in hypertensive subjects with and those without type 2 diabetes. Seventeen nondiabetic hypertensive patients and 33 hypertensive patients with type 2 diabetes were studied. Doxazosin (2 to 4 mg) was administered alone or with other previously received antihypertensive drugs for 6 months. Mean LDL size was measured by 2%∼16% gradient gel electrophoresis. Remnant-like particle (RLP)-cholesterol was measured with the use of an affinity column containing anti-apoA1 and B100 monoclonal antibodies. Doxazosin effectively decreased blood pressure (BP) without significantly affecting glucose, glycosylated hemoglobin (HbA_1c), or C-peptide levels in both nondiabetic and diabetic patients. Doxazosin significantly reduced triglyceride, apo CIII, and apo B, but did not alter total-, LDL- or HDL-cholesterol. Mean LDL particle diameter was significantly increased from 25.6 ± 0.6 nm to 25.9 ± 0.4 nm (P < .001) by doxazosin treatment, regardless of the presence of diabetes. Consequently, the prevalence of small dense LDL (<25.5 nm) was halved in both groups. The increase in LDL size significantly correlated with decrease in triglyceride level (r = −0.798, P < .0001). Doxazosin significantly reduced RLP-cholesterol in both groups. These results suggest that doxazosin may help to prevent coronary artery disease by reducing atherogenic lipoproteins, including small dense LDL and remnant lipoproteins, in hypertensive patients, regardless of the presence of diabetes.     

The atherogenic plasma remnant-like particle cholesterol concentration is increased in the fasting and postprandial state in active acromegalic patients

BACKGROUND: Premature atherosclerosis is a clinical feature in untreated acromegaly. Increased postprandial lipoprotein remnant levels are associated with premature atherosclerosis. In most studies, remnants have been measured indirectly using retinyl esters (RE) as a chylomicron core label. Remnants can also be directly quantified by immunoseparation using monoclonal antibodies to apolipoprotein (apo) AI and apo B100 to remove nonremnant lipoproteins. Cholesterol is quantified in the remaining apo E-rich remnant fraction (RLP-C). OBJECTIVE: The aim of the present study was to investigate the role of postprandial lipaemia in patients with acromegaly to further define abnormalities leading to increased susceptibility for atherosclerosis. PATIENTS: In a case-control study, the plasma postprandial lipoprotein remnant fraction (RLP-C and RE) were analysed in six patients with active acromegaly [two females, four males; aged 53 +/- 9 years; body mass index (BMI), 29 +/- 4 kg/m2] and in six normolipidaemic control subjects (matched for age, gender, BMI and apo E genotype). They underwent an oral vitamin A fat loading test. RESULTS: Baseline plasma triglycerides (TG) were not significantly different in patients (1.75 +/- 0.71 mM) and controls (1.15 +/- 0.46 mM). Lipoprotein lipase activity was significantly lower in patients than in controls (108 +/- 21 vs. 141 +/- 19 U/l, respectively; P < 0.05). Baseline plasma apo E levels were higher in patients (60.8 +/- 7.9 mg/l) than in controls (48.3 +/- 5.9 mg/l; P < 0.05). No differences were found in the area under the postprandial TG curve (AUC-TG), the incremental AUC-TG (DeltaAUC-TG) and AUC-RE in the Sf < 1000 remnant fraction. However, fasting plasma RLP-C concentrations, isolated by immunoseparation, were increased in patients with active acromegaly (0.41 +/- 0.13 mM) compared to control subjects (0.20 +/- 0.07 mM; P < 0.05). Incremental postprandial RLP-C response (corrected for fasting values) was also significantly elevated in patients (2.14 +/- 1.19 mM/h/l) compared to controls (0.86 +/- 0.34 mM/h/l; P < 0.05). In both groups, the maximal RLP-C concentration was reached between 2 and 4 h. CONCLUSIONS: In conclusion, the atherogenic postprandial remnants, represented by RLP-C, were significantly elevated at baseline and in the postprandial period, whereas the larger-sized remnants, represented by retinyl esters (Sf < 1000), were not different from controls. The disturbances in the postprandial RLP-C response increased the susceptibility for premature atherosclerosis as observed in patients with acromegaly.     

Growth hormone (GH) treatment decreases postprandial remnant-like particle cholesterol concentration and improves endothelial function in adult-onset GH deficiency

Premature atherosclerosis is a clinical feature in adult-onset GH deficiency. Evidence is accumulating that disturbances in triglyceride metabolism, reflected by abnormalities in circulating remnant lipoproteins, are associated with increased atherogenic potential. In a case-controlled intervention study, we investigated postprandial lipoprotein metabolism using a new remnant lipoprotein method based on immunoseparation principle [RLP-cholesterol (RLP-C)]. In addition, we analyzed retinyl ester (RE) analysis in plasma and in Sf < 1000 fraction. Endothelial function was assessed as flow-mediated dilatation (FMD). Eight patients diagnosed with acquired adult-onset GH deficiency and eight controls matched for gender, age, body mass index, and apolipoprotein (apo) E genotype were enrolled in the study. Oral vitamin A fat loading tests were performed at baseline in both groups and after 6 months of treatment with recombinant human GH (rh-GH) in the adult-onset GH-deficient patients. Adult-onset GH-deficient patients had significantly higher fasting RLP-C, postprandial RLP-C concentrations (plasma RLP-C, 0.29 +/- 0.14 mmol/L; and incremental area under the curve-RLP-C, 2.13 +/- 1.60 mmol*h/L, respectively) than controls (0.19 +/- 0.06 mmol/L and 1.05 +/- 0.72 mmol*h/L (P: < 0.05), respectively). They also had significantly higher postprandial RE in plasma and Sf < 1000 fraction. Treatment with rh-GH significantly reduced postprandial RLP-C concentrations (incremental area under the curve-RPL-C 0.73 +/- 0.34 mmol*h/L; P: < 0.05) but had no effects on the fasting RLP-C concentrations (0.317 +/- 0.09 mmol/L, P: < 0.05), or on the postprandial RE in plasma and in Sf < 1000 fraction. Endothelial function measured as FMD was improved from 5.9 +/- 3.3% to 10.2 +/- 4.0% (P: < 0.05) in patients treated with rh-GH. It is concluded that patients with adult-onset GH deficiency have increased levels of fasting and postprandial RLP-C and an impaired endothelial function as measured as FMD. Treatment with rh-GH resulted in a decrease of postprandial RLP-C concentration, thereby improving the postprandial atherogenic lipoprotein profile and improvement of endothelial function, however, the clearance of large chylomicron particles as reflected by RE remained disturbed.     

Predictive value of remnant-like particle cholesterol as an indicator of coronary artery stenosis in patients with normal serum triglyceride levels

OBJECTIVE: We designed the present study to evaluate the association of various lipid and fibrinolytic components with coronary artery stenosis with respect to the triglyceride (TG) level. METHODS: Levels of TG, remnant-like particle cholesterol (RLP-C), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein-(a), uric acid, blood glucose, tissue plasminogen activator (t-PA), t-PA inhibitor type 1, antithrombin III, and protein C were measured in 208 patients who underwent diagnostic coronary angiograms. PATIENTS: Of these 208 patients, 59 were hypertriglyceridemic (150 mg/dl or higher) and 149 were normotriglyceridemic. RESULTS: Both LDL-C and HDL-C showed significant differences between patients with and those without coronary artery stenosis in both hypertriglyceridemic and normotriglyceridemic patient subgroups. However, RLP-C showed a significant difference in the normotriglyceridemic patient subgroup (p=0.012) but not in the hypertriglyceridemic patient subgroup (p=0.736). CONCLUSION: Our current retrospective study disclosed that RLP-C levels are closely associated with coronary artery stenosis in patients with normal TG levels.     

Association between LDL particle size and postprandial increase of remnant-like particles in Japanese type 2 diabetic patients

Small, dense LDL, as well as chylomicron- and VLDL-remnant lipoproteins, are known to be important risk factors for coronary heart disease in patients with type 2 diabetes mellitus. The aim of this study was to clarify the relationship between LDL particle size and postprandial remnant lipoprotein levels in Japanese type 2 diabetic patients. Forty-six patients with type 2 diabetes mellitus were divided into tertiles according to LDL particle size. The peak LDL particle diameter was <26.30 nm in tertile 1, 26.30-26.85 nm in tertile 2, and >26.85 nm in tertile 3. After a test meal, tertile 1 had a significantly greater increment of triglycerides (TG), remnant-like particle (RLP)-TG, and RLP-cholesterol (RLP-C) than tertiles 2 and 3. There was a negative correlation between LDL particle size and the postprandial increases of TG, RLP-TG, and RLP-C. These results indicate that smaller sized LDL particles may be a marker of fasting state for an exaggerated postprandial increase of remnant lipoproteins as well as an increase of TG-rich lipoproteins.     

胆固醇与胆结石的关系

目的:探讨胆固醇与胆结石的关系.方法:对某高校3 905名教职员工进行健康检查,采用彩超进行肝胆检查,全自动生化分析仪进行血总胆固醇测定,分析他们二者的关系.结果:3905名教职员工健康检查发现胆结石189例,其中胆固醇增高(>5.17 mmol/L)68例(35.98%),胆固醇正常偏高(4.67-5.16mmol/L)40例(21.16%),胆固醇正常(<5.17mmol/L)81例(42.86%),胆固醇正常偏高和增高与胆固醇正常相比,其胆结石发病率明显增高(均P<0.01).结论:胆结石与高胆固醇增高有一定关系,在胆结石保守治疗时,应注意降低胆固醇.     

High plasma level of remnant-like particles cholesterol in familial combined hyperlipidemia

CONTEXT: The traditional lipid and lipoprotein levels in patients with familial combined hyperlipidemia (FCH) are relatively mildly elevated and do not fully explain the increased risk of cardiovascular disease (CVD). In other populations, high remnant-like particles cholesterol (RLP-C) levels are an independent risk factor for CVD. OBJECTIVE: The objective of the study was to investigate whether plasma RLP-C concentrations are elevated in patients with FCH and contribute to the increased prevalence of CVD. DESIGN, SETTING, PARTICIPANTS: In this cross-sectional study, we studied RLP-C levels in 37 FCH families comprising 582 subjects, of whom 134 subjects were diagnosed FCH based on total cholesterol, triglyceride, and apolipoprotein-B levels. Plasma RLP-C concentrations were determined using an immune-separation technique. RESULTS: For both men and women, the mean plasma RLP-C concentration (mmol/liter) was 2-fold elevated in FCH patients [0.59 (0.54-0.66) and 0.40 (0.37-0.43), respectively] compared with both normolipidemic relatives [0.27 (0.26-0.29) in male and 0.22 (0.21-0.23) in female, all P<0.000]; and spouses [0.27 (0.23-0.31) in male and 0.24 (0.21-0.27) in female, all P<0.000]. Plasma RLP-C levels above the 90th percentile predicted prevalent CVD, independently of nonlipid cardiovascular risk factors [odds ratio 2.18 (1.02-4.66)] and triglyceride levels [odds ratio 2.35 (1.15-4.83)]. However, in both FCH patients and controls, RLP-C did not provide additional information about prevalent CVD over and above non-high-density lipoprotein cholesterol levels. CONCLUSIONS: Patients with FCH have 2-fold elevated plasma RLP-C levels, which add to the atherogenic lipid profile and contribute to the increased risk for CVD. However, for clinical practice, non-high-density lipoprotein cholesterol is the best predictor of prevalent CVD.     

胆固醇结石病和代谢综合征的关系

近年来,代谢综合征(MS)和胆石病的发病率在我国均呈逐年上升趋势。流行病学研究显示两者具有一定的相关性,且MS导致的脂质代谢异常,可能引起胆囊胆汁胆固醇过饱和,并促进胆石的形成。此文就MS与胆固醇结石的相关性及其可能的发病机制作一综述。     

Relationship between pleural fluid and serum cholesterol levels

INTRODUCTION: Since the criteria of Light and colleagues for differentiating transudates and exudates were described, other tests, including the pleural fluid (PF) cholesterol test, have been proposed for the same purpose. However, the factors influencing PF cholesterol levels have not been clearly delineated. PURPOSE: To analyze the relationships among total cholesterol (CHOL), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TRIG) in serum (S) and PF. METHODS: PF and S from 99 patients (transudates, 13 patients; exudates, 86 patients) were analyzed for CHOL, HDL, LDL, TRIG, apolipoprotein AI, apolipoprotein B, and protein. The relationship between the PF and S level for each of these measurements was analyzed with linear regression and multiple regression using the ratio of PF to S protein for that measurement as a second independent variable. RESULTS: This study demonstrated that CHOL levels in PF are related to S cholesterol levels and to the permeability of the pleura (r = 0.88; p < 0.001). However, the percentage of CHOL associated with LDL and HDL (56%) in the PF was much lower than that associated with LDL and HDL in S (93%), suggesting that lipoproteins are modified once they enter the pleural space. The PF TRIG was not closely related to its S level or to the PF/S protein ratio (r = 0.49). CONCLUSION: PF cholesterol levels can be closely predicted from the S cholesterol levels and the permeability of the pleura, as reflected by the ratio of PF protein to S protein. Therefore, the CHOL ratio should not provide additional information to that provided by the protein ratio when trying to differentiate transudates from exudates. PF lipoproteins (LDL and HDL) undergo metabolic alterations once they enter the pleural space. PF TRIG levels are not closely related to S levels or to the permeability of the pleura.     

Relationship between plasma cholesterol and coronary artery disease in Asians

Cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride concentrations were measured in 150 male survivors of first myocardial infarction and in 115 age and ethnic matched healthy controls. The total cholesterol concentration was higher in whites than in respective Asian groups and higher in patients than in controls (P less than 0.001). The ratio of cholesterol to HDL cholesterol was significantly higher in patients (P less than 0.001) and in both ethnic groups was a powerful independent predictor of cases. In Asians, the extent of coronary atheroma assessed by arteriography 2-12 weeks after infarction correlated independently with the total cholesterol concentration (P = 0.03). Thus, in Asian men, the lower level of total cholesterol compared to whites may be misleading. In Asian men the extent of atheroma correlated with the total cholesterol concentration and the relative risk of infarction increased with the ratio of total to HDL cholesterol. At a given level of cholesterol different ethnic groups may be at differing levels of cardiac risk and the cholesterol ratio may be a more appropriate means of inter-ethnic comparison.     

非高密度脂蛋白胆固醇水平与中国人群心血管病发病危险的相关性

目的 探讨我国35～64岁人群血清非高密度脂蛋白胆固醇(non-HDL-C)水平与不同心血管病事件发病危险的相关性.方法 采用前瞻性队列研究方法 ,应用Cox比例风险模型对1992年建立的中国多省市心血管病危险因素队列中35～64岁基线无心血管疾病且资料完整的29 937名研究对象的基线non-HDL-C水平和12年间急性冠心病事件(AGE)、缺血性卒中、出血性卒中和缺血性心血管病事件(ICVD)的发病危险进行分析.结果 (1)多因素Cox回归分析显示,调整年龄、性别、吸烟、糖尿病、体质指数、收缩压等传统危险因素后,ACE、缺血性卒中及ICVD事件发病的相对危险均随non-HDL-C水平的升高而增加.以non-HDL-C＜3.37 mmol/L(130 mg/dl)为参照组,3.37～4.13 mmol/L(130～159 mg/dl)、4.14～4.91 mmol/L(160～189 mg/dl)和≥4.92 mmol/L(190 mg/dl)组ACE、缺血性卒中及ICVD事件发病相对危险分别为:1.24(0.91～1.70)、1.78(1.25～2.53)、2.23(1. 48～3.35);1.34(1.07～1.68)、1.38(1.04～1.83)、1.38(0.97～1.94)和1.37(1.12～1.63)、1.52(1.22～1.90)、1.70(1.30～2.22).而non-HDL-C≥4.92 mmol/L(190 mg/dl)时,出血性卒中发病危险明显下降.(2)对极低密度脂蛋白胆固醇(VLDL-C)和低密度脂蛋白胆固醇进行联合分析显示:VLDL-C与ACE的发病危险相关性最强,其次为ICVD事件.出血性卒中的危险随VLDL-C升高呈下降趋势.结论 non-HDL-C可增加ACE、缺血性卒中和ICVD事件的发病危险.VLDL-C对ICVD事件的发病也具有一定的作用,其中对ACE的作用最为明显.     

Evidence of dual pathways for lipid uptake during chylomicron remnant-like particle processing by human macrophages

BACKGROUND: Though it is now clear that chylomicron remnants are pro-atherogenic lipoproteins, events leading to their incorporation by macrophages are poorly understood. METHODS: This study investigates, in human macrophages, the fate of either [(3)H]cholesteryl oleate or [(3)H]triacylglycerol carried by human apolipoprotein-E-containing chylomicron remnant-like particles (CRLP) and the influence of CRLP containing trilinolein, (18:2)CRLP, or triolein, (18:1)CRLP, on lipid accumulation, newly synthesized cholesteryl ester (CE) and triacylglycerol (TG). RESULTS: Labelled fatty acids from TG were markedly incorporated into TG and phospholipid and, to a lesser extent, into free fatty acids and were scarcely recovered in cholesteryl esters. [(3)H]CE from CRLP accumulated in cells in a dose-dependent manner with a significant difference between concentrations of 10 and 40 microg cholesterol/ml with (18:2)CRLP. In the same concentration range, TG synthesis was enhanced by about 46 and 30% by (18:2)CRLP and (18:1)CRLP cholesterol, respectively, whereas the esterification of cholesterol, evaluated by [(3)H]oleate incorporation, was decreased by about 30% with both types of CRLP. Endocytosis inhibition did not prevent cell cholesterol and TG accumulation, whereas lipoprotein lipase inhibition reduced the TG content. CONCLUSIONS: The results are consistent with the hypotheses that in macrophages dietary remnants may support TG and CE internalization via different mechanisms. Extracellular lipolysis seems particularly important for internalization of dietary fatty acids, whereas the entrance of CE seems attributable to a concomitant selective CE uptake mediated by scavenger receptor class B type I, since the scavenger receptor class B type I antibody induces significant inhibition (38%) of [(3)H]CE transported by CRLP, but does not affect internalization of [(3)H]TG carried by the same particles.     

Relationship between total cholesterol/high-density lipoprotein cholesterol ratio, triglyceride/high-density lipoprotein cholesterol ratio, and high-density lipoprotein subclasses

Alterations in plasma lipid levels can influence the composition, content, and distribution of plasma lipoprotein subclasses that affect atherosclerosis risk. This study evaluated the relationship between plasma total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, and HDL subclass distribution. The apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 442 Chinese subjects. The particle size of HDL shifted toward smaller size with the elevation of TC/HDL-C and TG/HDL-C ratios. The ratio of large-sized HDL(2b) to small-sized prebeta(1)-HDL (HDL(2b)/prebeta(1)-HDL) was about 4.7 in the subjects with TC/HDL-C of 3.3 or lower and TG/HDL-C of 2.5 or lower, whereas it was only approximately 1.1 in subjects with TC/HDL-C greater than 6 and TG/HDL-C greater than 5. Pearson correlation analysis revealed that the TC/HDL-C ratio was positively correlated with prebeta(1)-HDL and HDL(3a) but negatively correlated with HDL(2a) and HDL(2b), whereas the TC/HDL-C ratio was only inversely correlated with HDL(2b). The TC/HDL-C and TG/HDL-C ratios together may be a good indicator of HDL subclass distribution. When these 2 ratios increased simultaneously, the trend toward smaller HDL size was obvious, which, in turn, indicated that the maturation of HDL might be impeded and the reverse cholesterol transport might be weakened. In addition, the TG/HDL-C ratio might be a more powerful factor to influence the distribution of HDL subclasses.     

红细胞膜总胆固醇含量与急性冠状动脉综合征的相关性

目的:研究红细胞膜总胆固醇含量(CEM)与急性冠状动脉综合征(ACS)的相关性。方法:204例胸痛患者行冠状动脉造影后分成ACS组98例,稳定型心绞痛(SAP)组45例和对照组61例。采用酶学的方法测定各组CEM水平,用ELISA法测定血清高敏C反应蛋白(hs-CRP)水平。结果:ACS组CEM值为(149.50μg/mg,120.33～180.11μg/mg),较SAP组(79.98μg/mg,56.75～97.56μg/mg)及对照组(76.64μg/mg,62.12～91.84μg/mg)均明显增高(均P<0.05)。多因素逻辑回归分析提示CEM与ACS发病显著相关(OR24.990,95%CI5.220～119.596,P<0.01)。CEM水平与血清hs-CRP呈显著正相关(r=0.328,P<0.01)。结论:CEM可能通过炎症反应参与ACS发病的进程,是动脉粥样易损斑块的一个潜在标记物,对于ACS的预测作用优于hs-CRP。