Association among retinol-binding protein 4, small dense LDL cholesterol and oxidized LDL levels in dyslipidemia subjects

ObjectivesTo investigate retinol-binding protein 4 (RBP4), small dense low-density lipoprotein cholesterol (sdLDL-C) and oxidized low-density lipoprotein (ox-LDL) levels and their associations in dyslipidemia subjects.Design and methodsWe determined RBP4, sdLDL-C, ox-LDL levels in 150 various dyslipidemia subjects and 50 controls. The correlation analysis and multiple linear regression analysis were performed.ResultsThe RBP4, sdLDL-C and ox-LDL levels were found increased in various dyslipidemia subjects. The sdLDL-C levels were positively correlated with RBP4 (r = 0.273, P = 0.001) and ox-LDL (r = 0.273, P = 0.001). RBP4 levels were also correlated with ox-LDL (r = 0.167, P = 0.043). The multiple regression analysis showed that only sdLDL-C was a significant independent predictor for RBP4 (β coefficient = 0.219, P = 0.009; adjusted R² = 0.041) and ox-LDL (β coefficient = 0.253, P = 0.003; adjusted R² = 0.057) levels, respectively.ConclusionsThe independent associations of sdLDL-C with RBP4 and ox-LDL were observed in dyslipidemia subjects. RBP4 may play an important role in lipid metabolism of atherosclerosis, particularly in formation of sdLDL.     

血清三酰甘油水平与小而密低密度脂蛋白胆固醇的关系

目的探讨健康人群和血脂代谢异常者小而密低密度脂蛋白胆固醇（sdLDL-C）水平分布及血清三酰甘油（TG）水平对sdLDL-C水平的影响。方法将693例血脂代谢异常者分为A组（542例,TG〈1.70 mmol/L）和B组（151例,TG≥1.70 mmol/L）,同时选取健康对照者181名。采用肝素-镁沉淀法检测血清sdLDL-C水平,同时检测空腹血糖、血脂[包括总胆固醇（TC）、TG、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）]及载脂蛋白A1（apo A1）、载脂蛋白B（apo B）。分析各组各指标间的差异及血清TG水平对sdLDL-C的影响。结果 B组TC、aopB水平高于健康对照组和A组（P〈0.05）,HDL-C水平明显低于健康对照组和A组（P〈0.05）。健康对照组sdLDL-C水平呈偏态分布,以第95百分位数（0.62 mmol/L）作为正常参考阈值。血脂异常组sdLDL-C水平为0.46（0.34～0.64）mmol/L,明显高于健康对照组[0.22（0.16～0.38）mmol/L]（P〈0.001）。多元逐步回归分析表明,对sdLDL-C水平有显著影响的因素为TG和LDL-C。17.6%的A组患者血清sdLDL-C水平高于正常参考阈值（P〈0.05）。受试者工作特征（ROC）曲线分析表明,TG识别sdLDL-C水平升高的Cut-off值为1.36 mmol/L。结论血清sdLDL-C水平受TG的影响最大,判断sdLDL-C水平是否升高的TG的界值应适当调低。     

Circadian rhythm of serum concentration of small dense low-density lipoprotein cholesterol

BACKGROUND: The atherogenicity of small dense low-density lipoprotein (sdLDL) has been reported and recently a new easy-handling method for measuring serum concentration of sdLDL cholesterol (sdLDLC) has been developed. Using this method, we observed the circadian rhythm of sdLDLC to determine the adequacy of fasting measurement of it and to seek the modulator of the atherogenic lipoprotein. METHODS: Study population was consisted of 20 healthy volunteers (10 women and 10 men, mean age 28 y). They had 3 meals per day and blood samples were taken before and 2 h after every meal and next morning. Serum concentrations of sdLDLC and other valuables including triglyceride (TG) and remnant-like particles cholesterol (RLPC) were determined. RESULTS: Serum concentration of sdLDLC had a unique circadian rhythm that was highest before breakfast (fasting status), decreased after each meal, hit the bottom after dinner and then increased during at night. Fasting sdLDLC was highly correlated with TG levels. The sum of the 6 TG values during a day (i.e., average TG level) had higher correlation coefficient with sdLDLC than fasting TG or fasting RLPC. CONCLUSIONS: From the observation of the unique circadian rhythm, measuring sdLDLC at fasting status is exactly reasonable because it never underestimate the risk of atherosclerotic diseases. Measuring sdLDLC can also be used as a marker for average TG levels regardless of the existence of postprandial hyperlipidemia.     

小而密低密度脂蛋白胆固醇与冠状动脉粥样硬化特征的相关性分析

目的结合影像学评价小而密低密度脂蛋白胆固醇(sdLDL-C)与冠状动脉(以下简称"冠脉")粥样硬化病变严重程度的关系。方法连续选取2015年7月至2016年3月阜外医院436例门诊初诊怀疑冠脉粥样硬化性心脏病(CAD)并行冠脉计算机断层摄影术检查(CT)的患者,从斑块性质、病变支数及狭窄程度3个方面分析sdLDL-C与冠脉粥样硬化严重程度的相关性。结果 sdLDL-C与载脂蛋白B(apoB)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、血糖(Glu)呈正相关(r依次为0.644、0.631、0.558、0.434、0.145,P均0.01),与高密度脂蛋白胆固醇(HDL-C)呈负相关(r=-0.241,P0.01);sdLDL-C、apoB可作为严重CAD(三支病变及重度狭窄75%)发生的危险因素,且独立于传统风险因素(年龄、性别、高血压史、糖尿病史、吸烟史、饮酒史)及他汀类降脂药的应用;对于三支病变,LDL-C、sdLDL-C、apoB预测价值依次增强(OR依次为1.936、2.673、31.707);对于重度狭窄,LDL-C非独立危险因素,sdLDL-C、apoB有预测价值(OR分别为2.000、9.457)。结论 sdLDL-C可作为独立于传统风险因素的严重CAD预测指标,预测价值优于LDL-C,有可能作为进一步的风险控制指标。     

血清小而密低密度脂蛋白胆固醇水平对冠心病患者心血管不良事件的预测价值

目的分析冠心病(CAD)患者血清小而密低密度脂蛋白胆固醇(sdLDL-C)的水平,并评估sdLDL-C对CAD患者主要心血管不良事件(MACE)发生风险的预测价值。方法检测93例急性冠状动脉综合征(ACS)、48例稳定性CAD(SCAD)患者和123例健康对照者的血清sdLDL-C水平。计算CAD患者的Gensini积分,随访CAD患者1年内MACE的发生情况。采用Spearman相关和多元线性回归分析CAD患者血清sdLDL-C水平与Gensini积分的关系。采用多元Logistic回归分析血清sdLDL-C评估CAD发生风险的预测价值。采用Cox回归分析血清sdLDL-C评估CAD患者MACE发生风险的预测价值。结果ACS组血清sdLDL-C水平高于对照组(P<0.001)和SCAD组(P=0.038)。CAD患者血清sdLDL-C水平与Gensini积分独立相关(β=0.315,P=0.017,校正R^2=0.083)。多因素Logisitic回归分析显示,血清高sdLDL-C水平与ACS发生风险密切相关(OR=7.895,95%CI:2.344~26.589,P=0.001),且对ACS和SCAD的区分具有统计学意义(OR=5.948,95%CI:1.158~30.558,P=0.033)。随访1年内,CAD患者的MACE发生率为22.70%;发生MACE的CAD患者血清sdLDL-C水平高于未发生MACE的CAD患者(P=0.001)。多因素Cox回归分析显示,血清高sdLDL-C水平与CAD患者MACE的发生风险密切相关(HR=5.326,95%CI:1.623~17.483,P=0.006)。结论ACS患者血清sdLDL-C水平升高;血清sdLDL-C可望作为评估CAD患者MACE发生风险的预测指标。     

2型糖尿病患者血清小而密低密度脂蛋白胆固醇水平与脂类代谢异常及胰岛素抵抗的关系

目的探讨2型糖尿病患者血清小而密低密度脂蛋白胆固醇（sdLDL-C）水平与脂类代谢异常及胰岛素抵抗的关系。方法 193例2型糖尿病患者按胰岛素抵抗情况分为胰岛素抵抗组144例与非胰岛素抵抗组49例。采用奥林巴斯AU2700全自动生化仪检测血清小而密低密度脂蛋白（sdLDL-C）、三酰甘油（TG）、总胆固醇（TC）、空腹血糖（FBG）等,采用化学发光法检测空腹胰岛素（FIN）、C肽,并计算胰岛素抵抗指数（HOMA-IR）等。结果 2型糖尿病患者中,与非胰岛素抵抗组相比,胰岛素抵抗组TG、TG/高密度脂蛋白（HDL）、TC/HDL、sdLDL-C水平显著升高（P〈0.05）,而HDL、载脂蛋白A（apo AⅠ）、脂蛋白（Lpa）水平显著降低（P〈0.05）;对2型糖尿病患者sdLDL-C、胰岛素抵抗指数进行多元逐步回归分析,sdLDL-C与TG（Log）、LDL-C/HDLC及TG/HDL-C（Log）呈正相比关性（r=0.638、0.601、0.290,P〈0.01）,与TG/HDL（Log）和LDL-C/apoB呈负相关关系（r=-0.589、-0.342,P〈0.01）;HOMA-IR与TG/HDL和sdLDL-C呈正相关关系（r=0.281、0.250,P〈0.01）,而与TC呈负相关（r=-0.233,P〈0.01）。结论 SdLDL-C能较好地反映2型糖尿病患者胰岛素抵抗对脂类代谢的影响,TG/HDL-C、LDL-C/HDL-C等提供的重要临床信息应在以后的临床应用中得到进一步认识和重视。     

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.     

Association between plasma adiponectin and high-density lipoprotein cholesterol in postmenopausal women

ObjectivesWe investigated the association of plasma adiponectin and high-density lipoprotein cholesterol (HDL-C) in postmenopausal women.Design and methodsThis was a cross-sectional study of 563 postmenopausal women with and 1029 without low HDL-C. Lipid profile, glucose, adiponectin, IL-1β, IL-6, and TNF-α concentrations were measured.ResultsPlasma adiponectin levels increased with age in elderly women. Plasma adiponectin levels were lower in subjects with low HDL-C (< 50 mg/dl), when compared with normal HDL-C subjects. In multiple stepwise linear regression analysis, adiponectin was a significant independent predictor of HDL-C concentration with body mass index, total cholesterol, and triglycerides. Values in the third and fourth quartile of adiponectin were associated with decreased odds ratio for low HDL-C (0.62; 95% CI, 0.44–0.87, 0.40; 95% CI, 0.27–0.58, respectively) when compared with values in the lowest quartile after multivariable adjustment.ConclusionsAdiponectin was significantly associated with HDL-C concentration in postmenopausal women. These findings suggest that high adiponectin levels may have a protective effect on atherosclerosis with increasing HDL-C in postmenopausal women.     

Correlation between total homocysteine, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in the serum of patients with myocardial infarction

OBJECTIVES: Determine the Low-density lipoprotein cholesterol (LDL-C), High-density lipoprotein cholesterol (HDL-C) and serum total homocysteine in myocardial infarction patients and control subjects. DESIGN AND METHODS: The study group consisted of 126 patients 67 male, and 59 females, aged 29-73 (mean 48.65 +/- 3.81) years. The entry criteria for the patient group was typical or atypical chest pain, unequivocal changes in the electrocardiogram. The control group consisted of 135 normal volunteers, 71 male and 64 females, age 21-63 (mean 42.73 +/- 5.79) years. Measurement of serum total homocysteine was performed using gas chromatography. Measurement of Low-density lipoprotein cholesterol, and High-density lipoprotein cholesterol were performed using spectrophotometer. RESULTS: Patients with myocardial infarction were found to have higher serum total homocysteine levels than controls, (P < 0.05). Serum total homocysteine levels were significantly correlated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. There was a negative correlation between total homocysteine and HDL-C levels (P < 0.05, r = -0.93). There was a positive correlation between total homocysteine and LDL-C levels (P < 0.05, r = 0.98). CONCLUSIONS: The above mentioned findings suggest the potential usefulness of LDL-C, HDL-C and serum total homocysteine as prognostic markers in myocardial infarction patients. These findings should influence future studies on the etiology and pathogenesis of myocardial infarction.     

Clinical importance and therapeutic modulation of small dense low-density lipoprotein particles

The National Cholesterol Education Programme Adult Treatment Panel III accepted the predominance of small dense low-density lipoprotein (sdLDL) as an emerging cardiovascular disease (CVD) risk factor. Most studies suggest that measuring low-density lipoprotein (LDL) particle size, sdLDL cholesterol content and LDL particle number provides additional assessment of CVD risk. Therapeutic modulation of small LDL size, number and distribution may decrease CVD risk; however, no definitive causal relationship is established, probably due to the close association between sdLDL and triglycerides and other risk factors (e.g., high-density lipoprotein, insulin resistance and diabetes). This review addresses the formation and measurement of sdLDL, as well as the relationship between sdLDL particles and CVD. The effect of hypolipidaemic (statins, fibrates and ezetimibe) and hypoglycaemic (glitazones) agents on LDL size and distribution is also discussed.     

南通地区健康体检人群小而密低密度脂蛋白水平调查

目的 初步调查南通地区健康人群小而密LDL(胆固醇和蛋白质)的分布情况.方法 体格检查和实验窜检查均无异常的健康人群254名(男137名,女117名),按年龄分成20～29岁(65名)、30～39岁(65名)、40～49岁(46名)、50～69岁(35名)、和370岁(43名)5组.检测采用全自动生化分析仪和芯片电泳技术.结果 小而密LDL胆固醇和蛋白质水平均值为(0.39±0.14)mmol/L和(241±158)mg/L,小而密LDL胆固醇与总胆固醇、三酰甘油、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇相关性较好(r=0.67、0.35、-0.42和0.46,P均<0.01),小而密LDL蛋白质与这些血脂指标相关性较好(r=O.54、0.24、-0.32和0.52,P均<0.01).小而密LDL蛋白质和胆固醇水平随年龄增高呈上升趋势,而70岁以上人群呈下降趋势;男性小而密低密度脂蛋白水平高于女性[(0.40±0.11)mmol/L vs.(O.37±0.17)mmol/L,P<0.01;(253±59)mg/L vs.(237±95)mg/L,P<0.05],P相似文献   

Circulating malondialdehyde-modified low-density lipoprotein is strongly associated with very small low-density lipoprotein cholesterol concentrations in healthy men

BACKGROUND: Despite the importance of oxidized LDL and small LDL particles as atherogenic lipoproteins, the relationship between oxidized LDL and the distributions of size subclasses of lipoproteins is not fully proved. We investigated the relationship of circulating malondialdehyde-modified (MDA)-LDL, an oxidized form of LDL, and lipoprotein subclasses in healthy men. METHODS: The study group consisted of a total of 170 healthy Japanese men (55+/-9 y). Plasma cholesterol concentrations in major lipoproteins and their subclasses were determined by HPLC with gel permeation columns. RESULTS: In univariate analysis, body mass index, waist circumference, blood pressure, white blood cell count, C-reactive protein, uric acid, fasting insulin, HOMA-IR, total cholesterol, triglycerides, each VLDL subclass cholesterol, each LDL subclass cholesterol, small HDL cholesterol, and very small HDL cholesterol were positively correlated with MDA-LDL, whereas adiponectin and large HDL cholesterol were inversely correlated with MDA-LDL. In stepwise multiple regression analysis, very small LDL cholesterol, medium VLDL cholesterol, very small HDL cholesterol, small HDL cholesterol, and systolic blood pressure were identified as independent determinants of MDA-LDL (R(2)=0.718, p<0.0001). CONCLUSIONS: Circulating MDA-LDL concentrations are strongly associated with very small LDL cholesterol concentrations in healthy men. HDL size heterogeneity has a biphasic effect on MDA-LDL.     

Five methods for measuring low-density lipoprotein cholesterol concentration in serum compared

Five methods for the quantification of low-density-lipoprotein cholesterol were compared: ultracentrifugation, electrophoresis, precipitation with polyvinyl sulfate or heparin, and an indirect calculation procedure (Friedewald formula). Excellent agreement of results was obtained with all procedures for 49 of 51 sera. Discrepancies were as much as 1.69 g/L for the remaining two cases, which contained appreciable amounts of "floating" beta-cholesterol as detected with a combination of ultracentrifugation and electrophoresis.     

Linkage between cholesterol 7alpha-hydroxylase and high plasma low-density lipoprotein cholesterol concentrations.

Interindividual differences in plasma low-density lipoprotein cholesterol (LDL-C) levels reflect both environmental variation and genetic polymorphism, but the specific genes involved and their relative contributions to the variance in LDL-C are not known. In this study we investigated the relationship between plasma LDL-C concentrations and three genes with pivotal roles in LDL metabolism: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and cholesterol 7alpha-hydroxylase (CYP7). Analysis of 150 nuclear families indicated statistically significant linkage between plasma LDL-C concentrations and CYP7, but not LDLR or APOB. Further sibling pair analyses using individuals with high plasma LDL-C concentrations as probands indicated that the CYP7 locus was linked to high plasma LDL-C, but not to low plasma LDL-C concentrations. This finding was replicated in an independent sample. DNA sequencing revealed two linked polymorphisms in the 5' flanking region of CYP7. The allele defined by these polymorphisms was associated with increased plasma LDL-C concentrations, both in sibling pairs and in unrelated individuals. Taken together, these findings indicate that polymorphism in CYP7 contributes to heritable variation in plasma LDL-C concentrations. Common polymorphisms in LDLR and APOB account for little of the heritable variation in plasma LDL-C concentrations in the general population.     

高脂血症中血清低密度脂蛋白的测定方法比较研究

目的 探讨高脂血症对血清低密度脂蛋白测定准确性的影响因素,并寻找可靠的测定方法.方法 对不同三酰甘油(TG)标本分别采用沉淀法和直接法检测低密度脂蛋白胆固醇(LDL-C)水平,并与电泳法LDL-C测定值进行比较.结果 TG＞4.50 mmol/L,采用电泳法与沉淀法测定的LDL-C 值具有显著差异(P＜0.05);TG＞6.00 mmol/L时,直接法与电泳法之间出现明显差异(P＜0.01).结论 TG对血清低密度脂蛋白的测定有一定的影响,TG≤6.00 mmol/L时,可采用直接法测定高TG标本LDL-C水平;当TG＞6.00 mmol/L时,尽可能采用电泳法测定高TG标本LDL-C水平.     

Association between measured or calculated small dense low‐density lipoprotein cholesterol and oxidized low‐density lipoprotein in subjects with or without type 2 diabetes mellitus

BackgroundSmall dense low‐density lipoprotein (sdLDL) possesses atherogenic potential and is predicted to be susceptible to atherogenic modifications, which further increases its atherogenicity. However, studies on the association between measured or estimated sdLDL cholesterol (sdLDL‐C) levels and atherogenic modification in diverse population groups are lacking.MethodsSurplus serum samples were collected from male subjects with type 2 diabetes mellitus (DM) under treatment (n = 300) and without DM (non‐DM; n = 150). sdLDL and oxidized LDL (oxLDL) levels were measured using the Lipoprint LDL subfractions kit (Quantimetrix Corporation) and the Mercodia oxidized LDL competitive enzyme‐linked immunosorbent assay kit (Mercodia), respectively. The estimated sdLDL‐Cs were calculated from two relevant equations. The effects of sdLDL‐C on oxLDL were assessed using multiple linear regression (MLR) models.ResultsThe mean (±SD) of measured sdLDL‐C and oxLDL concentrations were 11.8 ± 10.0 mg/dl and 53.4 ± 14.2 U/L in the non‐DM group and 0.20 ± 0.81 mg/dl and 46.0 ± 15.3 U/L in the DM group, respectively. The effects of measured sdLDL‐Cs were significant (p = 0.031), whereas those of estimated sdLDL‐Cs were not (p = 0.060, p = 0.116) in the non‐DM group in the MLR models. The effects of sdLDL‐Cs in the DM group were not significant.ConclusionIn the general population, high level of sdLDL‐C appeared to be associated with high level of oxLDL. The equation for estimating sdLDL‐C developed from a general population should be applied with caution to a special population, such as patients with DM on treatment.