非高密度脂蛋白胆固醇在冠心病危险性评估中的作用

目的探讨非高密度脂蛋白胆固醇(non-HDL-C)在冠心病危险性评估中的作用。方法对453例冠心病患者和336例健康对照血脂资料进行分析,比较non-HDL-C与其他血脂数据两组间差异的显著性,以及non-HDL-C和低密度脂蛋白胆固醇(LDL-C)的相关性。结果冠心病组non-HDL-C值[(4.02±1.20)mmol/L]明显高于健康对照组[(3.30±0.58)mmol/L],差异有统计学意义(t=10.132,P<0.001)。non-HDL-C在冠心病组和健康对照组间差异的显著性高于LDL-C和总胆固醇(TC)及三酰甘油(TG)。随着TG水平增高,non-HDL-C与LDL-C相关性下降。结论non-HDL-C对冠心病危险性评估作用优于LDL-C,而且方法简便易行,适合临床推广应用。     

Reflex testing I: algorithm for lipid and lipoprotein measurement in coronary heart disease risk assessment

We reviewed the current literature in order to construct a reflex testing algorithm that maximizes clinical utility and cost-effectiveness of lipid and lipoprotein testing. The algorithm was based on the 2nd Report of the National Cholesterol Education Program Adult Treatment Panel guidelines for use of total cholesterol (TC), triglycerides (TG), HDL-C, and LDL-C, and published reports describing the clinical use of apolipoprotein B and lipoprotein (a). The success of this algorithm was tested in a low-risk general and a high-risk hyperlipidemic patient population. Lipid data and non-lipid risk factors were obtained from a national database and from patients seen at two lipid clinics. A total of 16 968 individuals from the National Health and Nutrition Examination Survey III database comprised the low-risk group, and 239 patients examined in the Hartford Hospital and Washington University Lipid Clinics comprised the high-risk group. We found a solid scientific base to support the NCEP guidelines and reasonable support for limited testing of apoB and Lp(a). According to the algorithm, the direct LDL-C assay was deemed unnecessary in 98% and 91% of low- and high-risk subjects, respectively, if one assumes that the Friedewald equation is adequate with TG≤4.00 g/l. With a more conservative cutoff of TG≤2.50 g/l, the algorithm canceled 92% and 81% of direct LDL tests, respectively. The algorithm also limited TG to 20 and 64%, apoB to 6 and 20%, and Lp(a) to 15 and 56%, of low- and high-risk groups, respectively. Use of a comprehensive, reflex algorithm for coronary heart disease risk assessment will substantially reduce the utilization of laboratory services without diminishing the clinical value of these tests. The algorithm will prevent the overuse of certain expensive tests (direct LDL) while promoting the limited use of underutilized tests [apoB and Lp(a)].     

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。     

Association of apolipoprotein E polymorphism, low-density lipoprotein cholesterol, and coronary artery disease

We determined the frequencies of genetic apolipoprotein E isoforms in 570 survivors of myocardial infarction, all with demonstrable coronary heart disease, as compared with 624 healthy persons. In controls, E-4/E-3 heterozygosity was associated with total cholesterol concentrations of 1985 (SD 364) mg/L and low-density lipoprotein (LDL)-cholesterol concentrations of 1306 (SD 332) mg/L. Significantly lower values, 1811 (SD 312) mg/L and 1121 (SD 274) mg/L, respectively, were observed for E-3/E-2 heterozygous persons. In survivors of myocardial infarction, the respective values were significantly higher than in controls, differing between E-4/E-3 and E-3/E-2 heterozygous patients by 233 and 220 mg/L, respectively. Moreover, E-4/E-3 heterozygosity was accompanied by earlier age of myocardial infarction (48.8 +/- 7.4 years) as compared with E-3/E-2 heterozygosity (53.4 +/- 6.9 years) and E-3/E-3 homozygosity (51.2 +/- 7.7 years). Evidently, apolipoprotein E polymorphism can contribute to total and LDL-cholesterol concentrations in serum, thereby affecting risk of coronary heart disease and myocardial infarction.     

Calculated low-density lipoprotein cholesterol remains a viable and important test for screening and targeting therapy.

BACKGROUND: Most clinical laboratories use calculated (C) low-density lipoprotein cholesterol (LDL-C) for measurement. Some studies have questioned the linearity of CLDL-C in the clinically useful low range. Moreover, it is generally believed that calculation leads to poor precision such that variation in CLDL-C is greater than the 4% guideline since the calculation is dependent on three primary variables. Actually, the degree of variability of a calculated value will be small if the variability of each primary value is small as compared to its contribution to the calculated value. When LDL-C is low, high-density lipoprotein cholesterol (HDL-C), that has poorer precision, becomes more important in defining the precision of CLDL-C. New homogeneous (direct) HDL-C (dHDL) methods show better precision than the older heterogeneous methods. We hypothesized that a direct homogeneous HDL-C method would substantially improve the low range precision of LDL-C as compared to older heterogeneous HDL-C methods. METHODS: We compared CLDL-C to a standardized electrophoretic method that shows very high precision. We also compared the precision of CLDL-C calculated using a homogeneous dHDL and a heterogeneous indirect method. RESULTS: We found good linearity for CLDL-C down to 500 mg/L (x0.002586). The main source of CLDL-C variation was HDL-C. Precision was within guidelines when the dHDL method was used. Using our automated methods for lipoprotein lipids, assuming our reference method is accurate, the formula that calculated CLDL-C (mg/dL) using triglyceride (mg/dL) (x0.001129) x0.2 suggested by some gave more accurate results than the formula using triglyceride (mg/dL) x0.16 suggested by others. CONCLUSIONS: Given the potential for CLDL-C to meet the precision guidelines, until direct LDL-C methods can be refined, CLDL-C should continue to be the primary test used for assessing LDL-C clinically. Standardized testing for CLDL-C for manufacturers should be available so that the formula used for each instrument can provide well-defined accuracy.     

Small,dense low-density lipoprotein as a risk factor for coronary heart disease

Summary Data from case-control and cross-sectional studies uniformly demonstrate an association between small, dense low-density lipoprotein and risk of coronary heart disease. This relationship may be attributable to the association of small, dense low-density lipoprotein with other atherogenic lipoproteins, the presence of the insulin resistance syndrome in subjects with small low-density lipoprotein, and/or the increased oxidative susceptibility of small, dense low-density lipoprotein particles. Furthermore, because small low-density lipoprotein appears to be a common trait in the general population, more than one of these atherogenic mechanisms may be operating simulataneously to increase risk of coronary heart disease.     

总胆固醇/高密度脂蛋白胆固醇比值预测冠心病危险程度的评价

目的 评价总胆固醇/高密度脂蛋白胆固醇(TC/HDL-C)比值预测冠心病危险程度的价值.方法回顾性分析250例冠心病患者的临床资料分为:稳定型心绞痛组(SA组),不稳定型心绞痛组(UA组),并另选125例健康者为对照组,测定两组的TC/HDL-C、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和HDL-C并比较其差异性和异常率.结果SA组及UA组TC、TG、LDL-C及TC/HDL-C均高于对照组(P<0.01),HDL-C低于对照组(P<0.01),HDL-C分别为(1.08±0.36)mmol/L、(1.03±0.29)mmol/L vs(1.66±0.67)mmol/L,SA组、UA组HDL-C、LDL-C及TC/HDL-C异常率与对照组比较差异有统计学意义(P<0.05),分别为36.9%、39.1%Vs 20.0%,32.0%、32.8%Vs 16.0%,65.6%、72.7%vs 38.6%.结论TC/HDL-C作为冠心病危险因素的预测价值和灵敏度高于单项血脂指标.     

血尿酸、三酰甘油及高密度脂蛋白对冠心病及其严重程度的联合风险评估

目的评估血尿酸、三酰甘油及高密度脂蛋白对冠心病及其严重程度的联合风险,为冠心病的预防和临床诊疗提供参考依据。方法 2013年1月至2015年3月在复旦大学附属闵行医院收集研究对象1 188例,根据冠状动脉造影结果判定是否患病及其严重程度,按照血尿酸、三酰甘油及高密度脂蛋白中位数将研究对象分为高风险组和低风险组,采用χ2检验分析血尿酸、三酰甘油及高密度脂蛋白对冠心病及其严重程度的单独及联合风险,采用线性估计回归模型评估风险趋势。结果当两两风险因素联合存在时,冠心病及其轻、中、重度病变分布于高风险组的比例明显高于在低风险组中的分布;当3种风险因素联合存在时,冠心病及其轻、中、重度病变分布于高风险组的比例分别高达95.9%、96.4%、92.9%和98.0%。各因素对男性冠心病的联合风险呈现出大于女性的趋势;3种因素对男性冠心病轻度病变和女性冠心病重度病变的联合风险最为明显。在50岁以下人群中3种风险因素对冠心病及其轻、中和重度病变的联合风险明显大于50岁以上人群。结论血尿酸、三酰甘油及高密度脂蛋白对冠心病及其严重程度的两两联合风险及三者联合风险明显大于单风险因素的效应,联合风险在男性人群和50岁以下人群中的效应更为明显。     

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。     

Cyclosporine, low-density lipoprotein, and cholesterol

Lipoproteins are known to be able to transport a variety of drugs. This report suggests that low-density lipoprotein not only functions as an important carrier of cyclosporine in plasma but also facilitates transport of cyclosporine across the cell membrane by means of the low-density lipoprotein receptor. Such a mechanism would explain (1) the similar tissue distribution of cyclosporine and the low-density lipoprotein receptor, (2) the increase in immunosuppression and toxicity with low total serum cholesterol levels, and (3) the relative absence of immunosuppression and toxicity with high levels of cyclosporine in the blood in patients with hypertriglyceridemia. In addition to receptor-mediated uptake, a disturbance of the blood-brain barrier is suggested as an explanation of the high frequency of cyclosporine-induced central nervous system toxicity after liver transplantation. Cyclosporine-induced inhibition of the mitochondrial steroid 26-hydroxylase, an enzyme involved in the formation of bile acids from cholesterol and deficient in patients with cerebrotendinous xanthomatosis, may cause or contribute to the observed central nervous system toxicity. It also may explain the similar clinical features of cyclosporine-induced central nervous system toxicity and cerebrotendinous xanthomatosis.     

Five methods for determining low-density lipoprotein cholesterol compared

We evaluated three precipitation methods for determination of low-density lipoprotein cholesterol in serum and an indirect method involving the Friedewald formula (Clin Chem 18: 499-502, 1972) by comparison with results by ultracentrifugation. The results of all methods for 83 sera, including 59 hyperlipidemic type IIA, IIB, and IV sera agreed very well, at least for concentrations of serum triglycerides below 8 mmol/L. The accuracy of the Friedewald formula was confirmed in 285 other sera, including 66 sera with triglycerides content between 4.52 and 8.0 mmol/L. For type III sera, the precipitation methods produced similar values to those obtained with the Friedewald formula, all being much higher than the ultracentrifugation values. Density-gradient ultracentrifugation showed that the very-low-density lipoprotein remnants in type III sera almost completely coprecipitated with the low-density lipoproteins. The precipitation methods are not only accurate but also very precise (CV less than 5%); they can therefore be used in clinical laboratories to measure atherogenic low-density lipoproteins plus the remnants of very-low-density lipoproteins. However, when serum triglycerides and high-density lipoprotein cholesterol also are determined, the Friedewald formula is a reliable alternative.     

丙二酰二醛修饰的低密度脂蛋白与冠心病的相关性研究

目的探讨丙二酰二醛修饰的低密度脂蛋白(MDALDL)与冠心病及其他血脂之间的关系。方法选择冠心病患者组68例,正常对照组74名。采用酶联免疫吸附分析(ELISA)的方法检测人血清中MDALDL,同时对受检者的血脂水平进行检测,结果进行统计学分析。结果冠心病患者血清氧化低密度脂蛋白(oxLDL)水平为(115.62±53.4)U/L,明显高于正常对照组(86.7±27.6)U/L(P<0.05);MDALDL与低密度脂蛋白胆固醇(LDLC)水平的比值在冠心病患者组为(43.25±2.64)mmol/U,明显高于正常对照组(33.74±1.58)mmol/U(P<0.01)。血清总胆固醇(TG)、LDLC与MDALDL水平呈显著正相关,相关系数r=0.486,而高密度脂蛋白胆固醇(HDLC)与MDALDL水平呈负相关,相关系数r=0.402。结论MDALDL与冠心病有着非常密切的关系,参与冠心病的发生发展过程。     

Evaluation of methods for the measurement of low-density lipoprotein cholesterol

A high concentration of low-density lipoprotein cholesterol (LDL-C) in plasma is one of the strongest risk factors for atherosclerotic cardiovascular disease and mortality. The most common approach to determining LDL-C in the clinical laboratory is the Friedewald calculation. There is an increased interest to improve the accuracy of LDL-C estimated by this equation. The expert panel convened by National Cholesterol Education Program has recommended the development of accurate direct methods to measure LDL-C. Several homogeneous and fully automated methods have been introduced in recent years that show improved precision and accuracy over earlier methods, especially the Friedewald calculation. Each of the atherogenic particles in plasma--very-low, intermediate-, and low- density lipoprotein--as well as lipoprotein (a), contain one molecule of apolipoprotein B (apoB) and thus, plasma total concentration of apoB reflects the number of atherogenic particles. Several studies suggested that the measurement of apoB could improve the prediction of risk of coronary artery disease. Thus, in addition to the newly developed direct assays, alternative calculation procedures have been proposed that also take into consideration total serum apoB concentration for the estimation of LDL-C and the presence of small, dense LDL particles. The new generation of homogenous methods for the measurement of LDL-C and the use of serum apoB concentration for the estimation of LDL-C can contribute to the accurate LDL-C determination.     

空腹血糖受损人群血脂水平变化及低密度脂蛋白胆固醇升高的相关因素分析

目的分析空腹血糖受损人群血脂代谢状况及低密度脂蛋白胆固醇升高的危险因素。方法对2 656例30~80岁汉族居民进行横断面调查,筛查血糖、血脂等相关项目,筛查空腹血糖受损人群,分析该人群血脂代谢状况及低密度脂蛋白胆固醇升高相关危险因素。结果空腹血糖受损人群中,高甘油三酯血症患病率34.7%,男性(38.2%)高于女性(28.3%)(P0.05);高胆固醇血症患病率59.2%,男性(61.2%)、女性(53.9%),差异无统计学意义(P0.05);高低密度脂蛋白血症患病率29.4%,男性(33.2%)高于女性(22.3%)(P0.05);低高密度脂蛋白血症患病率22.7%,男性(18.7%)低于女性(30.1%)(P0.05)。血脂代谢紊乱的总患病率63.7%。Logistic回归分析显示低密度脂蛋白胆固醇升高的危险因素为性别和胆固醇。结论空腹血糖受损人群存在血脂代谢紊乱低密度脂蛋白胆固醇升高的危险因素有性别和胆固醇。     

血清总胆固醇与高密度脂蛋白胆固醇比值作为冠心病危险标志的意义

目的分析冠心病(CHD)患者的血脂水平,探讨血清总胆固醇(TC)与高密度脂蛋白胆固醇(HDL-C)比值作为CHD危险标志的临床意义。方法测定295例CHD患者的血清TC、三酰甘油(TG)、HDL-C及低密度脂蛋白胆固醇(LDL-C)水平,并计算TC/HDL-C比值。结果依据《中国成人血脂异常防治指南》颁布的血脂水平合适范围,CHD患者血清TC、TG及LDLC高于合适范围百分率分别为32.20%、34.24%及37.63%,血清HDL-C低于合适范围百分率为39.32%。血清TC/HDL-C比值高于合适范围百分率为57.29%。血清TC/HDL-C比值异常率显著高于血清TC、TG、HDL-C及LDL-C(χ2=37.540、31.576、19.066、22.866,P0.01)。结论与任一单项血脂检测相比,血清TC/HDL-C比值作为CHD危险标志可能更有临床意义,临床血脂检测报告单应增加TC/HDL-C比值。     

低密度脂蛋白胆固醇直接测定法的评价

目的　评价基于选择性水解原理的两种低密度脂蛋白胆固醇 (LDL C)的直接测定法 (Ⅰ法和Ⅱ法 )的精密度、准确度和特异性。方法　将这两种方法与聚乙烯硫酸沉淀法 (PVS法 )作了比较 ,并以超速离心分离的HDL和LDL组分分析了对LDL C测定的特异性与准确性。结果　高、低两种LDL C浓度混合血清所测定的结果表明这两种方法均有良好的精密度 ,总CV值直接测定Ⅰ法 3 96 %～ 4 42 % ,直接测定Ⅱ法 0 78%～ 3 91% ,都可达到临床满意的程度。 48份临床标本测定结果 ( x±s)分别为 3 6 8± 1 2 3mmol/L(PVS法 ) ,3 2 5± 1 11mmol/L(直接测定Ⅰ法 )和 3 37± 1 2 1mmol/L(直接测定Ⅱ法 ) ,直接测定法与PVS法测定结果的差异无统计学意义。PVS法 (X)与直接测定Ⅰ法 (Y)的回归方程为Y =0 .848X +0 .12 1(r=0 .942 7) ,与直接测定Ⅱ法 (Y)的回归方程为Y =0 .914X +0 .0 0 7(r=0 .935 3) ,两种直接测定法与PVS法有良好的相关。对超离心HDL和LDL组分测定的结果表明两种直接测定法对LDL C有较好的特异性。稀释试验的结果表明两种直接测定法均有良好的线性 ,线性范围至少可达 9 2 8mmol/L。结论　以选择性水解法直接测定LDL C具有较好的精密度 ,对LDL有很好的特异性 ,适应自动分析 ,可以真实反映LDL C的水平 ,值得在临床推     

Blood rheology and the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio in dyslipidaemic and normolipidaemic subjects

The association between blood rheology and the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) was investigated in 142 dyslipidaemic and 253 normolipidaemic subjects. Blood rheology was examined by the microchannel method and fasting serum concentrations of LDL-C, triglyceride and HDL-C were measured. Passage time of whole blood correlated positively with LDL-C concentration, triglyceride concentration and LDL-C/HDL-C ratio, and negatively with HDL-C concentration. Passage time of whole blood was significantly higher in dyslipidaemic and normolipidaemic subjects with LDL-C/HDL-C ratio > 2.0 than in those with ratio < 1.5. Thus, dyslipidaemic subjects had impaired blood rheology, elevated LDL-C and triglyceride concentrations and elevated LDL-C/HDL-C ratio, and reduced HDL-C concentrations. Dyslipidaemic and normolipidaemic subjects with a more elevated LDL-C/HDL-C ratio had greater blood rheology impairment than those with a less elevated ratio. These data suggest that an elevated LDL-C/HDL-C ratio may be helpful in predicting impaired blood rheology.     

Interference in a homogeneous assay for low-density lipoprotein cholesterol by lipoprotein X.

BACKGROUND: Homogeneous assays for cholesterol in low-density lipoprotein (LDL) are currently in wide use for guideline-based diagnosis and monitoring of dyslipaemic or coronary conditions. In some sera from patients with impaired liver function, we measured implausibly low LDL concentrations using a sugar compound-based assay [LDL-cholesterol (LDL-C), Roche Diagnostics]. We investigated whether an interfering factor, possibly associated with cholestasis, is consistently responsible for this disturbance. METHODS: We compared results of the LDL-C assay in samples with implausible (n=158) and plausible (n=65) LDL concentrations with those of another assay based on two selective detergents (LDLD, Beckman Coulter) and with sequential density ultracentrifugation. We measured total bilirubin, triglycerides, bile acids and lipoprotein X (Lp X) concentrations in samples with the described disturbance and examined the effect of bile salt addition to normal samples. RESULTS: The LDL-C assay was negatively biased compared to the LDLD assay (bias -0.63 mmol/L) and sequential density ultracentrifugation (bias -0.85 mmol/L) in samples with an implausible lipoprotein profile, but showed good method agreement in all other samples. The bile acid concentration did not correlate with the LDL bias, and addition of bile acids showed no interference with the LDL-C assay. The Lp X concentration correlated with the bias between the LDL-C and LDLD assays (R=0.66, p<0.0001); there was no interference with the LDLD assay, even at high Lp X concentrations. CONCLUSIONS: We conclude that the LDL-C assay is subject to interference by Lp X and can provide grossly negatively biased results in cholestatic conditions. In such patients, LDL measurement with an assay based on a different method should be performed.     

血清低密度脂蛋白胆固醇匀相测定法试剂的研制

目的 研制低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）直接法测定的试剂,方法 低密度脂蛋白（ＬＤＬ）与聚阴离子和表面活性剂Ⅰ形成稳定复合物,而非ＬＤＬ则在缺乏偶联剂条件下被胆固醇试剂消除,在表面活性剂Ⅱ和色原作用下,ＬＤＬ释放胆固醇并显色。结果 本室研制的试剂（Ｙ）与聚丙烯硫酸盐（ＰＶＳ）沉淀法（Ｘ１）、Ｆｒｉｅｄｅｗａｌｄ公式计算（Ｘ２）和日本第一化学试剂（Ｘ３）相关良好,分别为Ｙ＝１．０８４８Ｘ１－０．２