冠心病患者血脂水平与血清高密度脂蛋白亚类组成关系的研究

目的 :探讨冠心病 (CHD)患者血脂水平与血清高密度脂蛋白 (HDL)亚类组成的关系。方法 :采用双向电泳 免疫印迹检测法分析了 83例CHD患者血清HDL亚类组成及相对百分含量。结果 :按血清三酰甘油 (TG)浓度将CHD患者分为 4组 ,各组患者血清中前β1 HDL、HDL3c(除TG <1.35mmol L组外 )、HDL3b水平显著高于对照组 (P <0 .0 0 1) ,HDL2b水平显著低于对照组 (P <0 .0 1)。随着血清TG浓度的升高 ,前 β1 HDL、HDL3c及HDL3b颗粒逐渐增加 ,而HDL2a及HDL2b颗粒逐渐减少。按血清HDL胆固醇 (HDL C)浓度将CHD患者分为 3组 ,各组患者中 ,前 β1 HDL(除HDL C≥ 1.30mmol L组外 )、HDL3c及HDL3b水平显著高于对照组 (P <0 .0 5～ <0 .0 1) ,HDL2b水平显著低于对照组 (P <0 .0 1)。随着血清HDL C浓度的升高 ,前 β1 HDL、HDL3c、HDL3b及HDL3a颗粒逐渐减少 ,而HDL2b颗粒逐渐增加。结论 :CHD患者血清HDL颗粒直径呈变小趋势 ,并且随着TG水平的升高和HDL C水平的降低 ,其HDL颗粒的变小程度更加明显。     

Quantification of human plasma phospholipid transfer protein (PLTP): relationship between PLTP mass and phospholipid transfer activity

A sensitive sandwich-type enzyme-linked immunosorbent assay (ELISA) for human plasma phospholipid transfer protein (PLTP) has been developed using a monoclonal capture antibody and a polyclonal detection antibody. The ELISA allows for the accurate quantification of PLTP in the range of 25-250 ng PLTP/assay. Using the ELISA, the mean plasma PLTP concentration in a Finnish population sample (n = 159) was determined to be 15.6 +/- 5.1 mg/l, the values ranging from 2.30 to 33.4 mg/l. PLTP mass correlated positively with HDL-cholesterol (r = 0.36, P < 0.001), apoA-I (r = 0.37, P < 0.001), apoA-II (r = 0.20, P < 0.05), Lp(A-I) (r=0.26, P=0.001) and Lp(A-I/A-II) particles (r=0.34, P<0.001), and negatively with body mass index (BMI) (r = -0.28, P < 0.001) and serum triacylglycerol (TG) concentration (r = -0.34, P < 0.001). PLTP mass did not correlate with phospholipid transfer activity as measured with a radiometric assay. The specific activity of PLTP, i.e. phospholipid transfer activity divided by PLTP mass, correlated positively with plasma TG concentration (r=0.568, P<0.001), BMI (r=0.45, P<0.001), apoB (r = 0.45, P < 0.001). total cholesterol (r=0.42, P < 0.001), LDL-cholesterol (r = 0.34, P < 0.001) and age (r = 0.36, P < 0.001), and negatively with HDL-cholesterol (r= -0.33, P < 0.001), Lp(A-I) (r= -0.21, P < 0.01) as well as Lp(A-I/A-II) particles (r = -0.32, P < 0.001). When both PLTP mass and phospholipid transfer activity were adjusted for plasma TG concentration, a significant positive correlation was revealed (partial correlation, r = 0.31, P < 0.001). The results suggest that PLTP mass and phospholipid transfer activity are strongly modulated by plasma lipoprotein composition: PLTP mass correlates positively with parameters reflecting plasma high density lipoprotein (HDL) levels, but the protein appears to be most active in subjects displaying high TG concentration.     

Plasma phospholipid transfer protein activity, a determinant of HDL kinetics in vivo

OBJECTIVE: Phospholipid transfer protein (PLTP) is an important regulator in the transport of surface components of triglyceride-rich lipoprotein (TRL) to high density lipoprotein (HDL) during lipolysis and may therefore play an important role in regulating HDL transport. In this study we investigated the relationship of plasma PLTP activity with HDL metabolism in men. DESIGN AND METHODS: The kinetics of HDL LpA-I and LpA-I:A-II were measured using intravenous administration of [D3]-leucine, gas chromatography-mass spectrometry (GCMS) and a new multicompartmental model for HDL subpopulation kinetics (SAAM II) in 31 men with wide-ranging body mass index (BMI 18-46 kg/m2). Plasma PLTP activity was determined as the transfer of radiolabelled phosphatidylcholine from small unilamellar phosphatidylcholine vesicles to ultracentrifugally isolated HDL. RESULTS: PLTP activity was inversely associated with LpA-I concentration and production rate (PR) after adjusting for insulin resistance (P < 0.05). No significant associations were observed between plasma PLTP activity and LpA-I fractional catabolic rate (FCR). In multivariate analysis, including homeostasis model assessment score (HOMA), triglyceride, cholesteryl ester transfer protein (CETP) activity and PLTP activity, PLTP activity was the only significant determinant of LpA-I concentration and PR (P = 0.020 and P = 0.016, respectively). CONCLUSIONS: Plasma PLTP activity may be a significant, independent determinant of LpA-I kinetics in men, and may contribute to the maintenance of the plasma concentration of these lipoprotein particles in setting of hypercatabolism of HDL.     

Acute-phase HDL in phospholipid transfer protein (PLTP)-mediated HDL conversion

In reverse cholesterol transport, plasma phospholipid transfer protein (PLTP) converts high density lipoprotein(3) (HDL(3)) into two new subpopulations, HDL(2)-like particles and prebeta-HDL. During the acute-phase reaction (APR), serum amyloid A (SAA) becomes the predominant apolipoprotein on HDL. Displacement of apo A-I by SAA and subsequent remodeling of HDL during the APR impairs cholesterol efflux from peripheral tissues, and might thereby change substrate properties of HDL for lipid transfer proteins. Therefore, the aim of this work was to study the properties of SAA-containing HDL in PLTP-mediated conversion. Enrichment of HDL by SAA was performed in vitro and in vivo and the SAA content in HDL varied between 32 and 58 mass%. These HDLs were incubated with PLTP, and the conversion products were analyzed for their size, composition, mobility in agarose gels, and apo A-I degradation. Despite decreased apo A-I concentrations, PLTP facilitated the conversion of acute-phase HDL (AP-HDL) more effectively than the conversion of native HDL(3), and large fusion particles with diameters of 10.5, 12.0, and 13.8 nm were generated. The ability of PLTP to release prebeta from AP-HDL was more profound than from native HDL(3). Prebeta-HDL formed contained fragmented apo A-I with a molecular mass of about 23 kDa. The present findings suggest that PLTP-mediated conversion of AP-HDL is not impaired, indicating that the production of prebeta-HDL is functional during the ARP. However, PLTP-mediated in vitro degradation of apo A-I in AP-HDL was more effective than that of native HDL, which may be associated with a faster catabolism of inflammatory HDL.     

冠心病患者血清磷脂转运蛋白活性与冠状动脉病变严重程度的相关分析

目的分析冠心病患者血清磷脂转运蛋白活性水平与冠状动脉病变严重程度的相关性。方法 2015年6月至2016年6月期间,无锡市锡山人民医院心血管科顺序入选胸痛患者202例,行冠状动脉造影术后分为冠心病组(n=121)和非冠心病组(n=81),计算Gensini评分,测定血清磷脂转运蛋白活性水平并行常规实验室检查。结果冠心病组磷脂转运蛋白活性水平和Gensini评分显著高于非冠心病组[90.3(67~118)mg/dL比77.4(54.6~103.3)mg/dL,P0.05;29(8~48)比2(0~6),P0.001]。70~79岁与69岁及以下、男性与女性、糖尿病与非糖尿病患者相比,磷脂转运蛋白活性水平和Gensini评分明显升高(P0.05)。多重线性回归分析提示冠心病组患者磷脂转运蛋白与Gensini评分相关(Beta=0.356,P0.001)。ROC曲线分析显示磷脂转运蛋白曲线下面积为0.749(P0.001)。结论冠心病组磷脂转运蛋白活性水平与冠状动脉病变严重程度相关,磷脂转运蛋白活性水平可预测冠状动脉病变严重程度。     

代谢综合征患者白细胞介素6水平与HDL亚类分布的相关性分析

目的探究代谢综合征(MS)患者血浆白细胞介素6(IL-6)水平与高密度脂蛋白(HDL)亚类分布及其相关性。方法收集MS组患者135例和对照组健康体检人群77例的血样,酶联免疫吸附法(ELISA)测定IL-6含量,按IL-6浓度将MS患者分为低IL-6组(IL-6≤66.76 ng/L)、中IL-6组(66.76 ng/LIL-6113.84 ng/L)、高IL-6组(IL-6≥113.84 ng/L)。双向电泳-免疫印迹法测定血浆HDL亚类的相对含量,全自动生化分析仪测定血脂浓度及载脂蛋白含量。分析不同性别对IL-6、血脂、载脂蛋白及HDL亚类分布的影响,及IL-6水平与HDL亚类分布的相关性。结果与对照组比较,MS组IL-6、preβ1-HDL、HDL3b、HDL3c、TC、TG、LDLC含量以及LDLC/HDLC和Apo B100/Apo AI均显著增高(P0.05或P0.01),而HDL2a、HDL2b、preβ2-HDL、Apo AI和HDLC含量显著降低(P0.05或P0.01)。与对照组同性别比较,MS组男性或女性HDL亚类的相对含量有差异(P0.05或P0.01);与同组男性比较,对照组和MS组女性血脂、血浆载脂蛋白水平差异均无统计学意义(P0.05)。MS患者血浆IL-6含量的升高与HDL亚类分布异常存在相关性,即IL-6的含量与小颗粒的preβ1-HDL、HDL3b水平呈正相关,与大颗粒HDL2b水平呈负相关。结论 MS患者血浆IL-6水平升高,且HDL颗粒呈变小趋势,高水平的IL-6可能与HDL亚类分布异常和血脂紊乱有关。     

稳定型冠心病患者低血清白蛋白浓度与不良心血管事件相关性探讨

目的:稳定型冠心病患者中低血清白蛋白浓度与不良心血管事件的关系。方法:入组734例患者作为研究对象,根据血清白蛋白浓度,分为低血清白蛋白组(<35 g/L)98例,和正常血清白蛋白组(≥35g/L)636例。随访分析18个月内血清白蛋白水平与心血管不良事件转归的关系。结果:与正常白蛋白组相比,低白蛋白组患者年龄较大,糖尿病患者较多,血红蛋白水平较低,肾小球滤过率降低,总胆固醇水平降低,左心室射血分数降低,血糖升高。两组间总心血管事件差异无统计学意义(P=0.163),低血清白蛋白浓度与全因死亡率(10.2%vs.0.5%,P<0.001)和主要心血管事件相关(7.1%vs.1.4%,P<0.001)。校准混合因素后(全因死亡率,HR=6.81,95%CI:1.01~45.62,P=0.048;主要心血管事件,HR=3.68,95%CI:1.03~13.19,P=0.045),相关性仍然较显著。结论:血清白蛋白浓度低于35g/L的稳定型冠心病患者的预后较差。     

The impact of phospholipid transfer protein (PLTP) on HDL metabolism

High-density lipoproteins (HDL) play a major protective role against the development of coronary artery disease. Phospholipid transfer protein (PLTP) is a main factor regulating the size and composition of HDL in the circulation and plays an important role in controlling plasma HDL levels. This is achieved via both the phospholipid transfer activity of PLTP and its capability to cause HDL conversion. The present review focuses on the impact of PLTP on HDL metabolism. The basic characteristics and structure of the PLTP protein are described. The two main functions of PLTP, PLTP-mediated phospholipid transfer and HDL conversion are reviewed, and the mechanisms and control, as well as the physiological significance of these processes are discussed. The relationship between PLTP and the related cholesteryl ester transfer protein (CETP) is reviewed. Thereafter other functions of PLTP are recapitulated: the ability of PLTP to transfer cholesterol, alpha-tocopherol and lipopolysaccharide (LPS), and the suggested involvement of PLTP in cellular cholesterol traffic. The discussion on PLTP activity and mass in (patho)physiological settings includes new data on the presence of two forms of PLTP in the circulation, one catalytically active and the other inactive. Finally, future directions for PLTP research are outlined.     

Postprandial variations in the cholesteryl ester transfer protein activity,phospholipid transfer protein activity and plasma cholesterol efflux capacity in normolipidemic men

BACKGROUND AND AIM: Plasma cholesterol efflux capacity is stimulated during postprandial (PP) hypertriglycerdemia. Plasma cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are the key proteins in lipoprotein metabolism and remodelling, but their role during the PP cholesterol efflux process remains indeterminate. The aim of this study was to determine the effect of a fatty meal intake on plasma CETP and PLTP activities, and the capacity of plasma to promote cholesterol efflux, as well as to evaluate the relationship between these three key mechanisms of the reverse cholesterol transport process. METHODS AND RESULTS: CETP and PLTP activities and the cholesterol efflux capacity of plasma were measured over eight hours following a fatty meal (1000 kcal, 62% fat) in 13 normolipidemic men. CETP activity and the cholesterol efflux capacity of plasma from Fu5AH cells increased after the meal, reaching a maximum after eight hours (respectively 32%, p = 0.06, and 6.5%, p = 0.045), whereas PLTP activity remained unchanged. CETP and PLTP activities did not correlate with plasma cholesterol efflux capacity in the fasting or PP state. Plasma CETP activity in the fasting state positively correlated with the plasma non-esterified fatty acid (NEFA) levels, but no correlation was found with any lipid or apolipoprotein postprandially. The cholesterol efflux capacity of plasma correlated positively with high-density lipoprotein (HDL) components, the best correlation being with the HDL phospholipid fraction in both the fasting and PP states. CONCLUSIONS: These findings suggest that plasma CETP and PLTP activities in healthy normolipidemic subjects are differently regulated in the PP state, and are not correlated with the increased cholesterol efflux capacity of PP plasma. HDL-phospholipid remains the key factor in the regulation of the capacity of plasma to promote Fu5AH cell cholesterol efflux.     

糖尿病患者低血糖与心血管疾病的关系

控制血糖是糖尿病治疗的首要目标,但在降糖过程中,难以避免的低血糖会减少降糖益处,甚至增加死亡风险.近年来研究发现,低血糖可以改变心血管系统神经内分泌和电生理、损害血管内皮,进而诱发糖尿病急性心血管事件或加快慢性并发症进程.低血糖的发生会抵消糖尿病患者一生高血糖治疗所带来的益处.现将低血糖与糖尿病患者心血管疾病的关系作一综述.     

糖尿病患者低血糖与心血管疾病的关系

控制血糖是糖尿病治疗的首要目标,但在降糖过程中,难以避免的低血糖会减少降糖益处,甚至增加死亡风险.近年来研究发现,低血糖可以改变心血管系统神经内分泌和电生理、损害血管内皮,进而诱发糖尿病急性心血管事件或加快慢性并发症进程.低血糖的发生会抵消糖尿病患者一生高血糖治疗所带来的益处.现将低血糖与糖尿病患者心血管疾病的关系作一综述.     

糖尿病患者低血糖与心血管疾病的关系

控制血糖是糖尿病治疗的首要目标,但在降糖过程中,难以避免的低血糖会减少降糖益处,甚至增加死亡风险.近年来研究发现,低血糖可以改变心血管系统神经内分泌和电生理、损害血管内皮,进而诱发糖尿病急性心血管事件或加快慢性并发症进程.低血糖的发生会抵消糖尿病患者一生高血糖治疗所带来的益处.现将低血糖与糖尿病患者心血管疾病的关系作一综述.     

Different locations of cholesteryl ester transfer protein and phospholipid transfer protein activities in plasma

Activities of cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) were measured in plasma of four vertebrate species: man, rabbit, pig, and rat. The activities were measured in the absence and presence of antibodies raised against purified human CETP. PLTP activities were present in all four species with highest values in pig (11.7 ± 1.2 U/ml) and human plasma (9.2 ± 1.6 U/ml). Considerable lower activities were found in rabbit (3.5 ± 0.6 U/ml) and rat plasma (1.6 ± 0.7 U/ml). These activities were not affected significantly by antibody against human CETP. CETP activities could be measured in human (0.23 ± 0.05 U/ml) and in rabbit plasma (0.19 ± 0.03 U/ml). CETP activity in human plasma was inhibited over 97% by antibody against human CETP. Plasma was chromatographed on a Superose 6 gel filtration column. Average HDL particle sizes in the four species differed notably and decreased in the order: rat HDL > rabbit HDL > human HDL > pig HDL. A separation of the two lipid transfer activities was evident after gel filtration chromatography. The peak of the PLTP activity coeluted with a fraction of HDL particles with the size of human HDL₂ (particle weights 300–375 kDa). CETP activity in human and rabbit plasma coeluted largely with relatively small HDL particles (particle weights 140–180 kDa). These results show that CETP and PLTP activities are located in different macromolecular complexes.     

HDL metabolism and the role of HDL in the treatment of high-risk patients with cardiovascular disease

Developing new therapeutic approaches to treating residual cardiovascular risk of recurrent clinical events in statin-treated patients has been a major challenge for the cardiovascular field. Data from epidemiological evidence, animal models, and initial clinical trials indicate that increasing high-density lipoprotein (HDL) may be an effective new target for treating residual cardiovascular risk. Over the past several years, major advances have occurred in our understanding of HDL metabolism and of the important roles of the ABCA1 and ABCG1 transporters as well as the SR-BI receptor in cholesterol transport. Current approaches to HDL therapy include acute HDL infusion therapy in acute coronary syndrome patients and chronic oral HDL therapy in stable patients with cardiovascular disease. Definitive clinical trials will now be required to establish the safety and efficacy of increasing HDL in the treatment of patients with cardiovascular disease.     

冠心病患者对氧磷酯酶1活性与氧化型低密度脂蛋白的关系

目的　探讨冠心病患者血清对氧磷酯酶 1(PON1)活性变化与氧化型低密度脂蛋白 (oxLDL)水平的关系。方法用分光光度法测定 99例冠心病患者 [稳定性心绞痛 (SAP) 35例 ,不稳定性心绞痛 (UAP) 30例 ,急性心肌梗死 (AMI)34例 ]和 4 2例健康体检者 (对照组 )血清PON1活性 ,用酶联免疫吸附法测定血浆oxLDL水平。同时用直线相关分析法分析PON1活性和oxLDL水平的相关性。结果　冠心病组血清PON1活性与对照组比较显著下降 ,而血浆oxLDL水平与对照组比较显著增加。冠心病组中的SAP、UAP和AMI患者 ,血清PON1活性依次下降 ,而oxLDL浓度依次升高。PON1活性与oxLDL呈显著负相关。结论　冠心病患者存在的PON1活性降低 ,导致抗氧化能力的减弱 ,使血浆oxLDL水平增加 ,这种改变可能与冠心病的发生和发展有关。     

Relationship between oral health and physical frailty in patients with cardiovascular disease

BackgroundOral health is important for maintaining general health and is associated with components of physical frailty among the elderly. Oral health problems are common in hospitalized patients; however, no reports on oral health problems pertain to patients with cardiovascular diseases (CVD). The present study aimed to evaluate the association between oral health and physical frailty in these patients.MethodsIn this retrospective cohort study, we included consecutive patients admitted for CVD to our hospital between May 2014 and December 2018. Physical frailty was assessed using the Short Physical Performance Battery (SPPB). Oral health characteristics, such as the number of remaining teeth, denture use, occlusal support, and periodontal status, were assessed.ResultsIn our cohort (n = 457), 111 (24.3%) patients had physical frailty. Univariate linear regression showed that the number of teeth present and the prevalence of occlusal support were significantly lower in patients with than without physical frailty. Pearson correlation indicated that the number of teeth significantly correlated with the nutritional status (r = 0.27) and SPPB score (r = 0.24), grip strength (r = 0.33), and 6-minute walking distance (r = 0.26). Multiple linear regression analysis showed that the number of teeth was independently associated with physical frailty after adjusting for confounders.ConclusionsOral health was closely associated with physical frailty, and nutritional status in patients with CVD; thus, it could be an important screening marker for early frailty symptoms and a predictor of future malnutrition risk.     

Relationship between disease activity and infection in patients with spondyloarthropathies

OBJECTIVE: To assess the relationship between disease activity and signs and symptoms of infection in Mexican patients with spondyloarthropathies (SpA). METHODS: A cross sectional study of 95 non-selected patients with SpA (62 men; mean age 26.4 years), who were examined for signs and symptoms of infection and their association with disease activity. 52 had ankylosing spondylitis (AS), 32 undifferentiated SpA (uSpA), 6 chronic reactive arthritis (ReA), and 5 psoriatic arthritis (PsA). Categorical data were analysed by chi(2) or Fisher's tests. RESULTS: 53 (56%) patients had infections: 41 (43%) upper respiratory tract (URT), 34 (36%) enteric, and 20 (21%) genitourinary infections. More infections occurred in HLA-B27 positive patients as a whole (39 v 5; p = 0.003) and in uSpA (12 v 2; p = 0.005). In AS and uSpA, infections occurred in approximately 50%. 30/39 (77%) patients with active disease (group A) and 23/56 (41%) (group B) (p = 0.001) had infection. There were more enteric infections in group A (47%; p<0.001) and more URT infections in group B (52%; p = NS). 22/30 (73%) patients attributed disease activity to infection. CONCLUSION: Enteric, and less commonly, URT infections in Mexican patients with SpA, particularly those who were HLA-B27 positive, seem to have a role in the active phase of AS and uSpA.