47例系统性红斑狼疮患者血清PCSK9水平检测分析及意义

目的检测系统性红斑狼疮(SLE)患者血清前蛋白转化酶枯草溶菌素9(PCSK9)水平并分析与疾病各参数的相关性。方法本研究纳入47例SLE患者及30例年龄、性别匹配的健康对照者,比较两组间传统心血管危险因素的差异,ELISA检测血清PCSK9水平;行颈动脉彩超测量颈动脉内中膜厚度(c IMT),并根据c IMT将SLE患者分为SLE-AS与SLE-NonAS两个亚组(前者c IMT≥1. 0 mm,后者c IMT 1. 0 mm),并比较两个亚组的致动脉硬化因素及PCSK9水平;应用单因素相关分析方法探讨SLE患者血清PCSK9水平与疾病各参数的相关性。结果 SLE患者及健康对照组在总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A1(Apo A1)、载脂蛋白B(Apo B)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FBG)、体质量指数(BMI)、尿酸(UA)水平等传统心血管病危险因素方面无明显差异;但SLE患者出现c IMT增厚的比例较健康对照组仍显著偏高; SLE患者血清PCSK9水平显著高于健康对照组; SLE患者无论是否有c IMT增厚,其传统心血管病危险因素无显著差异,合并c IMT增厚的SLE患者C反应蛋白(CRP)水平、血清PCSK9水平明显升高; SLE患者血清PCSK9水平与年龄、疾病活动度(SLEDAI)、脂质参数(TC、LDL-C、Apo A1、Apo B、TG、HDL-C)、BMI、UA无显著相关性,仅与CRP水平呈正相关,且这一相关性在女性患者中更为显著。结论 SLE患者血清PCSK9表达水平明显增高;尤其在合并c IMT增厚的患者中,其PCSK9水平更高; PCSK9可能与SLE患者致动脉粥样硬化性炎症有关。     

脂蛋白(a)基因单核苷酸多态性与钙化性主动脉瓣疾病及冠心病的关系

目的 探讨脂蛋白(a)[Lp(a)]基因单核苷酸多态性(SNP)与钙化性主动脉瓣膜疾病(CAVD)、冠心病(CHD)的相关性。方法 前瞻性研究。纳入2018年1-12月天津市胸科医院心内科CAVD或CHD住院患者248例,根据心脏超声多普勒、冠状动脉造影或冠状动脉CT检查结果分为两组:CAVD组101例、CHD组147例;同时选取2018年3-12月天津市胸科医院体检中心排除CAVD或CHD的171位健康体检者为对照组。检测各组Lp(a)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、载脂蛋白A(ApoA)、载脂蛋白B(ApoB)等生化指标,采用SNaPshot SNP分型技术对Lp(a)基因rs7770628、rs6415084、rs10455872三个位点进行基因分型;采用二元logistic回归分析不同基因型及Lp(a)水平对钙化性主动脉瓣疾病及冠心病发病的影响,采用线性回归分析不同基因型及ApoB水平对Lp(a)水平的影响。结果 三组间比较,患者BMI和饮酒史差异均无统计学意义(P值均＞0.05),性别、年龄、吸烟史、糖尿病史、高血压病史差异均有统计学意义(P值均＜0.05)。Lp(a) 检测值在对照组、CAVD组、CHD组分别为23.6(9.4,48.6)、37.2(16.5,79.6)、46.7(21.5,104.6)nmol/L,三组间比较差异有统计学意义(H=13.337,P<0.01);LDL值各组分别为(2.74±0.80)、(3.07±0.81)、(3.14±1.18)mmol/L,三组间差异有统计学意义(F=3.662,P<0.05);HDL值各组分别为(1.24±0.93)、(1.18±0.30)、(1.09±0.33 )mmol/L,三组间比较差异有统计学意义(F=4.281,P<0.05);ApoA值各组分别为(1.42±0.25)、(1.30±0.26)、(1.26±0.26) g/L,三组间比较差异有统计学意义(F=7.339,P<0.01);ApoB检测值各组分别为0.97(0.82, 1.10)、1.04(0.87, 1.26)、1.12(0.88, 1.31)g/L,三组间比较差异有统计学意义(H=3.948,P<0.05)。Lp(a)基因rs7770628位点对照组、CAVD组、CHD组TT基因型分别为130(76.0%)、75(74.3%)、103(70.1%),CT基因型分别为36(21.1%)、23(22.8%)、40(27.2%),CC基因型分别为5(2.9%)、3(2.9%)、4(2.7%),三组间比较差异无统计学意义(F=1.718,P＞0.05);Lp(a)基因rs6415084位点对照组、CAVD组、CHD组TT基因型分别为5(2.9%)、2(2.0%)、4(2.7%),CT基因型分别为33(19.3%)、20(19.8%)、32(21.8%),CC基因型分别为133(77.8%)、79(78.2%)、111(75.5%),三组间比较差异无统计学意义(F=0.551,P＞0.05);Lp(a)基因rs10455872位点对照组、CAVD组、CHD组AA基因型分别为171(100%)、99(98.0%)、147(100%),AG基因型分别为0(0.0%)、2(2.0%)、0(0.0%),三组间比较差异无统计学意义(P=0.058)。经logistic回归分析,与对照组相比, CAVD组及CHD组的Lp(a)水平更高,其差异有统计学意义,但未发现Lp(a)基因rs7770628及rs6415084两个位点的基因分布频率的差异有统计学意义(P>0.05)。线性回归结果表明,rs7770628以及rs6415084两个基因位点的基因分布均与Lp(a)水平升高有关。rs10455872位点只有2例SNP基因型为AG,且皆出现于CAVD组。结论 Lp(a)基因rs7770628、rs6415084位点的基因分布均与Lp(a)的升高有关,Lp(a)高表达与CAVD以及CHD患病具有相关性。     

载脂蛋白E多态性与脑梗死及脂类代谢关系的研究

目的:探讨载脂蛋白E(ApoE)多态性与脑梗死及脂类代谢的关系。方法:缺血性脑梗死组110例,健康对照组60例。ApoE表型采用等电聚焦(IEF)电泳及免疫印迹(Westernblotting)技术测定,血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)采用酶法测定,低密度脂蛋白胆固醇(LDL-C)按Fridwald公式计算,ApoAⅠ、ApoB用火箭电泳法测定,ApoE、脂蛋白(a)用ELISA法测定。结果:脑梗死组ApoEε4等位基因表达显著高于对照组(P＜0.05);脑梗死组TC、TG、LDL-C、ApoB、ApoE、Lp(a)水平显著高于对照组(P＜0.05或P＜0.01),ApoAⅠ、HDL-C显著低于对照组(P＜0.05);脑梗死组各等位基因(ε2、ε3、ε4)之间血脂水平比较;含ε4等位基因者,TC、LDL-C、ApoB、Lp(a)水平高于含ε3者(P＜0.05),HDL-C、ApoAⅠ较低(P＜0.05);含ε2等位基因者,TG、HDL-C、ApoAⅠ、ApoE高于含ε3者(P＜0.05),TC、LDL-C、ApoB较低(P＜0.05)。结论:ApoEε4等位基因与脑梗死发病有关,ε2、ε4等位基因与脑硬死患者的脂类代谢改变有关。     

短暂性脑缺血发作患者脂蛋白(a)和D-二聚体水平的变化

目的探讨短暂性脑缺血发作(TC I)与血清脂蛋白(a)[Lp(a)]和血浆D-二聚体(D-d im er)的关系。方法99例TC I患者按病程划分为A、B、C三组,所有病例均在起病24 h内采用酶联免疫吸附法(ELISA)检测血清Lp(a)和血浆D-二聚体的含量,观察72 h内头CT或MR I后与正常对照组进行比较,结果进行组间比较。结果TC I患者血清Lp(a)和D-二聚体的含量明显高于正常对照组(P<0.01),B、C组Lp(a)和D-二聚体的含量均高于A组(P<0.01),而且C组高于B组(P<0.0 5),重型患者明显高于轻、中型患者。TC I各组Lp(a)和D-二聚体含量之间的相关性分析显示,Lp(a)与D-二聚体含量均呈显著正相关(A组r=0.692,P<0.01;B组r=0.731,P<0.01;C组r=0.794,P<0.01)。结论Lp(a)可能是D-二聚体含量升高的主要相关因素,Lp(a)和D-二聚体含量的升高是TC I患者的危险因素,可作为TC I患者诊断、治疗和预后评估的指标。     

妊娠期糖尿病孕妇合并甲状腺功能减退对其脂代谢的影响

目的探讨妊娠期糖尿病(Gestational diabetes mellitus,GDM)合并甲状腺功能减退(甲减)对其脂代谢的影响。方法选取2013年4月~2015年6月在佛山市妇幼保健院常规产检的孕妇为研究对象,所有孕妇于妊娠中期行口服葡萄糖耐量试验(oral glucose tolerance test,OGTT),同时检测其游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)。根据这些孕妇的OGTT结果及其甲状腺功能情况分为4组:A组(GDM合并甲减组)及B组(单纯GDM组),C组(单纯甲减组)及D组(正常对照组)。比较4组的血脂情况,并分析血脂与甲状腺功能的相关关系。结果 A组的TG、LDL-C明显高于其他三组,A组的TC明显高于B、D两组,B组的TG明显高于C、D两组,但低于A组,差异均有统计学意义(P0.05);A组与C组的TC,C组与D组的TG,B、C、D三组的LDL-C,4组的HDL-C比较,差异均无统计学意义(P0.05)。TG与FT4呈负相关(r=-0.179,P=0.000),TC与FT3呈负相关(r=-0.293,P=0.000),LDL-C与FT4及FT3呈负相关(r=-0.118、-0.189,P=0.007、0.000),其余指标之间无明显相关性。结论妊娠期糖尿病合并甲状腺功能减退孕妇的血脂水平明显高于单纯妊娠期糖尿病或单纯甲减孕妇,且甲状腺功能越低,其血脂水平越高。     

中老年急性脑出血和脑梗死患者血脂水平分析

目的:分析中老年急性脑出血(CH)与脑梗死(CI)患者血脂水平的变化。方法:检测50例CH和65例CI及50例健康人群的总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)、脂蛋白(a)〔Lp(a)〕的血浆含量,并进行比较分析。结果:CH组的TC高于对照组(P<0.01),HDL-C显著低于对照组(P<0.01),TC、LDL-C、ApoB显著低于CI组;中老年CH患者随年龄变化血脂代谢的变化不一致。豆纹动脉(LSA)出血组的HDL-C显著低于对照组,TC、LDL-C、ApoB显著高于非豆纹动脉出血(NLSA)组,与CI组无差别,NLSA出血组的TC显著低于对照组和CI组。结论:血脂代谢紊乱容易导致脑LSA粥样硬化,是中老年人CH的危险因素及常见出血部位。     

精神分裂症伴发高血压患者血脂和超敏C反应蛋白水平变化及危险因素分析

目的:探讨精神分裂症伴发高血压(HBP)患者血脂和超敏C反应蛋白(hs-CRP)水平变化及危险因素分析。方法:纳入2019-01-2021-05本院首次确诊的精神分裂症患者207例,根据患者的血压情况将其分为精神分裂症组(n=102)和精神分裂症伴发HBP组(n=105),精神分裂症伴发HBP组再分为HBPⅠ级组(n=36)、HBPⅡ级组(n=51)和HBPⅢ级组(n=18)三个亚组。检测并分析所有患者的血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)和hs-CRP水平。Logistic回归分析精神分裂症伴发HBP的危险因素。结果:精神分裂症伴发HBP组年龄、病程、TC、TG、LDL-C、ApoB和hs-CRP显著高于精神分裂症组(P均<0.05);HDL-C和ApoA1/ApoB显著低于精神分裂症组(P均<0.05)。精神分裂症伴发HBP各亚组TC、TG、ApoB和hs-CRP水平呈HBP I级组相似文献   

绞股蓝总苷对PCSK9基因表达及辛伐他汀降血脂作用的影响

目的:探讨绞股蓝总苷(gypenosides,GPs)对大鼠肝脏前蛋白转化酶枯草溶菌素9(PCSK9)基因表达及辛伐他汀的降血脂作用的影响。方法:采用高脂饲料喂饲建立大鼠高脂血症模型。60只健康雄性SD大鼠随机分为正常对照组(control组)、高脂模型组(model组)、辛伐他汀组(Simvastatin组)、GPs组和GPs与辛伐他汀联合用药组(combined组)。除正常对照组喂食普通饲料外,其余3组大鼠均喂食高脂饲料。将GPs溶于0.3%羧甲基纤维素钠(CMC-Na)溶液中,用灌胃方式给药。Control组和model组灌0.3%CMC-Na(1mL/100 g),GPs组灌GPs 160 mg·kg~(-1)·d~(-1),simvastatin组灌辛伐他汀5mg·kg~(-1)·d~(-1),combined组灌两者联合剂量。实验8周后,处死大鼠。取腹腔动脉血,测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C);称大鼠体重及肝脏组织湿重,测定肝指数;取肝脏用4%多聚甲醛固定,石蜡包埋,HE染色作常规形态学检测;另取肝脏提取总RNA,real-time PCR测定PCSK9和低密度脂蛋白受体(LDLR)的mRNA表达;提取肝脏总蛋白,Western blot测定PCSK9和LDLR蛋白的表达。结果:成功建立高脂血症大鼠模型。与model组大鼠比较,simvastatin组、GPs组以及combined组TC、TG和LDL-C水平均明显下降(P0.05),各组HDLC水平有不同程度的上升(P0.05)。与model组大鼠比较,simvastatin组、GPs组以及combined组肝指数均明显下降(P0.05)。肝组织病理结果显示,高脂血症性大鼠出现脂肪肝病变;Simvastatin组、GPs组以及combined组大鼠肝细胞脂肪变性程度有不同程度减轻,尤以combined组效果显著。与model组比较,simvastatin组PCSK9和LDLR的mRNA表达均明显升高,GPs组以及combined组PCSK9的mRNA表达明显降低(P0.05),GPs组LDLR的mRNA表达变化不明显,combined组LDLR的mRNA表达明显升高(P0.05)。与model组比较,Simvastatin组PCSK9和LDLR的蛋白表达均明显升高;GPs组和combined组的PCSK9蛋白表达明显降低,LDLR蛋白表达明显升高(P0.05)。结论:GPs能抑制肝脏PCSK9表达,增加LDLR表达量;与辛伐他汀联用可增强其降血脂和减轻肝脏脂肪病变的效果。     

2型糖尿病合并冠心病患者的血清25-羟基维生素D和血脂水平变化及其相关性

目的:回顾性分析2型糖尿病(T2DM)合并冠心病(CHD)患者血清25-羟基维生素D[25(OH)VitD]和血脂水平变化及其相关性。方法:2017-03—2018-03武汉大学中南医院收治的129例T2DM合并CHD患者,按其血清25(OH)VitD水平分为25(OH)VitD缺乏组(A组,n=93)和25(OH)VitD正常组(B组,n=36)。比较分析两组25(OH)VitD、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FBG)水平差异以及25(OH)VitD与上述指标的相关性。结果:A组25(OH)VitD显著低于B组(P0.01),TC、LDL-C水平明显高于B组(均P0.05),TG、HDL-C、FBG水平两组无显著差异(均P0.05)。T2DM合并CHD患者血清25(OH)VitD与TC、LDL-C水平呈显著负相关(P0.05),25(OH)VitD与TG、HDL-C和FBG无明显相关性(P0.05)。结论:T2DM合并CHD患者VitD缺乏,胆固醇代谢不良。     

MNT治疗联合二甲双胍对妊娠期糖尿病患者糖脂代谢及血清ADP、ApoM的影响

目的:观察医学营养疗法(Medical nutrition therapy,MNT)治疗联合二甲双胍对妊娠期糖尿病(Gestational diabetes mellitus,GDM)患者糖脂代谢及血清脂联素(ADP)、载脂蛋白M(Apo lipoprotein M,Apo M)的影响.方法:2021 年 4 月～2023 年 4 月我院收治的 192 例GDM患者,根据随机数字表法分为观察组(n=96)、对照组(n=96).对照组给予二甲双胍,观察组给予MNT联合二甲双胍.对比 2 组治疗效果、糖脂代谢指标[空腹血糖(FBG)、餐后 2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)]、病情相关指标[同型半胱氨酸(Hcy)、瘦素、C-反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)]及血清ADP、Apo M水平.结果:观察组治疗总有效率 97.92%高于对照组 88.54%(P＜0.05).FBG、2 hPG、HbA1c、TC、TG、LDL-C水平及血清Hcy、CRP、瘦素、TNF-α水平比较:治疗后＜治疗前,且观察组＜对照组.HDL-C水平及血清ADP、Apo M水平比较:治疗后＞治疗前,且观察组＞对照组(P＜0.05).结论:MNT联合二甲双胍可调节GDM患者血清ADP、Apo M水平,影响糖脂代谢,有效控制血糖,可作为提高GDM临床疗效的有效治疗方式.     

Proprotein Convertase Subtilisin/Kexin Type 9 Gene E670G Polymorphism Interacts with Alcohol Consumption to Modulate Serum Lipid Levels

Backgroud: Both alcohol consumption and the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene polymorphism modulate serum lipid levels, but their interactions on serum lipid profiles are still unknown. The present study was undertaken to detect the interactions of PCSK9 E670G polymorphism and alcohol consumption on serum lipid levels.Methods: Genotypes of the PCSK9 E670G in 1352 unrelated subjects (785 non-drinkers and 567 drinkers) were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions between PCSK9 E670G genotypes and alcohol consumption on serum lipid parameters were detected by using a factorial design covariance analysis after controlling for potential confounders.Results: The levels of serum triglyceride, high-density lipoprotein cholesterol, apolipoprotein (Apo) A1, and the ratio of ApoA1 to ApoB were higher in drinkers than in non-drinkers (P < 0.01 for all), whereas the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and ApoB were lower in drinkers than in non-drinkers (P < 0.001 for all). The genotypic and allelic frequencies of PCSK9 E670G were not different between non-drinkers and drinkers (P > 0.05 for each). The subjects with AA genotype in non-drinkers had higher serum LDL-C levels than the subjects with AG genotype, whereas the subjects with AG genotype in drinkers had higher serum TC levels than the subjects with AA genotypes (P < 0.05 for each). The effects of alcohol consumption on TC and LDL-C levels depended upon genotypes, the subjects with AA genotype had lower serum TC and LDL-C levels in drinkers than in non-drinkers.Conclusions: Alcohol consumption can modify the effects of the PCSK9 E670G polymorphism on serum TC and LDL-C levels. The subjects with AA genotype of the PCSK9 E670G benefit more from alcohol consumption than the subjects with AG genotype in decreasing serum TC and LDL-C levels.     

三七总皂苷对金黄地鼠PCSK9-LDLR表达及血脂水平的影响

目的:探讨三七总皂苷(PNS)对金黄地鼠实验性高脂血症的调节机制。方法:30只金黄地鼠随机分为正常组、模型组和PNS组3组,每组10只。正常组地鼠饲喂普通饲料,其余2组地鼠饲喂高脂饲料;4周后高血脂症模型已经建成,PNS组腹腔注射血塞通注射液(50 mg/kg),正常组和模型组给予同体积生理盐水。给药12周后,处死地鼠,收集血液,全自动生化分析仪检测血清中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)水平;取肝组织,采用real-time PCR、免疫组织化学和Western blot检测肝脏前蛋白转化酶枯草杆菌蛋白酶/kexin 9型(PCSK9)和低密度脂蛋白受体(LDLR)在mRNA和蛋白水平的表达。结果:成功建立高脂血症地鼠模型。与正常对照组相比,高脂模型组地鼠血清TC、TG、LDL-C和ALT水平显著增高(P<0.05),PNS干预组地鼠TC、TG、LDL-C和ALT水平显著下降(P<0.05),各组地鼠血清中HDL-C和AST水平无显著变化(P&g...     

Cholesterol ester transfer protein,apolipoprotein E and lipoprotein lipase genotypes in patients with coronary artery disease in the Turkish population

The aim of this study was to compare patients with coronary artery disease (CAD) to healthy objects, in order to explore a possible association between CAD and the variants in the gene encoding cholesterol ester transfer protein (CETP), apolipoprotein E (Apo E) and lipoprotein lipase (LPL). The relationship between CETP MspI, apo E and LPL PvuII gene polymorphisms and serum lipids were investigated in 173 patients with CAD and 111 healthy controls. The frequency of Apo epsilon4 (p < 0.05) and CETP M1 (p < 0.01) alleles were higher in the CAD group than in the control group. In the CAD group, those with the Msp M1 allele had higher levels of total cholesterol (TC) (p = 0026) and low-density lipoprotein cholesterol (LDL-C) than those with the Msp M2 allele. Subjects with an epsilon2 allele had the lowest levels of TC and LDL-C, while subjects with the epsilon4 allele had the highest. In the control group, CETP, the Msp M2 allele was associated with a higher level of high-density lipoprotein cholesterol (HDL-C) (p = 0.012) than the Msp M1 allele. The distributions of LPL genotype and allele did not differ between the CAD and control groups. The present study demonstrates that the CETP Msp1 and Apo E gene polymorphisms are associated with variations in lipids in patients with CAD and healthy controls in Turkish population.     

Amyloid substance within stenotic aortic valves promotes mineralization

Audet A, Côté N, Couture C, Bossé Y, Després J‐P, Pibarot P & Mathieu P
(2012) Histopathology  61, 610–619 Amyloid substance within stenotic aortic valves promotes mineralization Aims: Accumulation of apolipoproteins may play an important role in the pathobiology of calcific aortic valve disease (CAVD). We aimed to explore the hypothesis that apolipoprotein‐derived amyloid could play a role in the development of CAVD. Methods and results: In 70 explanted CAVD valves and 15 control non‐calcified aortic valves, we assessed the presence of amyloid by using Congo red staining. Immunohistochemistry was performed to document the presence of apolipoprotein AI (Apo‐AI). Apoptosis was documented by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) studies performed in control and CAVD valves. Control valves were free of amyloid. Deposition of amyloid was detected in all CAVD valves, and the amount was positively correlated with plasma high‐density lipoprotein and Apo‐AI levels. Apo‐AI within CAVD valves co‐localized with intense staining of fibrillar amyloid. In turn, deposition of amyloid co‐localized with apoptosis near mineralized areas. Isolation of amyloid fibrils confirmed that Apo‐AI is a major component of amyloid deposits in CAVD. In vitro, CAVD‐derived amyloid extracts increased apoptosis and mineralization of isolated aortic valvular interstitial cells. Conclusions: Apo‐AI is a major component of amyloid substance present within CAVD valves. Furthermore, amyloid deposits participate in mineralization in CAVD by promoting apoptosis of valvular interstitial cells.     

Transcatheter aortic valve replacement in a patient with premature coronary artery disease and calcific aortic stenosis complicated by heterozygous familial hypercholesterolemia

We describe a case of a 59-year-old man with severe heterozygous familial hypercholesterolemia (FH) and elevated lipoprotein(a) presenting with severe aortic stenosis, treated with transcatheter aortic valve replacement (TAVR). His history also includes premature coronary artery disease requiring coronary artery bypass surgery at age 48 and a stroke at age 55. His pre-treatment lipid values include an LDL-Cholesterol (LDL-C) of 458 mg/dL, total cholesterol of 588 mg/dL, and lipoprotein (a) level of 351 nmol/L. Since his FH diagnosis, he has received several lipid-lowering agents including statins, bile acid sequestrants, nicotinic acid derivatives, and PCSK9 inhibitors. This case reflects the association of FH and elevated lipoprotein(a) with aortic stenosis and TAVR as a viable and effective treatment.     

PCSK9抑制剂在冠状动脉粥样硬化性心脏病 治疗中的应用

低密度脂蛋白胆固醇（LDL-C）血浆水平升高是动脉粥样硬化性心血管疾病（ASCVD）的主要危险因素。他汀类药物虽然能够有效降低 LDL-C水平,但仍有部分患者无法达到降脂目标或者无法耐受。目前大量研究表明前蛋白转化酶枯草溶菌素9（PCSK9）与血浆LDL-C紧密相关,抑制PCSK9可以有效降低LDL-C水平及ASCVD发生率。本文主要对PCSK9机制以及PCSK9抑制剂治疗冠状动脉粥样硬化性心脏病的新研究进展作一综述。     

类风湿性关节炎患者的血清脂蛋白a水平与炎症指标相关性分析

目的 通过对类风湿性关节炎(RA)患者组与对照组(正常健康者)脂蛋白a(Lp-a)与脂代谢水平的比较,分析RA患者血清中的Lp-a水平与系统性炎症进展的风险相关性.方法 选取30例RA患者(血清类风湿因子阳性)与30例正常健康者,年龄为25～80岁,性别分布相同,采集血样并检测其脂代谢水平(Lp-a、甘油三酯(TG)、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)和极低密度脂蛋白胆固醇(VLDL-C))与炎症反应指标(肿瘤坏死因子α(TN F-α)、白细胞介素6(IL-6)和C反应蛋白(CRP)),对数据进行统计学分析.结果 与对照组比较,RA患者组的血清Lp-a水平显著增高(P＜0.001),HDL-C水平显著降低(P＜0.05),而TC、TG、LDL-C与VLDL-C水平则无明显变化,差异均无统计学意义(P＞0.05).同时,RA患者组的TNF-α、IL-6及CRP水平较对照组均显著增高(P＜0.05),且TNF-α与Lp-a水平的升高有相关性(r=0.753,P＜0.001).结论 RA患者常伴有高水平的Lp-a,且Lp-a水平的升高与RA患者的全身性炎症反应增强具有相关性,Lp-a水平可作为RA患者的风险评价指标.     

Genetic variants in <Emphasis Type="Italic">PCSK9</Emphasis> affect the cholesterol level in Japanese

Mutations in the proprotein convertase subtilisin/kexin 9 (PCSK9) gene have been reported in affected members of two families with autosomal dominant hypercholesterolemia. To investigate the effects of common variants in PCSK9 on the cholesterol level, we conducted an association study using a large cohort representing the general population in Japan (n=1,793). Direct sequencing in all of the exonic regions identified 21 polymorphisms. After consideration of linkage disequilibrium among these polymorphisms, we selected and genotyped nine polymorphisms by the TaqMan method. The intron 1/C(-161)T and exon 9/I474 V polymorphisms were associated with levels of total cholesterol (TC) [C(-161)T, P=0.0285; I474 V, P=0.0069] and low-density lipoprotein cholesterol (LDL-C) [C(-161)T, P=0.0257; I474 V, P=0.0007]. The distributions of these polymorphisms in subjects with miocardial infarction (MI) (n=649) were not different from those in the control population. These results provide the first evidence that common variants intron 1/C(-161)T and exon 9/I474 V in PCSK9 significantly affect TC and LDL-C levels in the general population in Japan.     

25(OH)D3与糖尿病视网膜病变的关系研究

目的 探讨25(OH)D3与糖尿病视网膜病变之间的关系。方法 回顾性分析2016年1月~2017年3月我科收治的2型糖尿病患者83例,根据患者是否合并视网膜病变,分为观察组43例和对照组40例。所有患者检测并比较血糖（FBG）水平、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDLC）、低密度脂蛋白（LDL-C）、糖化血红蛋白（HbA1c）以及25(OH)D3的水平。结果 两组患者在TG（t=5.572,P=0.037）、HDLC（t=5.548,P=0.037）、HbA1c（t=6.627,P=0.012）、25（OH）D3（t=9.738,P=0.000）等临床生化资料比较中差异均具有统计学意义（P＜0.05）。对25(OH)D3的Pearson进行相关性分析后发现,25(OH)D3与T2DM病程（r=0.163,P=0.027）、TC（r=0.170,P=0.025）、HDLC（r=0.177,P=0.023）、LDLC（r=0.185,P=0.015）具有高度相关性;偏相关显示,25(OH)D3与TC、HDLC、LDLC具有相关性。结论 25(OH)D3水平能够反映糖尿病视网膜病变患者的疾病发展状态,在诊断及评估中具有一定的参考价值。     

Apolipoproteins AI, B, and E polymorphisms in severe aortic valve stenosis

Hypercholesterolemia has been related to aortic valve stenosis (AS). Polymorphisms of apolipoproteins (apo) AI, B, and E are associated with variable levels of plasma lipids, but the association between these polymorphisms and AS is unknown. In a case-control study of groups matched by age, sex, comparable body mass index, hypertension, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol, we analyzed the distribution of apo AI A/G mutation, apo B signal peptide insertion/deletion, apo B XbaI restriction fragment length. and apo E polymorphisms in 62 non-diabetic patients with severe aortic valve stenosis and 62 control subjects. All patients underwent echocardiographic analysis. Univariate analysis showed a higher prevalence of the XbaI X + /X + genotype (p = 0.007) of apo B and the apo E2 allele (p = 0.034) in patients with severe AS. Apo polymorphisms were not associated with lipid levels, left ventricular mass, or the aortic gradient.