Klotho基因G-395A多态性与华中地区老年汉族人群颈动脉内中膜厚度的相关性

目的探讨Klotho基因G-395A位点多态性与华中地区老年(年龄≥60岁)汉族人群颈动脉内中膜厚度(IMT)的相关性。方法随机选取278例华中地区老年汉族患者,根据IMT分为IMT增厚组(IMT≥1 mm,132例)和对照组(IMT1 mm,146例),分别检测各组血压、血糖、血脂等生化指标,并用Taq Man基因探针法检测各组Klotho基因G-395A位点的基因型。结果与对照组相比,IMT增厚组GG基因型和G等位基因频率明显增高,AA基因型和A等位基因频率明显降低,AG基因型无明显差异。经多元Logistic回归分析后,G等位基因频率与IMT增厚存在相关性,为IMT增厚的独立危险因子。结论 Klotho基因G-395A位点多态性与华中地区老年汉族人群颈动脉IMT具有相关性,G-395A多态性有可能作为颈动脉IMT增厚的预测指标之一。     

甲烯四氢叶酸还原酶基因多态性与糖尿病大血管病变的关系研究

目的探讨甲烯四氢叶酸还原酶(MTHFR)基因C677T位碱基突变与2型糖尿病患者同型半胱氨酸(Hcy)水平和糖尿病大血管病变的关系。方法将患者分为对照组、糖尿病颈动脉内中膜厚度(IMT)正常组、糖尿病IMT增厚组。应用酶联免疫法测定Hcy水平,采用多聚酶链反应-限制性内切酶片段长度多态性技术(PCR-RFLP)检测MTHFRC677T基因型,用高分辨彩色多普勒检查颈动脉内中膜厚度(IMT)。结果糖尿病IMT增厚组MTHFR基因的TT基因型和T等位基因频率显著增高,与糖尿病IMT正常组及对照组存在统计学差异(P<0.05)。对照组与糖尿病IMT正常组之间T等位基因频率无统计学差异。MTHFR基因突变者血浆Hcy增高。糖尿病组MTHFR基因突变者IMT值明显高于无基因突变者。结论糖尿病IMT增厚组T等位基因频率增高。MTHFR基因C677T点突变组血浆Hcy水平升高,颈动脉IMT增厚。推测MTHFR基因C677T点突变可能是糖尿病合并大血管病变发病的重要遗传因素。     

脂肪酸结合蛋白4基因启动子rs77878271多态性与颈动脉粥样硬化的关系研究

目的探究脂肪酸结合蛋白4(FABP4)基因启动子rs77878271多态性与颈动脉粥样硬化的关系。方法选取2013年10月—2014年9月在河北省人民医院就诊的颈动脉粥样硬化患者580例,采用TaqMan SNP基因分型技术检测rs77878271多态性;采用实时荧光定量聚合酶链反应(qPCR)检测FABP4 mRNA相对表达量,采用酶联免疫吸附试验(ELISA)检测FABP4蛋白。rs77878271基因型与颈动脉中层内膜厚度(IMT)的关系分析采用多元线性回归分析,与颈动脉斑块的关系分析采用多因素Logistic回归分析。结果本组患者中携带TT基因型者占88.6%(514/580)、携带TC基因型者占10.0%(58/514)、携带CC基因型者占1.4%(8/58)。不同rs77878271基因型患者随访期间心血管事件发生率比较,差异无统计学意义(P>0.05)。不同rs77878271基因型患者男性比例、年龄、吸烟率、肥胖发生率、高血压发生率、糖尿病发生率、使用降压药物者所占比例、使用降糖药物者所占比例、使用降脂药物者所占比例、使用抗栓药物者所占比例及总胆固醇(TC)、高密度脂蛋白(HDL)、三酰甘油(TG)、空腹血糖(FBG)、空腹胰岛素(INS)、C反应蛋白(CRP)水平比较,差异均无统计学意义(P>0.05);不同rs77878271基因型患者体质指数(BMI)、IMT、颈动脉斑块者所占比例及低密度脂蛋白(LDL)水平比较,差异均有统计学意义(P<0.05)。多元线性回归分析结果显示,rs77878271基因型与颈动脉粥样硬化患者颈动脉IMT有关(β=0.23,P<0.05);多因素Logistic回归分析结果显示,rs77878271基因型是颈动脉粥样硬化患者颈动脉斑块的影响因素[OR=3.02,95%CI(1.46,7.97),P<0.05]。TC基因型患者FABP4 mRNA相对表达量和蛋白相对表达量均低于CC基因型患者(P<0.05)。结论 FABP4基因启动子rs77878271多态性与颈动脉粥样硬化程度有关。     

慢性肾脏病与非肌性肌球蛋白重链9基因多态性的相关性

目的:探讨我国慢性肾脏病(CKD)患者与非肌性肌球蛋白重链9(MYH9)基因多态性的相关性.方法:选取301例CKD患者作为观察组,294例体检健康者作为对照组.采用PCR法检测MYH9基因rs3752462、rs4821480两位点基因多态性,分析MYH9不同基因型与CKD患者的发病年龄、性别、血压、24h尿蛋白定量、血清肌酐、肾小球滤过率、原发病及服用降压药频率的相关性. 结果:单因素分析结果显示,CT基因型患者的收缩压高于CC基因型(147.94±27.40 mmHg,136.43±19.09 mmHg,P＜0.05);CC基因型患者的肾小球滤过率(32.00±29.98)显著高于CT基因型(21.62±23.67,P＜0.05)及TT基因型(21.99±24.18,P＜0.05).校正年龄因素后,多因素Logistic回归分析结果显示:rs3752462位点CC基因型是CKD患者收缩压增高的保护因素,CT基因型CKD患者患高血压的概率是CC基因型的0.175倍(95％CI 0.071～0.431);rs3752462位点CC基因型是CKD进展至终末期肾病(ESRD)的独立保护因素,CC基因型肾小球滤过率是TT基因型的0.410倍(95％CI 0.183～0.922). 结论:携带MYH9基因rs3752462位点CC基因型的CKD患者不易患高血压,且肾损害进展慢,CC基因型是CKD患者的保护因素,等位基因C突变为T可导致收缩压升高甚至ESRD的发生.     

老年糖尿病患者颈动脉内中膜变化的超声表现

目的探讨老年糖尿病患者颈动脉内中膜厚度(IMT)变化的超声表现。方法 100例确诊为2型糖尿病的患者为病例组,同期选择100例无糖尿病史的健康人群作为对照组,受试者均行颈部血管彩超检查了解IMT变化情况。并分析老年糖尿病患者IMT变化的影响因素。结果病例组IMT、弹性条数(Ep)及硬化程度(β)均较对照组明显升高,且内膜增厚及斑块形成比例明显高于对照组(P<0.05)。病例组软斑例数最高,其次为混合斑,硬斑最少,对照组硬斑例数最高,其次为软斑,混合斑数最少,差异有统计学意义(P<0.05)。内中膜变化组年龄、糖尿病病程、糖化血红蛋白(Hb A1c)、空腹血糖(FPG)、低密度脂蛋白胆固醇(LDL-C)水平显著高于内中膜无变化组(P<0.05)。年龄大,糖尿病病程长,Hb A1c、FPG水平升高是老年糖尿病患者发生颈动脉内中膜增厚或斑块形成的独立危险因素(P<0.05)。结论老年糖尿病患者更容易出现颈动脉内中膜增厚或斑块形成,且软斑比例更高,高龄、糖尿病病程长、血糖控制不佳可以促进老年糖尿病患者IMT变化的发生。     

血清淀粉样蛋白A1基因多态性对汉族人群颈动脉内中膜厚度的影响

目的 探讨血清淀粉样蛋白A1(SAA1)基因多态性对颈动脉内中膜厚度(IMT)的影响.方法资料来源于2007至2010年"新疆维吾尔自治区不同民族心血管疾病危险因素调查研究"数据,人选其中健康汉族人群449例,采用限制性片段长度多态性(RFLP)方法对SAA1基因rs2229338和rs12218进行分型.彩色超声检测颈总动脉干部内中膜厚度(CC-IMT)和膨大部内中膜厚度(CB-IMT),分析不同基因型之间颈动脉IMT的差异.结果 (1)rs2229338和rs12218存在强连锁不平衡(D'=0.89).(2)SAA1基因rs2229338突变型(GG+AG)与野生型(AA)的CC-IMT和CB-IMT值差异均无统计学意义.(3)SAA1基因rs12218突变型(CC+CT)CC-IMT值大于野生型(TT)[(0.081±0.071)cm比(0.068±0.019)cm,P=0.01],在校正年龄、性别、血压、腰围、肌酐和高密度脂蛋白胆固醇的影响后,差异仍具有统计学意义(P=0.04);rs12218突变型(CC+CT)与野生型(TT)的CB-IMT值差异无统计学意义[(0.085±0.038)cm比(0.081±0.052)cm,P=0.36].结论在新疆维吾尔自治区汉族人群,SAA1基因多态性和颈动脉IMT存在关联,rs12218突变型基因可能会增加颈动脉IMT.

Abstract：

Objective To explore the association between genetic polymorphism of serum amyloid protein A1 (SAA1) with carotid intima media thickness in a healthy Han Chinese population of Xinjiang. Methods A total of 449 healthy Han Chinese participating the cardiovascular risk survey between June 2007 and September 2009 were included, the genotypes of the SAA1 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The mean IMT of the right and left common carotid arteries were measured by B-mode ultrasonography. Results (1) There was strong linkage disequilibrium between rs12218 and rs2229338 (D'=0. 89). (2) The carotid common IMT (CC-IMT) and the carotid bulb IMT (CB-IMT) were similar between the AA genotype (wild genotype) and the GGFAG genotype (mutational genotype) in rs2229338 of SAA1 gene. (3) CC-IMT[(0.081 ±0.071)cm vs (0.068 ±0. 019 ) cm, P = 0. 01] was significantly thicker in CC + CT genotype ( mutational genotype) group than in TT genotype (wild genotype) of rs12218 group and the difference remains significant after adjustment for age,gender,blood pressure, waist circumference, creatinine and high density lipoprotein cholesferoL CB-IMT [(0.085±0. 038)cm vs. (0.081 ± 0. 052) cm,P =0. 36] was similar between CC +CT genotype and TT genotype of rs12218 groups. Conclusion Our results suggested that the genetic polymorphism of SAA1 might be linked with IMT and rs12218 mutation could serve as a promoting factor for IMT in Han Chinese people.     

C-反应蛋白与动脉粥样硬化性脑梗死颈动脉内-中膜厚度的相关性

目的探讨动脉粥样硬化(AS)性脑梗死患者C-反应蛋白(CRP)与颈动脉内中膜厚度(IMT)的相关性。方法收集AS性脑梗死患者138例,所有患者均行颈动脉彩色超声多普勒检查,测量颈总动脉IMT。根据IMT的不同,将所有患者分成2组:IMT≤1 mm,为IMT正常组;IMT>1 mm,为IMT增厚组;并测定患者血清CRP、肌酐(Cr)、葡萄糖、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、同型半胱氨酸(Hcy)浓度。结果颈动脉IMT增厚组与IMT正常组相比较,血清CRP浓度明显增高(P=0.001)。血清CRP水平与颈动脉IMT相关(r=0.508,P=0.000)。结论颈动脉IMT与血清CRP水平呈正相关。CRP水平可作为AS性脑梗死患者动脉IMT增厚的标志。     

环指蛋白145基因多态性与急性心肌梗死的关联性研究

目的探讨新疆地区维吾尔族人群环指蛋白145(RNF145)基因单核苷酸多态性(SNP)与急性心肌梗死(AMI)的关联性。方法选取2016年6月至2020年6月在新疆医科大学第一附属医院心脏中心住院的患者,根据是否为AMI,分为AMI组(410例)和对照组(484例)。比较两组的基线资料。采用改进的多重高温连接酶检测反应技术对RNF145基因3个SNP位点(rs12188266、rs17056583、rs7732603)进行基因分型。采用logistic回归分析RNF145基因SNP位点与AMI发病的关系。结果 AMI组中有饮酒史、合并高血压、糖尿病病史的患者比例以及收缩压、总胆固醇水平均高于对照组,差异均有统计学意义(均为P0.05)。RNF145基因rs17056583和rs7732603位点的基因型和等位基因比较均有统计学差异(均为P0.05)。在校正饮酒、合并疾病及血清学指标后,logistic回归分析结果显示,新疆维吾尔族人群中rs17056583位点的CC基因型患AMI风险是GC+GG基因型的2.891倍(OR=2.891,95%CI:1.608～5.196,P0.001)。rs7732603的CC基因型患AMI的风险也明显高于AA和AC基因型者(OR=1.860,95%CI:1.201～2.882,P=0.005)。结论在新疆地区维吾尔族人群中RNF145基因SNP与AMI具有相关性,rs17056583的CC基因型可能是AMI发病的危险因素,且携带rs7732603位点C等位基因者患AMI的风险也显著增加。     

亚甲基四氢叶酸还原酶C677T位点基因多态性对采用叶酸联合维生素B_(12)治疗的老年H型高血压患者的影响研究

目的探讨亚甲基四氢叶酸还原酶(MTHFR)C677T位点基因多态性对采用叶酸联合维生素B_(12)治疗的老年H型高血压患者的影响。方法选取2015年9月—2017年9月莱芜市人民医院收治的老年H型高血压患者146例,均在常规降压治疗基础上采用叶酸联合维生素B_(12)连续治疗4个月。采用聚合酶链反应(PCR)-芯片杂交法检测MTHFR C677T位点基因多态性,比较不同基因型患者高血压分级,治疗前后血浆同型半胱氨酸(Hcy)水平、颈动脉粥样硬化斑块积分及不稳定斑块检出率。结果 146例患者中CC基因型26例(占17.8%),CT基因型46例(占31.5%),TT基因型74例(占50.7%)。不同基因型患者高血压分级比较,差异无统计学意义(P0.05)。治疗前、后TT基因型患者血浆Hcy水平高于CC基因型、CT基因型(P0.05)。治疗后CC基因型、CT基因型患者血浆Hcy水平低于治疗前(P0.05)。治疗前、后TT基因型患者颈动脉粥样硬化斑块积分高于CC基因型、CT基因型,CT基因型患者颈动脉粥样硬化斑块积分高于CC基因型(P0.05)。治疗后CC基因型、CT基因型患者颈动脉粥样硬化斑块积分低于治疗前(P0.05)。治疗前、后不同基因型患者颈动脉不稳定斑块检出率比较,差异无统计学意义(P0.05)。结论叶酸联合维生素B_(12)降低老年H型高血压患者血浆Hcy水平、颈动脉粥样硬化斑块积分效果与MTHFR C677T位点基因多态性有关,其中TT基因型患者的降低效果不如CC基因型、CT基因型,临床应当考虑遗传因素和基因多态性。     

2型糖尿病颈动脉内中膜厚度与亚甲基四氢叶酸还原酶基因C677T多态性及血浆同型半胱氨酸水平的关系

目的探讨亚甲基四氢叶酸还原酶（MTHFR）基因C677T多态性及同型半胱氨酸水平与早期2型糖尿病（T2DM）颈动脉内中膜厚度（IMT）的关系及影响因素。方法测定T2DM患者及对照组（NC）颈动脉IMT,分为糖尿病无内中膜增厚组（DM1）和糖尿病合并内中膜增厚组（DM2）。用PCR—RFLP检测MTHFR基因C677T多态性。结果DM。组MTHFR C677T基因TT基因型频率与NC组比较明显增高（40．4％ vs 17．3％,P〈0．01）,与DM1组比较明显增高（40．4% vs 17．9％,P〈0．01）,DM1组与NC组比较无统计学差异（17．9％ vs 17．3％,P〉0．05）。T等位基因频率DMz组与NC组比较明显增高（57．0％ vs 33．7％,P〈0．01）,与DM1组比较明显增高（57．0％ vs 42．9％,P〈0．01）,差异有统计学意义。结论高同型半胱氨酸血症、T等位基因是早期糖尿病患者颈动脉内中膜增厚的危险因素之一,血浆同型半胱氨酸水平与MTHFR C677T基因多态性有关。     

Rosiglitazone and carotid IMT progression rate in a mixed cohort of patients with type 2 diabetes and the insulin resistance syndrome: main results from the Rosiglitazone Atherosclerosis Study

Objective. Insulin resistance is associated with progression of atherosclerosis. We assessed the effect of 12 months of treatment with rosiglitazone (RSG) on the progression of carotid intima–media thickness (IMT) in people with type 2 diabetes mellitus (T2DM) or the insulin resistance syndrome (IRS). Design. Randomized, double-blind, placebo-controlled trial. Setting. Malmö University Hospital, Malmö, Sweden. Subjects. 555 subjects (200 with T2DM and 355 nondiabetics with IRS according to EGIR criteria), aged 35–80 years. 447 subjects (165 T2DM and 282 IRS) completed the study. Intervention. Participants were allocated to placebo or RSG 4 mg for 2 months and then 8 mg daily. Main outcome measure. Change in composite IMT [mean IMT in the common carotid artery (CCA) and maximal IMT in the bulb] was the primary and various other IMT measures were secondary outcome variables. Results. There was no effect of RSG treatment in the mixed population. In T2DM patients there was a reduced progression of the composite IMT (mean change: 0.041 vs. 0.070 mm, P = 0.07), and of the mean IMT CCA (mean change: −0.005 mm vs. 0.021 mm, P = 0.007). RSG treatment led to significant reductions of HOMA-IR, fasting plasma glucose, HbA1c, PAI-1 activity, fibrinogen, C-reactive protein and matrix metalloproteinase-9. Conclusions. In a mixed study population of patients with T2DM and IRS RSG treatment was not associated with a statistically significant reduction of carotid IMT progression rate. Separate analyses of these two patient groups indicated, however, a significant beneficial effect on CCA IMT in T2DM patients but no similar effect in subjects with IRS.     

Increased intima-media thickness of the carotid artery in Japanese female type 2 diabetic patients with 'midband lipoprotein'

Among a number of different lipoprotein abnormalities, 'midband lipoprotein' migrating at a position between LDL and VLDL on polyacrylamide gel electrophoresis (PAGE), is an atherogenic lipoprotein and intima-media thickness (IMT) of the carotid artery is a useful marker of atherosclerotic diseases. The present study evaluated relationships between the presence of 'midband lipoprotein' and carotid IMT in subjects with type 2 diabetes. The average IMT of the carotid artery was determined from the means of maximal thicknesses of both left and right common carotid arteries, carotid bulb, and internal carotid artery using ultrasound B mode imaging in 118 Japanese patients (72 men, 46 women) and 43 healthy controls. Multivariate regression analyses indicated that the duration of diabetes and presence of 'midband lipoprotein' were independent determinants of carotid artery IMT in 46 female subjects with diabetes, and these subjects were then subclassified into midband-positive (n=24) and midband-negative (n=22) groups. IMT of the carotid artery was significantly different between midband-positive (0.98+/-0.32mm) and midband-negative (0.79+/-0.17mm) groups (P=0.02). These findings suggest that 'midband lipoprotein' is a possible risk factor for IMT of the carotid artery in Japanese female type 2 diabetic patients.     

罗格列酮对初诊2型糖尿病患者颈动脉内膜中层厚度的影响

目的 观察罗格列酮对初诊2型糖尿病患者颈动脉内膜中层厚度（IMT）的影响,探讨其对大血管的保护作用.方法 60例初诊2型糖尿病患者随机分为罗格列酮组和对照组,治疗12周后,高分辨超声测量IMT,并检测两组患者服药前后糖基化血红蛋白、血清胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆同醇.结果 与对照组比较,罗格列酮组IMT明显降低（P＜0.05）,两组治疗前后IMT值均具有显著差异.结论 罗格列酮能明显降低初诊2型糖尿病患者的IMT水平,可能延缓2型糖尿病患者动脉粥样硬化进展,从而改善2型糖尿病患者大血管并发症.     

血清晚期氧化蛋白产物与2型糖尿病患者动脉粥样硬化的关系

目的 探讨血清晚期氧化蛋白产物与2型糖尿病患者动脉粥样硬化性大血管并发症的关系.方法选择90例2型糖尿病患者和60例健康对照者,用酶联免疫吸附法及分光光度法分别检测血清基质细胞衍生因子1α生及晚期氧化蛋白产物水平,采用高分辨超声测定大动脉内膜中膜厚度.结果 2型糖尿病患者血清晚期氧化蛋白产物和基质细胞衍生因子1α水平明显高于健康对照者(P<0.05或P<0.01),2型糖尿病患者高晚期氧化蛋白产物组基质细胞衍生因子1α、空腹血糖、糖化血红蛋白及血清甘油三酯水平和体质指数与正常晚期氧化蛋白产物组比较显著升高(P<0.05),2型糖尿病患者中动脉粥样硬化组晚期氧化蛋白产物及基质细胞衍生因子1α水平明显高于非动脉粥样硬化组(P<0.01或P<0.05).单因素相关分析显示,血清晚期氧化蛋白产物水平与基质细胞衍生因子1α呈正相关(r=0.295,P=0.03),与空腹血糖、糖化血红蛋白、甘油三酯及体质指数呈正相关(r=0.286,P=0.03;r=0.310,P=0.01;r=0.461,P=0.001;r=0.257,P=0.04).结论 2型糖尿病患者蛋白氧化损伤增强,血清晚期氧化蛋白产物增加促进血管内皮细胞基质细胞衍生因子1α表达,晚期氧化蛋白产物增加可能与2型糖尿病动脉粥样硬化相关.     

老年2型糖尿病患者高密度脂蛋白亚类与氧化应激和颈动脉粥样硬化的相关性

目的 探讨老年2型糖尿病患者血清高密度脂蛋白(HDL)亚类的分布特点及其与氧化应激和颈动脉粥样硬化的相关性.方法 老年2型糖尿病患者56例,男40例、女16例;老年健康对照者41例,男31例、女10例.分别测定血清HDL亚类、血清8-异前列腺素F2α及颈动脉超声.结果 老年2型糖尿病组HDL3(0.51±0.21)mmol/L,较健康对照组(0.59±0.15)mmol/L降低(t=1.991,P＜0.05),HDL及HDL2亦较健康对照组降低,分别为(1.07±0.36)mmol/L对(1.18±0.32)mmol/L和(0.56±0.25)mmol/L对(0.64±0.33)mmol/L,但差异无统计学意义(t值分别为1.611和0.614,均为P＞0.05);HDL3与HbA1c负相关(r=-0.503,P=0.005);血清8-异前列腺素F2α吸光度A值较健康对照组降低,分别为0.017±0.004和0.021±0.008(t=2.245,P＜0.05);颈动脉平均内膜-中层厚度(IMT)较健康对照组升高,但差异无统计学意义;颈动脉斑块检出率63.3%,高于对照组的36.0%(x2=4.076,P＜0.05).结论 老年2型糖尿病患者HDL亚类水平存在异常,小颗粒的HDL3水平下降,氧化应激增加,可能是导致其动脉粥样硬化的原因之一.     

2型糖尿病性肾动脉狭窄危险因素的预测研究

目的:研究建立2型糖尿病(DM)患者合并肾动脉粥样硬化性狭窄(ARAS)的预测模型。方法:经肾动脉造影证实的2型糖尿病ARAS患者129例和无ARAS者122例。对两组年龄、DM病程等指标进行统计学分析。结果:最终进入模型的ARAS独立预测因子是年龄(≥65岁)(OR=42.66,P<0.01),加速性高血压(OR=24.78,P<0.01),DM病程≥5年(OR=4.76,P<0.05),颈动脉内膜中层厚度(IMT)≥1 mm(OR=3.41,P<0.01)及Ccr≥90 mL/min(OR=0.91,P<0.01)。预测ARAS的最佳概率值是0.54(敏感度86.0%,特异度93.4%)。Logistic回归方程ROC曲线下面积为0.868(95%CI=0.816～0.92,P<0.01),Cox and Snell决定系数R2=0.586。结论:年龄≥65岁、AH、DM病程≥5年、颈动脉IMT≥1 mm、Ccr≥90 mL/min是DM患者并发ARAS的独立预测因子,该预测模型可以对2型糖尿病患者进行肾动脉狭窄的风险预测,不仅有助于提高彩超及有创检查的诊断阳性率,而且可以减少不必要的漏诊以提高治疗的成本效益。     

高血压合并2型糖尿病患者颈动脉硬化与基质金属蛋白酶-9和脂蛋白(a)的关系

目的探讨基质金属蛋白酶-9(MMP-9)及脂蛋白-a[LP(a)]与高血压合并2型糖尿病(DM)患者颈动脉粥样硬化的关系。方法单纯高血压患者82例采用彩色超声仪进行颈动脉超声检查,检测颈动脉内膜-中膜厚度(IMT),采用ELISA法测定血清中MMP-9及LP(a)等指标;并以同样的方法观察高血压合并2型DM的患者86例辛伐他汀(10mg/d.次)治疗12周前后的上述指标。结果高血压合并2型DM的患者IMT值、斑块发生率、颈动脉斑块积分及MMP-9和LP(a)等值明显高于单纯高血压患者[IMT:(1.29±0.10vs0.96±0.15)mm;斑块发生率:(79.8%vs22.6%);颈动脉斑块积分:(6.0±0.4vs1.7±0.7);MMP-9:(649.1±51.0vs213.2±23.3)μg/L;LP(a):(2132.0±342.2vs765.4±154.1)mg/L(P<0.01)]。MMP-9及LP(a)与高血压合并2型DM的患者IMT值、颈动脉斑块发生率、斑块积分呈正相关,r值分别为(0.80、0.74、0.84、0.76、0.78、0.80,P<0.05)。经辛伐他汀治疗12周,MMP-9和LP(a)下降,颈动脉斑块有所消退。结论MMP-9及LP(a)在高血压合并2型糖尿病患者颈动脉粥样硬化发生发展过程中可能起重要作用。经辛伐他汀治疗,在MMP-9及LP(a)下降的同时颈动脉斑块有所消退。     

Effect of cilostazol, a phosphodiesterase inhibitor, on carotid IMT in Japanese type 2 diabetic patients

The aim of this study was to investigate the effect of cilostazol, a cAMP phosphodiesterase inhibitor, on carotid artery intima-media thickness (IMT) and on the incidence of cardiovascular events in Japanese subjects with type 2 diabetes. A total of 62 type 2 diabetic subjects were allocated equally to the cilostazol treatment group (n = 31) and the control group (n = 31). Carotid IMT was evaluated before and after treatment using B-mode ultrasonography. After the study period (mean +/- SD: 2.6 +/- 0.17 years), carotid IMT showed a significantly greater increase in the control group than in the cilostazol group (0.12 +/- 0.14 mm vs. 0.04 +/- 0.02 mm, p < 0.05). In the control group, 1 out of 31 patients suffered from symptomatic cerebral infarction and 1 had angina pectoris during the observation period. On the other hand, no subject in the cilostazol group developed cardiovascular events during the study period. At baseline, the diabetic patients given cilostazol had a significantly lower HbA1c level than the control subjects, but the other atherosclerotic risk factors (BMI, blood pressure, and serum lipids) and the duration of diabetes did not differ between the two groups. These results indicate that cilostazol therapy can attenuate the increase of carotid artery IMT in Japanese subjects with type 2 diabetes.     

Additional value of carotid artery intima-media thickness in cardiovascular risk assessment by Framingham risk-score in Type 2 diabetes: a retrospective cohort study

Background: The intima–media thickness (IMT) of the carotid artery is highly correlated with cardiovascular events in Type 2 diabetes mellitus (T2DM). The aim of the present study was to undertake a cardiovascular risk assessment in a group of patients (n = 102) who had been followed‐up for 10 years. Methods: Framingham risk score (FRS), IMT, and various other clinical parameters were evaluated retrospectively using Student’s t‐test, regression analysis, and χ² tests. Primary endpoints were defined as cardiovascular death, non‐fatal myocardial infarction, angina, and ischemic stroke. Results: The IMT (1.09 ± 0.32 vs 0.89 ± 0.25; P < 0.001) and percentage coronary risk as determined by the FRS (24.33 ± 11.07 vs 16.54 ± 8.35; P = 0.001) were significantly higher in patients presenting with any of the primary endpoints compared with patients in whom no cardiovascular morbidity or mortality was recorded. Other factors that significantly predicted cardiovascular mortality and morbidity included diastolic blood pressure and urinary albumin excretion (UAE; P < 0.001). The likelihood of primary endpoints could be predicted by UAE >30 mg/day, carotid artery IMT ≥0.9 mm, and FRS ≥20 (odds ratios 8.800, 3.377, and 2.807, respectively). Conclusion: Although FRS predicts 10‐year risk for cardiovascular mortality and morbidity in T2DM, we suggest that UAE and carotid artery IMT should also be considered in risk assessments.