血浆氧化型低密度脂蛋白水平与低密度脂蛋白循环免疫复合物的相关性

为探讨血浆氧化型低密度脂蛋白水平与低密度脂蛋白循环免疫复合物间关系.分别建立了以抗人IgG为包被抗体、酶标抗载脂蛋白B为检测抗体的低密度脂蛋白循环免疫复合物酶联免疫吸附试验;以抗氧化型低密度脂蛋白为包被抗体、酶标抗载脂蛋白B为检测抗体的氧化型低密度脂蛋白酶联免疫吸附试验.同时测定60例冠心病患者及50例对照人群低密度脂蛋白循环免疫复合物、氧化型低密度脂蛋白水平并进行相关性分析.结果发现,冠心病患者甘油三酯、脂蛋白(a)和载脂蛋白B水平均显著升高;高密度脂蛋白胆固醇和载脂蛋白AⅠ水平降低;且低密度脂蛋白循环免疫复合物(2.74±0.73比1.38±0.78,P＜0.001)、氧化型低密度脂蛋白水平(595.5±194.8比440.3±175.0μg/L,P＜0.001)均显著升高.低密度脂蛋白循环免疫复合物水平分别同血浆总胆固醇、甘油三酯、低密度脂蛋白胆固醇、脂蛋白(a)及载脂蛋白B正相关;同载脂蛋白AⅠ负相关.氧化型低密度脂蛋白水平亦分别同血浆总胆固醇、低密度脂蛋白胆固醇、脂蛋白(a)及载脂蛋白B正相关.氧化型低密度脂蛋白水平与低密度脂蛋白循环免疫复合物亦呈正相关(r=0.313,P＜0.005).结果提示,氧化型低密度脂蛋白及循环免疫复合物升高是动脉粥样硬化发生的危险因素.     

血浆氧化型低密度脂蛋白水平与低密度脂蛋白循环免疫复合物的相关性

为探讨血浆氧化型低密度脂蛋白水平与低密度脂蛋白循环免疫复合物间关系。分别建立了以抗人IgG为包被抗体、酶标抗载脂蛋白B为检测抗体的低密度脂蛋白循环免疫复合物酶联免疫吸附试验;以抗氧化型低密度脂蛋白为包被抗体、酶标抗载脂蛋白B为检测抗体的氧化型低密度脂蛋白酶联免疫吸附试验。同时测定60例冠心病患者及50例对照人群低密度脂蛋白循环免疫复合物、氧化型低密度脂蛋白水平并进行相关性分析。结果发现,冠心病患者甘油三酯、脂蛋白(a)和载脂蛋白B水平均显著升高;高密度脂蛋白胆固醇和载脂蛋白AI水平降低;且低密度脂蛋白循环免疫复合物(2.74±0.73比1.38±0.78,p<0.001)、氧化型低密度脂蛋白水平(595.5±194.8比440.3±175.0μg/L,p<0.001)均显著升高。低密度脂蛋白循环免疫复合物水平分别同血浆总胆固醇、甘油三酯、低密度脂蛋白胆固醇、脂蛋白(a)及载脂蛋白B正相关;同载脂蛋白A_Ⅰ负相关。氧化型低密度脂蛋白水平亦分别同血浆总胆固醇、低密度脂蛋白胆固醇、脂蛋白(a)及载脂蛋白B正相关。氧化型低密度脂蛋白水平与低密度脂蛋白循环免疫复合物亦呈正相关(r=0.313,p<0.005)。结果提示,氧化型低密度脂蛋白及循环免疫复合物升高是动脉粥样硬化发生的危险因素。     

低密度脂蛋白免疫复合物与2型糖尿病合并冠心病的关系

目的 探讨血清低密度脂蛋白免疫复合物(LDL-ICs)在2型糖尿病合并冠心病(DM-CHD)中的作用.方法 测定60例2型糖尿病患者和30例正常时照者的LDL-ICs水平,采用酶联免疫吸附法测定.结果 DM-CHD组血清LDL-ICs为70.24AU±12.37 AU与正常时照(NC)组27.56 AU±9.48 AU相比增高明显(P<0.001);较2型糖尿病无冠心病(DM)组45.44 AU±12.32 AU亦增高(P<0.05).2型糖尿病患者LDL-ICs浓度与其他因素的直线相关回归分析显示:LDL-Ics与糖化血红蛋白(HbAlc)、总胆固醇(TC)、三酰甘油(TG)浓度之阎呈显著正相关(r值分别为0.70、0.58、0.37,P<0.05);与血清高密度脂蛋白(HDL-C)浓度之间呈现显著负相关(r=-0.76,P<0.05).结论 2型糖尿病伴有冠心病的患者,血清LDL-ICs显著升高.在2型糖尿病患者中,LDL-ICs与TG、TC、HDL-C、HbAlc之间呈现显著相关性.LDL-ICs可能是糖尿病冠心病的危险因素.     

糖尿病患者血清低密度脂蛋白组成异常及氧化修饰水平升高

为探讨糖尿病患者动脉粥样硬化的高发机制，检测了44例糖尿病患者和50例健康者血脂、载脂蛋白、低密度脂蛋白中甘油三酯、总胆固醇和氧化型低密度脂蛋白水平。结果发现低密度脂蛋白中甘油三酯及甘油三酯／胆固醇比值升高为糖尿病患者脂质异常的显著特征。血清氧化型低密度脂蛋白水平及氧化程度显著升高，其氧化程度同低密度脂蛋白脂质组成相关。提示糖尿病患者动脉粥样硬化的高发生率同其低密度脂蛋白组成异常及氧化修饰水平相关联。     

急性冠状动脉综合征患者血浆氧化型低密度脂蛋白、高敏C反应蛋白与血管内皮损伤的关系

目的观察急性冠状动脉综合征患者外周血浆氧化型低密度脂蛋白、高敏C反应蛋白、循环内皮细胞计数和一氧化氮的变化,探讨氧化型低密度脂蛋白与高敏C反应蛋白的相关性,以及两者与血管内皮损伤的关系,研究其在急性冠状动脉综合征发生和发展中的意义。方法急性冠状动脉综合征患者51例,临床及选择性冠状动脉造影排除冠心病20例为对照组。测定外周血浆中的氧化型低密度脂蛋白、高敏C反应蛋白、循环内皮细胞计数和一氧化氮水平。结果急性冠状动脉综合征组氧化型低密度脂蛋白、高敏C反应蛋白、循环内皮细胞计数较对照组明显升高,分别为氧化型低密度脂蛋白(686±168μg/L比349±172μg/L,P<0.01)、高敏C反应蛋白(6.15±1.75mg/L比1.53±1.64mg/L,P<0.01)、循环内皮细胞计数[(8.9±1.6)×106个/L比(2.4±0.4)×106个/L,P<0.01]。急性冠状动脉综合征组一氧化氮水平较对照组明显降低(52.2±16.5μmol/L比77.3±21.0μmol/L,P<0.05)。血浆氧化型低密度脂蛋白与循环内皮细胞计数(r=0.781,P<0.001)和一氧化氮(r=0.792,P<0.001)均呈正相关,血浆高敏C反应蛋白与循环内皮细胞计数(r=0.776,P<0.001)和一氧化氮(r=0.897,P<0.001)也均呈正相关,血浆氧化型低密度脂蛋白与高敏C反应蛋白呈正相关(r=0.768,P<0.001),血浆循环内皮细胞计数与一氧化氮呈正相关(r=0.951,P<0.001)。结论血浆氧化型低密度脂蛋白、高敏C反应蛋白可能与血管内皮损伤有关,相互协同作用参与了急性冠状动脉综合征的发病过程。     

慢作用抗风湿药对类风湿关节炎患者血脂的影响

目的 探讨类风湿关节炎患者抗风湿治疗对血脂及疾病活动相关指标的影响. 方法 选择在我院治疗的符合1987年美国风湿病学会诊断标准的类风湿关节炎患者82例,联合应用慢作用药甲氨蝶呤、柳氮磺胺吡啶、硫酸羟氯喹治疗,以健康体检者79例作为对照.分别测定健康对照组、类风湿关节炎组治疗前及治疗后12个月的疾病活动分数(DAS28)、血沉、C-反应蛋白、血脂.结果类风湿关节炎患者血胆崮醇、低密度脂蛋白胆固醇、三酰甘油治疗前较对照组高(均P<0.01);高密度脂蛋白治疗前较对照组低(P<0.01);治疗12个月后,类风湿关节炎患者疾病活动分数、血沉、C-反应蛋白与治疗前比较明显降低[(6.7±0.6)与(2.1±0.9)、(62±18)mm/h与(13±9)mm/h、(2.2±0.3)mg/L与(0.3±0.2)mg/L,均P<0.01];血高密度脂蛋白与治疗前比较明显增高,分别为(1.0±0.1)mmol/L与(1.5±0.3)mmol/L(P<0.01). 结论 病情活动的类风湿关节炎患者血脂水平异常,控制炎症过程的药物,使疾病活动分数、血沉或C-反应蛋白下降的同时,导致血清高密度脂蛋白的水平升高,可能使类风湿关节炎患者动脉粥样硬化及心血管事件的风险降低.     

血脂水平与类风湿关节炎伴2型糖尿病患者疾病活动程度的影响

目的探讨血脂水平与类风湿关节炎伴2型糖尿病患者疾病活动程度的影响。方法收集2016年1月—2018年5月类风湿关节炎伴2型糖尿病的50例患者,定义为研究组。选择单纯2型糖尿病的50例患者作为对照组。对比两组血脂、血糖水平对比;两组血清炎症指标水平。结果对照组总胆固醇、甘油三酯、低密度脂蛋白、空腹血糖、糖化血红蛋白水平明显低于研究组,比较差异有统计学意义(P0.05);研究组和对照组高密度脂蛋白比较差异无统计学意义(P0.05);研究组CRP及ESR水平明显高于对照组,比较差异有统计学意义(P0.05)。结论类风湿关节炎伴2型糖尿病患者血脂水平及血糖水平低于单纯2型糖尿病患者,可能与体内高水平炎症状态有关。     

对氧磷脂酶1、载脂蛋白E基因多态性与2型糖尿病患者氧化型低密度脂蛋白水平相关

采用限制性片段长度多态性(RFLP)检测福建地区192例2型糖尿病组、116例单纯动脉粥样硬化(AS)患者和105名正常人对氧磷脂酶1(PON1)、载脂蛋白E(ApoE)基因多态性,血清氧化型低密度脂蛋白(Ox-LDL)水平采用酶联免疫吸附法检测.结果 显示,2型糖尿组Ox-LDL高于单纯AS组及正常对照组[(754.2±279.9对526.1±186.2和421.1±163.2)μg/L,P<0.01].在2型糖尿患者中,PON1基因QQ型Ox-LDL水平高于QR和RR型[(846.6±147.5对763.4±126.7和713.2±132.4)μg/L,P<0.01];ApoE基因ε3/4+ε4/4型Ox-LDL水平高于ε3/3和ε2/2+ε2/3型[(824.3±173.5对741.6±182.5和718.3±167.5)μg/L,P<0.05],而在单纯AS患者中未发现这种差别.多元同归分析显示,病程、PON1、ApoE是2型糖尿患者血浆Ox-LDL增高的危险因素.     

颈动脉粥样斑块和脂质代谢的关系

目的探讨颈动脉粥样斑块和脂质代谢的关系方法检测９８例老年颈动脉粥样斑块患者和９８例正常老年人血浆中血脂、氧化低密度脂蛋白、丙二醛水平结果病例组中,总胆固醇、低密度脂蛋白胆固醇、载脂蛋白Ｂ、氧化低密度脂蛋白、丙二醛均高于对照组（Ｐ＜００５）,载脂蛋白Ａ低于对照组（Ｐ＜００５）。结论脂质代谢异常,氧化低密度脂蛋白、丙二醛等参与老年人颈动脉粥样斑块的形成。     

高脂血症患者脂代谢紊乱对补体表达及活化的影响

目的探讨脂代谢紊乱对补体表达及其活化的影响。方法选择高脂血症患者并根据合并症分为单纯高脂血症组和高脂血症合并心脑血管病变组,同期设立正常对照组,分别测定并分析各组血清补体成分C3、C4、P因子、可溶性终末补体复合物及炎症因子肿瘤坏死因子α和白细胞介素6水平。结果单纯高脂血症组及合并心脑血管病变组血清补体C3水平均显著高于对照组(1.57±0.41 g/L、1.60±0.40 g/L比1.30±0.27 g/L,P<0.05),单纯高脂血症组血清P因子水平较对照组显著升高(0.46±0.08 g/L比0.38±0.07 g/L,P<0.01);合并心脑血管病变组可溶性终末补体复合物水平显著高于单纯高脂血症组和对照组(298±110 mg/L比233±101 mg/L、228±84mg/L,P<0.05);合并心脑血管病变组肿瘤坏死因子α水平显著高于单纯高脂血症组和对照组(5.66±1.54 g/L比4.45±1.47 g/L、4.42±1.07 g/L,P<0.01),单纯高脂血症组、合并心脑血管病变组白细胞介素6水平较对照组升高(0.139±0.017 g/L、0.143±0.024 g/L比0.120±0.025 g/L,P<0.05,P<0.01)。相关分析显示,血清C3、C4、P因子与总胆固醇、甘油三酯、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇呈正相关(P因子与甘油三酯除外);可溶性终末补体复合物与收缩压、舒张压和肿瘤坏死因子α呈正相关,与血脂水平无相关;肿瘤坏死因子α、白细胞介素6与血脂水平无相关。结论高脂血症患者外周循环血中补体成分明显升高,其浓度与血脂水平呈正相关;可溶性终末补体复合物与血脂无相关,但与动脉病变有关。     

Ethnicity may be a reason for lipid changes and high Lp(a) levels in rheumatoid arthritis

There are so many studies that suggest the changes in lipid profiles and lipoprotein (a) [Lp(a)] are associated with early atherosclerosis in rheumatoid arthritis (RA). But there are some opposite studies also. Because of marked ethnicity differences in the distribution of Lp(a), we aimed to investigate the associations of Lp(a) levels and lipid changes in Turkish RA patients. There were 30 women and 20 men, a total of 50 patients with RA (mean age 47.6±13.2 years), included and 21 healthy women and 14 healthy men (mean age 45.7±14.5 years) were recruited as a control (C) group. Serum Lp(a), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were analysed for each group. Analysis of six different studies was performed. In the RA and C groups, mean serum Lp(a) levels were 39.7±64.4 and 10.5±13.4 mg/dl, respectively (P=0.001). Mean TC levels were 189.2±142.5 and 174.0±29.3 mg/dl (P=0.294), mean TG levels were 121.4±65.4 and 106.5±80.0 mg/dl (P=0.030), mean HDL-C levels were 44.5±10.0 and 47.7±4.8 mg/dl (P=0.014) and mean LDL-C levels were 94.3±35.3 and 102.0±24.6 mg/dl (P=0.98), respectively. Analysis of the six studies showed Lp(a) level was higher and HDL level was lower in RA patients than in healthy controls. Patients with RA may have altered lipid profiles from one country to another one. Especially in Turkey, higher serum Lp(a), lower HDL-C and higher TG levels may be found in RA patients instead of some findings of other countries showing different results. Ethnicity may be a reason for these findings.     

Increased circulating malondialdehyde-modified LDL levels in patients with coronary artery diseases and their association with peak sizes of LDL particles

Recent establishment of a sensitive ELISA system using antibodies against malondialdehyde-modified low density lipoprotein (MDA-LDL) made it possible to determine the circulating oxidized lipoprotein levels. Here, we investigated the serum levels of MDA-LDL in 62 patients with coronary artery disease (CAD) compared with the levels in 42 patients without CAD [groups CAD(+) and CAD(-), respectively], which are adjusted for age, serum total cholesterol, LDL and high density lipoprotein cholesterol, and triglyceride levels. Serum MDA-LDL levels were 113.4+/-49.1 IU/L in CAD(+), which were significantly higher than the levels in CAD(-) (85.2+/-22.5 IU/L, P<0.0005). The ratio of MDA-LDL/LDL cholesterol was 0.95+/-0.32 in CAD(+), indicating a significant increase compared with the ratio in CAD(-) (0.68+/-0.19, P<0.0005). The positive correlation of MDA-LDL level and the ratio of MDA-LDL/LDL cholesterol with intima-media thickness in carotid arteries was observed. Age was not clearly associated with the MDA-LDL level (P=0.865). The serum MDA level was positively correlated with LDL cholesterol (P<0.0001) and with triglycerides (P<0.001) and negatively correlated with high density lipoprotein cholesterol (P<0.05). Furthermore, the MDA-LDL level was negatively correlated with the peak size of the LDL particle (P<0.01). The LDL subclasses that were identified by using the sera collected from the subjects by sequential ultracentrifugation showed that the ratios of MDA-LDL/apolipoprotein B in LDL3 and LDL4 were nearly 3-fold higher than those in LDL1 and LDL2 for CAD(+) and CAD(-). These results indicate that the circulating MDA-LDL level is increased in CAD(+), independent of the serum LDL cholesterol level but in association with the peak size of LDL particles. The measurement of serum MDA-LDL level may be useful for the identification of patients with advanced atherosclerosis.     

Serum immunoreactive erythropoietin in rheumatoid arthritis: impaired response to anemia

Serum immunoreactive erythropoietin (EP) levels were measured in 116 patients with rheumatoid arthritis (RA) and 20 control patients with iron deficiency anemia. Serum EP levels were significantly higher in the 46 anemic RA patients than in the 70 nonanemic RA patients (mean ± 1 SD 31.0 ± 19.8 mU/ml versus 16.8 ± 12.4 mU/ml; P < 0.0001). Furthermore, although a significant inverse correlation between the serum EP level and the hemoglobin value was present in the anemic RA patients (r = −0.57, P < 0.0001), the regression coefficient describing the relationship between serum EP and hemoglobin was significantly lower for the anemic RA patients than for patients with iron deficiency anemia (F = 6.01, P < 0.025).     

Increased levels of autoantibodies against copper-oxidized low density lipoprotein,malondialdehyde-modified low density lipoprotein and cardiolipin in patients with rheumatoid arthritis

Objectives. To analyse the association of autoantibodiesagainst cardiolipin (CL) and oxidized low density lipoproteins[copper-oxidized low density lipoprotein (oxLDL), malondialdehyde-modifiedLDL (MDA-LDL)] with rheumatoid arthritis (RA) and cardiovascularcomplications. Methods. One hundred and twenty-one patients with RA wereconsecutively included. Autoantibodies were determined by ELISA.Healthy individuals from the same region were used as controls. Results. Levels of IgG, IgM and IgA antibodies against MDA-LDLand CL, as well as IgG and IgA antibodies against oxLDL wereincreased in the patients (P<0.01). The prevalence of IgG,IgM and IgA antibodies against CL was higher than in the normalpopulation (74, 82 and 14%, respectively). The prevalenceof IgG and IgA antibodies against oxLDL was also significantlyincreased (35 and 25%, respectively) and so was the prevalenceof IgG and IgM antibodies against MDA-LDL (17 and 26%, respectively)compared with controls. The levels of IgM and IgA antibodiesagainst aCL and IgM against MDA-LDL were increased in patientswith extra-articular manifestations. Patients who developedmyocardial infarction had a higher prevalence of IgG antibodiesagainst MDA-LDL (P=0.04). There were substantial correlationsbetween the levels of antibodies against oxLDL, MDA-LDL andCL. Conclusions. RA patients had increased levels and prevalenceof autoantibodies against CL, oxLDL and MDA-LDL, with associationsto severity of disease and cardiovascular complications. KEY WORDS: Autoantibody, Rheumatoid arthritis, Cardiolipin, oxLDL, MDA-LDL, Cardiovascular disease. Correspondence to: A. K. Lefvert, Immunological Research Unit,CMM L8:03, Karolinska Hospital, 171 76 Stockholm, Sweden.     

Anti-agalactosyl IgG antibodies in Thai patients with rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis

This study was performed to determine the prevalence of anti-agalactosyl IgG antibodies in Thai patients with RA, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), and determine the sensitivity and specificity of anti-agalactosyl IgG antibodies in the diagnosis of RA in comparison with IgM-rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Serum samples were obtained from 100 patients with RA, 50 cases of SLE, 50 cases of SSc, and 100 healthy controls and analyzed for the presence of anti-agalactosyl IgG antibodies, IgM-RF and anti-CCP antibodies. A serum value greater than mean + 2 standard deviation of normal value of anti-agalactosyl IgG antibodies and anti-CCP antibodies was considered positive. The prevalence of anti-agalactosyl IgG antibodies in RA, SLE, and SSc patients was 88.0%, 14.0%, and 12.0%, respectively. The serum level of anti-agalactosyl IgG antibodies in patients with RA (227.10 ± 353.64 AU/mL) was significantly higher than those in SLE (11.84 ± 52.04 AU/mL), SSc (18.85 ± 99.60 AU/mL), and healthy controls (2.14 ± 1.97 AU/mL), (p < 0.001). There was a good correlation between the log serum level of anti-agalactosyl IgG antibodies and IgM-RF (r = 0.92, p < 0.001), anti-CCP antibodies and IgM-RF (r = 0.49, p < 0.001), and anti-agalactosyl IgG antibodies and anti-CCP antibodies (r = 0.55, p < 0.001). The sensitivity and specificity in the diagnosis of RA was 88.00% and 96.00% for anti-agalactosyl IgG antibodies, 90.00% and 99.00% for anti-CCP antibodies, and 91.00% and 95.00% for IgM-RF, respectively. The serum level of anti-agalactosyl IgG antibodies was significantly higher in RA than in SLE, SSc, and healthy controls. There was a good correlation between serum levels of anti-agalactosyl IgG antibodies, anti-CCP antibodies, and IgM-RF. These three tests had comparable sensitivity and specificity.     

Elevated plasma asymmetric dimethyl‐L‐arginine levels are linked to endothelial progenitor cell depletion and carotid atherosclerosis in rheumatoid arthritis

Objective

Similarities between rheumatoid arthritis (RA) and atherosclerosis include endothelial dysfunction (an antecedent of plaque formation) and depletion of circulating bone marrow–derived endothelial progenitor cells. This study was undertaken to test the hypothesis that endothelial progenitor cell depletion and subclinical atherosclerosis in RA may be related to accumulation of an endogenous inhibitor of nitric oxide (NO) synthesis, asymmetric dimethyl‐L ‐arginine.

Methods

We studied 30 patients with active RA and 20 age‐ and sex‐matched healthy controls. Exclusion criteria were clinically evident atherosclerosis, traditional risk factors, hyperhomocysteinemia, and renal dysfunction. The blood endothelial progenitor cell count was assayed by flow cytometry and expressed as a percentage of lymphocytes. Plasma L ‐arginine, asymmetric dimethyl‐L ‐arginine, and symmetric dimethyl‐L ‐arginine were measured with liquid chromatography–mass spectrometry. Mean carotid intima‐media thickness (IMT) was assessed by B‐mode ultrasound.

Results

In RA patients, we found elevated levels of asymmetric dimethyl‐L ‐arginine (mean ± SD 0.49 ± 0.07 μmoles/liter versus 0.40 ± 0.07 μmoles/liter in controls; P < 0.001), a depressed endothelial progenitor cell count (0.039 ± 0.025% versus 0.063 ± 0.035%; P < 0.05), and increased IMT (0.65 ± 0.13 mm versus 0.55 ± 0.10 mm; P < 0.01), with no differences in levels of L ‐arginine or symmetric dimethyl‐L‐ arginine. The endothelial progenitor cell count was inversely correlated with the level of asymmetric dimethyl‐L ‐arginine. IMT was positively related to the ratio of asymmetric dimethyl‐L ‐arginine to L ‐arginine and negatively related to the endothelial progenitor cell count, in univariate and multivariate analyses.

Conclusion

Plasma asymmetric dimethyl‐L ‐arginine levels are elevated in RA patients free of cardiovascular disease or risk factors. Asymmetric dimethyl‐L ‐arginine accumulation may contribute to endothelial progenitor cell depletion via depressed NO‐dependent endothelial progenitor cell mobilization and/or survival, with consequent impairment of endothelial progenitor cell–mediated endothelial repair, which can promote atherogenesis in RA.

     

Merging Veterans Affairs rheumatoid arthritis registry and pharmacy data to assess methotrexate adherence and disease activity in clinical practice

Objective

The Veterans Affairs (VA) Rheumatoid Arthritis (VARA) registry and the VA Pharmacy Benefits Management database were linked to determine the association of methotrexate (MTX) adherence with rheumatoid arthritis (RA) disease activity.

Methods

For each patient, the medication possession ratio (MPR) was calculated for the first episode of MTX exposure of a duration of ≥12 weeks for both new and established MTX users. High MTX adherence was defined as an MPR ≥0.80 and low MTX adherence was defined as an MPR <0.80. For each patient, the mean Disease Activity Score with 28 joints (DAS28) score, erythrocyte sedimentation rate (ESR), and C‐reaction protein (CRP) level observed during registry followup were compared in high‐ versus low‐adherence groups.

Results

In 455 RA patients, the prescribed doses of MTX (mean ± SD 16 ± 4 mg versus 16 ± 4 mg; P = 0.6) were similar in high‐adherence patients (n = 370) in comparison to low‐adherence patients (n = 85). However, the actual observed MTX doses taken by patients were significantly higher in the high‐adherence group (mean ± SD 16 ± 5 mg versus 11 ± 3 mg; P < 0.001). DAS28 (mean ± SD 3.6 ± 1.2 versus 3.9 ± 1.5; P < 0.02), ESR (mean ± SD 24 ± 18 versus 29 ± 24 mm/hour; P = 0.05), and CRP level (mean ± SD 1.2 ± 1.3 versus 1.6 ± 1.5 mg/dl; P < 0.03) were lower in the high‐adherence group compared to those with low MTX adherence. These variances were not explained by differences in baseline demographic features, concurrent treatments, or whether MTX was initiated before or after VARA enrollment.

Conclusion

High MTX adherence was associated with improved clinical outcomes in RA patients treated with MTX. Adjustment for potential confounders did not alter the estimated effect of adherence. These results demonstrate the advantages of being able to merge clinical observations with pharmacy databases to evaluate antirheumatic drugs in clinical practice.     

The S447X variant of lipoprotein lipase gene is inversely associated with severity of coronary artery disease

Hyperlipidemia is a major risk factor for coronary artery disease (CAD). Lipoprotein lipase (LPL) is an important enzyme in lipoprotein metabolism. S447X polymorphism of the LPL gene has been implicated in the pathogenesis of CAD. Carriers of X447 allele were reported to have lower triglyceride and higher high-density lipoprotein cholesterol levels as well as a reduced risk of CAD. We hypothesized that S447X gene polymorphism might have a protective effect for CAD. A total of 178 subjects (mean age 42.97 ± 6.5 years) who underwent coronary angiography for clinical indications were included in the study. The patients had been referred for evaluation of chest pain and/or abnormal stress tests, and were selected consecutively. Gensini scores were used to assess the severity of CAD; 97 patients were diagnosed with angiographically proven CAD, and 81 subjects did not display significant CAD (≥70%) angiographically. Genotyping of LPL S447X polymorphism was performed by real-time polymerase chain reaction amplification and fluorescent probe melting point analysis on the light cycler. The minor allele frequencies of LPL 447X allele were 11.1% and 6.2% among subjects without CAD compared with CAD subjects (P = 0.081) and 447X allele had favorable effects on lipid levels among CAD patients; 447X homozygotes and heterozygotes displayed lower total cholesterol (171 ± 37 vs 208 ± 48 mg/dl, P = 0.02), lower triglycerides (121 ± 72 vs 184 ± 86 mg/dl, P = 0.02), lower low-density lipoprotein cholesterol (102 ± 27 vs 129 ± 39 mg/dl, P = 0.03). Gensini scores were significantly lower among the heterozygotes and homozygotes of LPL 447X allele than in the LPL S447 homozygotes (15 ± 23 vs 25 ± 30, P = 0.048). S447X polymorphism of LPL gene may have a protective role for the severity of CAD. The beneficial effects of S447X polymorphism of the LPL gene may be through its favorable effects on lipid levels.     

Oxidised LDL/LDL-cholesterol ratio and coronary artery calcification in haemodialysis patients

Background and aimsSerum malondialdehyde-modified low-density lipoprotein (MDA-LDL) and MDA-LDL/LDL-cholesterol (LDL-c) ratio are risk factors for arteriosclerosis and cardiovascular disease (CVD). However, no information is available on these parameters or their associations with coronary artery calcification (CAC) in haemodialysis (HD) patients.Methods and resultsFifty-seven HD patients and 26 control subjects were included in this cross-sectional study. Serum MDA-LDL concentrations and MDA-LDL/LDL-c ratios were examined. HD patients had significantly higher MDA-LDL/LDL-c ratios than the controls (105.1 ± 27.5 vs. 81.4 ± 18.9 mU/mg, P < 0.001); however, there was no significant difference in serum MDA-LDL levels between the 2 groups. CAC scores were examined only in HD patients and their possible associations with the clinical/laboratory data were analysed. Analysis of HD patients showed that MDA-LDL/LDL-c ratio has an association with presence of CVD, CAC score, HD duration, MDA-LDL, or haemoglobin A_1C. In addition, the CAC score was positively correlated with serum MDA-LDL level (P = 0.048) and MDA-LDL/LDL-c ratio (P = 0.006). Furthermore, multivariate logistic regression analysis showed that MDA-LDL/LDL-c ratio (β = 0.04, P = 0.003) and HD duration (β = 0.16, P = 0.007) were independently associated with CAC score.ConclusionThe MDA-LDL/LDL-c ratio of HD patients was significantly higher than that of non-HD subjects and was independently associated with the CAC score. Therefore, this ratio could be an important risk factor for CAC in HD patients.     

Rotational vs. standard coronary angiography: An image content analysis

Objective : To evaluate the clinical utility of images acquired from rotational coronary angiographic (RA) acquisitions compared to standard “fixed” coronary angiography (SA). Background : RA is a novel angiographic modality that has been enabled by new gantry systems that allow calibrated automatic angiographic rotations and has been shown to reduce radiation and contrast exposure compared to SA. RA provides a dynamic multiple‐angle perspective of the coronaries during a single contrast injection. Methods : The screening adequacy, lesion assessment, and a quantitative coronary analysis (QCA) of both SA and RA were compared by independent blinded review in 100 patients with coronary artery disease (CAD). Results : SA and RA recognize a similar total number of lesions (P = 0.61). The qualitative assessment of lesion characteristics and severity between modalities was comparable and lead to similar clinical decisions. Visualization of several vessel segments (diagonal, distal RCA, postero‐lateral branches and posterior‐descending) was superior with RA when compared to SA (P < 0.05). A QCA comparison (MLD, MLA, LL, % DS) revealed no difference between SA and RA. The volume of contrast (23.5 ± 3.1 mL vs. 39.4 ± 4.1; P = 0.0001), total radiation exposure (27.1 ± 4 vs. 32.1 ± 3.8 Gycm²; P = 0.002) and image acquisition time (54.3 ± 36.8 vs. 77.67 ± 49.64 sec; P = 0.003) all favored RA. Conclusion : Coronary lesion assessment, coronary screening adequacy, and QCA evaluations are comparable in SA and RA acquisition modalities in the diagnosis of CAD however RA decreases contrast volume, image acquisition time, and radiation exposure. © 2009 Wiley‐Liss, Inc.