Changes in lipid profile during infliximab and corticosteroid treatment in rheumatoid arthritis

OBJECTIVE: To evaluate the effects of infliximab and corticosteroid treatment on the lipid profile in patients with active rheumatoid arthritis (RA). METHODS: Infliximab infusions were given at weeks 0, 2, 6 and then every 8 weeks. Before each infusion, disease activity parameters (Disease Activity Index 28-Joint Score (DAS28)) C reactive protein (CRP) and lipid levels (total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, apolipoprotein A1 (apo A1) and apolipoprotein B) were measured in 80 consecutive patients with RA, who completed the study period of 48 weeks. Longitudinal analyses were used to investigate (1) the course of lipid levels over a period of time and (2) the relationship between lipids, prednisone dose and disease activity. RESULTS: Infliximab treatment causes a significant reduction in disease activity and a concomitant decrease in prednisone dose. Although they initially improved significantly, all lipid levels had returned to baseline levels after 48 weeks, except for apo A1. Longitudinal analyses revealed significant yet opposite associations between lipid levels and disease activity and between lipid levels and prednisone dose. DAS28 improvement by 1 point was associated with an increase of 0.016 mmol/l (0.618 mg/dl) total cholesterol and 0.045 mmol/l (1.737 mg/dl) HDL-cholesterol. Reduction of 10 mg prednisone was associated with a decrease of 0.04 mmol/l (1.544 mg/dl) total cholesterol and 0.16 mmol/l (6.177 mg/dl) HDL-cholesterol. CONCLUSION: Overall, no changes in serum lipid levels were observed after 48 weeks of infliximab treatment. The initial beneficial effects of infliximab on the lipid profile, by means of a reduction of disease activity, are attenuated by a concomitant decrease in prednisone dose.     

Impact of TNF inhibition on insulin resistance and lipids levels in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have increased cardiovascular mortality. TNF-α is a critical mediator of inflammation and metabolic response in patients with RA. Increased insulin resistance and dyslipidemia were known risk factors in patients with active RA, however, the regulation of these metabolic parameters by TNF-α is poorly understood. Neutralization of TNF-α with infliximab offers a unique opportunity to study TNF-α-mediated regulation of these metabolic parameters in RA. The aim of the study was to assess the in vivo TNF-α-mediated regulation of insulin resistance and lipids levels in RA. Nineteen patients with active RA treated with infliximab were prospectively followed for 14 weeks. Plasma lipids levels and insulin resistance were measured at baseline, 6 and 14 weeks after infliximab treatment. At week 14, the disease activity (DAS-28 score) improved significantly (p < 0.000), with a significant reduction in both C-reactive protein (p = 0.007) and erythrocyte sedimentation rate (p = 0.006) levels. The body weight did not change during the study period. After infliximab treatment, insulin resistance improved as reflected by the significant reduction in the Homeostasis Model Assessment Index. Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and apolipoprotein B (apoB) levels all increased significantly from baseline. Nonetheless, the atherogenic index, LDL-cholesterol/HDL-cholesterol ratio, and the LDL/apoB ratio remained unchanged. Infliximab improves insulin sensitivity and alters lipid profile in patients with active RA.     

Effects of infliximab treatment on lipoprotein profile in patients with rheumatoid arthritis and ankylosing spondylitis

OBJECTIVE: To investigate the longterm effects of the anti-tumor necrosis factor (TNF) therapy infliximab, a drug known to reduce disease activity in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: Eighty-two patients (50 with RA, 32 with AS) aged 17-77 years were enrolled. All patients were treated with intravenous infliximab. Lipid profile was assessed at baseline and after 6 months of treatment. RESULTS: Disease activity significantly decreased in patients with RA and AS at the end of infliximab therapy. Infliximab treatment significantly increased total cholesterol from 206 to 216 mg/dl (p < 0.05) and triglycerides from 109 to 122 mg/dl (p < 0.05). The low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol did not change during treatment. Furthermore, the total cholesterol/HDL cholesterol and triglycerides/HDL cholesterol ratios did not change significantly. CONCLUSION: The influence of infliximab treatment on lipid profile seems to be neutral, since neither LDL cholesterol levels nor total cholesterol/HDL cholesterol and triglycerides/HDL cholesterol ratios changed significantly during the 6-month therapy. Our findings suggest that the favorable effect of infliximab treatment on cardiovascular comorbidity may not be mainly mediated by the effects on the lipid profile, but further investigations are needed in order to confirm this hypothesis.     

Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis

BACKGROUND: Glucocorticoids induce hypercholesterolaemia, a cardiovascular risk factor, in patients with diseases other than rheumatoid arthritis (RA), but the data in RA are contradictory. OBJECTIVE: To determine the effects of antirheumatic treatment, including prednisolone (combination) therapy on total and high density lipoprotein (HDL) cholesterol levels in RA, taking disease activity into account. METHODS: HDL cholesterol and total cholesterol levels were determined in:(a) established RA (b) two cohorts with early active RA, (c) a previously conducted 56 week trial among patients with early RA comparing the value of intensive combination therapy (that included glucocorticoids) with sulfasalazine alone (COBRA trial). RESULTS: In established RA total cholesterol levels were only slightly raised, irrespective of disease activity. However, HDL cholesterol was significantly higher in patients in remission than in patients with active disease. In contrast, in active early RA at baseline total cholesterol was low normal: between 4.6 and 5.1 mmol/l in the different populations. The level of HDL cholesterol was highly dependent on the duration of storage. In both COBRA groups total cholesterol increased by a mean of 0.6 mmol/l. HDL cholesterol increased by more than 50% after treatment, leading to an improvement of the total cholesterol/HDL ratio (atherogenic index). This increase (and index improvement) was much more rapid in the group receiving combination treatment. A similar pattern was seen in the 2001 cohort with early RA. In all the groups with active disease HDL and total cholesterol levels correlated inversely with disease activity. CONCLUSION: In established, but especially in early RA, disease activity is accompanied by atherogenic lipid levels. This dyslipidaemia can be rapidly reversed by aggressive antirheumatic treatment including glucocorticoids.     

Modulation of lipoprotein plasma concentrations during long-term anti-TNF therapy in patients with active rheumatoid arthritis

OBJECTIVE: Durable blockade of tumour necrosis factor-alpha (TNF-alpha) in patients with rheumatoid arthritis (RA) suppresses disease activity and its progression. Cardiovascular diseases are 1.5-2-fold more frequent in RA patients than in the general population. Although TNF-alpha has well-established effects on lipid metabolism, the long-term effects of TNF-alpha blockade on lipid pattern are still unclear. In the present study, we investigated the effects of 1-year therapy with anti-TNF on the lipid profile of RA patients. METHODS: Disease activity (DAS28) and plasma lipoproteins concentrations (total, HDL and LDL-cholesterol, triglycerides, ApoA, ApoB) were assessed in 55 RA patients and 55 controls. The whole RA group was followed up for 6 months, and 31 of the patients were followed up for 1 year. RESULTS: In RA patients, DAS28 decreased after 2 weeks from the start of therapy (p<0.001) and remained low during the entire study duration. Short-term effects of anti-TNF on plasma lipid concentrations seemed beneficial and anti-atherogenic. However, these changes did not persist: plasma concentrations of total and LDL-cholesterol and the atherogenic index increased after 6 months and 1 year from the start of therapy. During therapy, the changes in disease activity and inflammatory status were inversely correlated with changes in plasma total and HDL cholesterol levels and positively correlated with the variation of atherogenic index. CONCLUSION: We conclude that one-year therapy with infliximab is likely to lead to a more pro-atherogenic pattern of the plasma lipids concentrations. However, the overall impact of these changes on the cardiovascular risk is more complex, considering the strong anti-inflammatory effects of anti-TNF drugs.     

Association of total cholesterol versus other serum lipid parameters with the short-term prediction of cardiovascular outcomes: Tehran Lipid and Glucose Study.

OBJECTIVE: The aim of this study was to evaluate and compare the role of lipid markers including total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol with lipid indices (total/HDL cholesterol, LDL-cholesterol/HDL-cholesterol and non-HDL-cholesterol) as predictors of cardiovascular outcomes in adults over 30 years. RESEARCH DESIGN AND METHOD: In a nested case-control study, 207 cardiovascular events among participants of the Tehran Lipid and Glucose Study (TLGS) were documented during 3 years of follow-up. Those cases that were free of cardiovascular disease at baseline (132 subjects) were matched to 264 controls for age and sex. In all subjects, demographic and clinical data including blood pressure and anthropometric measurements as well as serum lipids, fasting and 2-h plasma glucose were obtained from the database of the TLGS. We estimated the relative risk for each lipid parameter in a multiple stepwise regression model after adjustment for family history of premature coronary heart disease, smoking, systolic and diastolic blood pressure, fasting and 2-h plasma glucose and waist-to-hip ratio. RESULTS: The relative risks associated with an increase of approximately 1 SD of independent lipid predictors in the multivariate model were as follows: total cholesterol, 1.6 (1.2-2.1), SD=1.3 mmol/l; LDL-cholesterol 1.5 (1.1-2.0), SD=1 mmol/l; non-HDL-cholesterol 1.6 (1.2-2.1), SD=1.2 mmol/l and cholesterol/HDL-cholesterol 1.5 (1.1-2.0), SD=1.8. Comparison of these four independent variables with receiver-operating characteristic curve analysis showed no significant difference in their predictive power for cardiovascular outcome. There was no association between HDL-cholesterol, triglyceride and LDL/HDL cholesterol and cardiovascular disease outcomes in multivariate analysis. CONCLUSION: It seems that for short-term prediction of cardiovascular disease outcome, serum total cholesterol is the preferred lipid parameter to measure in the Iranian population.     

VEGETARIAN DIETS, LIPIDS AND CARDIOVASCULAR RISK

Vegetarian diets produce moderate but appreciable changes in serum lipid levels. A six-weeg intervention study in which other aspects of life-style were kept constant showed that levels of total cholesterol, LDL-cholesterol and HDL-cholesterol fell 0.22, 0.19 and 0.07 mmol/l, respectively, while triglyceride levels increased non-significantly 0.12 mmol/l. The ratio of total cholesterol to HDL-cholesterol did not change. A comparison of grous of habitual vegetarians and omnivores matched for other aspects of lifestyle showed rather larger differences in atherogenic lipid levels: 0.71 and 0.67 mmol/l for total— and LDL—cholesterol; the difference in HDL-C levels was 0.04 mmol/l; triglyceride was 0.19 mmol/l greater in vegetarians. 92% of the variation in intakes of major nutrients was accounted for by three derived factors; changes in levels of most of the lipids were associated in each case with one of the factors. The resultant falls in the levels of total-and LDL-cholesterol in people adopting a vegetarian diet probably contribute to a reduction in cardiovascular risk.     

Induction of autoantibodies in refractory rheumatoid arthritis treated by infliximab

OBJECTIVES: To investigate autoantibody induction in rheumatoid arthritis (RA) patients treated with infliximab. METHODS: We included 59 refractory RA patients treated with infliximab in combination with low-dose prednisone and methotrexate or leflunomide. We tested the sera of the patients for antinuclear antibodies (ANA), rheumatoid factor (RF), anti double-stranded DNA antibodies (anti dsDNA), anti-histone and anti-extractable nuclear antigen antibodies (aENA) at baseline and before infusion at weeks 6 and 30. Infliximab, initiated at a dose of 3 mg/kg, was increased to 5 mg/kg if insufficient improvement was observed after three infusions. RESULTS: At week 6, only the frequency of anti-histone IgM antibody-positive patients had significantly increased (19 vs 42%, p = 0.009). At week 30, the frequency of patients with ANA had increased from 29% to 69% (p < 0.001), that of patients with anti-dsDNA antibodies had increased from 0% to 3% for IgG (NS) and from 0% to 32% for IgM (p < 0.001); the frequency of antihistone IgG detection had increased from 22% to 32% (p = 0.04) and that of IgM detection, from 18% to 79% (p < 0.001). No lupus-like syndrome was observed. RF decreased significantly (87 IU to 52.5 IU, from baseline to week 30; p < 0.001). No significant difference was observed between the 16 non-responders and the responders, in terms of autoantibody status at baseline and changes with infliximab therapy. CONCLUSION: Infliximab therapy lead to the selective and delayed induction of autoantibodies. This induction was not associated with clinical symptoms until week 30 and did not differ between responders and non-responders.     

Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis.

OBJECTIVES: The aim of this study was to investigate the effect of simvastatin and ezetimibe on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in a cohort of rheumatoid arthritis (RA) patients. BACKGROUND: Rheumatoid arthritis is a chronic inflammatory condition associated with increased cardiovascular risk. Statins reduce inflammation and disease activity in RA patients, but whether this is due to pleiotropism or cholesterol lowering per se is unclear. METHODS: Twenty patients received 20 mg simvastatin or 10 mg ezetimibe each for 6 weeks in a randomized double-blind crossover study. Disease activity, blood pressure, aortic pulse wave velocity (PWV), brachial artery flow-mediated dilation (FMD), and serum inflammatory markers were measured before and after each treatment. RESULTS: Both ezetimibe and simvastatin significantly reduced total cholesterol (-0.62 +/- 0.55 mmol/l and -1.28 +/- 0.49 mmol/l, respectively; p < 0.001), low-density lipoprotein cholesterol (-0.55 +/- 0.55 mmol/l and -1.28 +/- 0.49 mmol/l; p < 0.0001), and C-reactive protein (-5.35 +/- 9.25 mg/l and -5.05 +/- 6.30 mg/l; p < 0.001). Concomitantly, Disease Activity Score (-0.55 +/- 1.01 and -0.67 +/- 0.91; p = 0.002), aortic PWV (-0.69 +/- 1.15 m/s and -0.71 +/- 0.71 m/s; p = 0.001), and FMD (1.37 +/- 1.17% and 2.51 +/- 2.13%; p = 0.001) were significantly improved by both drugs. CONCLUSIONS: This study demonstrates that both ezetimibe and simvastatin reduce disease activity and inflammatory markers to a similar extent in patients with RA. Therapy is also associated with a concomitant reduction in aortic PWV and improvement in endothelial function. This suggests that cholesterol lowering per se has anti-inflammatory effects and improves vascular function in RA.     

Influence of anti-tumour necrosis factor therapy on cardiovascular risk factors in patients with active rheumatoid arthritis

BACKGROUND: Tumour necrosis factor (TNF) is known to increase the concentrations of interleukin (IL) 6 and C reactive protein (CRP) and to induce proatherogenic changes in the lipid profile and may increase the cardiovascular risk of patients with rheumatoid arthritis (RA) and other inflammatory disorders. OBJECTIVE: To assess whether anti-TNF therapy modifies the cardiovascular risk profile in patients with RA. METHODS: The lipoprotein spectrum and the inflammation markers CRP and IL6 were investigated in 33 patients with RA treated with human anti-TNF monoclonal antibodies (D2E7, adalimumab, Humira) and 13 patients with RA given placebo, before and after 2 weeks' treatment. RESULTS: In the anti-TNF treated group, the mean (SD) concentrations of HDL-cholesterol were significantly higher after 2 weeks' treatment (0.86 (0.30) mmol/l v 0.98 (0.33) mmol/l, p<0.01), whereas LDL and triglyceride levels were not significantly changed. Additionally, a significant decrease in CRP (86.1 (54.4) mg/l v 35.4 (35.0) mg/l, p<0.0001), and IL6 (88.3 (60.5) pg/ml v 42.3 (40.7) pg/ml, p<0.001) concentrations was seen in this group. No changes in lipid profile, IL6, or CRP levels were seen in the placebo group. CONCLUSIONS: TNF neutralisation with monoclonal anti-TNF antibodies increased HDL-cholesterol levels and decreased CRP and IL6 levels after 2 weeks. Therefore this treatment may improve the cardiovascular risk profile of patients with RA.     

Lipid levels and the use of lipid-lowering agents in England and Scotland.

OBJECTIVE: Preventing cardiovascular events with lipid-lowering drugs has been established in several trials reported since 1994. Consequently national guidelines recommend statins for those with established cardiovascular disease (CVD) and those at high risk of developing CVD. We evaluated blood lipid levels, and compare treatment and control of dyslipidaemia in English and Scottish adults with national recommendations for lipid lowering. DESIGN AND METHODS: In 1998 the nationally-representative Health Survey for England and the Scottish Health Survey included valid cholesterol results for 9631 (England) and 6065 (Scotland) adults aged 16-74. Mean blood levels of total, high-density lipoproteins (HDL-), and total:HDL-cholesterol ratio; prevalence of elevated total cholesterol levels, and total:HDL-cholesterol ratios; prevalence of use of lipid-lowering agents in high risk subgroups; and lipid levels of those on treatment were calculated. RESULTS: Levels of dyslipidaemia, treatment and control were not significantly different between Scotland and England. Combining these data, mean total cholesterol levels were 5.43 and 5.48 mmol/l in men and women respectively; and mean HDL-cholesterol levels were 1.29 and 1.56 mmol/l. Overall 64.6% of adults had a total cholesterol > or =5 mmol/l, 24.6% had a total:HDL ratio > or =5 and 2.3% reported taking lipid-lowering drugs. Treatment rates among those with a total cholesterol >5 mmol/l and a history of coronary heart disease or stroke, hypertension, or diabetes, were 27.3%, 15.4% and 17.8% respectively, and control rates (total cholesterol <5 mmol/l) among those treated were 45.3%, 38.5% and 32.7%. CONCLUSIONS: Low treatment rates with lipid-lowering drugs existed overall, among high-risk patients suitable for primary prevention, and among those with established cardiovascular disease.     

Induction of hyperadiponectinemia following long-term treatment of patients with rheumatoid arthritis with infliximab (IFX), an anti-TNF-alpha antibody

Tumor necrosis factor-alpha (TNF-alpha) plays an important role in forming atherosclerosis based on chronic inflammatory condition in vivo and animal models. In human system, it is not clear the involvement of TNF-alpha to atherosclerosis. To clarify the relevance of TNF-alpha to atherosclerotic factors in human, We performed a prospective cohort study to investigate the inhibition of TNF-alpha with anti-TNF-alpha antibody infliximab may contribute to increase serum adiponectin levels, adipocyte-derived hormone with antiatherogenic properties, in patients with RA. 97 patients with active RA had been treated every 8 weeks for 1 year(13 men and 84 women, 54.2 +/- 12.6 years, disease duration; 8.5 +/- 1.5 years). They received a fixed dose of infliximab of 3 mg/kg every 8 weeks for 52 weeks. We evaluated changes of inflammatory markers, high molecular weight form of adiponectin levels and blood lipid levels. We also studied the association between increment rate of serum adiponectin and improvement of disease activity and inflammatory markers. Infliximab were strikingly dropped inflammatory markers (p<0.01), increased total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) (p<0.05). Besides, serum adiponectin significantly increased, independent of RA activity and clinical backgrounds, suggesting that TNF-alpha and adiponectin exhibit opposite effects in human body. TNF-alpha blockade may interfere in the atherosclerosis directly or indirectly, by increasing serum adiponectin levels, therefore TNF-alpha blockade may improve cardiovascular morbidity and mortality in chronic inflammatory disease such as RA.     

Intensive lipid-lowering strategy in patients with diabetes mellitus.

AIMS: To assess the feasibility of an intensive lipid-lowering strategy in diabetic subjects pursuing target plasma lipid levels. METHODS: Patients with diabetes mellitus (DM), Type 1 or 2, with plasma lipid levels exceeding target values (LDL-cholesterol <2.6 mmol/l, triglycerides < 1.7 mmol/l, HDL-cholesterol > 0.9 mmol/l for men and > 1.1 mmol/l for women) were eligible. After 6-12 weeks of diet and glycaemic control, lipid-lowering medication (simvastatin/gemfibrozil/acipimox) was prescribed in steps of incremental dosages and combinations for 30 weeks. RESULTS: Of all eligible clinic patients, 25% initially responded and finally 12% were entered. Thirty-six patients with Type 1 and 59 with Type 2 DM were studied. Mean baseline lipid levels in Type 1 and Type 2 diabetic subjects were: LDL-cholesterol 3.6 and 3.7 mmol/l, triglycerides 1.7 and 2.2 mmol/l, HDL-cholesterol for men 1.1 and 1.0 mmol/l, and for women 1.4 and 1.2 mmol/l, respectively. All three target values were reached in 66% of the patients. LDL-cholesterol was reduced by 1.2 mmol/l in Type 1 and 1.3 mmol/l in Type 2 diabetic patients and triglycerides by 0.7 mmol/l and 1.1 mmol/l, respectively. HDL-cholesterol increased by 0.15 mmol/l and 0.34 mmol/l in men and women with Type 1 diabetes mellitus, respectively. The cholesterol-triglyceride ratio decreased significantly in VLDL in Type 1 diabetes and in IDL in Type 2 diabetes and increased significantly in HDL in Type 2 DM. CONCLUSIONS: A minority of subjects eligible for intensive lipid lowering agreed to participate in a feasibility study, suggesting a potentially large compliance problem for a general lipid-lowering programme in a diabetes clinic. Nevertheless, intensive lipid lowering with drug combinations can attain the recommended target lipid levels in 66% of subjects with diabetes. With this strategy the plasma lipoprotein composition shifts towards a less atherogenic profile. Subjects with diabetes should therefore receive lipid-lowering therapy tailored to reach target levels, rather than standard dosages, in order to reduce atherogenic risk.     

A dose adjustment in patients with rheumatoid arthritis not optimally responding to a standard dose of infliximab of 3 mg/kg every 8 weeks can be effective: a Belgian prospective study

OBJECTIVES: To analyse the effect of a dose increase in patients with severe rheumatoid arthritis (RA) with insufficient clinical response to 3 mg/kg infliximab every 8 weeks. METHODS: Patients suffering from active refractory RA despite methotrexate, were treated with i.v. infusions of infliximab (3 mg/kg) on week 0, 2, 6 and every 8 weeks thereafter. Based on the clinical judgement at week 22, patients received a dose increase of 100 mg from week 30 on. The American College of Rheumatology (ACR) core set for disease activity measures was regularly assessed. RESULTS: Five hundred and eleven RA patients were included. At week 22, 61.4, 34 and 14.1% of all patients met ACR 20, ACR 50 and ACR 70 criteria, respectively, and 6.1% of patients were in remission. A low swollen joint count at baseline was correlated with improvement at week 22 for ACR 20 (P < 0.06), ACR 50 (P < 0.06) and ACR 70 (P < 0.005). The change in HAQ score between weeks 0 and 22 was predictive for response at week 54 (P < 0.01). The dose of infliximab was increased by 100 mg in 22% of the patients. Most baseline values of patients requiring dose increase were higher (P < or = 0.001) than the baseline values of the remaining patients. Increasing the dose of infliximab by one vial from week 30 on could circumvent the partial loss of response in these patients. CONCLUSION: Infliximab use in this large out-patient cohort resulted in a significant clinical improvement. A subgroup that partially lost response during the first 22 weeks could regain response by adding 100 mg of infliximab to the subsequent doses. Due to the current study design, however, a regression to the mean like effect could not be ruled out.     

Association of plasma viscosity with cardiovascular risk factors in obesity: an old marker, a new insight

OBJECTIVE: Although obesity is related with cardiovascular disease, the exact mechanism of the relationship is not fully understood. We aim to examine the relationship between plasma viscosity and obesity as a cardiovascular disease risk factor in obese and non-obese groups. METHODS: We recruited 75 obese subjects (mean age: 40.2+/-8.4 years, Body Mass Index: 33.61+/-2.57 kg/m(2)) who were admitted to the Clinic of Endocrinology and Metabolism of Cerrahpasa Medical Faculty. As a non-obese group (n=70, mean age: 41.78+/-9.7 years, Body Mass Index: 21.84+/-3.42 kg/m(2)) healthy subjects from medical and laboratory staff were selected. Plasma viscosity and lipid profile were measured and atherogenic index was calculated as atherogenic risk factors. RESULTS: Plasma viscosity, total cholesterol and LDL-cholesterol levels and atherogenic index were significantly increased in obese group compared to non-obese group for each p<0.001. We found no significant difference in plasma fibrinogen, insulin, albumin and HDL-cholesterol levels between obese and non-obese groups. Plasma viscosity was correlated with total cholesterol and atherogenic index only in the obese group (p<0.05 and p<0.05 respectively). In the non-obese group regarding PV, we determined a positive correlation with triglycerides (r: 0.470, p<0.05) and negative correlation with HDL-C (r: -0.518, p<0.05). CONCLUSION: Plasma viscosity, an early atherosclerotic risk factor, might be helpful in the assessment of cardiovascular risk in obese subjects along with classical cardiovascular risk factors such as plasma cholesterol and atherogenic index.     

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.     

Comparative study on the efficacy of pioglitazone in Caucasian and Maori-Polynesian patients with poorly controlled type 2 diabetes

AIM: Although the pharmodynamic properties of the thiazolidinedione (TZD) insulin-sensitizing agents in the treatment of type 2 diabetes are well established, there are no studies comparing the pharmacoefficacy of these drugs in different ethnic groups. The aim of this pilot, prospective study was to examine the hypothesis that the efficacy of TZDs may vary depending on ethnicity. This aim was achieved by comparing the effects of 6-months treatment with pioglitazone (45 mg/day) on glucose control and metabolic and cardiovascular risk factors in Caucasian and Maori-Polynesian patients with poorly controlled type 2 diabetes. METHODS: Ninety-seven patients (40 Caucasian and 57 Maori-Polynesian) with type 2 diabetes were selected for the study from our clinical databases if they were on the maximum tolerated dose of oral agents and had a haemoglobin A(1c) (HbA(1c)) > 8.0% for at least 2 months. All the patients received pioglitazone (45 mg/day) for 6 months in addition to their regular diabetes therapy. Clinical data and blood samples were collected at monthly intervals and the following indices measured: weight, blood pressure, oedema score, HbA(1c), plasma glucose, alanine amino transferase and adiponectin levels and plasma lipid profile, including low-density lipoprotein (LDL)-cholesterol particle size and atherogenic index of plasma (AIP). The data of the 81 patients who finished the study were analysed using analysis of variance, chi-square analysis and multiple regression methods. RESULTS: The absolute change from baseline in mean HbA(1c) (Caucasian -1.4% vs. Maori-Polynesian -1.3%) and fasting glucose levels (Caucasian -2.1 mmol/l vs. Maori-Polynesian -2.8 mmol/l) was similar in the two groups. Pioglitazone caused an improvement in lipid profile in both ethnic groups, with a reduction in mean values of atherogenic fractions (triglyceride: Caucasian -0.5 mmol/l, p < 0.001 vs. Maori-Polynesian -0.3 mmol/l, p = 0.05; very low-density lipoprotein (VLDL)-cholesterol: Caucasian -0.11 mmol/l, p = 0.001 vs. Maori-Polynesian -0.04 mmol/l, p = 0.85; VLDL-triglyceride: Caucasian -0.36 mmol/l, p < 0.001 vs. Maori-Polynesian -0.22 mmol/l, p = 0.14; apolipoprotein B: Caucasian -0.09 mmol/l, p = 0.03 vs. Maori-Polynesian -0.08 mmol/l, p = 0.18). These changes were associated with an increase in LDL-cholesterol particle size (Caucasian +0.23 nm, p = 0.05 vs. Maori-Polynesian +0.26 nm, p = 0.04) and a decrease in AIP (Caucasian -0.14, p < 0.001 vs. Maori-Polynesian -0.08, p = 0.04). While the changes in the lipid indices tended to be greater in the Caucasian group, the difference in lipid response between the two ethnic groups was not statistically significant. Multiple regression analyses showed that the baseline value of the individual lipid fractions was the main determinant of the changes in lipid levels. CONCLUSIONS: These results demonstrated that pioglitazone has similar beneficial effects on glucose control and plasma lipid profile in Caucasian and Maori-Polynesian patients with poorly controlled type 2 diabetes. Our data showed that while the improvement in lipid profile was more pronounced in Caucasian patients than in Maori-Polynesian patients, this difference was not statistically significant.     

Early treatment reduces the cardiovascular risk factors in newly diagnosed rheumatoid arthritis patients

OBJECTIVE: To investigate subclinical atherosclerosis and the effect of treatment in patients with early rheumatoid arthritis (RA). PATIENTS AND METHODS: Forty patients with early RA who met the revised American College of Rheumatology (ACR) criteria and disease duration of <1 year were included in the study. Smokers and patients with classical risk factors for atherosclerosis were excluded. The serum levels of total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were determined in all patients before and after 1 year of therapy. Carotid artery intima-media thickness (IMT) and carotid plaque were measured before and after treatment. RA disease activity was measured using the 28 joint indices score (DAS-28) and clinical improvement was determined by the ACR response criteria. Forty-five age- and sex-matched nonsmoking volunteers were used as controls. All patients were treated with methotrexate and prednisone. RESULTS: RA patients had a baseline mild dyslipidemia characterized by a decrease in serum HDL-C levels and a high TC/HDL-C atherogenic ratio compared with controls. Both lipid parameters were significantly improved after treatment (P<0.01). Common carotid artery IMTs at baseline were higher in RA patients compared with controls (P<0.05). After 1 year of therapy there was a significant decrease in the IMTs (P<0.001). Thirty-five patients (88%) achieved the ACR 20%, while 30 (75%) reached the ACR 50% response criteria. A significant decrease of DAS-28 was observed after treatment (P<0.03). CONCLUSIONS: The atherogenic lipid profile and subclinical atherosclerosis are features of early RA, which improved after therapy. Early intervention and control of the disease activity may reduce the risk of atherosclerosis and cardiovascular events in patients with RA.     

Effect of anti TNFalpha therapy on arterial diameter and wall shear stress and HDL cholesterol

It has been recently hypothesized that both TNFalpha and anti TNFalpha treatment have a stimulating effect on nitric oxide synthesis and release. Moreover, an in vitro experiment has demonstrated that HDL-cholesterol binds TNFalpha. Aims of our study were to investigate wall shear stress of peripheral arteries and endothelial function of brachial artery in subjects with Rheumatoid Arthritis (RA) at baseline and after infliximab. Moreover, we evaluated the effect of anti TNFalpha therapy on lipid profile. Ten patients with RA received infliximab therapy at weeks 0, 2 and 6. Lipids and vascular parameters were measured before and the day after each infusion. After the first treatment, FMD increased (3.7 +/- 1.9% versus 17.5 +/- 2.9%, P <0.01) and common carotid and brachial artery diameters decreased (5.9 +/- 0.2 mm versus 5.5 +/- 0.2 mm; 3.5 +/- 0.4 mm versus 3.1 +/- 0.4 mm, respectively, P <0.005). Common carotid and brachial artery wall shear stress increased (21.1 +/- 1.1 dynes/cm2 versus 23.9 +/- 1.4 dynes/cm2; 42.0 +/- 4.7 dynes/cm2 versus 51.6 +/- 5.7 dynes/cm2, P <0.01). Similar results were observed after the second and third infusion. All these parameters returned to pre-treatment level at the following infusion. HDL-cholesterol and apolipoprotein AI significantly decreased after each treatment (1st treatment: 1.4 +/- 0.05 mmol/L versus 1.2 +/- 0.06 mmol/L, P <0.01; 1.73 +/- 0.05 g/L versus 1.57 +/- 0.02 g/L, P <0.03). The present data show vasoconstriction and an increase of wall shear stress in studied arteries after infliximab. HDL cholesterol is reduced by treatment and does not seem to influence FMD.     

Anti-tumor necrosis factor-alpha antibody treatment reduces serum CXCL16 levels in patients with rheumatoid arthritis

The aim of this study was to analyze the change of serum chemokins levels of CXCL16, CX3CL1/Fractalkine, and CXCL10/interferon-gamma inducible protein-10 (IP-10) with rheumatoid arthritis (RA), by infliximab treatment. The effects of infliximab treatment were studied in 23 patients with RA, over a period of 30 weeks. The serum levels of CXCL16, Fractalkine, and IP-10, were measured at the baseline, just before initial treatment, and at 14 and 30 weeks after the initial treatment, with infliximab by ELISA. The higher levels of serum CXCL16 in the RA patients before treatment with infliximab significantly decreased at 14 and 30 weeks after the initial treatment with infliximab, but the serum Fractalkine and IP-10 levels did not decrease significantly. Infliximab treatment significantly lowered the serum levels of CXCL16 in patients with RA. CXCL16 is one of the crucial chemokines regulated by infliximab treatment.