Association between plasma lipids, and apolipoproteins and coronary artery disease: a cross-sectional study in a low-risk Korean population

BACKGROUND: Due to the lower level of the traditional lipid profiles in Koreans than in the series of patients from the western countries, the need to investigate other lipid parameters to help identify the individuals at high risk of CAD has been emphasized. AIM AND METHODS: To investigate whether apolipoprotein B (apo B), apolipoprotein A-I (apo A-I) and their ratio give additional information to the traditional lipid risk factors for discriminating the individuals at high-risk for coronary artery disease (CAD), 544 subjects, who met the lipid criteria of total cholesterol (TC) <230 mg/dl, low-density lipoprotein cholesterol (LDL-C) <120 mg/dl and high-density lipoprotein cholesterol (HDL-C) >40 mg/dl were recruited. Patients were considered to be CAD(+) if they had > or =50% stenosis in at least one coronary artery. RESULTS: In men, TC and apo B/apo A-I ratio were significantly different between groups with and without CAD after adjusting for age and diabetes (P = 0.037 and 0.035), and in women, triglyceride (TG), HDL-C and apo B/apo A-I ratio were significantly different after adjusting for age, diabetes and smoking status (P = 0.006, 0.007 and 0.030, respectively). In the lowest quartile of TC, TG and LDL-C, and the highest quartile of HDL-C, only apo B/apo A-I ratio was associated with CAD in both men and women. The only variable showing a significant difference between patients with and without CAD was apo B/apo A-I ratio. In models assessing whether apolipoproteins give additional information to traditional lipid risk factors, HDL-C, LDL-C, apo B/apo A-I ratio and in women but not in men, TG and apo B were all independent markers for the presence of CAD. Among the nontraditional lipid factors, only apo B/apo A-I ratio showed its additional value for identifying the presence of CAD. CONCLUSION: Apo B/apo A-I ratio is the only variable that differentiates the patients with CAD from those without and, furthermore, gives additional information to that supplied by traditional lipid risk factors in a low-risk Korean population.     

Effects of antirheumatic therapy on serum lipid levels in patients with rheumatoid arthritis: a prospective study

BACKGROUND: Patients with newly diagnosed rheumatoid arthritis have adverse serum lipid profiles. We sought to determine the effects of treating rheumatoid arthritis with antirheumatic drugs on these abnormal lipid levels. SUBJECTS AND METHODS: We studied 42 patients with newly diagnosed rheumatoid arthritis who had not been treated with corticosteroids or disease-modifying antirheumatic drugs. We measured serum lipid profiles at baseline and 1 year later, and determined whether there were differences in the changes in lipid levels between patients who met the American College of Rheumatology criteria for a 20% improvement in rheumatoid arthritis and those who did not. RESULTS: Of the 42 patients, 27 (64%) met the criteria for a 20% improvement in rheumatoid arthritis during the 12-month study. In these patients, mean high-density lipoprotein (HDL) cholesterol levels increased by 21% (P <0.001), apolipoprotein A-I levels increased by 23% (P <0.001), and the ratio of low-density lipoprotein (LDL) cholesterol to HDL cholesterol level decreased by 13% (P = 0.10). There were significant between-group differences (responders-nonresponders) in the mean 12-month changes in HDL cholesterol levels (8.0 mg/dL; 95% confidence interval [CI]: 3 to 13 mg/dL; P = 0.002), apolipoprotein A-I levels (21 mg/dL; 95% CI: 8 to 33 mg/dL; P = 0.003), and the LDL cholesterol to HDL cholesterol ratio (-0.6; 95% CI: -0.1 to -1.0; P = 0.03), but not in LDL cholesterol, apolipoprotein B-100, or lipoprotein(a) levels. CONCLUSION: Active rheumatoid arthritis is associated with an adverse lipid profile that improves substantially following effective treatment of rheumatoid arthritis. This improvement may reduce the risk of cardiovascular disease.     

Basic treatment of early rheumatoid arthritis. Abstaining from rheumatological care and preferring alternative medicine increase the risk of undertreatment

The major challenge in the management of rheumatoid arthritis (RA) is the early initiation and long-term continuation of disease-modifying antirheumatic drug (DMARD) therapy. A total of 916 RA patients (ACR criteria, disease duration <2 years) were investigated in regard to frequency and reasons for DMARD discontinuation. All patients were under rheumatological care at the start of the observation and almost all were receiving DMARDs at study entry (95%). The proportion decreased to 87% within 3 years. Of the 171 patients without DMARD, 5% abstained due to (planned) pregnancy, 28% due to contraindications and/or severe adverse events and 54% due to remission. Only 12% were non-compliant. Multivariate regression analysis revealed non-specialised care (OR 4.6; 59% CI 3.2-6.7), RF seronegativity (OR 2.6; 95% CI 1.8-3.8), no patient education (OR 2.2; CI 95% 1.5-3.4), preference for alternative medicine (OR 8.2; 95% CI 4.0-16.8) and > or =10 years of education (OR 1.8; 95% CI 1.3-2.7) as independent risks for DMARD abstention. Age, sex, comorbidity or disease activity did not influence adherence to DMARD therapy. Since preference for alternative medicine was the strongest risk predictor, further investigations are needed to determine the characteristics of this preference regarding compliance with DMARD medication in RA. The positive influence of patient education on DMARD continuation emphasizes its importance.     

The good initial response to therapy with a combination of traditional disease‐modifying antirheumatic drugs is sustained over time: The eleven‐year results of the Finnish rheumatoid arthritis combination therapy trial

Objective

To evaluate the evolution of functional and clinical outcomes over 11 years in patients with early rheumatoid arthritis (RA) initially treated with a combination of 3 disease‐modifying antirheumatic drugs (DMARDs) or with a single DMARD.

Methods

A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the drug treatment strategy became unrestricted, but still targeted remission. At 11 years, function was assessed with the Health Assessment Questionnaire (HAQ), and clinical outcomes were assessed with the modified Minimal Disease Activity (MDA) measure and the American College of Rheumatology (ACR) criteria for remission.

Results

At 11 years, 138 patients were assessed (68 in the combination‐DMARD group and 70 in the single‐DMARD group). The mean ± SD HAQ scores were 0.34 ± 0.54 in the combination‐DMARD group and 0.38 ± 0.58 in the single‐DMARD group (P = 0.88). Modified MDA was achieved by 63% (95% confidence interval [95% CI] 51, 77) and by 43% (95% CI 32, 55) (P = 0.016) of the combination‐DMARD group and the single‐DMARD group, respectively, and ACR remission by 37% (95% CI 26, 49) and by 19% (95% CI 11, 29) (P = 0.017), respectively.

Conclusion

Initial therapy with a combination of DMARDs in early RA results in higher rates of patients achieving modified MDA and strict ACR remission even over the long term than initial single‐DMARD therapy. Targeting remission with tight clinical controls results in good functional and clinical outcomes in most RA patients.

     

Differential effects of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I are consistent across hypercholesterolemic patient subgroups

BACKGROUND: In addition to lowering plasma levels of low-density lipoprotein cholesterol (LDL-C), statins also raise high-density lipoprotein cholesterol (HDL-C). HYPOTHESIS: Recent studies have shown that treatment with simvastatin results in larger increases in HDL-C than those seen with atorvastatin. The results of three clinical studies are analyzed, comparing the effects of simvastatin and atorvastatin on HDL-C and apolipoprotein A-I (apo A-I) in the total cohort and in several subgroups of hypercholesterolemic patients. The three studies were all multicenter, randomized clinical trials that included simvastatin (20-80 mg) and atorvastatin (10-80 mg) treatment arms. The subgroup analyses performed were gender; age (< 65 and > or = 65 years); baseline HDL-C (male: < 40 or > or = 40 mg/dl; female: < 45 or > or = 45 mg/dl), baseline LDL-C (< 160 or > or = 160 mg/dl), and baseline triglycerides (< 200 or > or = 200 mg/dl). RESULTS: Both drugs produced similar increases in HDL-C levels at low doses; however, at higher drug doses (40 and 80 mg), HDL-C showed a significantly greater increase with simvastatin than with atorvastatin (p < 0.05 to < 0.001). Therefore, while HDL-C remained consistently elevated across all doses of simvastatin, there appeared to be a pattern of decreasing HDL-C with an increasing dose of atorvastatin. A similar negative dose response pattern was also observed with apo A-I in atorvastatin-treated patients, suggesting a reduction in the number of circulating HDL particles at higher doses. Both drugs reduced LDL-C and triglycerides in a dose-dependent fashion, with atorvastatin showing slightly greater effects. The differential effects of atorvastatin and simvastatin on HDL-C and apo A-I were observed for both the whole study cohorts and all subgroups examined; thus, no consistent treatment-by-subgroup interactions were observed. CONCLUSION: The data presented show that, across different hypercholesterolemic patient subgroups, simvastatin increases HDL-C and apo A-I more than atorvastatin at higher doses, with evidence of a negative dose response effect on HDL-C and apo A-I with atorvastatin, but not simvastatin.     

Significance of a polymorphism (G-->A transition) in the -75 position of the apolipoprotein A-I gene promoter on serum high density lipoprotein-cholesterol levels in Japanese hyperlipidemic subjects

High density lipoprotein-cholesterol (HDL-C) levels are inversely related to the incidence of coronary artery disease. We studied the influence of a G(-75)-->A transition in the promoter of the apolipoprotein (apo) A-I gene, a major protein component of HDL, on serum HDL-C levels in hyperlipidemic subjects. Seventy three hyperlipidemic subjects with serum levels of high HDL-C (HDL-C > or = 70 mg/dl, Group H) were compared with hyperlipidemic subjects with levels of HDL-C between 40 and 70 mg/dl (Group N) and those with HDL-C < 40 mg/dl (Group L). Group H showed a higher incidence (45.2%) of low plasma cholesteryl ester transfer protein (CETP) activity than Groups N (9.1%) and L (5.3%) (p < 0.001). Group H had a higher incidence of the G(-75)-->A transition (0.275) than Groups N (0.117, p < 0.05) and L (0.056, p < 0.01), among subjects with normal CETP activities. The HDL-C levels in subjects with the transition (84 +/- 16 mg/dl) were higher than those in subjects without the transition (56 +/- 12 mg/dl) (p < 0.05). These data suggest that a G(-75)-->A transition of the apo A-I gene promoter, in addition to the common mutation of CETP gene, contributes to high HDL-C levels among hyperlipidemic patients in Japan.     

Effects of fenofibrate on atherogenic dyslipidemia in hypertriglyceridemic subjects

BACKGROUND: The metabolic syndrome (MS) is often accompanied by atherogenic dyslipidemia, which is characterized by elevated triglycerides (TG), reduced high-density lipoprotein cholesterol (HDL-C), and elevated numbers of small, dense low-density lipoprotein (LDL) particles. HYPOTHESIS: It was hypothesized that a threshold exists for the circulating TG level needed to produce changes in LDL subclass distribution. METHODS: Hypertriglyceridemic (TG > or =300 and <1000 mg/dl) subjects with the MS were randomly assigned to placebo (n=50) or 130 mg/day of micronized fenofibrate-coated microgranules (n=96) for 8 weeks. RESULTS: In the overall analysis, fenofibrate treatment resulted in significant (p < 0.05) changes versus placebo in TG (-36.6%), non-HDL-C (-7.5%), very low-density lipoprotein-C (-32.7%), LDL-C (15.0%), HDL-C (14.0%), remnant lipoprotein-C (-35.1%), apolipoprotein B (-6.0%), apolipoprotein A-I (5.3%), and apolipoprotein C-III--29.7%). Changes in LDL particle diameter in the fenofibrate group were significantly inversely associated with the TG level achieved on treatment (p = 0.019). When individually matched for percent change in TG, subjects with on-treatment TG < 200 mg/dl, in contrast to those with on-treatment values > or =200 mg/dl, had significantly different median responses (p < 0.05) in LDL size (0.79 vs. -0.06 nm) and cholesterol carried by small (-35 vs. 21 mg/dl) and large (31 vs. 11 mg/dl) particles. CONCLUSION: These data support the view that a threshold exists below which the TG level must be lowered to produce shifts in LDL particle size.     

Dyslipidemia and changes in lipid profiles associated with rheumatoid arthritis and initiation of anti–tumor necrosis factor therapy

Objective

To investigate the frequency of lipid testing in clinical practice and to explore the relationship between rheumatoid arthritis (RA), dyslipidemia, and other cardiovascular (CV) risk factors with RA treatment.

Methods

Patients in this retrospective database study were ages ≥18 years and had ≥2 physician diagnoses for RA or osteoarthritis (OA; comparator group) between March 2004 and March 2008. Outcomes of interest included the percentage of RA and OA patients receiving lipid tests, lipid profiles (total cholesterol, low‐density lipoprotein [LDL] cholesterol, and high‐density lipoprotein [HDL] cholesterol) of RA versus OA patients, and lipid profiles of RA patients before and after initiation with a tumor necrosis factor (TNF) inhibitor. We used multivariable regression to control potential confounders between the cohorts.

Results

Over a median ≥2‐year followup, fewer RA patients than OA patients had ≥1 lipid test (62.0% [95% confidence interval (95% CI) 61.5–62.5] versus 69.8% [95% CI 69.5–70.1]). Mean total cholesterol and LDL cholesterol were each 4 mg/dl lower in the RA cohort (P < 0.0001); HDL cholesterol was similar between the cohorts. Across the RA cohort, 25.2% of patients had suboptimal LDL cholesterol levels (≥130 mg/dl). Among RA patients not receiving lipid‐lowering therapy who initiated TNF inhibitor therapy (n = 96), mean total cholesterol and LDL cholesterol increased by 5.4 and 4.0 mg/dl, respectively.

Conclusion

Patients with RA were less likely to be tested for hyperlipidemia and had more favorable lipid profiles than patients with OA. TNF inhibitor therapy modestly increased all lipid parameters. Additional studies are needed to determine the effect of traditional CV risk factors and inflammation and the impact of biologic agents on CV outcomes in RA patients.     

Aerobic exercise and lipids and lipoproteins in children and adolescents: a meta-analysis of randomized controlled trials

OBJECTIVE: Use the meta-analytic approach to examine the effects of aerobic exercise on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) in children and adolescents. STUDY DESIGN: Randomized controlled trials which were limited to aerobic exercise >or=4 weeks in children and adolescents 5-19 years of age. RESULTS: Twelve outcomes representing 389 subjects were available for pooling. Using random-effects modeling, a trend for statistically significant decreases of 12% was found for TG (X +/-S.E.M., -11.0+/-6.1mg/dl; 95% CI, -22.8-0.8 mg/dl) with no statistically significant changes for TC, HDL-C, and LDL-C. Decreases in LDL-C were associated with increased training intensity (r=-0.89; 99% CI, -0.99 to -0.04) and older age (r=-0.90; 99% CI, -0.99 to -0.25) while increases in HDL-C were associated with lower initial HDL-C (r=-0.75; 99% CI, -0.94 to -0.80). Statistically significant decreases in TG were observed in overweight/obese subjects with a trend for increases in HDL-C (TG, X +/-S.E.M., -23.9+/-7.0mg/dl; 95% CI, -37.6 to -10.1mg/dl; HDL-C, X +/-S.E.M., 4.0+/-2.3mg/dl; 95% CI, -0.5-8.5mg/dl). CONCLUSIONS: Aerobic exercise decreases TG in overweight/obese children and adolescents.     

Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed

OBJECTIVE: To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed. METHODS: In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, 40 mg weekly, or placebo. The primary efficacy end point was > or =20% improvement in the ACR core criteria (ACR20 response). Secondary efficacy end points included ACR50, ACR70, EULAR responses, and the Disability Index of the Health Assessment Questionnaire (HAQ DI). RESULTS: After 26 weeks, patients treated with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, and 40 mg weekly had significantly better response rates than those treated with placebo: ACR20 (35.8%, 39.3%, 46.0%, 53.4%, respectively v 19.1%; p< or =0.01); ACR50 (18.9%, 20.5%, 22.1%, 35.0% v 8.2%; p< or =0.05); ACR70 (8.5%, 9.8%, 12.4%, 18.4% v 1.8%; p< or =0.05). Moderate EULAR response rates were significantly greater with adalimumab than with placebo (41.5%, 48.2%, 55.8%, 63.1% v 26.4%; p< or =0.05). Patients treated with adalimumab achieved better improvements in mean HAQ DI than those receiving placebo (-0.29, -0.39, -0.38, -0.49 v -0.07; p< or =0.01). No significant differences were found between adalimumab and placebo treated patients for serious adverse events, serious infections, or malignancies. Injection site reaction occurred in 10.6% and 0.9% of adalimumab and placebo treated patients, respectively (p< or =0.05). CONCLUSION: Among patients with RA for whom previous DMARD treatment had failed, adalimumab monotherapy achieved significant, rapid, and sustained improvements in disease activity and improved physical function and was safe and well tolerated.     

Modest but sustained increase of serum high density lipoprotein cholesterol levels in patients with inflammatory arthritides treated with infliximab

OBJECTIVE: Tumor necrosis factor-a (TNF-a) is a key cytokine in the pathogenesis of chronic inflammatory arthritides, has proatherogenic effects, and may be positively correlated with impairment of the action of insulin. Patients with chronic inflammatory arthritides have an increased risk for cardiovascular diseases. We assessed whether anti-TNF-a treatment modifies the unfavorable lipid profile induced by chronic inflammatory arthritides. METHODS: Sixty patients (24 with rheumatoid arthritis, 26 ankylosing spondylitis, and 10 psoriatic arthritis) receiving infliximab because of ongoing disease activity despite disease modifying drugs (DMARD) were prospectively studied for 6 months. Lipid profile, total cholesterol/high density lipoprotein cholesterol (TC/HDL-C), and low density lipoprotein cholesterol (LDL-C)/HDL-C ratios, as well as disease activity indices (DAS28 and BASDAI), were assessed. RESULTS: A sustained increase of serum HDL-C was observed [mean increase (95% CI)] 5 (3-7) mg/dl, 3.5 (1-6) mg/dl, and 3 (1-5) mg/dl at 1, 3, and 6 months, respectively (p < 0.01). Compared to nonresponders, HDL-C increased significantly more in EULAR or BASDAI responders (0.8 vs 5.8 mg/dl; p = 0.05). Serum TC was significantly increased [11 (4-8) mg/dl; p = 0.001] only after the first month of treatment. TC/HDL-C and LDL-C/HDL-C decreased only after the first month [0.3 (0.1-0.4), p < 0.01, and 0.2 (0.1-0.4), p < 0.01, respectively]. For patients with baseline LDL-C > 130 mg/dl, LDL-C/HDL-C decreased (p < 0.05) during the whole study period and TC/HDL-C decreased (p < 0.05) at 1 and 3 months. CONCLUSION: Anti-TNF-a treatment in patients with chronic inflammatory arthritides induces a modest, but sustained, increase in serum HDL-C levels, which may have a favorable effect in reducing the cardiovascular risk in these patients.     

The risk of hospitalized infection in patients with rheumatoid arthritis

OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) are at increased risk of hospitalized infection and whether the risk varies by RA treatment. METHODS: A retrospective cohort study was conducted using data from a medical and pharmacy claims managed-care database from 1999 to 2006. A total of 24,530 patients were included in the RA cohort; a random sample of non-RA patients served as a comparison cohort (n = 500,000). Rates of hospitalized infection were compared between the cohorts. A nested case-control analysis was performed within the RA cohort to assess the effect of current RA medication use on hospitalized infection risk. RESULTS: A total of 1,993 patients with RA and 11,977 non-RA patients experienced a hospitalized infection. The rate of first hospitalized infection was higher in the RA cohort [adjusted hazard ratio = 2.03; 95% confidence interval (CI) 1.93-2.13]. In the case-control analysis, the current use of biological disease modifying antirheumatic drugs (DMARD) was associated with slightly increased risk of hospitalized infection [rate ratio (RR) = 1.21; 95% CI 1.02-1.43]. Methotrexate and hydroxychloroquine were associated with decreased risk. Oral corticosteroid use increased risk (RR = 1.92; 95% CI 1.67-2.21), and there was a dose-related effect [< or = 5 mg/day: RR = 1.32 (95% CI 1.06-1.63), 6-10 mg/day: RR = 1.94 (95% CI 1.53-2.46), > 10 mg/day: RR = 2.98 (95% CI 2.41-3.69)]. CONCLUSION: These data confirm that individuals with RA are at increased risk of hospitalized infection compared to those without RA. Oral corticosteroid use was associated with a dose-related increase. Biological DMARD use was associated with slightly elevated risk; however, this may reflect confounding and channeling bias.     

The value of serum albumin and high-density lipoprotein cholesterol in defining mortality risk in older persons with low serum cholesterol

OBJECTIVES: To investigate the relationship between low cholesterol and mortality in older persons to identify, using information collected at a single point in time, subgroups of persons with low and high mortality risk. DESIGN: Prospective cohort study with a median follow-up period of 4.9 years. SETTINGS: East Boston, Massachusetts; New Haven, Connecticut; and Iowa and Washington counties, Iowa. PARTICIPANTS: Four thousand one hundred twenty-eight participants (64% women) age 70 and older at baseline (mean 78.7 years, range 70-103); 393 (9.5%) had low cholesterol, defined as < or =160 mg/dl. MEASUREMENTS: All-cause mortality and mortality not related to coronary heart disease and ischemic stroke. RESULTS: During the follow-up period there were 1,117 deaths. After adjustment for age and gender, persons with low cholesterol had significantly higher mortality than those with normal and high cholesterol. Among subjects with low cholesterol, those with albumin> 38 g/L had a significant risk reduction compared with those with albumin < or =38 g/L (relative risk (RR) = 0.57; 95% confidence interval (CI) = 0.41-0.79). Within the higher albumin group, high-density lipoprotein cholesterol (HDL-C) level further identified two subgroups of subjects with different risks; participants with HDL-C <47 mg/dl had a 32% risk reduction (RR = 0.68; 95% CI = 0.47-0.99) and those with HDL-C > or =47 mg/dl had a 62% risk reduction (RR = 0.38; 95% CI = 0.20-0.68), compared with the reference category; those with albumin < or =38 g/L and HDL-C <47 mg/dl. CONCLUSIONS: Older persons with low cholesterol constitute a heterogeneous group with regard to health characteristics and mortality risk. Serum albumin and HDL-C can be routinely used in older patients with low cholesterol to distinguish three subgroups with different prognoses: (1) high risk (low albumin), (2) intermediate risk (high albumin and low HDL-C), and (3) low risk (high albumin and high HDL-C).     

Sustained remission and reduced radiographic progression with combination disease modifying antirheumatic drugs in early rheumatoid arthritis

OBJECTIVE: To study sustainability of remission and good treatment response, and the association of both with radiographic progression, in early rheumatoid arthritis (RA) in the Finnish Rheumatoid Arthritis Combination Therapy trial (FIN-RACo). METHODS: Patients were randomized to receive either a combination of disease modifying antirheumatic drugs (DMARD; COMBI, n = 97) or a single DMARD (SINGLE, n = 98). Remission was defined according to modified American College of Rheumatology (ACR) remission criteria and Disease Activity Score 28 joint count (DAS28) < or = 2.6, and sustained remission as presence of remission at 6, 12, and 24 months. Good treatment response was defined as DAS28 (3/4) 3.2 and decrease of DAS28 >1.2. RESULTS: In 169 patients with complete data, 33 (42%) COMBI and 18 (20%) SINGLE patients achieved modified ACR remission at 2 years, which was sustained in 11 (14%) COMBI and 3 (3%) SINGLE patients. Fifty-four (68%) COMBI and 37 (41%) SINGLE patients were in DAS28 remission at 2 years, which was sustained in 40 (51%) COMBI and 14 (16%) SINGLE patients. Good treatment response was sustained in 67% of COMBI and 27% of SINGLE patients. Over 2 years, the Larsen score increased by a median of 1 (95% CI 0-2) in patients in sustained DAS28 remission compared to 4 (95% CI 2-16) in patients who were in DAS28 remission at 6 months but lost it later; and by 6 (95% CI 2-10) in patients who were not in remission at 6 months. CONCLUSION: A remarkable proportion of patients with early RA treated with combinations of DMARD were in remission at 2 years, and remission was more often sustained compared to patients treated with a single DMARD. Sustained remission protects against radiographic joint damage.     

Basistherapie bei früher rheumatoider Arthritis

The major challenge in the management of rheumatoid arthritis (RA) is the early initiation and long-term continuation of disease-modifying antirheumatic drug (DMARD) therapy. A total of 916 RA patients (ACR criteria, disease duration <2 years) were investigated in regard to frequency and reasons for DMARD discontinuation. All patients were under rheumatological care at the start of the observation and almost all were receiving DMARDs at study entry (95%). The proportion decreased to 87% within 3 years. Of the 171 patients without DMARD, 5% abstained due to (planned) pregnancy, 28% due to contraindications and/or severe adverse events and 54% due to remission. Only 12% were non-compliant. Multivariate regression analysis revealed non-specialised care (OR 4.6; 59% CI 3.2–6.7), RF seronegativity (OR 2.6; 95% CI 1.8–3.8), no patient education (OR 2.2; CI 95% 1.5–3.4), preference for alternative medicine (OR 8.2; 95% CI 4.0–16.8) and ≥10 years of education (OR 1.8; 95% CI 1.3–2.7) as independent risks for DMARD abstention. Age, sex, comorbidity or disease activity did not influence adherence to DMARD therapy. Since preference for alternative medicine was the strongest risk predictor, further investigations are needed to determine the characteristics of this preference regarding compliance with DMARD medication in RA. The positive influence of patient education on DMARD continuation emphasizes its importance.     

Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia and coronary heart disease: secondary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT).

Hyperlipidemia is primarily implicated in the progression of coronary heart disease (CHD) and its treatment is essential for patients with a history of CHD. Statins such as simvastatin, the lipid-lowering agents, are well-known for their ability to normalize patient's serum lipid levels. The Japan Lipid Intervention Trial study of simvastatin is the first nationwide investigation of the relationship between serum lipid levels and the development of CHD in Japanese patients with hypercholesterolemia. Of 5,127 patients, exclusively with a history of documented CHD at enrollment, 4,673 were treated with open-labeled simvastatin at an initial dose of 5-10 mg/day and were monitored for 6 years. The risk of coronary events tended to be higher in patients with a serum total cholesterol (TC) > or =240 mg/dl compared with total cholesterol <240 mg/dl. The concentration of low-density lipoprotein cholesterol (LDL-C) positively correlated and that of high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of CHD. Each 10 mg/dl decrease in LDL-C and each 10 mg/dl increase in HDL-C concentration reduced the risk of CHD by 8.0% (95% confidence interval 3.8-12.0) and 28.3% (95% CI 13.9-40.3), respectively. A reasonable therapeutic strategy to reduce CHD progression in patients with prior CHD under low-dose statin treatment might be regulating the serum LDL-C concentration to at least <120 mg/dl and HDL-C >40 mg/dl, respectively.     

Prevalence of rheumatoid arthritis in Tucumán,Argentina

OBJECTIVE: To ascertain the prevalence of rheumatoid arthritis (RA) in Tucumán, Argentina. METHODS: The study was conducted between January 1, 1998, and December 31, 1999, in Tucumán province in northwest Argentina. Outpatient and hospitalization medical records for all patients with RA aged > or = 16 years were reviewed. Diagnosis was by 1987 American College of Rheumatology (ACR) criteria for RA and the population data were based on the 1991 national census. Prevalence rates, with 95% CI, were calculated using the number of San Miguel de Tucumán residents who fulfilled the 1987 ACR criteria for RA as numerator, and the city population aged > or = 16 as denominator. Crude and age-specific prevalence rates were calculated as number of cases/1,000 inhabitants. RESULTS: We identified 695 cases of RA. Sex-specific and overall prevalence rates (per 1,000) were 1.97 (95% CI 1.8-2) for all, 0.6 (95% CI 0.49-0.73) for men, 3.2 (95% CI 2.9-3.5) for women. CONCLUSION: Prevalence of RA is low in residents of Tucumán, Argentina, and comparable with rates observed in epidemiological surveys from Southern European countries.     

The efficacy and safety of rituximab for the treatment of active rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials

The aims of this study were to assess the efficacy and safety of rituximab in patients with active rheumatoid arthritis (RA). The authors surveyed randomized controlled trials (RCTs) that examined the efficacy of rituximab in disease modifying anti-rheumatic drug (DMARD) (including methotrexate [MTX]) or tumor necrosis factor (TNF)-blocker-resistant or intolerant patients with active RA using Medline, the Cochrane Controlled Trials Register, and manual searches. Meta-analysis of RCTs was performed to determine the treatment efficacy and safety outcomes of rituximab (1 course, consisting of two infusions of 1,000 mg each) concomitant with MTX. The three RCTs included 938 DMARD or TNF-blocker-resistant or intolerant RA patients. Follow-up periods ranged from 24 to 48 weeks. American College of Rheumatology response (ACR) 20, ACR50, and ACR70 response rates were significantly higher for the rituximab plus MTX than for placebo controls (primary efficacy outcome, ACR50; risk ratio [RR] 3.648, 95% confidence interval [CI] 2.478–5.369, P < 0.001). For those treated with rituximab, the incidence adverse events of all systems were not higher than in those treated with placebo (RR 1.062, 95% CI 0.912–1.236, P = 0.438). With respect to the number of patients that experienced at least one serious adverse event, no significant difference was observed between patients treated with rituximab and placebo (RR 0.855, 95% CI 0.622–1.174, P = 0.333). A single course of rituximab with concomitant MTX therapy was found to be effective in DMARD or TNF-blocker-resistant or intolerant patients with active RA.     

Association of the ApoB/ApoA-I ratio with stroke risk: Findings from the China Health and Nutrition Survey (CHNS)

Background and aimsStudies on associations of apolipoprotein B (ApoB), apolipoprotein A-I (ApoA-I) and the ApoB/ApoA-I ratio with stroke risk are scarce. We aimed to prospectively examine the associations of the ApoB/ApoA-I ratio and other lipid profiles with the risk of stroke using data from the China Health and Nutrition Survey (CHNS).Methods and resultsA total of 7318 participants without stroke at baseline in 2009 were included in the final analysis and followed for a median of 6.1 years. The serum lipid profiles including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), ApoA-I, and ApoB were measured at baseline. Multivariable Cox proportional hazards models were used to evaluate the associations between these parameters and stroke risk. The ApoB/ApoA-I ratio was positively associated with incident stroke, yielding adjusted hazard ratio (HR) of 1.32 (95% CI: 1.09–1.59, P = 0.004). In comparison, ratio of ApoB and ApoA-I containing lipoproteins, the non-HDL-C/HDL-C ratio, possessed relatively weaker association with incident stroke (HR: 1.24, 95% CI: 1.01–1.52, P = 0.036). Furthermore, the risk associations for the ApoB/ApoA-I and non-HDL-C/HDL-C ratios were prominent among those participants aged >51, body mass index ≤23, or female. There were no significant associations of other lipids and their ratios with the stroke risk.ConclusionsHigher ApoB/ApoA-I ratio was associated with an increased risk of stroke. Our findings suggest that the ApoB/ApoA-I ratio may serve as a better risk indicator of stroke than other lipid profiles and their ratios.