Hypomagnesemia associated with chondrocalcinosis: a cross-sectional study

OBJECTIVE: To determine an association between magnesium (Mg) depletion and chondrocalcinosis, which has been reported but not investigated in a cross-sectional study. METHODS: Prevalence of chondrocalcinosis was investigated in 144 individuals: 72 patients receiving home parenteral nutrition (HPN) compared with 72 age- and sex-matched controls. Presence of chondrocalcinosis was assessed by knee radiographs. Blood serum and globular Mg levels and 24-hour urinary Mg content were compared. RESULTS: Mean +/- SD age for both patients and controls was 51 +/- 17 years, and 51% in both groups were women. Mean duration of HPN was 6.4 years. Prevalence of chondrocalcinosis was markedly higher in patients receiving HPN than controls (16.6% versus 2.7%; P = 0.006, odds ratio [OR] 7.0, 95% confidence interval [95% CI] 1.45-66.1). Mean +/- SD serum and globular Mg levels were significantly lower in patients than controls (serum: 0.75 +/- 0.09 mmoles/liter versus 0.81 +/- 0.08 mmoles/liter, P = 0.0006; globular Mg: 1.8 +/- 0.31 mmoles/liter versus 2.0 +/- 0.35 mmoles/liter, P = 0.0003). Twenty-four-hour urinary Mg level was lower in patients than controls (mean +/- SD 3.85 +/- 1.50 mmoles versus 5.37 +/- 3.71 mmoles; P = 0.001). Prevalence of chondrocalcinosis was significantly higher in patients with a low serum Mg level (OR 13.5, 95% CI 2.76-127.3, P < 0.0001), with a similarly high but not significant occurrence of chondrocalcinosis in patients with a low globular Mg level (OR 4.09, 95% CI 0.603-20.26, P = 0.08) and in patients with a low 24-hour urinary Mg level (OR 3.9, 95% CI 0.77-16.34, P = 0.05). CONCLUSION: Long-lasting Mg depletion is strongly associated with chondrocalcinosis.     

Association of C‐reactive protein with high disease activity in systemic sclerosis: Results from the Canadian Scleroderma Research Group

Objective

This study was performed to determine the prevalence of elevated C‐reactive protein (CRP) levels and the significance of CRP in clinical parameters in systemic sclerosis (SSc; scleroderma) patients.

Methods

Canadian Scleroderma Research Group data were used. Statistical comparisons were made for CRP levels ≤8 mg/liter versus >8 mg/liter, early (≤3 years from first non–Raynaud's phenomenon symptom) versus late SSc, and diffuse cutaneous SSc (dcSSc) versus limited cutaneous SSc (lcSSc). A survival analysis was analyzed between patients with normal versus elevated CRP levels.

Results

A total of 1,043 patients (mean ± SD age 55.4 ± 12.1 years, mean ± SD disease duration of 11.0 ± 9.5 years) were analyzed; elevation of CRP level and erythrocyte sedimentation rate (ESR; >20 mm/hour) occurred in 25.7% and 38.2%, respectively. Mean ± SD baseline CRP level in dcSSc (11.98 ± 25.41 mg/liter) was higher than in lcSSc (8.15 ± 16.09 mg/liter; P = 0.016). SSc patients with an early disease duration had a higher mean ± SD CRP level (12.89 ± 28.13 mg/liter) than those with a late disease duration (8.60 ± 17.06 mg/liter; P = 0.041). Although not consistent in all subsets, CRP was significantly associated (P < 0.01) with ESR, modified Rodnan skin score (MRSS), worse pulmonary function parameters, disease activity, damage, and Health Assessment Questionnaire. CRP level seemed to normalize in many SSc patients over time. Total lung capacity <80% predicted, MRSS, and serum creatinine were predictors of elevated CRP levels in SSc (odds ratio [OR] 2.76 [95% confidence interval (95% CI) 1.73–4.40], P = 0.0001; OR 1.03 [95% CI 1.01–1.05], P = 0.005; and OR 1.005 [95% CI 1.001–1.010], P = 0.02, respectively). Survival for patients with elevated CRP levels was less than for patients with normal CRP levels (P = 0.001).

Conclusion

CRP level is elevated in one‐quarter of SSc patients, especially early disease. It is correlated with disease activity, severity, poor pulmonary function, and shorter survival.     

Effect of fluvastatin on cardiac outcomes in kidney transplant patients with systemic lupus erythematosus: A randomized placebo‐controlled study

Objective

Patients with systemic lupus erythematosus (SLE), with or without end‐stage renal failure, are at increased risk of premature cardiovascular disease. Although statin therapy has been found to reduce cardiovascular risk in the general population, its effectiveness in kidney transplant recipients with SLE has not been examined. This study was undertaken to investigate the effect of fluvastatin on cardiac end points in a randomized controlled trial of renal transplant patients with SLE.

Methods

Patients with SLE were identified from among participants in the Assessment of Lescol in Renal Transplantation trial, a randomized, double‐blind, placebo‐controlled study of the effect of fluvastatin (40–80 mg/day) on cardiovascular outcomes in renal transplant recipients. Patients were randomized to either a group receiving fluvastatin or a placebo group for the duration of the 5–6‐year trial, and then invited to continue in a 2‐year open‐label extension during which all participants, regardless of original group, received fluvastatin. Patients were followed up for a total of 7–8 years for assessment of the primary end point of major cardiac events, comprising nonfatal myocardial infarction, cardiac death, and coronary intervention procedures.

Results

Fluvastatin reduced low‐density lipoprotein cholesterol levels by 29.2% (95% confidence interval [95% CI] 18.3–40%), from a mean ± SD of 4.0 ± 0.9 mmoles/liter to 2.8 ± 1.1 mmoles/liter, and total cholesterol by 19.6% (95% CI 11.7–27.5%), from 6.4 ± 0.9 mmoles/liter to 5.1 ± 1.1 mmoles/liter. Compared with placebo‐treated patients, patients randomized to receive fluvastatin exhibited a 73.4% reduction in the risk of major cardiac events (relative risk 26.6 [95% CI 5.9–119.4], P = 0.064).

Conclusion

Our results indicate that the effect of fluvastatin on cardiac events in renal transplant recipients with SLE is similar to that observed with statin therapy in the renal transplant population as a whole.

     

Cancer preceding giant cell arteritis: A case–control study

Objective

To study the association between previous cancer and giant cell arteritis (GCA).

Methods

Using the resources of the Rochester Epidemiology Project, we identified incident cases of GCA diagnosed between January 1, 1950 and December 31, 2004. Each GCA patient was matched for age, sex, and length of medical history to 2 subjects without GCA from the same population. Medical records were reviewed. Diagnosis of cancer was confirmed by histopathologic analysis.

Results

We identified 204 GCA cases and 407 controls. The GCA group included 163 women (80%) and 41 men (20%). Their mean ± SD age was 76.0 ± 8.2 years. The non‐GCA group consisted of 325 women (80%) and 82 men (20%). Their mean ± SD age was 75.6 ± 8.4 years. At the index date, 45 GCA patients (22%) and 125 non‐GCA patients (31%) had had a previous cancer. The odds ratio (OR) for previous cancer in cases compared with controls, adjusted for age, sex, and calendar year, was 0.63, and the 95% confidence interval (95% CI) was 0.42–0.94 (P = 0.022). The mean age at diagnosis of the first cancer before the index date was similar in the cases (67.5 ± 11.9 years) and the controls (64.9 ± 13.2 years) (P = 0.32). The mean ± SD duration from the first cancer to the index date was 9.8 ± 9.9 years in the cases and 11.7 ± 10.8 years in the controls (P = 0.31). Cancer types were similar in both groups, but fewer gynecologic malignancies were noted in GCA patients (OR 0.39 [95% CI 0.13–1.15], P = 0.09). Colon cancer also appeared less commonly in the cases compared with the controls (OR 0.22 [95% CI 0.03–1.74], P = 0.15).

Conclusion

The findings of this population‐based case–control study indicate that GCA patients had significantly fewer malignancies prior to the index date as compared with controls.

     

Increased frequency of DRB1*11:01 in anti–hydroxymethylglutaryl‐coenzyme A reductase–associated autoimmune myopathy

Objective

To investigate the association of anti–hydroxymethylglutaryl‐coenzyme A reductase (anti‐HMGCR) myopathy with HLA class I and II antigens.

Methods

HLA antigens were determined in 1) 20 white and 8 African American anti‐HMGCR patients, 2) 487 white and 167 African American controls, and 3) 51 white subjects with mild self‐limited statin intolerance.

Results

White anti‐HMGCR patients had a higher frequency of the combination HLA–DR11, DQA5, and DQB7 than controls or statin‐intolerant subjects (70% versus 17%; odds ratio [OR] 11.7 [95% confidence interval (95% CI) 4.0–35.3], P = 4.1 × 10^?7 and 70% versus 21%; OR 8.3 [95% CI 2.2–33.9], P = 5.4 × 10^?4, respectively). This combination was not increased in African American anti‐HMGCR subjects compared to controls (13% versus 3%; OR 4.6 [95% CI 0.2–53.3], P = 0.2). However, DR11 was increased in African American anti‐HMGCR patients compared to controls (88% versus 21%; OR 26.4 [95% CI 3.1–590.3], P = 0.0002). High‐resolution mapping showed that 95% with DR11 had DRB1*11:01. DQA1 and DQB6 were less frequent in white anti‐HMGCR–positive patients compared to controls (25% versus 65%; OR 0.2 [95% CI 0.1–0.5], P = 5.5 × 10^?4 and 0% versus 45%; OR 0.0 [95% CI 0.0–0.3], P = 2.1 × 10^?5, respectively). DRB11 was not associated with particular disease features.

Conclusion

DRB1*11:01 is associated with an increased risk of anti‐HMGCR myopathy in whites and African Americans. These findings suggest a mechanistic link between statin exposure, increased HMGCR expression, and the possible presentation of HMGCR‐derived peptide(s) by DRB1*11:01.

     

Effects of rosuvastatin on vascular biomarkers and carotid atherosclerosis in lupus: a randomized, double-blind, placebo-controlled trial

Objective

To study the effect of rosuvastatin on vascular biomarkers and carotid intima‐media thickness (IMT) in systemic lupus erythematosus (SLE).

Methods

SLE patients with inactive disease and subclinical atherosclerosis were randomized in a double‐blinded manner to receive either rosuvastatin (10 mg/day) or matching placebo (half in each group were also randomly allocated low‐dose aspirin). After 12 months, treatment was unblinded. Patients treated with rosuvastatin and aspirin were continued on the same medications for another 12 months. Plasma levels of homocysteine, high‐sensitivity C‐reactive protein (hsCRP), soluble vascular cell adhesion molecule 1, P‐selectin, and thrombomodulin were measured at baseline, 6 months, and 12 months. Measurement of carotid IMT was repeated at 24 months.

Results

Seventy‐two patients were studied (97% women, mean ± SD age 50.8 ± 9.7 years). Thirty‐six patients were randomly assigned to each of the study arms (18 patients in each arm also received aspirin). Baseline clinical characteristics and medications were similar between the two groups. At 12 months, the mean low‐density lipoprotein cholesterol (mean ± SD 2.62 ± 1.04 mmoles/liter to 1.69 ± 0.72 mmoles/liter; P < 0.001) and median hsCRP levels (1.26 mg/liter, interquartile range [IQR] 2.3 to 0.88 mg/liter, IQR 1.1; P = 0.02) decreased significantly in the rosuvastatin group. There was no significant change in homocysteine, and aspirin use did not influence the levels of the biomarkers studied. A subgroup analysis of patients with a Systemic Lupus Erythematosus Disease Activity Index score ≤2 revealed a significant decrease in hsCRP (1.20 mg/liter, IQR 2.3 to 0.92 mg/liter, IQR 1.1; P = 0.04) and thrombomodulin levels (0.76 ng/ml, IQR 1.2 to 0.67 ng/ml, IQR 1.0; P = 0.001) with rosuvastatin treatment. At 24 months, the IMT of the internal carotid arteries appeared to be decreased in patients treated with rosuvastatin, which was well tolerated.

Conclusion

In stable SLE patients, low‐dose rosuvastatin leads to a significant reduction in hsCRP and thrombomodulin levels, which may possibly help to reduce cardiovascular risk.     

Kidney dysfunction and deterioration of ejection fraction pose independent risk factors for mortality in implantable cardioverter-defibrillator recipients for primary prevention

Background:

A growing number of patients with advanced heart failure fulfill a primary‐prevention indication for an implantable cardioverter‐defibrillator (ICD). This study seeks to identify new predictors of overall mortality in a Sudden Cardiac Death in Heart Failure Trial (SCD‐HeFT)‐like collective to enhance risk stratification.

Hypothesis:

An impaired renal function and severely depressed left ventricular ejection fraction pose relevant risk factors for mortality in primary prevention ICD recipients.

Methods:

Ninety‐four consecutive ICD patients with New York Heart Association class II–III heart failure and depressed left ventricular function (left ventricular ejection fraction [LVEF] ≤35%) with no history of malignant ventricular arrhythmias were followed for 34 ± 20 months.

Results:

During this period, 30 patients died (32%). Deceased patients revealed a significantly worse renal function before ICD implantation (1.55 ± 0.7 mg/dL vs 1.1 ± 0.4 mg/dL; P = 0.007), suffered more often from coronary artery disease (53 vs 29; P = 0.006), and were older (69.5 ± 8 y vs 67 ± 12 y; P = 0.0002) than surviving patients. Furthermore, increased serum creatinine at baseline (2 mg/dL vs 1 mg/dL; odds ratio [OR]: 3.96, 95% confidence interval [CI]: 1.2–13.04, P = 0.02), presence of coronary artery disease (OR: 8.6, 95% CI: 1.1–65, P = 0.036), and low LVEF (OR per 5% baseline LVEF deterioration: 1.4, 95% CI: 1–1.8, P = 0.034) represented strong and independent predictors for overall mortality.

Conclusions:

Impaired renal function, the presence of coronary artery disease, and reduced LVEF before implantation represent independent predictors for mortality in a cohort of patients with advanced systolic heart failure. These conditions still bear a high mortality risk, even if ICD implantation effectively prevents sudden arrhythmic death. Indeed, in patients suffering from several of the identified “high‐risk” comorbidities, primary‐prevention ICD implantation might have a limited survival benefit. The possible adverse effects of these comorbidities should be openly discussed with the potential ICD recipient and his or her close relatives. Clin. Cardiol. 2012 doi: 10.1002/clc.22018 The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Prevalence of atherosclerotic risk factors and the metabolic syndrome in patients with chronic inflammatory arthritis

Objective

To evaluate the prevalence of the metabolic syndrome in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA).

Methods

Consecutive patients with RA, AS, or PsA who attended our outpatient arthritis clinics between July and November 2009 were recruited for a study of atherosclerotic risk factors and the metabolic syndrome, defined according to the 2009 joint statements using the Asian criteria for central obesity.

Results

Nine hundred thirty patients were studied (699 with RA, 122 with AS, and 109 with PsA; 70% women, mean ± SD age 51.1 ± 12.7 years). The mean ± SD disease duration for patients with RA, AS, and PsA was 5.3 ± 5.4, 6.0 ± 5.6, and 3.6 ± 3.1 years, respectively. The prevalence of metabolic syndrome was significantly higher in PsA (38%) than RA (20%) or AS (11%; P < 0.001). The odds ratios (ORs) for the metabolic syndrome compared to age‐ and sex‐matched controls were 0.98 (95% confidence interval [95% CI] 0.78–1.23, P = 0.88), 0.59 (95% CI 0.30–1.15, P = 0.12), and 2.68 (95% CI 1.60–4.50, P < 0.001), respectively, for RA, AS, and PsA. Patients with PsA had a significantly higher prevalence of impaired fasting glucose (30%; P < 0.001), low high‐density lipoprotein (HDL) cholesterol (33%; P < 0.001), high triglycerides level (21%; P = 0.008), central obesity (65%; P < 0.001), and high blood pressure (56%; P = 0.045). In a logistic regression model, the adjusted OR for the metabolic syndrome in PsA was 2.44 (95% CI 1.48–4.01, P < 0.001) relative to RA or AS. The adjusted ORs for central obesity, impaired fasting glucose, hypertriglyceridemia, and low HDL cholesterol were also significantly higher in PsA patients.

Conclusion

Patients with PsA, but not RA or AS, have a significantly higher prevalence of the metabolic syndrome compared to the general population. Among the 3 diseases studied, PsA has the highest prevalence of the metabolic syndrome and is associated with the highest cardiovascular risk.     

Study of functional variants of the BANK1 gene in rheumatoid arthritis

Objective

To investigate 1 functional (rs17266594) and 2 potentially functional (rs10516487 and rs3733197) BANK1 variants, which were previously identified as systemic lupus erythematosus (SLE) susceptibility markers, to test whether they are associated with rheumatoid arthritis (RA).

Methods

Four different cohorts were included in the study: 1,080 RA patients and 1,368 healthy controls from Spain, 278 RA patients and 568 healthy controls from Sweden, 288 RA patients and 287 healthy controls from Argentina, and 288 RA patients and 288 healthy controls from Mexico. Samples were genotyped for BANK1 single‐nucleotide polymorphisms (SNPs) using a TaqMan 5′‐allele discrimination assay. Statistical analysis comparing allele and genotype distributions was performed with the chi‐square test.

Results

We did not find a significant association between RA and the rs10516487 and rs17266594 BANK1 polymorphisms. However, there was an increase in the major alleles among RA patients. Similarly, for rs3733197, there was an increase in the major allele among patients in every cohort. Nevertheless, this skewing reached statistical significance in the Spanish (P = 0.01, odds ratio [OR] 1.17 [95% confidence interval (95% CI) 1.03–1.32]) and Argentinean (P = 0.04, OR 1.31 [95% CI 1.00–1.72]) populations. We found a significant association of rs10516487 (P = 0.005, OR 1.15 [95% CI 1.04–1.28]) and rs3733197 (P = 0.0009, OR 1.17 [95% CI 1.07–1.29]) with RA in the pooled analysis. In a 3‐SNP haplotype analysis, we found that the major TGG haplotype was significantly associated with RA (P = 0.005, OR 1.14 [95% CI 1.04–1.25]). In addition, we found a common CAA haplotype that was protective against RA (P = 0.0004, OR 0.82 [95% CI 0.74–0.92]).

Conclusion

These results suggest that BANK1 SNPs and haplotypes may contribute to RA susceptibility with a low risk.

     

Dyslipidemia,Alcohol Consumption,and Obesity as Main Factors Associated With Poor Control of Urate Levels in Patients Receiving Urate‐Lowering Therapy

Objective

In real life, in a substantial proportion of gouty patients receiving urate‐lowering therapy (ULT), urate levels are not maintained below the target of 6.0 mg/dl. We aimed to search for factors associated with poor control of serum uric acid (UA) levels in a large population of patients with gout receiving ULT.

Methods

This cross‐sectional study involved adults with gout in primary care who were receiving ULT. Demographics, gout history, comorbidities, lifestyle, clinical factors, concomitant treatments, and laboratory data were compared in well‐controlled gout (serum UA ≤6.0 mg/dl) versus poorly controlled gout (serum UA >6.0 mg/dl) on univariate and multivariate analyses.

Results

Among the 1,995 patients receiving ULT, only 445 (22.3%) had reached the target of 6.0 mg/dl serum UA. Such patients had a lower rate of gout flares within the previous year than patients without the target (mean ± SD 1.7 ± 1.4 versus 2.1 ± 1.4; P < 0.0001). The main factors associated with poor serum UA level control in multivariate analysis were low high‐density lipoprotein cholesterol level (adjusted odds ratio [OR] 0.5 [95% confidence interval (95% CI) 0.26–0.96]; P = 0.04), high total cholesterol level (OR 1.83 [95% CI 1.29–2.60]; P = 0.0007), increased waist circumference (OR 1.55 [95% CI 1.11–2.13]; P = 0.008), and alcohol consumption (OR 1.52 [95% CI 1.15–2.00]; P = 0.003).

Conclusion

Dyslipidemia, abdominal obesity, and alcohol consumption are the main factors associated with a poor response to ULT. Knowledge of these factors might help physicians identify cases of gout that may be less likely to achieve target urate level.

     

Post‐dilation in transcatheter aortic valve replacement: A systematic review and meta‐analysis

Objectives

The aim of this study was to perform a meta‐analysis to compare the outcomes of patients undergoing TAVR with and without balloon post‐dilation (PD).

Background

PD is a commonly used technique in TAVR to minimize paravalvular regurgitation (PVR), albeit supported by little evidence.

Methods

Systematic review and meta‐analysis of 6 studies comparing 889 patients who had PD compared to 4118 patients without PD.

Results

Patients undergoing PD were more likely male (OR 1.92; 95% CI, 1.41‐2.61; P < 0.001) and to have coronary artery disease (OR 1.31; 95% CI, 1.03‐1.68; P = 0.03) than those patients not requiring PD. There were no significant differences in 30‐day mortality (OR 1.24; 95% CI, 0.88‐1.74; P = 0.22) and myocardial infarction (OR 0.93; 95% CI, 0.46‐1.90; P = 0.85). Patients undergoing TAVR did not have higher 1‐year mortality rates (OR 0.98; 95% CI, 0.61‐1.56; P = 0.92). The incidence of stroke was significantly greater in patients with PD (OR, 1.71; 95% CI, 1.10‐2.66). PD was able to reduce the incidence of moderate‐severe PVR by 15 fold (OR 15.0; 95% CI, 4.2‐54.5; P < 0.001), although rates of moderate‐severe PVR were still higher after PD than patients who did not require PD (OR 3.64; 95% CI, 1.96‐6.75; P < 0.001).

Conclusions

PD significantly improves rates of PVR, however careful patient selection is needed to minimize increased risk of strokes.

     

Insulin resistance, inflammation, and vascular disease in nondiabetic predialysis chronic kidney disease patients

Background:

Chronic kidney disease (CKD) is associated with high cardiovascular morbidity and mortality, which is not fully explained by traditional risk factors; hence, the interest in nontraditional risk factors such as inflammation and insulin resistance (IR). Though IR is shown in nondiabetic CKD, its association with vascular disease and inflammation in this population is unknown, and is what this study aims to investigate.

Hypothesis:

IR and inflammation are related to vascular disease in nondiabetic predialysis CKD patients.

Methods:

We studied carotid‐artery intima‐media thickness (IMT) and endothelial function (brachial artery flow mediated dilation [FMD]) in 35 nondiabetic predialysis patients with stage 3–5 CKD and 35 age‐ and gender‐matched controls. Insulin resistance was measured using the homeostasis model assessment for insulin resistance score (HOMA‐IR), inflammation by high‐sensitivity CRP (hsCRP), and their relationship with FMD and IMT.

Results:

Patients with CKD showed reduced FMD (3.34 ± 2.14% vs 5.27 ± 1.78%, P<0.001) and increased IMT (0.78 ± 0.22 mm vs 0.64 ± 0.16 mm, P = 0.003) compared with controls. The CKD patients had a higher HOMA‐IR (2.20 ± 1.08 vs 1.13 ± 0.64, P<0.001) and hsCRP (3.25 ± 5.47 mg/L vs 1.10 ± 1.85 mg/L [median ± interquartile range], P = 0.02). In the study population, HOMA‐IR was directly related to hsCRP. After adjusting for traditional risk factors, high HOMA‐IR and hsCRP were significantly related to decreased FMD (adjusted β = ? 0.44, 95% confidence interval [CI]: ? 1.55 to ? 0.08, P = 0.003 and adjusted β = ? 0.51, 95% CI: ? 0.51 to ? 0.15, P = 0.001) and increased IMT (adjusted β = 0.62, 95% CI: 0.54–1.90, P = 0.001 and adjusted β = 0.43, 95% CI: 0.08–0.57, P = 0.011), respectively.

Conclusions:

Subjects with systemic inflammation were more insulin‐resistant, and in nondiabetic predialysis CKD, IR and systemic inflammation were independently associated with endothelial dysfunction and atherosclerosis. © 2011 Wiley Periodicals, Inc. Dr. Debasish Banerjee and Dr. Alejandro Recio‐Mayoral are joint first authors. This study has been supported by grants awarded by the Spanish Society of Cardiology to Dr. A. Recio‐Mayoral and by the St. George's Charitable Foundation to Dr. D. Banerjee. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

     

A strong initial systemic inflammatory response is associated with higher corticosteroid requirements and longer duration of therapy in patients with giant‐cell arteritis

Objective

To assess whether the intensity of the initial systemic inflammatory response is able to predict response to therapy in patients with giant cell arteritis (GCA).

Methods

Retrospective review of 75 patients (49 women and 26 men) with biopsy‐proven GCA who had regular followup and were treated according to uniform criteria. Four parameters were used to evaluate the baseline inflammatory response at diagnosis: fever, weight loss, erythrocyte sedimentation rate ≥ 85 mm/hour, and hemoglobin < 110 gm/liter. Patients were considered to have a weak inflammatory response if they had 2 or fewer inflammatory parameters (group 1) and a strong inflammatory response if 3 or 4 parameters were present (group 2). Time required to achieve a maintenance dose of less than 10 mg prednisone/day was recorded and analyzed by the Kaplan–Meier survival analysis method. Tumor necrosis factor α (TNFα) and interleukin 6 (IL‐6) serum levels were also determined in 62 patients and 15 controls.

Results

Forty patients had a weak (group 1) and 35 had a strong (group 2) initial inflammatory response. Patients in group 2 had significantly higher levels of circulating TNFα (31.9 ± 16.8 versus 22.3 ± 9 pg/ml; P = 0.01) and IL‐6 (28.2 ± 17.4 versus 16.6 ± 13 pg/ml; P = 0.004) than patients in group 1. In group 1, 50% of patients required a median of 40 weeks (95% CI 37–43) to reach a maintenance dose of <10 mg, whereas in group 2 a median of 62 weeks (95% CI 42–82) was necessary (P = 0.0062). Patients in group 2 experienced more flares than patients in group 1 (P = 0.01) and received higher cumulative steroid doses (8.974 ± 3.939 gm versus 6.893 ± 3.075 gm; P = 0.01).

Conclusion

GCA patients with a strong initial systemic inflammatory reaction have more elevated circulating levels of IL‐6 and TNFα, have higher and more prolonged corticosteroid requirements, and experience more disease flares during corticosteroid therapy than patients with a weak systemic acute phase response.

     

Clinical predictors and outcomes of patients with pericardial effusion in chronic kidney disease

Background

Pericardial effusion is common in hospitalized patients with chronic kidney disease (CKD). We sought to identify predictors and prognostic impact of pericardial effusion in CKD patients.

Hypothesis

Clinical and biochemical parameters can predict pericardial effusion in CKD patients.

Methods

In a retrospective nested case‐control design, we analyzed hospitalized adult patients with CKD stage 4, 5, or end‐stage renal disease diagnosed with pericardial effusion. Controls were same‐stage CKD patients without effusion.

Results

Among 84 cases and 61 controls, 44% and 34% were on dialysis, respectively. The mean creatinine was higher among cases versus controls (8.4±6.0 vs. 6.0±3.4 mg/dL, P = 0.002). Effusion was moderate to large in 46% of cases. Independent predictors of any pericardial effusion were serum potassium (OR: 1.95 per 1‐mEq/L increment, 95% CI: 1.21–3.13, P = 0.006), serum corrected calcium (OR: 1.33 per 1‐mg/dL decrement, 95% CI: 1.11–1.67, P = 0.015), and admission heart rate (OR: 1.29 per 10‐bpm increment, 95% CI: 1.03–1.62, P = 0.027). Corrected calcium level was an independent predictor of moderate to large pericardial effusion (OR: 1.38 per 1‐mg/dL decrement, 95% CI: 1.04–1.82, P = 0.023). Corrected calcium <8.0 mg/dL demonstrated 95% specificity for moderate to large effusion. Patients with effusion had no significant difference in the composite endpoint of mortality or cardiovascular rehospitalization (P = 0.408).

Conclusions

In hospitalized CKD patients, hypocalcemia may be useful in identifying those with moderate to large pericardial effusion. In this population, pericardial effusion does not seem to be associated with adverse outcomes.     

Positive association of SLC26A2 gene polymorphisms with susceptibility to systemic‐onset juvenile idiopathic arthritis

Objective

To investigate SLC26A2, the gene that causes diastrophic dysplasia, in juvenile idiopathic arthritis (JIA).

Methods

Nine polymorphisms across the SLC26A2 gene locus were investigated using MassArray genotyping in 826 UK Caucasian JIA cases and 617 ethnically matched healthy controls.

Results

Significant associations between multiple single‐nucleotide polymorphisms (SNPs) across SLC26A2 and systemic‐onset JIA were found. In each case, homozygosity for the minor allele conferred the increased risk of disease susceptibility: rs1541915 (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 1.4–3.7, P = 0.0003), rs245056 (OR 2.8, 95% CI 1.7–4.6, P = 0.00002), rs245055 (OR 2.5, 95% CI 1.2–5.0, P = 0.004), rs245051 (OR 2.3, 95% CI 1.4–3.7, P = 0.0005), rs245076 (OR 2.7, 95% CI 1.3–5.4, P = 0.0015), and rs8073 (OR 2.3, 95% CI 0.9–5.6, P = 0.04).

Conclusion

These findings show the value of using monogenic disease loci as candidates for investigation in JIA. We identified a subgroup‐specific association between SNPs within the SLC26A2 gene and systemic‐onset JIA. Our findings also highlight systemic‐onset JIA as being a distinctly different disease from that in the other JIA subgroups.

     

Combined spa–exercise therapy is effective in patients with ankylosing spondylitis: a randomized controlled trial

Objective

To determine the efficacy of combined spa–exercise therapy in addition to standard treatment with drugs and weekly group physical therapy in patients with ankylosing spondylitis (AS).

Methods

A total of 120 Dutch outpatients with AS were randomly allocated into 3 groups of 40 patients each. Group 1 (mean age 48 ± 10 years; male:female ratio 25:15) was treated in a spa resort in Bad Hofgastein, Austria; group 2 (mean age 49 ± 9 years; male:female ratio 28:12) in a spa resort in Arcen, The Netherlands. The control group (mean age 48 ± 10 years; male:female ratio 34:6) stayed at home and continued their usual drug treatment and weekly group physical therapy during the intervention weeks. Standardized spa–exercise therapy of 3 weeks duration consisted of group physical exercises, walking, correction therapy (lying supine on a bed), hydrotherapy, sports, and visits to either the Gasteiner Heilstollen (Austria) or sauna (Netherlands). After spa–exercise therapy all patients followed weekly group physical therapy for another 37 weeks. Primary outcomes were functional ability, patient's global well‐being, pain, and duration of morning stiffness, aggregated in a pooled index of change (PIC).

Results

Analysis of variance showed a statistically significant time–effect (P < 0.001) and time‐by‐treatment interaction (P = 0.004), indicating that the 3 groups differed over time with respect to the course of the PIC. Four weeks after start of spa–exercise therapy, the mean difference in PIC between group 1 and controls was 0.49 (95% confidence interval [CI] 0.16–0.82, P = 0.004) and between group 2 and controls was 0.46 (95% CI 0.15–0.78, P = 0.005). At 16 weeks, the difference between group 1 and controls was 0.63 (95% CI 0.23–1.02, P = 0.002) and between group 2 and controls was 0.34 (95% CI − 0.05–0.73; P = 0.086). At 28 and 40 weeks, more improvement was found for group 1 compared with controls (P = 0.012 and P = 0.062, respectively) but not for group 2 compared with controls.

Conclusion

In patients with AS, a 3‐week course of combined spa–exercise therapy, in addition to drug treatment and weekly group physical therapy alone, provides beneficial effects. These beneficial effects may last for at least 40 weeks.

     

Association of a functional single‐nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase,with rheumatoid arthritis and systemic lupus erythematosus

Objective

To assess the possible association between the PTPN22 gene 1858C→T polymorphism and the predisposition and clinical expression of 2 systemic autoimmune diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

Methods

Our study population consisted of 826 RA patients, 338 SLE patients, and 1,036 healthy subjects. All subjects were of Spanish Caucasian origin. Genotyping of the PTPN22 gene 1858C→T polymorphism was performed by real‐time polymerase chain reaction technology, using the TaqMan 5′‐allele discrimination assay.

Results

The overall distribution of genotypes in the RA patients was significantly different from that in the controls (P = 0.005, by chi‐square test with 2 × 3 contingency tables). We observed a statistically significant difference in the distribution of the PTPN22 1858T allele between healthy subjects (7.4%), and RA patients (10.4%) (P = 0.001, odds ratio [OR] 1.45 [95% confidence interval (95% CI) 1.15–1.83]). In addition, PTPN22 1858 C/T and T/T genotypes were present at a significantly higher frequency in SLE patients than in controls (P = 0.02, OR 1.55 [95% CI 1.05–2.29]). Differences were also observed when allele frequencies were compared, with the PTPN22 1858T allele being present at a higher frequency among SLE patients (P = 0.03, OR 1.45 [95% CI 1.01–2.09]).

Conclusion

These results suggest that the PTPN22 1858T allele may confer differential susceptibility to RA and SLE in the Spanish population.

     

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.

     

Presence of peripheral arthritis and male sex predicting continuation of anti–tumor necrosis factor therapy in ankylosing spondylitis: An observational prospective cohort study from the South Swedish arthritis treatment group register

Objective

To examine clinical characteristics as possible predictors of long‐term treatment continuation with adalimumab, etanercept, and infliximab in ankylosing spondylitis (AS) patients who had never taken biologics treated in clinical practice.

Methods

Patients in southern Sweden with active AS starting biologic therapy for the first time between October 1999 and December 2008 (n = 243, 75% men) were included in a structured clinical followup over 2 years. Patients with clinical spondylitis had not responded to at least 2 nonsteroidal antiinflammatory drugs, whereas patients who also had peripheral arthritis (n = 121) had additionally failed at least 1 conventional disease‐modifying antirheumatic drug (DMARD) treatment course. The mean ± SD age at inclusion was 43 ± 12 years, with a mean ± SD disease duration prior to treatment of 16 ± 12 years.

Results

The 2‐year drug continuation rate was 74%. Male sex (hazard ratio [HR] of premature discontinuation 0.36 [95% confidence interval (95% CI) 0.19–0.68]) and the presence of peripheral arthritis (HR 0.49 [95% CI 0.27–0.88]) were found to be significant predictors of better drug survival. Furthermore, a trend was seen for more favorable drug continuation on treatment with etanercept as compared with infliximab (HR 0.50 [95% CI 0.25–1.04], P = 0.062), whereas no differences were found comparing the 3 anti–tumor necrosis factor agents in other ways. Higher baseline C‐reactive protein level (HR 0.99 [95% CI 0.97–1.00], P = 0.12) and concomitant treatment with nonbiologic DMARDs (HR 0.61 [95% CI 0.34–1.10], P = 0.10) also showed trends to entail better drug adherence.

Conclusion

AS patients in this study have an excellent 2‐year drug survival rate of 74%. Significant predictors for treatment continuation in this study were male sex and the presence of peripheral arthritis.     

Link between traditional cardiovascular risk factors and inflammation in patients with early arthritis: Results from a French Multicenter Cohort

Objective

To compare the characteristics of traditional cardiovascular risk factors for untreated patients with early arthritis (EA) and healthy subjects, and to look for a link between cardiovascular risk factors and inflammation in EA patients.

Methods

This multicenter case–control study enrolled 607 patients with EA (ESPOIR cohort) and 1,821 age‐ and sex‐matched controls (World Health Organization MONICA survey). Lipid levels, blood pressure, glucose levels, and exposure to smoking were characterized in patients and controls. Systemic inflammation was quantified in EA patients. Traditional cardiovascular risk factor characteristics were compared between patients with EA and controls. The link between cardiovascular risk factors and inflammation was assessed in EA patients.

Results

Mean ± SEM total cholesterol (2.14 ± 0.022 versus 2.34 ± 0.017 gm/liter; P < 0.001), high‐density lipoprotein (HDL) cholesterol (0.60 ± 0.011 versus 0.63 ± 0.007 gm/liter; P = 0.020), and low‐density lipoprotein (LDL) cholesterol (1.28 ± 0.025 versus 1.51 ± 0.016 gm/liter; P < 0.001) were lower in EA patients than in controls. Triglycerides, triglycerides/HDL ratio, and pulse pressure were higher in patients with EA. Diastolic blood pressure and glucose levels were lower in EA patients. Former or current smokers were more frequent in patients with EA. Total and HDL cholesterol levels were negatively associated with C‐reactive protein or serum interleukin‐6 levels.

Conclusion

Total, HDL, and LDL cholesterol, triglycerides, diastolic blood pressure, pulse pressure, glucose, and triglycerides/HDL ratio differ between patients with EA and controls. Some of these risk factors appear to be linked to systemic inflammation. Such initial differences could modulate the risk of cardiovascular events later in the course of arthritis.