Patrick D. Fitz-Gibbon

Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease

Objective To examine the impact of systemic inflammation and serum lipids on cardiovascular disease (CVD) in rheumatoid arthritis (RA). Methods In a population-based RA incident cohort (1987 American College of Rheumatology criteria first met between 1988 and 2007), details were collected of serum lipid measures, erythrocyte sedimentation rates (ESRs), C-reactive protein (CRP) measures and cardiovascular events, including ischaemic heart disease and heart failure. Cox models were used to examine the association of lipids and inflammation with the risk of CVD and mortality, adjusting for age, sex and year of RA incidence. Results The study included 651 patients with RA (mean age 55.8 years, 69% female); 67% were rheumatoid factor positive. ESR was associated with the risk of CVD (HR=1.2 per 10 mm/h increase, 95% CI 1.1 to 1.3). Similar findings, although not statistically significant, were seen with CRP (p=0.07). A significant non-linear association for total cholesterol (TCh) with risk of CVD was found, with 3.3-fold increased risk for TCh <4 mmol/l (95% CI 1.5 to 7.2) and no increased risk of CVD for TCh ≥4 mmol/l (p=0.57). Low low-density lipoprotein cholesterol (LDL <2 mmol/l) was associated with marginally increased risk of CVD (p=0.10); there was no increased risk for LDL ≥2 mmol/l (p=0.76). Conclusion Inflammatory measures (particularly, ESR) are significantly associated with the risk of CVD in RA. Lipids may have paradoxical associations with the risk of CVD in RA, whereby lower TCh and LDL levels are associated with increased cardiovascular risk.

Total Cholesterol and LDL levels decrease before rheumatoid arthritis

Objectives To compare lipid profiles in patients with rheumatoid arthritis (RA) and in non-RA subjects during the 5 years before and 5 years after the RA incidence/index date. Methods Lipid measures were abstracted in a population-based incident cohort of patients with RA (1987 American College of Rheumatology criteria) first diagnosed between 1 January 1988 and 1 January 2008 and in non-RA subjects. Random-effects models adjusting for age, sex and calendar year were used to examine trends in lipid profiles, accounting for multiple measurements for each subject. Results The study population included a cohort of 577 patients with RA (a total of 3088 lipid measurements) and 540 non-RA subjects (a total of 3048 lipid measurements). There were significant decreases in total (TC) and low-density lipoprotein cholesterol (LDL) levels in the RA cohort during the 5 years before RA, compared with the non-RA cohort (p<0.001). Decreases of 0.58 mmol/l for TC and 0.61 mmol/l for LDL were noted in RA compared with decreases of 0.09 mmol/l for TC and 0.22 mmol/l for LDL in the non-RA cohort. Trends in other lipid measures (triglycerides (TGs) and high-density lipoprotein cholesterol (HDL)) were similar in RA and non-RA cohorts during the 5 years before and 5 years after the RA incidence/index date. During the 5 years before the RA incidence/index date, the proportion of patients with RA with elevated TC or LDL measures, but not with abnormal HDL and TG measures, significantly decreased compared with non-RA subjects. Lipid-lowering drugs (statins in particular) were less often prescribed to patients with RA than to non-RA subjects (34% vs 41%; p=0.02). Conclusion TC and LDL levels and the prevalence of abnormal TC or LDL measures decreased significantly during the 5 years before the RA incidence/index date in patients with RA as compared with the non-RA cohort. These trends in lipid profile in RA are unlikely to be solely due to lipid-lowering treatment.

Podocyturia Predates Proteinuria and Clinical Features of Preeclampsia: Longitudinal Prospective Study

Podocyturia, the shedding of live podocytes, is present at delivery in women with preeclampsia. The aim of this study was to test whether podocyturia is present earlier in pregnancy and predicts for preeclampsia. We also aimed to compare test characteristics of podocyturia with those of angiogenic factors previously implicated in the pathogenesis of this disorder. We prospectively enrolled 315 women who provided blood and urine samples at the end of the second trimesters of their pregnancies (median, 27 gestational weeks) and within 24 hours of their deliveries (median, 39.5 gestational weeks). Blood samples were analyzed for angiogenic markers, including placental growth factor, the soluble receptor fms-like tyrosine kinase receptor-1 for vascular endothelial growth factor, and endoglin. The urine sediments were analyzed for podocytes, identified by staining for podocin after culturing the urinary sediments for 24 hours. This analysis included all women who developed preeclampsia (n=15), gestational hypertension (n=15), and a subsample of women who remained normotensive throughout pregnancy (n=44), matched for maternal age and number of previous pregnancies to those who developed preeclampsia. At the second trimester collection, all women who developed preeclampsia had podocyturia, compared with none of those who remained normotensive or were diagnosed with gestational hypertension. Podocyturia in the second trimester had a significantly greater sensitivity and specificity for the subsequent diagnosis of preeclampsia than any single angiogenic marker or a combination thereof. Screening for podocyturia at the end of the second trimester may allow for accurate identification of pregnant women at risk for preeclampsia.

Increased Prevalence of Metabolic Syndrome Associated with Rheumatoid Arthritis in Patients without Clinical Cardiovascular Disease

Objective. To examine whether patients with rheumatoid arthritis (RA) with no overt cardiovascular disease (CVD) have a higher prevalence of metabolic syndrome (MetS) than subjects without RA or CVD. We also examined whether RA disease characteristics are associated with the presence of MetS in RA patients without CVD. Methods. Subjects from a population-based cohort of patients who fulfilled 1987 American College of Rheumatology criteria for RA between January 1, 1980, and December 31, 2007, were compared to non-RA subjects from the same population. All subjects with any history of CVD were excluded. Waist circumference, body mass index (BMI), and blood pressure were measured during the study visit. Data on CVD, lipids, and glucose measures were ascertained from medical records. MetS was defined using NCEP/ATP III criteria. Differences between the 2 cohorts were examined using logistic regression models adjusted for age and sex. Results. The study included 232 RA subjects without CVD and 1241 non-RA subjects without CVD. RA patients were significantly more likely to have increased waist circumference and elevated blood pressure than non-RA subjects, even though BMI was similar in both groups. Significantly more RA patients were classified as having MetS. In RA patients, MetS was associated with Health Assessment Questionnaire Disability Index, large-joint swelling, and uric acid levels, but not with C-reactive protein or RA therapies. Conclusion. Among subjects with no history of CVD, patients with RA are more likely to have MetS than non-RA subjects. MetS in patients with RA was associated with some measures of disease activity.

Gadolinium Enhanced Magnetic Resonance Urography for Upper Urinary Tract Malignancy

PURPOSE We retrospectively evaluated the accuracy of gadolinium enhanced magnetic resonance urography to detect upper urinary tract tumors. MATERIALS AND METHODS A total of 91 magnetic resonance urography studies for suspected upper tract malignancy were done in 70 males and 18 females with a mean age of 71.7 years. Breath hold coronal T2-weighted single shot fast spin-echo and breath-hold coronal 3-dimensional T1-weighted spoiled gradient-recalled echo images with fat suppression were obtained during the nephrographic and excretory phases after intravenous injection of gadolinium based contrast material. Two radiologists independently reviewed magnetic resonance images for a tumor by 4 regions (right/left and renal collecting system/ureter). Sensitivity, specificity and accuracy were calculated. RESULTS A total of 35 urinary tract regions in 18 males and 7 females with a mean age of 70.4 years were confirmed to have an upper tract malignant tumor and 219 urinary tract regions were confirmed to be tumor-free. Sensitivity, specificity and accuracy to detect upper urinary tract malignancy were 74.3%, 96.8% and 93.7% for reviewer 1, and 62.9%, 96.3% and 91.7% for reviewer 2, respectively. When patients with a ureteral stent or nephrostomy tube were excluded from analysis, sensitivity, specificity and accuracy were 86.2%, 99.5% and 97.7% for reviewer 1, and 72.4%, 97.9% and 94.6% for reviewer 2, respectively. CONCLUSIONS Gadolinium enhanced magnetic resonance urography is accurate to detect upper urinary tract malignant tumors.

Efficacy of Intra-Articular Botulinum Toxin Type A in Painful Knee Osteoarthritis: A Pilot Study

To evaluate the efficacy and safety of botulinum toxin type A (BoNT‐A) injected intra‐articularly in 60 subjects with moderate pain and functional impairment secondary to knee osteoarthritis. The study investigators hypothesized that intra‐articular BoNT‐A would result in statistically significant improvements in pain and function at 8 weeks.

Development and validation of a risk score for serious infection in patients with rheumatoid arthritis

OBJECTIVE Infection risk is increased in patients with rheumatoid arthritis (RA), and accurate assessment of the risk of infection could inform clinical decision-making. This study was undertaken to develop and validate a score to predict the 1-year risk of serious infection in patients with RA. METHODS We studied a population-based cohort of Olmsted County, Minnesota residents with incident RA ascertained in 1955-1994 whose members were followed up longitudinally, via complete medical records, until January 2000. The validation cohort included residents with incident RA ascertained in 1995-2007. The outcome measure included all serious infections (requiring hospitalization or intravenous antibiotics). Potential predictors were examined using multivariable Cox models. The risk score was estimated directly from the multivariable model, and performance was assessed in the validation cohort using Harrells C statistic. RESULTS Among the 584 RA patients in the original cohort (72% female; mean age 57.5 years), who were followed up for a median of 9.9 years, 252 had ≥ 1 serious infection (646 total infections). Components of the risk score included age, previous serious infection, corticosteroid use, elevated erythrocyte sedimentation rate, extraarticular manifestations of RA, and comorbidities (coronary heart disease, heart failure, peripheral vascular disease, chronic lung disease, diabetes mellitus, alcoholism). Validation analysis revealed good discrimination (C statistic 0.80). CONCLUSION RA disease characteristics and comorbidities can be used to accurately assess the risk of serious infection in patients with RA. Knowledge of risk of serious infection in RA patients can influence clinical decision making and inform strategies to reduce and prevent the occurrence of these infections.

Enchondromas of the Hand: Factors Affecting Recurrence, Healing, Motion, and Malignant Transformation

PURPOSE Enchondromas represent the most common primary bone tumor in the hand. Despite their frequency, a standardized treatment protocol is lacking. This study examines the outcome of surgically treated enchondromas of the hand with regard to tumor location, graft choice, and presence or absence of fracture. METHODS We retrospectively reviewed 102 enchondromas in 80 patients, identified between 1991 and 2008, with a mean clinical follow-up of 38 months. We assessed the effects of age, tumor location, and graft choice on outcomes for all lesions. Patients presenting with Ollier disease, Maffucci syndrome, pathologic fractures, or recurrent disease were separated for additional analysis. RESULTS Of the 102 lesions, 62 (61%) achieved complete radiographic healing in a median time of 6 months. Full range of motion was achieved following treatment of 68 lesions (67%) in a median time of 3 months. A total of 95 lesions (93%) remained recurrence free following surgery. One case of malignant transformation occurred in a patient with Maffucci syndrome. Tumor location and graft choice did not affect healing grade, time to healing, range of motion, or recurrence rate. Age at presentation greater than 30 was associated with more rapid healing. Monocentric, nonexpanding lesions were associated with improved postoperative range of motion. Patients with a diagnosis of multiple enchondromas had a higher rate of recurrence following surgery, and patients presenting with a recurrent lesion had a higher rate of complications. Following pathologic fracture, no differences in outcomes were observed when enchondromas were treated primarily or following fracture healing. CONCLUSIONS Following surgical treatment of enchondromas in the hand, the majority of patients achieve complete bony healing and full range of motion, regardless of the graft material used. Malignant transformation is rare, and aggressive follow-up measures should be reserved for patients with a diagnosis of multiple enchondromas. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV.

Persistent Urinary Podocyte Loss following Preeclampsia May Reflect Subclinical Renal Injury

Objective Studies have shown that podocyturia, i.e., urinary loss of viable podocytes (glomerular epithelial cells), is associated with proteinuria in preeclampsia. We postulated that urinary podocyte loss may persist after preeclamptic pregnancies, thus resulting in renal injury. This may lead to future chronic renal injury. In addition, we compared the postpartum levels of the angiogenic factors, which previously have been associated with preeclampsia, between normotensive versus preeclamptic pregnancies. Study Design The diagnosis of preeclampsia was confirmed using standard clinical criteria. Random blood and urine samples were obtained within 24 hours prior to delivery and 5 to 8 weeks postpartum. Urine sediments were cultured for 24 hours to select for viable cells and staining for podocin was used to identify podocytes. Serum samples were analyzed for the levels of angiogenic markers using ELISA (enzyme-linked immunosorbent assay) methodology. Results At delivery, preeclamptic patients (n = 10) had significantly higher proteinuria (p = 0.006) and podocyturia (p<0.001) than normotensive pregnant patients (n = 18). Postpartum proteinuria was similar between these two groups (p = 0.37), while podocyturia was present in 3 of 10 women with preeclampsia and in none of the normotensive controls (p = 0.037). Angiogenic marker levels, including placental growth factor, soluble vascular endothelial growth factor receptor fms-like tyrosine kinase receptor-1 and endoglin, were not significantly different between women with preeclampsia and women with a normotensive pregnancy, either at delivery or postpartum. Conclusion Persistent urinary podocyte loss after preeclamptic pregnancies may constitute a marker of ongoing, subclinical renal injury.

Do Rheumatoid Arthritis Patients Have a Higher Risk for Sleep Apnea

Objective. Patients with rheumatoid arthritis (RA) have an increased risk for developing cardiovascular disease (CVD) compared to subjects in the general population. The development of CVD has also been linked to chronic sleep apnea. The purpose of this study was to examine the risk for sleep apnea in patients with RA compared to subjects without RA. Methods. We recruited RA patients and non-RA subjects who were age and sex matched from the same population. These persons completed the Berlin Sleep Questionnaire, which evaluated their level of risk (high or low) for sleep apnea. In addition, there were 3 subscales evaluating snoring, fatigue, and relevant comorbidities [i.e., high blood pressure and obesity [body mass index (BMI) ≥ 30 kg/m2)]. Chi-squared tests were used for comparisons. Results. The study population consisted of 164 patients with RA and 328 patients without RA. Age, sex and BMI were similar for both groups. There was no difference in snoring (p = 0.31) or in the comorbidities subscale (p = 0.37). However, RA patients reported more fatigue (38%) than subjects without RA (13%; p < 0.001). Overall, the risk for sleep apnea was significantly higher for the RA patients (50%) than the non-RA subjects (31%; p < 0.001). Conclusion. Patients with RA may be at a higher risk for sleep apnea compared to non-RA subjects. This apparent risk difference may be attributed to reports of fatigue in RA patients, which may be associated with sleep apnea or RA disease itself.