Joshua F. Baker

Serum uric acid level and risk for peripheral arterial disease : Analysis of data from the multiple risk factor intervention trial

Although several studies report an association between hyperuricemia and coronary artery disease, little is known about the effect of hyperuricemia and gout on the risk of peripheral arterial disease (PAD). Data on 283 incident clinical cases of PAD during a randomized controlled trial of multiple cardiovascular risk factor intervention are evaluated. The serum uric acid levels among these individuals are compared with those of individuals who did not develop PAD during the study period. Multivariate logistic regression analyses measure the risk of developing PAD associated with higher levels of serum uric acid after adjusting for the effect of traditional vascular risk factors. Age and smoking are independently associated with development of PAD, with odds ratios of 1.08 (95% confidence interval [CI], 1.06-1.09) and 3.83 (95% CI, 2.49-5.91) per year, respectively. Hyperuricemia (serum uric acid level, >7.0 mg/dL) is an independent risk factor, with an odds ratio of 1.23, but the confidence interval of the estimate is wide (95% CI, 0.98-1.54). In this multivariate model, a history of gout was associated with an odds ratio of 1.33 (95% CI, 1.07-1.66). Serum uric acid level is independently associated with a higher (but statistically nonsignificant) risk of PAD. A history of gouty arthritis is an independent and statistically significant predictor of incidence of PAD even after adjustment for the effect of underlying hyperuricemia.

Early MRI measures independently predict 1-year and 2-year radiographic progression in rheumatoid arthritis: secondary analysis from a large clinical trial

Objective To determine if early MRI measures predict X-ray progression at 1 and 2 years in a large RA trial cohort. Design This study included 256 methotrexate (MTX)-naïve RA patients from a randomised placebo-controlled trial of golimumab (GO-BEFORE). MRIs of wrist and 2nd–5th metacarpophalangeal joints at 0, 12, 24, 52 and 104 weeks were obtained and scored using the RAMRIS system. Multivariable logistic regression examined if baseline and early change (weeks 12/24) in RAMRIS scores independently predicted progression of the van der Heijde-Sharp (vdHS) score and MRI erosion score at 1 and 2 years of follow-up. Results High baseline score and poor improvement over the first 24 weeks in synovitis (p=0.003 and p=0.003, respectively) and in bone oedema (p=0.02 and p=0.001, respectively) were independent predictors of X-ray progression at 1 year. Associations were significant or tended towards an association at 2 years. An increase in RAMRIS bone erosion >0.5 at weeks 12 and 24 also predicted X-ray progression (p<0.003). Poor 12-week improvement in bone oedema was associated with X-ray and MRI progression at 1 year (p<0.05). Regression models that incorporated baseline and 12-week and 24-week changes in MRI measures of synovitis (AUC=0.71) and bone oedema (AUC=0.70) improved the prediction of X-ray progression at 1 year above clinical disease activity alone (AUC=0.66, p<0.04). Conclusions Baseline and early changes in MRI measures independently predicted X-ray and MRI progression at later time-points. The predictive validity established here supports potential use in shorter-duration studies to determine efficacy of RA therapies in preventing structural damage.

Physical Performance and Frailty in Chronic Kidney Disease

Background: Poor physical performance and frailty are associated with elevated risks of death and disability. Chronic kidney disease (CKD) is also strongly associated with these outcomes. The risks of poor physical performance and frailty among CKD patients, however, are not well established. Methods: We measured the Short Physical Performance Battery (SPPB; a summary test of gait speed, chair raises and balance; range 0-12) and the five elements of frailty among 1,111 Chronic Renal Insufficiency Cohort participants. Adjusting for demographics and multiple comorbidities, we fit a linear regression model for the outcome of SPPB score and an ordinal logistic regression model for frailty status. Results: Median (interquartile range, IQR) age was 65 (57-71) years, median estimated glomerular filtration rate (eGFR) for non-dialysis patients was 49 (36-62) ml/min/1.73 m2, and median SPPB score was 9 (7-10). Seven percent of participants were frail and 43% were pre-frail. Compared with the SPPB score for eGFR >60 ml/min/1.73 m2, the SPPB was 0.51 points lower for eGFR 30-59; 0.61 points lower for eGFR 15-29, and 1.75 points lower for eGFR <15 (p < 0.01 for all comparisons). eGFR 30-59 (odds ratio, OR 1.45; p = 0.024), eGFR 15-29 (OR 2.02; p = 0.002) and eGFR <15 (OR 4.83; p < 0.001) were associated with worse frailty status compared with eGFR >60 ml/min/1.73 m2. Conclusions: CKD severity was associated with poor physical performance and frailty in a graded fashion. Future trials should determine if outcomes for CKD patients with frailty and poor physical performance are improved by targeted interventions.

Greater body mass independently predicts less radiographic progression on X-ray and MRI over 1–2 years

Introduction Greater body mass index (BMI) has been associated with less radiographic progression in rheumatoid arthritis (RA). We evaluated the association between BMI and joint damage progression as measured by X-ray and MRI. Methods 1068 subjects with RA from two clinical trials of golimumab (GO-BEFORE and GO-FORWARD) had radiographs performed at weeks 0, 52 and 104 and evaluated using the van der Heijde–Sharp (vdHS) scoring system. Contrast-enhanced MRIs of the dominant wrist and hand were obtained at weeks 0, 12, 24, 52 and 104. Multivariable logistic regression evaluated the risk of radiographic progression for each BMI category (<25, 25–30, >30 kg/m2). Within GO-BEFORE, piecewise, robust generalised estimating equations marginal models assessed the probability of MRI erosion progression for each BMI category. Multivariable linear regression models assessed baseline associations between BMI and bone oedema (a precursor of bone erosion). Results Higher BMI category was associated with a lower probability of progression in vdHS score at weeks 52 and 104 independent of potential confounders. Higher BMI was also independently associated with a lower probability of progression in MRI erosion score over 2 years. Subjects with greater BMI demonstrated less bone oedema independent of differences in other disease severity measures, including MRI synovitis in the same joints. Conclusions Greater BMI is associated with a lower risk of progression on X-ray and MRI over 2 years. Subjects with greater BMI also demonstrate less bone oedema at baseline. Greater BMI may indicate a less aggressive RA phenotype and aid in risk stratification.

Identifying and Cultivating Superforecasters as a Method of Improving Probabilistic Predictions

Across a wide range of tasks, research has shown that people make poor probabilistic predictions of future events. Recently, the U.S. Intelligence Community sponsored a series of forecasting tournaments designed to explore the best strategies for generating accurate subjective probability estimates of geopolitical events. In this article, we describe the winning strategy: culling off top performers each year and assigning them into elite teams of superforecasters. Defying expectations of regression toward the mean 2 years in a row, superforecasters maintained high accuracy across hundreds of questions and a wide array of topics. We find support for four mutually reinforcing explanations of superforecaster performance: (a) cognitive abilities and styles, (b) task-specific skills, (c) motivation and commitment, and (d) enriched environments. These findings suggest that superforecasters are partly discovered and partly created—and that the high-performance incentives of tournaments highlight aspects of human judgment that would not come to light in laboratory paradigms focused on typical performance.

Associations between body composition and bone density and structure in men and women across the adult age spectrum.

BACKGROUND/PURPOSE The objective of this study was to identify independent associations between body composition and bone outcomes, including cortical structure and cortical and trabecular volumetric bone mineral density (vBMD) across the adult age spectrum. METHODS This cross-sectional study evaluated over 400 healthy adults (48% male, 44% black race), ages 21-78years. Multivariable linear regression models evaluated associations between whole-body DXA measures of lean body mass index (LBMI) and fat mass index (FMI) and tibia peripheral quantitative CT (pQCT) measures of cortical section modulus, cortical and trabecular vBMD and muscle density (as a measure of intramuscular fat), adjusted for age, sex, and race. All associations reported below were statistically significant (p<0.05). RESULTS Older age and female sex were associated with lower LBMI and muscle strength. Black race was associated with greater LBMI but lower muscle density. Greater FMI was associated with lower muscle density. Cortical section modulus was positively associated with LBMI and muscle strength and negatively associated with FMI. Adjustment for body composition eliminated the greater section modulus observed in black participants and attenuated the lower section modulus in females. Greater LBMI was associated with lower cortical BMD and greater trabecular BMD. FMI was not associated with either BMD outcome. Greater muscle density was associated with greater trabecular and cortical BMD. Associations between body composition and bone outcomes did not vary by sex (no significant tests for interaction). CONCLUSIONS These data highlight age-, sex- and race-specific differences in body composition, muscle strength and muscle density, and demonstrate discrete associations with bone density and structure. These data also show that age-, sex- and race-related patterns of bone density and strength are independent of differences in body composition. Longitudinal studies are needed to examine the temporal relations between changes in bone and body composition.

Vitamin D, immunoregulation, and rheumatoid arthritis.

In addition to being important in calcium and phosphorus metabolism, bone formation, and mineralization, vitamin D also plays a part in the maintenance of immune homeostasis. Vitamin D receptors are expressed in a number of different tissues, including, and perhaps most notably, on immune cells. The presence or absence of activated vitamin D has a number of effects on in vitro immune cell function. This review describes the possible immunoregulatory role of vitamin D in rheumatoid arthritis with clinical and animal studies.

Adverse Fat Depots and Marrow Adiposity Are Associated With Skeletal Deficits and Insulin Resistance in Long-Term Survivors of Pediatric Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem‐cell transplantation (alloHSCT) survivors treated with total body irradiation (TBI) exhibit bone deficits and excess adiposity, potentially related to altered mesenchymal stem cell differentiation into osteoblasts or adipocytes. We examined associations among fat distribution, bone microarchitecture, and insulin resistance in alloHSCT survivors after TBI. This was a cross‐sectional observational study of 25 alloHSCT survivors (aged 12 to 25 years) a median of 9.7 (4.3 to 19.3) years after alloHSCT compared to 25 age‐, race‐, and sex‐matched healthy controls. Vertebral MR spectroscopic imaging and tibia micro‐MRI were used to quantify marrow adipose tissue (MAT) and trabecular microarchitecture. Additional measures included DXA whole‐body fat mass (WB‐FM), leg lean mass (Leg‐LM), trunk visceral adipose tissue (VAT), and CT calf muscle density. Insulin resistance in alloHSCT survivors was estimated by HOMA‐IR. AlloHSCT survivors had lower Leg‐LM (p < 0.001) and greater VAT (p < 0.01), MAT (p < 0.001), and fat infiltration of muscle (p = 0.04) independent of WB‐FM, versus matched controls; BMI did not differ. Survivors had lower bone volume fraction and abnormal microarchitecture including greater erosion and more rod‐like structure versus controls (all p = 0.04); 14 had vertebral deformities and two had compression fractures. Greater WB‐FM, VAT, MAT, and muscle fat infiltration were associated with abnormal trabecular microarchitecture (p < 0.04 for all). AlloHSCT HOMA‐IR was elevated, associated with younger age at transplantation (p < 0.01), and positively correlated with WB‐FM and VAT (both p < 0.01). In conclusion, the markedly increased marrow adiposity, abnormal bone microarchitecture, and abnormal fat distribution highlight the risks of long‐term treatment‐related morbidity and mortality in alloHSCT recipients after TBI. Trabecular deterioration was associated with marrow and visceral adiposity. Furthermore, long‐term survivors demonstrated sarcopenic obesity, insulin resistance, and vertebral deformities. Future studies are needed to identify strategies to prevent and treat metabolic and skeletal complications in this growing population of childhood alloHSCT survivors.

Vitamin D, metabolic dyslipidemia, and metabolic syndrome in rheumatoid arthritis.

PURPOSE Vitamin D deficiency is a potential risk factor for cardiometabolic disease. We investigated the associations between vitamin D and dyslipidemia and the metabolic syndrome in patients with rheumatoid arthritis, a group at high risk for cardiovascular disease. METHODS Serum 25(OH)vitamin D and lipoprotein levels were measured at baseline in a random sample of 499 participants, ages 18-85 years, enrolled in a randomized trial of golimumab (GOlimumab Before Employing methotrexate as the First-line Option in the treatment of Rheumatoid arthritis of Early onset or GO-BEFORE Trial). Participants had rheumatoid arthritis with active disease, and were naïve to methotrexate and biologic therapies. Multivariable linear regression was performed to assess associations between vitamin D levels and lipoprotein fractions. Multivariable logistic regression was performed to determine the odds of hyperlipidemia and the metabolic syndrome in participants with vitamin D deficiency (<20 ng/mL). RESULTS In multivariable linear regression, vitamin D levels (per 10 ng/mL) were associated inversely with low-density lipoprotein (β: -0.029 [-0.049, -0.0091], P=.004) and triglyceride (β: -0.094 [-0.15, -0.039] P=.001) levels, adjusted for demographic, cardiovascular, and disease-specific variables. Vitamin D and high-density lipoprotein levels were not associated in univariate or multivariate analyses. Vitamin D deficiency was associated independently with an increased odds of hyperlipidemia (odds ratio 1.72; 95% confidence interval, 1.10-2.45; P=.014) and metabolic syndrome (odds ratio 3.45; 95% confidence interval, 1.75-6.80; P <.001) in adjusted models. CONCLUSIONS In conclusion, vitamin D deficiency was associated with the metabolic syndrome and dyslipidemia in rheumatoid arthritis, suggesting a potential role in cardiovascular disease risk. Large-scale, prospective studies are needed to determine if vitamin D supplementation improves lipoprotein levels and reduces cardiovascular risk in rheumatoid arthritis.

Associations between body mass, radiographic joint damage, adipokines and risk factors for bone loss in rheumatoid arthritis

OBJECTIVE To evaluate the association between BMI and radiographic joint damage (RJD) in RA. METHODS van der Heijde-Sharp (vdHS) erosion scores were determined in 499 participants with RA, ages 18-85 years, while enrolled in a clinical trial of golimumab (GO-BEFORE trial). Subjects were MTX and biologic therapy naïve. Multivariable logistic regressions determined the odds of prevalent RJD (defined as vdHS score >10) according to BMI category. Longitudinal analyses evaluated the association between BMI category and progression of vdHS score over 52 weeks. Analyses in a subset of 100 participants examined the association between adipokines and vdHS scores. RESULTS At enrolment and 52 weeks, 37.6 and 43.6% of participants had RJD. Compared with normal weight, obese subjects had lower odds of RJD [0.40 (95% CI 0.22, 0.74); P = 0.003], and underweight subjects had greater odds [3.86 (95% CI 1.66, 9.00); P = 0.002] at baseline, adjusted for demographic and disease characteristics. The baseline associations between BMI category and RJD were greater among participants with multiple risk factors for bone loss (female >50 years, smoking, glucocorticoid exposure and vitamin D deficiency); test for interaction P = 0.05. Adjustment for adiponectin levels did not attenuate the association between BMI and vdHS scores. Baseline BMI and change in weight did not independently predict radiographic progression (P > 0.1). CONCLUSIONS Higher BMI was independently associated with less RJD and was greatest in participants with risk factors for bone loss. Future studies are needed to examine the associations between RJD, obesity, weight loss and osteoporosis.