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1.  Pay attention to the man behind the curtain 
Arthritis care & research  2014;66(8):1263-1268.
PMCID: PMC4153596  PMID: 24664962
2.  Body Mass Index, Obesity, and Prevalent Gout in the United States in 1988–1994 and 2007–2010 
Arthritis care & research  2013;65(1):127-132.
To determine the association and prevalence of gout among overweight, obese and morbidly obese segments of the US population.
Among participants (age 20 and older) of the National Health and Nutrition Examination Surveys, in 1988–1994 and 2007–2010, gout status was ascertained by self-report of a physician-diagnosis. BMI was examined in categories of <18.5, 18.5–24.9, 25–29.9, 30–34.9, and ≥35 kg/m2 and as a continuous variable. The cross-sectional association of BMI category with gout status was adjusted for demographic and obesity-related medical disorders.
In the US, the crude prevalence of gout was 1–2% among participants with a normal BMI (18.5–24.9 kg/2), 3% among overweight participants, 4–5% with class I obesity, and 5–7% with class II or class III obesity. The adjusted prevalence ratio comparing the highest to a normal BMI category was 2.46 (95% CI: 1.44, 4.21) in 1988–1994, and 2.21 (95% CI: 1.50, 3.26) in 2007–2010. Notably, there was a progressively greater prevalence ratio of gout associated with successively higher categories of BMI. In both survey periods, for an average American adult standing 1.76m (5 feet, 9 inches), a 1 unit higher BMI, corresponding to 3.1 kg (~6.8 lbs) greater weight, was associated with a 5% greater prevalence of gout, even after adjusting for serum uric acid (P < 0.001).
Healthcare providers should be aware of the elevated burden of gout among both overweight and obese adults, applicable to both women and men, and observed among non-Hispanic White, non-Hispanic Black and Mexican Americans in the US.
PMCID: PMC3482278  PMID: 22778033
3.  Incident Gout in Women and Association with Obesity in the Atherosclerosis Risk in Communities (ARIC) Study 
The American Journal of Medicine  2012;125(7):717.e9-717.e17.
We hypothesized that women with early- and mid-adult life obesity, as well as high mid-adult life waist-to-hip ratios, and high weight gain during adulthood, experience a greater incidence of gout.
We examined the incidence of gout in the Atherosclerosis Risk in Communities (ARIC) Study, a population-based biracial cohort comprised of individuals aged 45–65 years of age at baseline (1987–1989). A total of 6,263 women without prior history of gout were identified. We examined the association of BMI and obesity at cohort entry and at age 25 years, waist-to-hip ratio and weight change, with gout incidence (1996–1998).
Over 9 years of follow-up, 103 women developed gout. The cumulative incidence of gout, by age 70 years, according to BMI category at baseline of <25, 25–29.9, 30–34.9, and ≥ 35 kg/m2, was 1.9, 3.6, 7.9, and 11.8%, respectively (P <0.001). Obese women (BMI≥30) at baseline had an adjusted 2.4-fold greater risk of developing gout than non-obese women (95% confidence interval (CI) 1.53, 3.68). This association was attenuated after further adjustment for urate levels. Further, early adult obesity in women was associated with a 2.8-fold increased risk of gout compared to non-obese women (95% CI 1.33, 6.09), which remained statistically significant after baseline urate adjustment. There was a graded association between each anthropometric measure, including weight gain, with incident gout (each P for trend <0.001). The results were similar in black and white women.
In a large cohort of African American and Caucasian women, obesity in early and mid-adulthood, and weight gain during this interval, were each independent risk factors for incident gout in women.
PMCID: PMC3383456  PMID: 22571781
Gout; Women; Obesity; Weight; Arthritis
4.  Race and Association With Disease Manifestations and Mortality in Scleroderma 
Medicine  2013;92(4):191-205.
Experience suggests that African Americans may express autoimmune disease differently than other racial groups. In the context of systemic sclerosis (scleroderma), we sought to determine whether race was related to a more adverse expression of disease. Between January 1, 1990, and December 31, 2009, a total of 409 African American and 1808 white patients with scleroderma were evaluated at a single university medical center. While the distribution by sex was virtually identical in both groups, at 82% female, African American patients presented to the center at a younger mean age than white patients (47 vs. 53 yr; p < 0.001). Two-thirds of white patients manifested the limited cutaneous subset of disease, whereas the majority of African American patients manifested the diffuse cutaneous subset (p < 0.001). The proportion seropositive for anticentromere antibody was nearly 3-fold greater among white patients, at 34%, compared to African American patients (12%; p < 0.001). Nearly a third of African American (31%) patients had autoantibodies to topoisomerase, compared to 19% of white patients (p = 0.001). Notably, African American patients experienced an increase in prevalence of cardiac (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3–2.2), renal (OR, 1.6; 95% CI, 1.2–2.1), digital ischemia (OR, 1.5; 95% CI, 1.4–2.2), muscle (OR, 1.7; 95% CI, 1.3–2.3), and restrictive lung (OR, 6.9; 95% CI, 5.1–9.4) disease. Overall, 700 (32%) patients died (159 African American; 541 white). The cumulative incidence of mortality at 10 years was 43% among African American patients compared to 35% among white patients (log-rank p = 0.0011). Compared to white patients, African American patients experienced an 80% increase in risk of mortality (relative risk [RR], 1.8; 95% CI, 1.4–2.2), after adjustment for age at disease onset and disease duration. Further adjustment by sex, disease subtype, and scleroderma-specific autoantibody status, and for the socioeconomic measures of educational attainment and health insurance status, diminished these risk estimates (RR, 1.3; 95% CI, 1.0–1.6). The heightened risk of mortality persisted in strata defined by age at disease onset, diffuse cutaneous disease, anticentromere seropositivity, decade of care at the center, and among women. These findings support the notion that race is related to a distinct phenotypic profile in scleroderma, and a more unfavorable prognosis among African Americans, warranting heightened diagnostic evaluation and vigilant care of these patients. Further, we provide a chronologic review of the literature regarding race, organ system involvement, and mortality in scleroderma; we furnish synopses of relevant reports, and summarize findings.
PMCID: PMC4553970  PMID: 23793108
5.  Effect of Oral Vitamin C Supplementation on Serum Uric Acid: A Meta-analysis of Randomized Controlled Trials 
Arthritis care & research  2011;63(9):1295-1306.
To assess the effect of vitamin C supplementation on serum uric acid (SUA) by pooling the findings from published randomized, controlled trials (RCTs).
A total of 2,082 publications identified through systematic search were subjected to the following inclusion criteria: (1) RCTs conducted on human subjects; (2) reported end-trial SUA means and variance; (3) study design with oral vitamin C supplementation and concurrent control groups; and (4) trial duration of at least one week. Trials that enrolled children or patients on dialysis were excluded. Two investigators independently abstracted trial and participant characteristics. SUA effects were pooled by random-effects models and weighted by inverse variance.
Thirteen RCTs were identified in MEDLINE, EMBASE, and CENTRAL databases. The total number of participants was 556, median dose of vitamin C was 500 mg/d, trial size ranged from 8 to 184 participants, and median study duration was 30 days. Pretreatment SUA values ranged from 2.9 to 7.0 mg/dL (SI: 172.5 – 416.4 μmol/L). The combined effect of these trials was a significant reduction in SUA of -0.35 mg/dL (95% CI: -0.66, -0.03; P = 0.032; SI: -20.8 μmol/L). Trial heterogeneity was significant (I2 = 77%; P < 0.01). Subgroup analyses based on trial characteristics indicated larger reductions in uric acid in trials that were placebo-controlled.
In aggregate, vitamin C supplementation significantly lowered SUA. Future trials are needed to determine whether vitamin C supplementation can reduce hyperuricemia or prevent incident and recurrent gout.
PMCID: PMC3169708  PMID: 21671418
6.  More than meets the eye 
Rheumatologists take great pride in making elegant diagnoses. We carefully assess seemingly disparate signs and symptoms and use these clinical clues to make diagnoses based on predictable disease phenotypes. However, few clinical features of rheumatic disease are unique to a single disease process. Here we describe a case where the overlap of clinical features led to an initially broad differential diagnosis of seemingly unrelated diseases. Ultimately, the discovery of a radiographic finding allowed us to more clearly define the diagnosis, make inferences regarding the underlying pathophysiology, and intervene therapeutically with the goal of averting potentially significant morbidity.
PMCID: PMC3182107  PMID: 20541239
7.  Temporal Relationship Between Uric Acid Concentration and Risk of Diabetes in a Community-based Study Population 
American Journal of Epidemiology  2014;179(6):684-691.
Some observational studies have identified elevated uric acid concentration as a risk factor for diabetes, while others have found an inverse relationship. We examined both the association of uric acid level with incident diabetes and the change in uric acid concentration after a diabetes diagnosis. We analyzed data from the Atherosclerosis Risk in Communities (ARIC) Study and quantified the independent association between uric acid level and incident diabetes via Cox proportional hazards models. The association between duration of diabetes and change in uric acid level was examined via linear regression. Among 11,134 participants without diagnosed diabetes at baseline (1987–1989), there were 1,294 incident cases of diabetes during a median of 9 years of follow-up (1987–1998). Uric acid level was associated with diabetes even after adjustment for risk factors (per 1 mg/dL, hazard ratio = 1.18, 95% confidence interval: 1.13, 1.23), and the association remained significant after adjustment for fasting glucose and insulin levels. Among participants with diabetes (n = 1,510), every additional 5 years’ duration of diabetes was associated with a 0.10-mg/dL (95% confidence interval: 0.04, 0.15) lower uric acid level after adjustment. We conclude that uric acid concentration rises prior to diagnosis of diabetes and then declines with diabetes duration. Future studies investigating uric acid as a risk factor for cardiovascular disease should adequately account for the impact and timing of diabetes development.
PMCID: PMC3939847  PMID: 24418684
cohort studies; diabetes mellitus; uric acid
8.  Racial Differences in Gout Incidence in a Population-Based Cohort: Atherosclerosis Risk in Communities Study 
American Journal of Epidemiology  2013;179(5):576-583.
We examined racial differences in gout incidence among black and white participants in a longitudinal, population-based cohort and tested whether racial differences were explained by higher levels of serum urate. The Atherosclerosis Risk in Communities Study is a prospective, US population–based cohort study of middle-aged adults enrolled between 1987 and 1989 with ongoing annual follow-up through 2012. We estimated the adjusted hazard ratios and 95% confidence intervals of incident gout by race among 11,963 men and women using adjusted Cox proportional hazards models. The cohort was 23.6% black. The incidence rate of gout was 8.4 per 10,000 person-years (15.5/10,000 person-years for black men, 12.0/10,000 person-years for black women, 9.4/10,000 person-years for white men, and 5.0/10,000 person-years for white women; P < 0.001). Black participants had an increased risk of incident gout (for women, adjusted hazard ratio (HR) = 1.69, 95% confidence interval (CI): 1.29, 2.22; for men, adjusted HR = 1.92, 95% CI: 1.44, 2.56). Upon further adjustment for uric acid levels, there was modest attenuation of the association of race with incident gout (for women, adjusted HR = 1.62, 95% CI: 1.24, 2.22; for men, adjusted HR = 1.49, 95% CI: 1.11, 2.00) compared with white participants. In this US population–based cohort, black women and black men were at increased risk of developing gout during middle and older ages compared with whites, which appears, particularly in men, to be partly related to higher urate levels in middle-aged blacks.
PMCID: PMC3927975  PMID: 24335384
gout; inflammatory arthritis; race; uric acid
10.  Association of kidney disease with prevalent gout in the United States in 1988–1994 and 2007–2010☆ 
To determine the prevalence of gout associated with progressive degrees of kidney disease in the US population.
We performed a cross-sectional analysis among non-institutionalized adults (age 20 and older) of the National Health and Nutrition Examination Surveys in 1988–1994 and 2007–2010. Gout status was ascertained by self-report of physician-diagnosed gout. Chronic kidney disease (CKD) was defined in stages based on estimated glomerular filtration rate (GFR) and single albuminuria measurements (albumin-to-creatinine ratio). Prevalence ratios comparing successive categories of GFR, albuminuria, and CKD as well as temporal trends over a 22-year interval were determined via Poisson regression.
In the US, the crude prevalence of gout was 2–3% among participants without CKD, 4% among participants with CKD stage 1, 6–10% for stage 2, 11–13% for stage 3, and over 30% for stage 4. The adjusted prevalence ratio comparing the CKD stage 4 stratum to participants without CKD was 3.20 (95% CI: 1.96, 5.24) in 2007–2010 and remained significant even after adjustment for serum uric acid. Notably, there was a statistically significant, progressively greater adjusted prevalence ratio of gout associated with successively lower categories of GFR and higher categories of albuminuria.
Among US adults, there exists a strong dose–response association between impaired renal function and prevalent gout. Health providers should be aware of the elevated burden of gout among patients with CKD especially when evaluating new onset joint pain and swelling.
PMCID: PMC3754853  PMID: 23312548
Gout; Chronic kidney disease; Glomerular filtration rate; Albuminuria; NHANES
11.  More than Skin Deep 
PMCID: PMC3614151  PMID: 22878853
dermatology; infectious disease; arthritis; medical education cognition; problem solving
12.  Progression of coronary artery atherosclerosis in rheumatoid arthritis: comparison with participants from the Multi-Ethnic Study of Atherosclerosis 
Arthritis Research & Therapy  2013;15(5):R134.
In cross-sectional studies, patients with rheumatoid arthritis (RA) have higher coronary artery calcium (CAC) than controls. However, their rate of progression of CAC and the predictors of CAC progression have heretofore remained unknown.
Incidence and progression of CAC were compared in 155 patients with RA and 835 control participants. The association of demographic characteristics, traditional cardiovascular risk factors, RA disease characteristics and selected inflammatory markers with incidence and progression of CAC were evaluated.
The incidence rate of newly detected CAC was 8.2/100 person-years in RA and 7.3/100 person-years in non-RA control subjects [IRR 1.1 (0.7-1.8)]. RA patients who developed newly detectable CAC were older (59±7 vs. 55±6 years old, p=0.03), had higher triglyceride levels (137±86 vs. 97±60 mg/dL, p=0.03), and higher systolic blood pressure (129±17 vs. 117±15 mm Hg, p=0.01) compared to those who did not develop incident CAC. Differences in blood pressure and triglyceride levels remained significant after adjustment for age (p<=0.05). RA patients with any CAC at baseline had a median rate of yearly progression of 21 (7–62) compared to 21 (5–70) Agatston units in controls. No statistical differences between RA progressors and RA non-progressors were observed for inflammatory markers or for RA disease characteristics.
The incidence and progression of CAC did not differ between RA and non-RA participants. In patients with RA, incident CAC was associated with older age, higher triglyceride levels, and higher blood pressure, but not with inflammatory markers or RA disease characteristics.
PMCID: PMC3978773  PMID: 24286380
13.  Dose-Response Association of Uncontrolled Blood Pressure and Cardiovascular Disease Risk Factors with Hyperuricemia and Gout 
PLoS ONE  2013;8(2):e56546.
First-line therapy of hypertension includes diuretics, known to exert a multiplicative increase on the risk of gout. Detailed insight into the underlying prevalence of hyperuricemia and gout in persons with uncontrolled blood pressure (BP) and common comorbidities is informative to practitioners initiating antihypertensive agents. We quantify the prevalence of hyperuricemia and gout in persons with uncontrolled BP and additional cardiovascular disease (CVD) risk factors.
Methods and Findings
We performed a cross-sectional study of non-institutionalized US adults, 18 years and older, using the National Health and Nutrition Examination Surveys in 1988–1994 and 1999–2010. Hyperuricemia was defined as serum uric acid >6.0 mg/dL in women; >7.0 mg/dL in men. Gout was ascertained by self-report of physician-diagnosed gout. Uncontrolled BP was based on measured systolic BP≥140 mmHg and diastolic BP≥90 mmHg. Additional CVD risk factors included obesity, reduced glomerular filtration rate, and dyslipidemia. The prevalence of hyperuricemia was 6–8% among healthy US adults, 10–15% among adults with uncontrolled BP, 22–25% with uncontrolled BP and one additional CVD risk factor, and 34–37% with uncontrolled BP and two additional CVD risk factors. Similarly, the prevalence of gout was successively greater, at 1–2%, 4–5%, 6–8%, and 8–12%, respectively, across these same health status categories. In 2007–2010, those with uncontrolled BP and 2 additional CVD risk factors compared to those without CVD risk factors had prevalence ratios of 4.5 (95% CI 3.5–5.6) and 4.5 (95% CI: 3.1–6.3) for hyperuricemia and gout respectively (P<0.01).
Health care providers should be cognizant of the incrementally higher prevalence of hyperuricemia and gout among patients with uncontrolled BP and additional CVD risk factors. With one in three people affected by hyperuricemia among those with several CVD risk factors, physicians should consider their anti-hypertensive regimens carefully and potentially screen for hyperuricemia or gout.
PMCID: PMC3584090  PMID: 23460805
14.  Prevalence of Traditional Modifiable Cardiovascular Risk Factors in Patients with Rheumatoid Arthritis: Comparison with Control Subjects from the Multi-Ethnic Study of Atherosclerosis 
Despite the recognized risk of accelerated atherosclerosis in patients with rheumatoid arthritis (RA), little is known about cardiovascular risk management in contemporary cohorts of these patients. We tested the hypotheses that major modifiable cardiovascular risk factors were more frequent and rates of treatment, detection, and control were lower in patients with RA than in non-RA controls.
The prevalence of hypertension, diabetes, elevated low-density lipoprotein (LDL) cholesterol, elevated body mass index, smoking, moderate-high 10-year cardiovascular risk and the rates of underdiagnosis, therapeutic treatment, and recommended management were compared in 197 RA patients and 274 frequency-matched control subjects, and their associations with clinical characteristics were examined.
Eighty percent of RA patients and 81% of control subjects had at least 1 modifiable traditional cardiovascular risk factor. Hypertension was more prevalent in the RA group (57%) than in controls [42%, P =0.001]. There were no statistically significant differences in the frequency of diabetes, elevated body mass index, smoking, intermediate-high 10-year coronary heart disease risk, or elevated LDL in patients with RA versus controls. Rates of newly identified diabetes, hypertension, and hyperlipidemia were similar in RA patients versus controls. Rates of therapeutic interventions were low in both groups but their use was associated with well-controlled blood pressure (OR = 4.55, 95% CI: 1.70, 12.19) and lipid levels (OR = 9.90, 95% CI: 3.30, 29.67).
Hypertension is more common in RA than in controls. Other traditional cardiovascular risk factors are highly prevalent, underdiagnosed, and poorly controlled in patients with RA, as well as controls.
PMCID: PMC3538033  PMID: 22340996
rheumatoid arthritis; cardiovascular risk; epidemiology
15.  Diuretic Use, Increased Serum Urate and the Risk of Incident Gout in a Population-based Study of Hypertensive Adults: the Atherosclerosis Risk in the Communities Cohort 
Arthritis and Rheumatism  2012;64(1):121-129.
To quantify the role of diuretic use on gout development in an adult population with hypertension.
ARIC, a prospective population-based cohort from 4 US communities, consists of 4 visits over a 9-year period. Participants were included in this analysis if they answered the gout query, were free of gout at baseline, and had hypertension (medication to treat hypertension or a blood pressure ≥ 140/90 mmHg). Trained interviewers recorded antihypertensive use. Incident gout was defined as self-reported onset after baseline. Using a time-dependent Cox Proportional Hazards model, we estimated the hazard rate ratio (HR) of incident gout by time-varying diuretic use, adjusted for confounders, and tested for mediation by serum urate level.
There were 5,789 hypertensive participants; 37% were treated with a diuretic. Use of any diuretic (HR=1.48, 95% CI: 1.11, 1.98), thiazide diuretic (HR=1.44, 95% CI: 1.00, 2.10), and loop diuretic (HR=2.31, 95% CI: 1.36, 3.91) was associated with incident gout compared with not using any diuretic, thiazide diuretic or loop diuretics, respectively. After adjusting for serum urate, the association between diuretic use and gout was null. Use of antihypertensive medication other than diuretic agents was associated with decreased gout risk (adjusted HR=0.64 95% CI: 0.49, 0.86) compared to untreated hypertension. The longitudinal change in serum urate was 0.72 mg/dL (95% CI: 0.57, 0.87) higher in those who initiated a diuretic compared with those who did not (p-value<0.001).
Thiazide and loop diuretics were associated with increased gout risk, an association mediated by a change in serum urate.
PMCID: PMC3253199  PMID: 22031222
gout; hypertension; diuretics; uric acid
16.  Longitudinal Predictors of Progression of Carotid Atherosclerosis in Rheumatoid Arthritis 
Arthritis and rheumatism  2011;63(11):3216-3225.
To explore predictors of change in measures of carotid atherosclerosis among rheumatoid arthritis (RA) patients without known cardiovascular disease (CVD) at baseline
RA patients underwent carotid ultrasonography at two timepoints, separated by an average of 3.2 ± 0.3 years. The associations of baseline and average patient characteristics with the average yearly change in mean maximal intima-medial thickness (IMT) of the common (CCA) and internal carotid arteries (ICA), and with incident or progressive plaque in the ICA/carotid bulb, were explored.
Among the 158 RA patients, maxCCA-IMT increased in 82% (median=16 μm/year; p<0.001) and maxICA-IMT increased in 70% (median=25 μm/year; p<0.001). Incident plaque was observed in 14% without baseline plaque [incidence rate=4.2/100 person-years (95% CI 1.61–6.82)]. Plaque progression was observed in 5% with baseline plaque. Among RA predictors, the adjusted average yearly change in maxCCA-IMT was significantly greater in patients with earlier RA vs. longer disease. Those prescribed TNF inhibitors at baseline had a 37% lower adjusted rate of maxCCA-IMT progression vs. non-users (14 vs. 22 μm/year; p=0.026). For maxICA-IMT, cumulative prednisone exposure was associated with progression [1.2 μm/year per gram (95% CI 0.1–2.4)] after adjustment, and was lower in patients prescribed statins concomitant with prednisone. Higher swollen joint count and higher average CRP were both associated with incident or progressive plaque, primarily in patients with elevated baseline CVD risk based on the Framingham score.
These prospective data provide evidence for inflammation as a contributor to subclinical atherosclerosis progression in RA, potentially modified favorably by TNF inhibitors and detrimentally by glucocorticoids.
PMCID: PMC3205252  PMID: 21965129
Atherosclerosis; Inflammation; prediction; carotid ultrasound
17.  Younger age at gout onset is related to obesity in a community-based cohort 
Arthritis care & research  2011;63(8):1108-1114.
Obesity is associated with gout risk. It is unclear whether obesity is associated with a younger age of gout onset. We examined whether obesity is related to age at gout onset and quantified the risk of incident gout by obesity status in the Campaign Against Cancer and Heart Disease (CLUE II) study, a longitudinal community-based cohort.
CLUE II began in 1989 as a cohort study of residents living within or surrounding Washington County, Maryland. Follow-up questionnaires queried whether each participant had been diagnosed with gout by a healthcare professional. Among participants with gout, we assessed whether obesity was related to age at disease onset. We also ascertained the eighteen-year risk of incident gout according to obesity status (BMI ≥30 kg/m2) at baseline with cumulative incidence ratios (RR) and 95% confidence intervals (CI) from Poisson regression.
Among the study population (n=15,533), 517 developed incident gout. The prevalence of obesity at baseline was 16.2%. The overall mean age at gout onset was 59.3 years. The onset of gout was 3.1 years (95% CI: 0.3, 5.8) earlier in those who were obese at baseline and 11.0 years earlier (95% CI: 5.8, 16.1) in participants who were obese at age 21, compared to their non-obese participants. The 18-year adjusted RR of gout in obese participants compared to non-obese participants was 1.92 (95% CI: 1.55, 2.37).
Obesity is not only a risk factor for incident gout but was associated with an earlier age at gout onset.
PMCID: PMC3149749  PMID: 21485022
Gout; Obesity; Epidemiology; Age
The Journal of rheumatology  2011;38(7):1317-1325.
Although patients who develop scleroderma (SSc) later in life (≥ 65 years) may express the entire clinical spectrum of disease, we hypothesize that patients with late-age onset incur a different risk for specific organ manifestations of disease compared to those with younger-age onset SSc.
In total, 2300 SSc patients were evaluated between 1990–2009 and reviewed from a university-based Scleroderma Center cohort. Demographic profile, SSc subtype, autoantibody status, Medsger severity scores, pulmonary function tests, echocardiography, and right heart catheterization parameters were compared between late-age versus younger-age onset patients.
Overall, 2084 (91%) patients developed SSc prior to age 65; whereas 216 (9%) were ≥65 years. Late-age onset patients had a significantly higher proportion of anti-centromere antibodies (42% vs 27%; p=0.001) compared to younger-age onset. Risk of pulmonary hypertension (OR 1.77; 95%CI 1.00, 3.12), muscle weakness (OR 1.85; 95%CI 1.30, 2.64), renal impairment (OR 2.83; 95%CI 1.98, 4.04) and cardiac disease (OR 2.69; 95%CI 1.92, 3.78) was greater among those with late-age onset SSc; although risk of digital ischemia (OR 0.64; 95%CI 0.47, 0.86) was reduced. The cumulative incidence of pulmonary hypertension at 5 years was greater among those with late-age (9%) compared to younger-age (2.5%) onset SSc (log-rank, p<0.001).
These findings suggest that older SSc patients are at greater risk for pulmonary hypertension, renal impairment, cardiac disease, and muscle weakness. Awareness of the distinct risk for specific organ manifestations in SSc, in particular pulmonary hypertension, should guide the care of older SSc patients whose disease begins after age 65 years.
PMCID: PMC3136880  PMID: 21685299
scleroderma; systemic sclerosis; elderly; aging
19.  Reliability and Sensitivity of the Self-report of Physician-diagnosed Gout in the Campaign Against Cancer and Heart Disease and the Atherosclerosis Risk in the Community Cohorts 
The Journal of Rheumatology  2010;38(1):135-141.
Gout is often defined by self-report in epidemiologic studies. Yet the validity of self-reported gout is uncertain. We evaluated the reliability and sensitivity of the self-report of physician-diagnosed gout in the Campaign Against Cancer and Heart Disease (CLUE II) and the Atherosclerosis Risk in the Community (ARIC) cohorts.
The CLUE II cohort comprises 12,912 individuals who self-reported gout status on either the 2000, 2003, or 2007 questionnaires. We calculated reliability as the percentage of participants reporting having gout on more than 1 questionnaire using Cohen’s κ statistic. The ARIC cohort comprises 11,506 individuals who self-reported gout status at visit 4. We considered a hospital discharge diagnosis of gout or use of a gout-specific medication as the standard against which to calculate the sensitivity of self-reported, physician-diagnosed gout.
Of the 437 CLUE II participants who self-reported physician-diagnosed gout in 2000, and subsequently answered the 2003 questionnaire, 75% reported gout in 2003 (κ = 0.73). Of the 271 participants who reported gout in 2000, 73% again reported gout at the 2007 followup questionnaire (κ = 0.63). In ARIC, 196 participants met the definition for gout prior to visit 4 and self-reported their gout status at visit 4. The sensitivity of a self-report of physician-diagnosed gout was 84%. Accuracy was similar across sex and race subgroups, but differed across hyperuricemia and education strata.
These 2 population-based US cohorts suggest that self-report of physician-diagnosed gout has good reliability and sensitivity. Thus, self-report of a physician diagnosis of gout is appropriate for epidemiologic studies.
PMCID: PMC3285109  PMID: 21123328
20.  Abdominal Adiposity in Rheumatoid Arthritis: Association with Cardiometabolic Risk Factors and Disease Characteristics 
Arthritis and rheumatism  2010;62(11):3173-3182.
Abdominal adiposity, especially visceral adiposity, is an emerging cardiometabolic risk factor. How abdominal fat is distributed in rheumatoid arthritis (RA) and its RA-related determinants have not been explored.
Men and women with RA were compared to non-RA controls from the Multi-Ethnic Study of Atherosclerosis. Participants underwent anthropometric measures and quantification of visceral and subcutaneous fat areas (VFA, SFA) using abdominal computed tomography.
A total of 131 RA patients were compared with 121 controls. Despite similar body mass index and waist circumference between the RA and control groups, the adjusted mean VFA was 45cm2 higher (+51%) for RA vs. control men (p=0.005) but not significantly different by RA status in women. The adjusted mean SFA was 119cm2 higher (+68%) for RA vs. control women (p<0.001) but not significantly different by RA status in men. Elevated VFA (>75th percentile) was associated with a significantly higher adjusted probability of having an elevated fasting glucose, hypertension, or the composite definition of the metabolic syndrome for the RA group compared with controls. Within the RA group, rheumatoid factor seropositivity and higher cumulative prednisone exposure were significantly associated with a higher mean adjusted VFA. Higher C-reactive protein levels and lower Sharp scores were significantly associated with both VFA and SFA.
The distribution of abdominal fat differs significantly by RA status. Higher VFA in men with RA, and the more potent association of VFA with cardiometabolic risk factors in men and women with RA, may contribute to cardiovascular risk in RA populations.
PMCID: PMC2962724  PMID: 20589684
21.  Left Ventricular Structure and Function by Cardiac Magnetic Resonance Imaging in Rheumatoid Arthritis 
Arthritis and rheumatism  2010;62(4):940-951.
Heart failure is a major contributor to cardiovascular morbidity and mortality in rheumatoid arthritis. However, little is known about myocardial structure and function in this population.
Using cardiac magnetic resonance imaging, measures of myocardial structure and function were assessed in men and women with rheumatoid arthritis enrolled in ESCAPE RA, a cohort study of subclinical cardiovascular disease in rheumatoid arthritis, and compared with controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis.
Myocardial measures were compared between 75 rheumatoid arthritis patients and 225 matched controls. After adjustment, mean left-ventricular mass was 26 grams lower for the RA group compared to controls (p<0.001), an 18% difference. After similar adjustment, mean left-ventricular ejection fraction, cardiac output, and stroke volume were modestly lower in the rheumatoid arthritis group vs. controls. Mean left-ventricular end-systolic and end-diastolic volumes did not differ by rheumatoid arthritis status. Within the rheumatoid arthritis group, higher levels of anti-CCP antibodies and current use of biologics, but not other disease activity or severity measures, were associated with significantly lower adjusted mean left-ventricular mass, end-diastolic volume, and stroke volume, but not ejection fraction. The combined associations of anti-CCP antibody level and biologic use on myocardial measures were additive, without evidence of interaction.
These findings suggest that the progression to heart failure in RA may occur through reduced myocardial mass rather than hypertrophy. Both modifiable and non-modifiable factors may contribute to lower levels of left-ventricular mass and volume.
PMCID: PMC3008503  PMID: 20131277
myocardial dysfunction; heart failure; inflammation; cardiac imaging
22.  Coronary arterial calcification in rheumatoid arthritis: comparison with the Multi-Ethnic Study of Atherosclerosis 
Although cardiovascular morbidity and mortality are increased in rheumatoid arthritis, little is known about the burden of subclinical coronary atherosclerosis in these patients.
Using computed tomography, coronary artery calcification was measured in 195 men and women with rheumatoid arthritis aged 45 to 84 years without clinical cardiovascular disease and compared with 1,073 controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis.
The prevalence of coronary calcification (Agatston score > 0) was significantly higher in men, but not women, with rheumatoid arthritis after adjusting for sociodemographic and cardiovascular risk factors (prevalence ratio = 1.19; P = 0.012). Among participants with prevalent calcification, those with rheumatoid arthritis had adjusted mean Agatston scores 53 units higher than controls (P = 0.002); a difference greater for men than women (P for interaction = 0.017). In all analyses, serum IL-6 attenuated the association between rheumatoid arthritis and coronary calcification, suggesting its role as a potential mediator of enhanced atherosclerosis. Notably, increasing severity of rheumatoid arthritis was associated with a higher prevalence and extent of coronary calcification among both men and women with rheumatoid arthritis, and for all age categories. The largest percentage difference in coronary arterial calcification between rheumatoid arthritis patients and their nonrheumatoid arthritis counterparts was observed in the youngest age category.
Increasing rheumatoid arthritis disease severity was associated with a higher prevalence and greater extent of coronary artery calcification, potentially mediated through an atherogenic effect of chronic systemic inflammation. Gender and age differences in association with coronary calcification suggest that preventive measures should be emphasized in men with rheumatoid arthritis, and considered even in younger rheumatoid arthritis patients with low levels of traditional cardiovascular risk factors.
PMCID: PMC2688181  PMID: 19284547

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