Allopurinol use and type 2 diabetes incidence among patients with gout: A VA retrospective cohort study.

To assess the impact of allopurinol on diabetes in a retrospective cohort of Veterans' Affairs patients with gout.The New York Harbor VA computerized patient record system was searched to identify patients with an ICD-9 code for gout meeting at least 4 modified 1977 American Rheumatology Association gout diagnostic criteria. Patients were divided into subgroups based on >30 continuous days of allopurinol, versus no allopurinol. New diagnoses of diabetes, defined according to American Diabetes Association diagnostic criteria or clinical documentation explicitly stating a new diagnosis of diabetes, were identified during an observation period from January 1, 2000 through December 31, 2015.Six hundred six gout patients used allopurinol >30 continuous days, and 478 patients never used allopurinol. Over an average 7.9 ±â€Š4.8 years of follow-up, there was no significant difference in diabetes incidence between the allopurinol and non-allopurinol groups (11.7/1000 person-years vs 10.0/1000 person-years, P = .27). A lower diabetes incidence in the longest versus shortest quartiles of allopurinol use (6.3 per 1000 person-years vs 19.4 per 1000 person-years, P<.0001) was attributable to longer duration of medical follow-up.In this study, allopurinol use was not associated with decreased diabetes incidence. Prospective studies may further elucidate the relationship between hyperuricemia, gout, xanthine oxidase activity, and diabetes, and the potential impact of gout treatments on diabetes incidence.

Initiating guideline-concordant gout treatment improves arterial endothelial function and reduces intercritical inflammation: a prospective observational study.

BACKGROUND: Patients with gout have arterial dysfunction and systemic inflammation, even during intercritical episodes, which may be markers of future adverse cardiovascular outcomes. We conducted a prospective observational study to assess whether initiating guideline-concordant gout therapy with colchicine and a urate-lowering xanthine oxidase inhibitor (XOI) improves arterial function and reduces inflammation. METHODS: Thirty-eight untreated gout patients meeting American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for gout and ACR guidelines for initiating urate-lowering therapy (ULT) received colchicine (0.6 mg twice daily, or once daily for tolerance) and an XOI (allopurinol or febuxostat) titrated to ACR guideline-defined serum urate (sU) target. Treatment was begun during intercritical periods. The initiation of colchicine and XOI was staggered to permit assessment of a potential independent effect of colchicine. Brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent (smooth muscle) arterial responsiveness, respectively. High-sensitivity C-reactive protein (hsCRP), IL-1ß, IL-6, myeloperoxidase (MPO) concentrations, and erythrocyte sedimentation rate (ESR) assessed systemic inflammation. RESULTS: Four weeks after achieving target sU concentration on colchicine plus an XOI, FMD was significantly improved (58% increase, p = 0.03). hsCRP, ESR, IL-1ß, and IL-6 also all significantly improved (30%, 27%, 19.5%, and 18.8% decrease respectively; all p ≤ 0.03). Prior to addition of XOI, treatment with colchicine alone resulted in smaller numerical improvements in FMD, hsCRP, and ESR (20.7%, 8.9%, 13% reductions, respectively; all non-significant), but not IL-1ß or IL-6. MPO and NMD did not change with therapy. We observed a moderate inverse correlation between hsCRP concentration and FMD responsiveness (R = - 0.41, p = 0.01). Subgroup analyses demonstrated improvement in FMD after achieving target sU concentration in patients without but not with established cardiovascular risk factors and comorbidities, particularly hypertension and hyperlipidemia. CONCLUSIONS: Initiating guideline-concordant gout treatment reduces intercritical systemic inflammation and improves endothelial-dependent arterial function, particularly in patients without established cardiovascular comorbidities.

Impaired arterial responsiveness in untreated gout patients compared with healthy non-gout controls: association with serum urate and C-reactive protein.

To determine whether arterial responsiveness is impaired among patients with gout, and whether arterial responsiveness inversely correlates with serum urate and inflammatory measures. This is a cross-sectional study of untreated gout subjects (n = 34) and non-gout healthy controls (n = 64). High-resolution dynamic ultrasound-measured flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent arterial responsiveness respectively. Serum urate (sUA) and high-sensitivity C-reactive protein (hsCRP) were measured in the gout group, and correlated with FMD and NMD responses. Both FMD (2.20 ± 0.53 vs 3.56 ± 0.31, p = 0.021) and NMD (16.69 ± 1.54 vs 24.51 ± 0.90, p = 0.00002) were impaired in the gout versus control group. Stratification for individual comorbidities suggested that no single risk factor accounted for impaired FMD/NMD in the gout subjects. However, the degree of association between gout and FMD, but not NMD impairment, was dampened after multivariable adjustment (FMD unadjusted beta = - 1.36 (SE 0.58), p = 0.02; adjusted beta = - 1.16 (SE 0.78), p = 0.14 and NMD unadjusted beta = - 7.68 (SE 1.78), p < 0.0001; adjusted beta = - 5.33 (SE 2.46), p = 0.03). Within the gout group, there was an inverse correlation between FMD and sUA (R = - 0.5, p = 0.003), and between FMD and hsCRP (R = - 0.42, p = 0.017), but not between NMD and sUA or hsCRP. Compared with healthy controls, subjects with gout have reduced arterial function. Individual comorbidities are insufficient to account for differences between gout and control groups, but multiple comorbidities may collectively contribute to impairment in endothelium-dependent arterial responsiveness. Endothelial impairment is also related to sUA and hsCRP, markers of gout severity and inflammation respectively. Studies to determine whether gout therapy may improve arterial responsiveness are warranted.

Comparison of dual-energy CT, ultrasound and surface measurement for assessing tophus dissolution during rapid urate debulking.

Tophaceous gout is painful and impairs quality of life. The optimal modality for assessing tophus resolution in response to urate-lowering treatment remains poorly defined. Using pegloticase as a model system for resolving tophi, we compared multiple imaging and physical diagnostic strategies for assessing tophus resolution. A 32-year-old subject with chronic refractory tophaceous gout was enrolled and received 6 months of pegloticase treatment. Measurements of tophi using vernier calipers (monthly), photographs and musculoskeletal ultrasound (MSK-US; every 3 months), and dual-energy CT (DECT) were compared. Pegloticase persistently lowered the patient's sUA to <0.5 mg/dl. After 6 months, caliper measurements revealed 73, 60, and 61% reductions of three index tophi, while MSK-US revealed 47, 65, and 48% reductions. In contrast, DECT revealed 100% resolution of monosodium urate deposition in all three index tophi, and resolution or improvement of all other tophi identified. On caliper and MSK-US measurement, index tophus size fluctuated, with some lesions enlarging before ultimately contracting. Correlation between assessment modalities during tophus resolution may be poor. DECT identifies urate deposits invisible to physical exam and reveals that some urate deposits completely resolve even as their physically/sonographically measurable lesions persist. Recognition of urate resorption during the urate-lowering process may be confounded by fluctuating lesion volumes during initial tophus breakdown. While DECT was superior for identifying total (including occult) urate deposition, and assessing volume of deposits, other modalities may permit better assessment of non-urate tophus components.

Serum Urate Levels Predict Joint Space Narrowing in Non-Gout Patients With Medial Knee Osteoarthritis.

OBJECTIVE: The pathogenesis of osteoarthritis (OA) includes both mechanical and inflammatory features. Studies have implicated synovial fluid uric acid (UA) as a potential OA biomarker, possibly reflecting chondrocyte damage. Whether serum UA levels reflect/contribute to OA is unknown. We investigated whether serum UA levels predict OA progression in a non-gout knee OA population. METHODS: Eighty-eight patients with medial knee OA (body mass index [BMI] <33 kg/m2 ) but without gout were studied. Baseline serum UA levels were measured in previously banked serum samples. At 0 and 24 months, patients underwent standardized weight-bearing fixed-flexion posteroanterior knee radiography to determine joint space width (JSW) and Kellgren/Lawrence grades. Joint space narrowing (JSN) was calculated as the change in JSW from 0 to 24 months. Twenty-seven patients underwent baseline contrast-enhanced 3T knee magnetic resonance imaging for assessment of synovial volume. RESULTS: Serum UA levels correlated with JSN values in both univariate (r = 0.40, P < 0.01) and multivariate (r = 0.28, P = 0.01) analyses. There was a significant difference in mean JSN after dichotomization at a serum UA cut point of 6.8 mg/dl, the solubility point for serum urate, even after adjustment (JSN of 0.90 mm for a serum UA ≥6.8 mg/dl and 0.31 mm for a serum UA <6.8 mg/dl; P < 0.01). Baseline serum UA levels distinguished progressors (JSN >0.2 mm) and fast progressors (JSN >0.5 mm) from nonprogressors (JSN ≤0.0 mm) in multivariate analyses (area under the receiver operating characteristic curve 0.63 [P = 0.03] and 0.62 [P = 0.05], respectively). Serum UA levels correlated with the synovial volume (r = 0.44, P < 0.01), a possible marker of JSN, although this correlation did not persist after controlling for age, sex, and BMI (r = 0.13, P = 0.56). CONCLUSION: In non-gout patients with knee OA, the serum UA level predicted future JSN and may serve as a biomarker for OA progression.

Association Between Gout and Aortic Stenosis.

BACKGROUND: An independent association between gout and coronary artery disease is well established. The relationship between gout and valvular heart disease, however, is unclear. The aim of this study was to assess the association between gout and aortic stenosis. METHODS: We performed a retrospective case-control study. Aortic stenosis cases were identified through a review of outpatient transthoracic echocardiography (TTE) reports. Age-matched controls were randomly selected from patients who had undergone TTE and did not have aortic stenosis. Charts were reviewed to identify diagnoses of gout and the earliest dates of gout and aortic stenosis diagnosis. RESULTS: Among 1085 patients who underwent TTE, 112 aortic stenosis cases were identified. Cases and nonaortic stenosis controls (n = 224) were similar in age and cardiovascular comorbidities. A history of gout was present in 21.4% (n = 24) of aortic stenosis subjects compared with 12.5% (n = 28) of controls (unadjusted odds ratio 1.90, 95% confidence interval 1.05-3.48, P = .038). Multivariate analysis retained significance only for gout (adjusted odds ratio 2.08, 95% confidence interval 1.00-4.32, P = .049). Among subjects with aortic stenosis and gout, gout diagnosis preceded aortic stenosis diagnosis by 5.8 ± 1.6 years. The age at onset of aortic stenosis was similar among patients with and without gout (78.7 ± 1.8 vs 75.8 ± 1.0 years old, P = .16). CONCLUSIONS: Aortic stenosis patients had a markedly higher prevalence of precedent gout than age-matched controls. Whether gout is a marker of, or a risk factor for, the development of aortic stenosis remains uncertain. Studies investigating the potential role of gout in the pathophysiology of aortic stenosis are warranted and could have therapeutic implications.