No abstract

BackgroundDiuretics have been associated with impaired response and refractoriness in gout, but whether this effect is still present with new urate-lowering drugs (ULD) and treat-to-target strategies is unknown. The aim of the present study was to assess the impact of the diuretics on the response to ULD in patients with gout. MethodsThis was a retrospective analysis of an inception cohort. Participants were classified according to the type of ULD prescribed. We analysed the maximal dose of ULD (primary outcome variable), serum urate (SU) reduction, and the achievement of different SU targets (6 mg/dL, 5 mg/dL, and 4 mg/dL), according to the type of ULD prescribed and use of diuretics (loop and/or thiazide). We adjusted for confounders using multiple linear regression analysis.ResultsWe included 245 patients: 208 treated with allopurinol (66 on diuretics, 31.7%), 35 with febuxostat (19 on diuretics, 57.6%), and 2 with benzbromarone. Significantly fewer participants in the allopurinol plus diuretics subgroup achieved SU levels of less than 5 mg/dL, but we found no other significant differences in SU targets associated with diuretics. Regarding the maximum ULD dose, a simple linear regression suggested an inverse relationship with diuretics (beta = − 0.125, p = 0.073), but this did not hold in the multivariable analysis (beta = − 0.47, p = 0.833). There was no association with febuxostat (beta = − 0.116, p = 0.514).ConclusionDiuretics do not appear to have a significant impact on managing gout.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1559-2) contains supplementary material, which is available to authorized users.

BackgroundUse of diuretics is a common bystander in patients with gout, and it has been reported to impair response to allopurinol [1,2] and likely lead to treatment failure and refractoriness. However, after the introduction of new urate-lowering therapies (ULT) and treat-to-target strategies, whether this inconvenient effect of diuretics persists has not received critical attention to date.ObjectivesTo analyze the impact of the diuretic therapy on the response to ULT in patients with gout.MethodsRetrospective analysis of an inception cohort in patients with crystal-proven gout (Jan2014-Nov2016). Patients were classified according to the use of diuretics (loop and/or thiazide) at baseline. The primary outcome variables were the reduction of serum uric acid (SUA) levels and the achievement of different objectives of SUA (6, 5, and 4mg/dL); as secondary outcome variable the maximum dose of ULT was registered, as well as other clinical, analytical, and ULT-related data. A comparative analysis was performed according to the use of diuretics, using Student's t and chi-2 tests. Also, the analysis was stratified according to the ULT used.ResultsThe inception cohort included 225 patients with an average age of 65 years (SD 14.1), being 86.2% of them men. The median duration of gout at inclusion was 4 years (p25–75 1–10) and 21.3% presented tophi. At baseline, the median (p25–75) SUA and estimated glomerular filtration rate were 8.2 mg/dL (7.2–9.2) and 75.9 mL/min (27.2–88.3), respectively. A total of 98 patients (43.6%) were on diuretics mainly for hypertension (64.7%), heart failure (9.4%), and renal failure (5.9%). Follow-up data was available from 209 patients (92.9%), with a median 9 months of follow-up (4–14). ULT used was allopurinol in 172 patients (82.6%), febuxostat in 34 (16.5%), and benzbromarone in only 2 cases (0.9%). Regarding the baseline characteristics, patients on diuretics were older, had higher rates of females, hypertension, diabetes, and cardiovascular disease, and showed higher SUA and lower glomerular filtration rate. The table shows the outcomes comparison according to diuretic treatment, globally and stratified by type of ULT (excluding the two cases of benzbromarone). Except for a lower achievement of SUA<5 in the allopurinol subgroup, no significant differences were found either globally or by type of ULT.Outcome variableDiuretic therapyp NoYes Whole sample (N=209)N=117n=92– SUA reduction (mg/dL), mean (SD)3.2 (2.1)3.7 (2.5)0.196– SUA<6 (%)80.0%75.9%0.458– SUA<5 (%)61.0%50.6%0.126– SUA<4 (%)31.4%28.9%0.575Allopurinol (n=158)N=92N=66– SUA reduction (mg/dL), mean (SD)3.1 (1.9)3.2 (2.0)0.813– SUA<6 (%)80.6%74.2%0.337– SUA<5 (%)60.2%43.9%0.043– SUA<4 (%)28.0%21.2%0.334– Maximum dose (mg/day), mean (SD)316.5 (126.9)278.6 (121.8)0.053Febuxostat (n=33)N=14N=19– SUA reduction (mg/dL), mean (SD)3.7 (3.4)5.6 (3.1)0.147– SUA<6 (%)70.0%82.4%0.456– SUA<5 (%)70.0%76.5%0.711– SUA<4 (%)60.0%58.8%0.952– Maximum dose (mg/day), mean (SD)80.0 (16.3)80.0 (25.3)0.348ConclusionsDespite its high rate, diuretics cur...

Background:Gout is an independent cardiovascular (CV) risk factor. This excess of morbidity and mortality requires optimal management, especially in high-risk individuals. So, the inclusion of subclinical atherosclerosis screening by carotid ultrasound in the initial evaluation may help to accurately stratify the CV risk. However, longitudinal outcomes using this technique are not available in gout.Objectives:To analyze the new CV events occurred in patients with gout after structured CV assessment incorporating carotid ultrasound.Methods:Retrospective analysis of an inception cohort of new patients with crystal-proven gout. At baseline, a structured CV assessment was performed considering age, gender, traditional risk factors, CV and renal disease, laboratory data, SCORE and Framingham risk tools and carotid ultrasound; according to 2013 ESC guidelines, CV risk was stratified as low, moderate, high or very high. The cohort includes 356 patients, mean aged 64 years (SD 14.0) mostly males (86.0%), 21.8% with tophaceous gout and mean serum urate at diagnosis of 8.2mg/dL (SD 1.8). The CV risk stratification was: low in 20 (5.6%), moderate in 47 (13.2%), high in 34 (9.6%), and very high risk in 242 (68.0%). Major CV events (coronary disease (CD), heart failure (HF), stroke, peripheral artery disease (PAD) and CV death) were recorded during the follow-up by electronic case reports review. A binary composite endpoint of “new major CV event” was used. The incidence after inclusion in the cohort was estimated. To evaluate potential baseline predictors (clinical and gout-related) of CV events, a Cox regression model was built.Results:Mean follow-up in the cohort was 41.5 months (SD 16.8). Forty new major CV events have been identified (incidence 3.25%/patient-year), distributed as follows: HF 1.46 (n=18), CV death 0.65 (n=8), CD 0.49 (n=6), stroke 0.33 (n=4), and PAD 0.33%/patient-year (n=4). Per risk stratification, the incidence of a new event was 0.16%/patient-year in the high-risk group and 3.01%/patient-year in the very high-risk, while no events occurred in low and moderate groups. The table shows the univariate and multivariate analysis of baseline variables. An independent association and a trend towards significance were noted for age and to be classified at a very high CV risk at baseline, respectively.Univariate regressionMultivariate regressionHR (95%CI)PHR (95%CI)PAge1.07 (1.04-1.11)<0.0011.04 (1.00-1.08)0.031Female gender3.27 (1.68-6.33)<0.0011.24 (0.55-2.81)0.605Body mass index1.00 (0.94-1.06)0.863--Glomerular filtration rate0.98 (0.97-0.99)<0.0011.00 (0.99-1.01)0.766Very high CV risk at baseline9.54 (2.30-39.64)0.0024.11 (0.89-19.02)0.070Serum urate at diagnosis1.19 (1.00-1.42)0.0521.12 (0.94-1.33)0.227ULT at diagnosis0.81 (0.29-2.27)0.688--Tophi1.33 (0.66-2.66)0.422--Years since first flare1.00 (0.97-1.03)0.772--Number of flares suffered0.99 (0.97-1.00)0.255--Number of involved joints1.00 (0.89-1.12)0.976--Joint pattern at presentation-Monoarticular1.00(ref)-1.00(ref)--Oligoarticular1.86 (0.91-3.80)0.0891.35 (0.65-2.82)0.421-Polyarticular2.75 (1.05-7.22)0.0391.34 (0.48-3.76)0.579HR: Hazard ratio; 95%CI: 95% confidence interval.Conclusion:First longitudinal study assessing the use of subclinical atherosclerosis screening as part of CV risk assessment in new patients with gout. Those classified at the very high-risk group presented the majority of events, being HF the most frequent. Age, and likely to be classified as very high risk, independently predicted a new CV event during follow-up, data that may be of interest in terms of management of the patient with gout at the time of diagnosis.Disclosure of Interests: :Mar Monzó: None declared, Neus Quilis Marti: None declared, Laura Ranieri: None declared, Alejandro San-Martín: None declared, Mariano Andrés Grant/research support from: Grünenthal, Consultant of: Grünenthal, Menarini, Speakers bureau: Grünenthal, Horizon

Background:Despite having passed more than fifty years after its initial description, essential questions for calcium pyrophosphate (CPP) crystal disease, such as clinical spectrum, diagnosis or management schemes, remain unsolved. Acute flares often occurred during hospitalizations. Scant reports have addressed this common setting for CPP crystal disease, and whether these patients behave similarly to ambulatory cases is unknown.Objectives:The aim of this work was to describe in a prospective way a crystal-proven case series of patients developing acute CPP crystal arthritis during hospitalizations for another conditions.Methods:An observational, cross sectional descriptive study was conducted in two Spanish centers from November 2013 to December 2018. A prospective convenience sampling was employed to select patients with crystal-proven CPP acute arthritis seen during hospital admissions. Demographic, clinical and CPP-related variables were collected, and X-rays (pelvis, knees, hands, affected joint when different) and laboratory tests (to rule out associated metabolic conditions) were systematically requested. A descriptive analysis is presented.Results:90 episodes of acute CPP arthritis in 87 patients were seen in the study period, with an average age of 81.8 years (SD 7.7), 50.6% of them men. Approximately 26% of patients reported prior episodes of arthritis, most of them (68.4%) as outpatients. Only three patients were on preventive treatment for CPP arthritis (two on colchicine and one on low dose glucocorticoids). Regarding the acute CPP arthritis during admissions, they were predominantly monoarticular (81.0%) and the main involved joints were knee (46.0%), wrist (13.8%) and ankles (6.9%). The reasons for admission were diverse, with a mean of 7.7 days (SD 9.1) from admission to flare. About X-rays, 23.8% showed no chondrocalcinosis (CC) in the evaluated joints [61/80]. In 57.1% of patients there was chondrocalcinosis in the affected joint [44/77] and regarding usual joints: 74.3% in knees [55/74], 51.5% in triangular carpal ligament [34/66], 25.4% in metacarpo-phalangeal joints [17/67], 20% in pubic symphysis [14/70] and 17.6% in coxofemoral joints [12/68]. A secondary form of osteoarthritis was only seen in 10 patients (12.5%). About associated metabolic diseases, one case of primary hyperparathyroidism-related hypercalcemia and five cases of hypomagnesemia at the time of the flare were detected. In all six patients with a polyarticular presentation, laboratory tests for rheumatoid factor and ACPA were negative.Conclusion:From the findings of this prospective, crystal-proven series of CPP crystal arthritis in an intrahospital setting, we can remark:1. The low numbers of previous ambulatory flares may suggest a different clinical entity of CPP disease.2. Radiological CC was absent in around a quarter of patients despite a extensive assessment, so synovial fluid analysis remains essential for diagnosis.3. The rarity of associated metabolic diseases seen runs against ruling out secondary causes of CPP dise...