Background:Gout is often associated with diabetes mellitus (DM), but the role of serum uric acid (sUA) and urate-lowering drugs in its development in patients with gout remains controversial [1].Objectives:To study risk factors for DM in patients with gout based on the results of long-term prospective follow-up study.Methods:The prospective study included 444 patients with a crystal-verified diagnosis of gout, aged ≥18 years, 49 (11%) women, 395 (89%) men. Patients were followed up at the V.A. Nasonova Research Institute of Rheumatology from 2010 to January 2021, the median follow-up was 6.1 [2.8; 7.8] years. The exclusion criteria were the presence of other rheumatic diseases with symptoms of arthritis, DM. DM was diagnosed on the 1998 WHO criteria. The following parameters were considered as risk factors: gender, family history for diabetes mellitus, body mass index (BMI)>25 kg/m2 and > 30 kg/m2, waist volume ≥88 cm for women and ≥102 cm for men, alcohol consumption > 20 units per week, chronic kidney disease (CKD), intake of diuretics and glucocorticoids, and serum total cholesterol >5 mmol/l, triglycerides>2.25 mmol/l, serum C-reactive protein (CRP) level> 5 mg/l, as well as clinical manifestations of gout: subcutaneous tophi, polyarthritis (simultaneous involvement of ≥5 joints), intake of urate-lowering drugs, sUA (> 480 μmol/L,> 420 μmol/L,> 360 μmol/L,> 300 μmol/L). Statistica 12.0 package was used for statistical data processing.Results:A total of 444 patients were included, the mean age was 51.0±12.9 years, the median follow-up was 6.1 [2.8; 7.8] years. In dynamics: 35 (8%) patients died, 6 (1%) patients were not available, 403 patients were examined (44 (11%) - women and 359 (89%) - men). 290 (72%) patients received urate-lowering therapy (263 (65%) patients used allopurinol, 27 (7%) - febuxostat). The target sUA <360 μmol/L was reached by 165 (41%) patients and <300 μmol/L - by 92 (23%) patients. All patients with sUA<300 μmol/L received urate-lowering therapy, 62 (67%) patients used allopurinol, 17 (18%) - febuxostat, 13 (14%) - uricosuric drugs. Diabetes mellitus was developed in 106 (26%) patients. The factors influencing the risk of developing diabetes were - the presence of diabetes in family history (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.37; 3.76); BMI> 30 kg / m2 (OR 1.79, 95% CI 1.14; 2.80), diuretics (OR 2.32, 95% CI 1.36; 3.96) and sUA> 300 μmol / l (OR 2.89, 95% CI 1.50, 5.56).Conclusion:The risk of developing DM in patients with gout is associated with sUA> 300 μmol/l, which may be one of the probable reasons for choosing this as a target level. Large prospective studies are needed to confirm the antidiabetic effect of urate-lowering drugs.References:[1]Chang HW, Lin YW, Lin MH, Lan YC, Wang RY. Associations between urate-lowering therapy and the risk of type 2 diabetes mellitus. PLoS One. 2019 Jan 7;14(1):e0210085. doi: 10.1371/journal.pone.0210085.Disclosure of Interests:Olga Sheliabina: None declared, Maxim Elisеev Speakers bureau: Berlin Chemie Menarini Group, Novartis International AG, EGIS, Aleksandra Novikova: None declared, Maria Chikina: None declared.

Background:Cardiovascular risk in CPPD patients is not so well evaluated as in other rheumatic diseases, and optimal risk calculators for patients withcalcium pyrophosphatecrystal deposition disease have not yet been studied.Objectives:To assess CVR and compare stratification results using АТР III and Reynolds Risk Score (RRS) calculators in CPPD, RA and gout patients versus the control subjects.Methods:The case-control study included 168 patients aged 18 - 80 years old, with 42 participants in each subgroup – CPPD, gout, RA patients and healthy volunteers, matched by gender (10 males and 32 females) and age (mean age 54 years). CPPD diagnosis was based on McCarty 1961 y criteria, RA – following ACR/EULAR 2010 y criteria, and gout - ACR/EULAR 2015 criteria. CPPD and gout diagnosis was crystal- verified in all cases. Exclusion criteria were as follows: diabetes mellitus and eGFR<60 ml/min/1.73m2. The following data was collected for all patients: anthropometric parameters, BP, lab tests, including serum glucose level, creatinine, total cholesterol (TC), HDLp, CRP; CVR was assessed using АТР III and RRS scales. Statistica 12.0 package was used for statistical data processing.Results:Both groups were comparable in terms of anthropometric parameters, rates of individual indicators and factors did not differ, except for family history of cardiovascular disease, systolic BP, HDLp, hsCRP (see Table).Table 1.Risk factors and CVR stratification by ATP III and RRS in CPPD, RA, gout and control group.CPPD (n=42)RA (n=42)Gout (n=42)Control (n=42)Smoking, n (%)11 (26,2)12 (28,6)8 (19,0)12 (28,6)Systolic BP, mmHg, M±SD124±14*/**138±17##144±26###127±16TC, mg/dl, M±SD261.9±64.2244.1±77.5249.3±62.7244.1±52.6HDLp, mg/dl, M±SD63.2±20.2*/**49.2±16.5##52.0±9.7###58.1±16.4hsCRP, mg/l, Me [25-75thpercentiles]3.8 [1,0;12,4] */**/***8,6 [4.1;20.6]##8.5 [4.1;2.9]###1,5[0.8;2.6]hsCRP ≥5 mg/l,n (%)18 (43)*/**/***27 (64)##29 (69)###3 (7)Family history of CVD, n %6 (14)*/***16 (38)#4 (10)###17 (40)High and very high CVR levels, ATP III scale (>10%), n (%)5 (12)9 (21)7 (17)8 (19)High and very high CVR levels, RRS scale (>10%), n (%)9 (21)14 (33)12 (29)7 (17)*p<0.05 between CPPD and RA, **р<0.05 between CPPD and gout, ***р<0.05 between CPPD and controls,#р<0.05 between RA and gout,##р<0.05 between RA and controls,###р<0.05 between gout and controls.Based on ATP III risk calculation the number of CPPD patients with high and very high CVR was 5 (12%) patients and was close to that in RA (9(21%)), gout (7 (17%)) and the control group (8 (19%)). Mean CRP levels and number of pts with CRP ≥5 mg/l were significantly lower in CPPD and control group pts, than in RA and gout, however CRP ≥5 mg/l levels were documented almost in half of CPPD pts (43%) and only in 7% of pts from the control group (р<0.05).Although CVR calculations based on RRS scale yielded similar results, and all groups remained comparable, nevertheless, the number of pts with high and very high CVR increased in each group, except for the control. There were no meaningful differences in between the groups in TC levels, however HDLp was significantly higher in CPPD pts (p<0.05), than in RA and gout, and in the control group pts vs RA pts (p<0.05).Conclusion:CPPD associated cardiovascular risk is considerably high and comparable to CVR levels in RA and gout. Given that RRS based CVR calculation resulted in increased number of patients with high and very high risks in all groups, except for the control group, it can be suggested that use of calculators including CRP is appropriate not only in RA pts, but also in microcrystal deposition arthritis, associated with inflammation, therefore prospective studies on larger samples are deemed necessary.Disclosure of Interests: :Aleksandra Novikova: None declared, Maxim Elisеev Speakers bureau: Novartis, Menarini Group, Alium, Olga Sheliabina: None declared, Helen Gerasimova: None declared

Background:The adherence to lowering therapy for gout is low, including in chronic severe gout. Whether interleukin 1 inhibitors may contribute to better adherence is unknown.Objectives:To compare adherence to urate-lowering therapy in patients with severe gout who received canakinumab versus patients who received standard anti-inflammatory therapy (NSAIDs, glucorticoids, colchicine).Methods:Of the 513 patients with gout observed at the V.A. Nasonova Research Institute of Rheumatology, Moscow from 2013 to 2014 y 247 patients with the most severe gout, requiring regular symptomatic treatment, were selected. Of these, 25 patients (3 (12%) women and 22 (88%) men), the average age of 54.5 ± 12.7 g, received (at least 1) canakinumab injection of 150 mg subcutaneously as a symptomatic therapy, the remaining 222 patients (men) mean age 51.9 ± 11.4 g. received standard anti-inflammatory therapy (colchicine (55% of patients), glucorticoids (5%), NSAIDs (40%), or a combination of these (3%). On average, after 4,8 ± 1.7 years, a comparative analysis of adherence to reducing therapy was carried out, as well as the need for anti-inflammatory therapy and assessment of adherence according to the Score compliance on the scale of the Moriscy-Green patients who received and did not receive canakinumab.Results:Evaluation was available in 180 patients (16 who received canakinumab and 164 who received standard anti-inflammatory therapy) who were initially given reducible therapy. 11 patients died (2 patients (8%) who received canakinumab and 9 (4%) patients on standard anti-inflammatory therapy), 56 patients (7 (28%) and 49 (22%), respectively) were not available for observation. Adherence to urate-lowering therapy was better in patients who received canakinumab (see table 1).Table 1.Score compliance on the scale of the Moriscy-GreenAdherence to therapyPatients receiving canakinumab, (n %)Patients receiving standard anti-inflammatory therapy, (n %)р=High (> 4 points)14 (87)83 (51)0,07Moderate (3 points)2 (13)46 (28)0,13Low (2 and <points)035 (21)0,03The likelihood of maintaining the target uric acid level when taking urate-lowering drugs in patients who previously received canakinumab was higher (12 patients (75%) who received canakinumab and 32 (20%) patients received standard anti-inflammatory therapy (p = 0.005).During the year preceding the analysis, there were no acute attacks of arthritis in 12 (75%) patients who received canakinumab and 46 (28%) patients received standard anti-inflammatory therapy (p = 0.002).132 patients who previously received regular anti-inflammatory therapy and received standard anti-inflammatory therapy and 1 patient (1 attack) (p = 0.005) who previously received canakinumab took anti-inflammatory drugs over the past year due to the development of exacerbations (an average of 3 seizures per year): NSAIDs (54%) or colchicine (46%).Conclusion:Therapy with interleukin 1 Kanakinumab may contribute to a better adherence to lowering therapy and isidentified with a lesser need for symptomatic therapy with long-term follow-up.Disclosure of Interests: :Maxim Elisеev Speakers bureau: Novartis, Menarini Group, Alium, Olga Sheliabina: None declared

Background:The association between chondrocalcinosis and primary hyperparathyroidism (PHPT) is known, but chondrocalcinosis is considered as a late complication of PHPT.Objectives:To investigate whether calcium pyrophosphate crystal deposition is an early clinical sign of PHPT.Methods:The prospective study included 113 patients aged ≥18 years, 42 (37.2%) men and 71 (62.8%) women, with a crystal-verified diagnosis of calcium pyrophosphate crystal deposition disease (CPPD) (McCarty criteria). Exclusion criteria were the presence of other rheumatic diseases with symptoms of arthritis, the presence of hyperparathyroidism (HPT). Patients were examined at their enrollment and over time, the median follow-up was 3.86 [2.07; 8.36] years. The examination of the patients included assessment of anthropometric parameters, information about the affected joints and the time of onset of symptoms.Laboratory tests included determination of the following in blood serum: creatinine (with estimating glomerular filtration rate (eGFR) according to the MDRD formula), total and ionized calcium (Ca and Ca++), phosphorus (P), parathyroid hormone (PTH), vitamin D (25-OH); ultrasound and X-ray investigations of the target joints (hands, knee joints) were made for all patients. Scintigraphy and ultrasound of the parathyroid glands were performed if medically required. Statistica 12.0 package was used for statistical data processing.Results:113 patients were examined, the average age was 58.4±12.4 years. 10 patients were excluded due to diagnosed HPT at screening. 41 patients dropped out of observation: 5 - died, 36 were not available for dynamic examination. 62 patients were examined in dynamics, 4 (6.5%) of those had HPT. In 1 (1.6%) case, HPT was associated with chronic renal failure, 3 (4.8) patients were diagnosed PHPT. The results of the examination of patients who developed PHPT during screening and in dynamics are presented in Table 1 above.Table 1.Results of patients with PHPT at screening and in dynamics.Сrystals of calcium pyrophosphate in synovial fluidChondrocalcinosis by ultrasoundChondrocalcinosis by X-rayConvulsionsECG changes (shortening of the QT interval)Arthralgias / arthritisPTH, pg/ml (15,0-65,0)Ca, µmol/l (2.10-2.62)Са++, µmol/l (1.10-1.33)vitamin D (25-ОН), ng/ml (30-100)screening / dynamicsРatient А.yes/yesyes/yesnot/yesnot/notnot/notyes/yes61.6/96.22.73/2.671.37/1.24-/31Рatient В.yes/yesyes/yesyes/yesnot/yesnot/yesyes/yes40.7/2522.63/2.561.34/1.7719.1/14.2Рatient С.yes/yesyes/yesnot/yesnot/notnot/notyes/yes26.6/102.42.60/2.651.25/1.26-/40In all three patients, chondrocalcinosis was revealed by ultrasound and Сrystals of calcium pyrophosphate in synovial fluid during the screening examination, in one patient chondrocalcinosis was revealed by X-ray. In two out of three cases, the level of serum Ca and Ca++ was minimally increased at a normal level of PTH, no other disorders of calcium metabolism were observed during the screening.Interestingly, the first clinical manifestation of HPT in all patients was damage of the musculoskeletal system - mainly arthralgia, as well as arthritis of large and small joints. Moreover, all patients had a different CPPD phenotype: patient A - asymptomatic chondrocalcinosis, patient B - chronic arthritis (pseudo-rheumatoid form) and patient C - chronic arthritis (pseudosteoarthritis).Conclusion:The deposition of calcium pyrophosphate crystals may be an early predictor of the development of PHPT and precedes other manifestations.Disclosure of Interests:Aleksandra Novikova: None declared, Maxim Elisеev Speakers bureau: Berlin Chemie Menarini Group, Novartis International AG, EGIS, Olga Sheliabina: None declared, Maria Chikina: None declared

Background:Crystal-induced inflammation can significantly increase cardiovascular risk (CVR) and cause early development of atherosclerosis [1]. However, no studies have been performed in patients with calcium pyrophosphate crystal deposition disease (CPPD).Objectives:To compare the presence of atherosclerosis early signs (increased thickness of the intima-media complex (CIMT)) in patients with CPPD and osteoarthritis (OA).Methods:A cross-sectional study included 48 patients, aged 18 to 65 years, 26 patients with crystal-verified diagnosis of CPPD (McCarty criteria) (6 (23%) men and 20 (77%) women) and 22 patients with OA (7 (32%) men and 15 (68%) women). Exclusion criteria are the presence of other rheumatic diseases with symptoms of arthritis, diabetes mellitus, coronary heart disease (CHD), prior myocardial infarction, stroke or myocardial revascularization surgery, estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, high and very high CVR on the SCORE scale. The examination of the patients included the history taking, assessment of anthropometric parameters and the following laboratory tests: determination of serum creatinine level (eGFR according to the MDRD formula), total cholesterol (TC), high density lipoprotein cholesterol (HDL cholesterol) and low density lipoprotein cholesterol (LDL cholesterol), C-reactive protein (CRP). Doppler ultrasound of the carotid arteries with an assessment of the thickness of the intima media complex (CIMT) was made for all patients - CIMT up to 0.9 mm was taken as the norm, CIMT> 0.9 mm and <1.3 mm as increased, and CIMT>1.3 mm was regarded as an atherosclerotic plaque. Statistica 12.0 package was used for statistical data processing.Results:The groups were completely comparable by gender, age and all laboratory parameters (see Table 1), an increase in CRP>5 mg/l was more often detected in patients with CPPD - 31% vs 14% patients with OA (p=0.16).Table 1.Clinical characteristics of patients included in the study.ParametersCPPD (n=26)OA(n=22)p value (reliable at р<0,05)Age, years M±SD55.9±5.952.4±8.30.14Gender, men/women,n (%)6 (23)/20 (77)7 (32)/15 (68)0.50Smoking, n (%)5(19)6(27)0.50Systolic blood pressure, mmHg, M±SD134±20127±150.19Arterial hypertension, n (%)13(50)10(45)0.75Family history of CVD, n %6(23)7(32)0.50TC, mmol/L, M±SD5.4±1.35.3±1.30.95TC >5,0 mmol/L, n (%)17(65)10(45)0.17HDL, mmol/L M±SD1.7±0.51.4±0.50.10LDL, mmol/L, M±SD2.9±1.33.4±1.40.33Creatinine, μmol/l, M±SD73.2±13.878.9±11.50.16CRP, mg/l, Me [25-75th percentiles]1.1 [0.6; 6.4]1.2 [0.3; 2.8]0.60CRP ≥5 mg/l,n (%)8 (31)3(14)0.16Mean CIMT values on the right (0.76±0.22 mm vs 0.70±0.18 mm) and on the left (0.75±0.18 mm vs 0.70±0.17 mm) did not significantly differ in CPPD and OA (p=0.34 and 0.32, respectively), the maximum CIMT values on the right (0.67±0.16 mm vs 0.67±0.16 mm) and on the left (0.67±0.14 mm vs 0,66±0.16 mm) with CPPD and OA were also comparable (p=0.95 and 0.77, respectively). However, an increase in CIMT> 0.9 mm was found in 13 (50%) patients with CPPD and only 5 (23%) with OA (p=0.02). No increase in CIMT>1.3 mm was found in patients of both groups.Conclusion:Early signs of atherosclerosis are detected in 50% of patients with CPPD without clinical signs of atherosclerosis and with low or moderate CVR according to SCORE, significantly more often than in patients with OA (23%), which can be reflection of chronic crystal-induced inflammation.References:[1]Hoseini Z, Sepahvand F, Rashidi B, Sahebkar A, Masoudifar A, Mirzaei H. NLRP3 inflammasome: Its regulation and involvement in atherosclerosis. J Cell Physiol. 2018 Mar;233(3):2116-2132. doi: 10.1002/jcp.25930. Epub 2017 May 23. PMID: 28345767.Disclosure of Interests:Maxim Elisеev Speakers bureau: Berlin Chemie Menarini Group, Novartis International AG, EGIS, Aleksandra Novikova: None declared, Olga Sheliabina: None declared, Maria Chikina: None declared, Eugenia Markelova: None declared.