[Diastolic dysfunction of ventricles in patients with calcium pyrophosphate crystal deposition disease while receiving anti-inflammatory therapy].

BACKGROUND: Calcium pyrophosphate crystal deposition disease (CPPD) may be associated with developing of diastolic dysfunction (DD). AIM: To determine the variability of echocardiographic parameters in patients with CPPD receiving anti-inflammatory therapy. MATERIALS AND METHODS: Twenty six patients with CPPD and osteoarthritis (OA) from 18 to 65 years old were included in the case-control study. All patients underwent echocardiography, laboratory parameters at baseline and after 6 months. Patients with CPPD received methotrexate 15 mg per week or hydroxychloroquine 200 mg once a day, or colchicine 1 mg per day. Diastolic function according to echocardiography was assessed. RESULTS: Diastolic dysfunction was detected in 19 patients: in 11 (42%) patients with CPPD and 8 (31%) patients with OA (p=0.39). The baseline serum CRP level was higher in the CPPD group (p=0.03), no differences were found for other indicators. Twenty-two patients with CPPD and 19 patients with OA completed the study. In patients with OA, there were no significant changes in indicators reflecting the diastolic function of ventricles. CONCLUSION: CPPD therapy with colchicine, hydroxychloroquine and methotrexate has a positive effect on indicators of diastolic ventricular function.

Contributing Factors of Diabetes Mellitus among Patients with Gout (Results of the Long-Term Prospective Study).

It is assumed that the risk of developing type 2 diabetes mellitus (T2DM) in patients with gout is influenced by both generally accepted risk factors and factors related to gout. The aim of the study was to evaluate the impact of various risk factors for T2DM in patients with gout. A total of 444 patients (49 women, 395 men) ≥18 years old with gout and without DM were included. The duration of observation was 5.66 [2.69; 7.64] years. To identify the factors associated with the risk of developing T2DM, multivariate logistic regression was used, which included sex; T2DM in relatives; insufficient physical activity; unbalanced diet; age  ≥ 45 years; ≥4 attacks per year; presence of tophi; BMI ≥30 kg/m2; allopurinol, febuxostat, glucocorticoids, diuretics, metformin, colchicine; GFR < 60 mL/min/1.73 m2; serum uric acid level (sUA) ≥ 420 µmol/L and  ≥ 480 µmol/L. T2DM developed in 108 (24.3%) patients. According to the multivariate model, the presence of ≥4 attacks of arthritis per year increased the risk of T2DM (OR = 5.23; 95% CI: 2.98-9.19; p = 0.0001); presence of tophi (OR = 2.61; 95% CI: 1.50-4.54; p = 0.001); sUA ≥ 480 µmol/L (OR = 2.26; 95% CI: 1.02-5.00; p = 0.144); diuretics (OR = 2.35; 95% CI: 1.19-4.64; p = 0.014). Febuxostat (OR = 0.31; 95% CI: 0.11-0.84; p = 0.022) and metformin (OR = 0.49; 95% CI: 0.21-1.16; p = 0.107) reduced the risk of developing T2DM. Risk of T2DM in patients with gout is associated with high incidence of arthritis attacks, MK ≥ 480 µmol/L, hypertension, diuretic use, and febuxostat and metformin reduces risk.

[Advantages of the use of metformin in patients with impaired uric acid metabolism].

Metformin is one of the oldest and at the same time relevant and effective drugs for the treatment of type 2 diabetes. At the same time, the mechanism of the hypoglycemic effect was not completely clear until recently. Current data suggest that the mechanism of action of metformin contributes to the development of an anti-inflammatory effect, as well as a decrease in the level of uric acid, and its use can be potentially useful in patients with hyperuricemia and gout.

[Advantages of therapy with sodium glucose cotransporter type 2 inhibitors in patients with type 2 diabetes mellitus in combination with hyperuricemia and gout].

Currently, only two drugs for reducing uric acid (UA), allopurinol and febuxostat, are registered in the Russian Federation, but their use does not allow to achieve the target level of UA in all cases. According to the results of numerous randomized trials, hyperuricemia and gout are associated with the corresponding components of the metabolic syndrome, including diabetes mellitus. The influence of factors is due to the need to search for new drugs that have a complex effect on several components of metabolic syndrome at once. Potentially attractive in this regard is a new group of drugs for the treatment of type 2 diabetes mellitus inhibitors of the sodium-glucose cotransporter of type 2, which, in addition to the main hypoglycemic actions, showed positive effects on the cardiovascular system, kidneys, as well as lowering UA.

[Comorbidity in gout and hyperuricemia: prevalence, causes, prospects of urate lowering therapy].

Nowadays, there is increased interest in the connection of gout and asymptomatic hyperuricemia with comorbid conditions such as diabetes mellitus, cardiovascular diseases, hypertension, chronic kidney disease and other. Studies conducted over the past few decades suggest that not only gout, but also asymptomatic hyperuricemia can significantly worsen the prognosis in patients with cardiovascular diseases, as the deposition of urate crystals can be both an immediate cause and a factor in the progression of renal failure. In that way, the timely appointment of urate - lowering therapy and achieving the target serum uric acid level can not only affect joint damage, but also can significantly slow the progression of life - threatening comorbid conditions.

[Independent risk factors for severe cardiovascular events in male patients with gout: Results of a 7-year prospective study]. / Nezavisimye faktory riska razvitiia tiazhelykh serdechno-sosudistykh oslozhnenii u muzhchin s podagroi: rezul'taty 7-letnego prospektivnogo issledovaniia.

AIM: To determine risk factors for severe cardiovascular (CV) events (CVEs) in male patients with crystal-verified gout. SUBJECTS AND METHODS: 251 male patients with crystal-verified gout were prospectively followed up in 2003 to 2013. The mean follow-up period was 6.9±2.0 years. New severe CVE cases and deaths were recorded. Logistic regression was used to analyze the impact of traditional and other risk factors and allopurinol use on the risk for severe CVEs. RESULTS: 32 patients died during the follow-up period. Severe CVEs were recorded in 58 (23.1%) patients; CVE deaths were notified in 22 (8.8%) patients. The risk of all severe CVEs was high for hypertension, increased serum high-sensitivity C-reactive protein (hs-CRP) level (>5 mg/l), ≥ stage III chronic kidney disease (CKD) (glomerular filtration rate, <60 ml/min/1.73 m2), alcohol intake (>20 g/day), coronary heart disease (CHD), and a family history of premature CHD. The risk of fatal CVEs was highest for elevated serum hs-CRP level, ≥ stage III CKD, a family history of premature CHD, hypercholesterolemia, upper quartile of serum uric acid levels (>552 µmol/l), and regular intake of allopurinol. CONCLUSION: In addition to the traditional risk factors of CV catastrophes, the presence of chronic inflammation and the impact of high serum uric acid levels may explain the high frequency of CV catastrophes.

[Time course of changes in the clinical manifestations of gout in men: data of a 7-year retrospective follow-up].

AIM: To estimate the time course of changes in the clinical manifestations of gout and their risk factors during a long-term follow-up. SUBJECTS AND METHODS: A total of 160 male patients with gout were examined and followed up for a mean of 6.9 ± 2.0 years. Their clinical assessment included determination of the type of arthritis over time, the frequency of arthritis attacks during one year prior to the examination, the presence and number of subcutaneous tophi, inflamed joints, comorbid or co-occurring diseases (CD), allopurinol adherence, dietary compliance, frequency of taking non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, and alcohol. The serum levels of uric acid (UA), glucose, total cholesterol, and glomerular filtration rate were estimated. RESULTS: The number of patients taking allopurinol increased from 19% to 64% (p < 0.0001), its average daily dose was 167.6 ± 94.6 mg. The serum level of UA decreased; 16% of the patients achieved its target level. The number of patients with chronic arthritis was not significantly changed. Their serum level of UA was unchanged; the detection rate of subcutaneous tophi and CD rose. During one year, arthritis attacks were absent in 13% of the patients; 90% of them took allopurinol. In these patients, serum UA levels and body mass index significantly declined and the rate of CD was unchanged. None of 18 patients who had their diet and no allopurinol achieved the target level of UA. CONCLUSION: Among the gouty patients, 36% refrain from the use of allopurinol, only 23% out of them require that its dose be adjusted to achieve the target level of UA. Dietary compliance is insufficient to reach the target level of UA. Chronic arthritis is associated with the increased incidence of CD.

[Main factors of gender dimorphism of gout (estrogens and diuretics vs alcohol and genetics)].

The article analyses factors underling gender dimorphism of gout, gender epidemiological differences. Discussion covers the role of estrogens and menopause, alcohol, diuretics, gender-associated genetic characteristics in gout genesis.

[Carbohydrate metabolic disorders in gout: incidence and clinical features].

AIM: To study the clinical features of gout concurrent with carbohydrate metabolic disturbances. SUBJECTS AND METHODS: One hundred and ninety-five patients with gout were examined. Their mean age was 54.8 +/- 10.4 years; disease duration was 10 (6-15) years. Anthropometry was estimated; the levels of uric acid (UA), creatinine, and lipid metabolic parameters were measured fasting; the concentrations of glucose were estimated fasting and 2 hours after use of 75 g of glucose; UA excretion and glomerular filtration rate were calculated. RESULTS: Carbohydrate metabolic disorders were found in 112 (57.4%) patients with gout: type 2 diabetes (T2D) in 67 (34.3%); impaired fasting glycemia in 23 (11.8%); impaired glucose tolerance in 22 (11.3%); the diagnosis of T2D was first detected in 35 patients with gout, i 12 of the 35 (34%) cases after oral glucose tolerance test (OGTT). The detection rate of carbohydrate metabolic disturbances was in direct proportion to serum UA levels. This value was 513.7 +/- 122.2 pmicromol/l in gouty patients with carbohydrate metabolic disturbances and 472.4 +/- 121.9 micromol/l in normoglycemic patients (p = 0.026). High body mass index and elevated serum were significantly determined in hyperglycemic patients; coronary heart disease (CHD) and arterial hypertension were more frequently diagnosed. CONCLUSION: OGTT causes a 34% increase in the detection rate of T2D in patients with gout. Carbohydrate metabolic disturbances are revealed in the majority of patients with gout and associated with obesity, hypertriglyceridemia, high serum UA levels, chronic disease forms, the high incidence of CHD and arterial hypertension.

[Effect of metformin on the clinical course of gout and insulin resistance].

UNLABELLED: The aim of this prospective study was to evaluate results of metformin (MF) therapy during 1 year of uric acid (UA) metabolism and the clinical course of gout with insulin resistance (IR). The study included 30 patients (28 men and 2 women) of mean age 51 yr and duration of he disease 4-11 yr. IR was diagnosed based on the HOMA index. INCLUSION CRITERIA: the absence of anti-gout therapy, normal renal and hepatic function, abstinence. The patients were given 1500 mg MF/day. The measured parameters included anthropometric and clinical characteristics, 24 hour AP, plasma UA, glucose, insulin, urea, creatinine, ALT, AST, lipid spectrum at the first and subsequent visits. UA clearance and excreted UA fraction were calculated. UA level decreased from 569 +/- 109.5 to 442.8 +/-107.4 mcmol/l (p < 0.01) after 12 months of MF therapy. Normouricemia ( < 360 mcmol/l) was achieved in 11 patients. Fasting insulin level dropped by 35% (from 23.9 to 15.9 mcU/ml, p < 0.01), HOMA index from 6.5 to 3. 7(p < 0.01). Serum glucose, cholesterol, triglycerides, and LDL cholesterol decreased while HDL cholesterol increased. Parameters of renal UA regulation and anthropometry remained unaltered. MF therapy resulted in a decrease of serum UA, insulin, and the degree of IR. The hypouricemic effect of MF was unrelated to renal UA excretion, reduced AP and body weight. It is hypothesized that MF reduces production of UA in patients with gout due to inhibition of synthesis of free fatty acids.

[Metabolic syndrome in gout].

The presence of metabolic syndrome (MS) is characteristic for many patients with gout. MS is closely associated with a generalized disorder called insulin resistance (IR) or impaired tissue responsiveness to the normal action in insulin. MS and IR define cardiovascular disease risks and are the main factors leading to severe disease associated with chronic arthritis and struck joints in gout patients. Given serious complications associated with MS, this frequent comorbidity should be recognized and be taken into account in the long-term treatment and overall health of individuals with gout. The review is devoted to studying MS and IR in gout patients.

[Comparison of the time to analgetic and anti-inflammatory effect in the treatment of gouty arthritis with nimesulide and sodium diclofenac].

AIM: To compare the time to presentation of the analgetic and anti-inflammatory effects of granulated and tablet nimesulide and sodium diclofenac since the start of therapy for gouty arthritis (GA). MATERIAL AND METHODS: Ninety males with gout were randomized into 3 equal groups. The patients were included in the study by the following criteria: a documented diagnosis of gout (Wallace S. criteria), age over 18 years, acute arthritis for less than 3 weeks, affection of 4 and more joints. For 7 days patients of group 1 received nimesil (200 mg/day), those of group 2--aponil (200 mg/day), group 3 --sodium diclofenac (150 mg/day). Swelling, articular, pain indices were estimated daily for 7 days. RESULTS: Patients of group 1 (nimesil) experienced pain relief on min 20; patients taking nimesulide (aponil) experienced pain attenuation within the first hour. Pain (at rest and movement) and the indices declined faster in group 1 than in group 2 as well as in groups 1 and 2 compared to group 3. Arthritis was arrested in 24 (80%) patients of group 1, 11 (36%) of group 2 and 4 (13%) of group 3. CONCLUSION: Efficacy of nimesulide for arrest of an acute gout attack exceeds that of sodium diclofenac. Granulated nimesulide has advantages over tablets.

[Use of metformin (siofor) in patients with gout and insulin resistance (pilot 6-month results)].

AIM: To evaluate metformin efficacy and safety in patients with gout and insulin resistance (IR). MATERIAL AND METHODS: The trial included 26 patients with gout (criteria of the American collage of rheumatologists) and IR (index HOMA). The inclusion criteria were the following: absence of antigout therapy, normal hepatic and renal function, rejection of alcohol. The drug dose was 1500 mg/day. The study was made of anthropometric and clinical characteristics, 24-h blood pressure monitoring, blood tests for uric acid, glucose, insulin, urea, creatinin, alaninaminotransferase, aspartataminotransferase, lipid spectrum at the first and further visits. RESULTS: A 6-month metformin therapy significantly changed the levels of glucose, insulin, HDLP and LDLP cholesterol, uric acid, HOMA index. Normouricemia was achieved in 11 patients, a significant lowering of uric acid--in 12 patients. The number of affected joints in 23 patients reduced from 4 (1-5) to 1 (0-2), p < 0.01. Seven patients with achieved normouricemia had no arthritis attacks. In 3 of 10 patients with chronic arthritis joint inflammation persisted. Six patients had dyspepsia during the first week of therapy, 1 patient discontinued the drug because of persistent diarrhea. CONCLUSION: Metformin therapy is safe. It reduces IR. The principal result of the study was lowering of uric acid and attenuation of the articular syndrome.

[Insulin resistance syndrome in patients with gout and its influence on formation of clinical characteristics of the disease]. / Sindrom insulinorezistentnosti u bol'nykh podagroi i ego vliianie na formirovanie klinicheskikh osobennostei bolezni.

AIM: To evaluate the occurrence of immunoresistance (IR) syndrome in gout and its correlation with a gout course. MATERIAL AND METHODS: Anthropometric parameters, blood lipid spectrum, levels of glucose, uric acid (UA), immunoreactive insulin, HOMA index were studied in 55 male patients with gout (mean age 50.1 +/- 7.9 years, mean duration of the disease 7.5 +/- 7.2 years). Statistic processing was made with computer program Statistica 6.0. RESULTS: IR was revealed in 49% patients. Immunoresistant patients had visceral obesity, arterial hypertension, abnormal lipid profile, high UA concentrations, longer disease, chronic articular syndrome, high occurrence of diabetes mellitus and vascular events significantly more frequently. CONCLUSION: IR in gout patients is the risk factor of cardiovascular diseases; combination of IR and hyperinsulinemia is characterized by marked hyperuricemia and a trend to chronic course of the articular syndrome. Longer duration of gout, especially treated inadequately, raises the risk of IR. IR deteriorates prognosis in relation to cardiovascular diseases, diabetes mellitus type 2, course of gout itself.

[The effectiveness and safety of nimesulide (nimesile) in patients with gouty arthritis]. / Effektivnost' i bezopasnost' primeneniia nimesulida (nimesila) u bol'nykh podagricheskim artritom.

Patients with gout are at a high risk for drug-induced complications associated with the use of nonsteroidal anti-inflammatory drugs due to the baseline renal and hepatic abnormalities, metabolic disturbances, and concomitant diseases, such as arterial hypertension or type 2 diabetes mellitus. In this connection, it is expedient to use safer selective cycloxygenase-2 (COG-2) inhibitors. However, there are only single reports dealing with studies of the effectiveness and safety of selective COG-2 inhibitors in gout. The study was undertaken to evaluate the effectiveness and safety of the selective COG-2 inhibitor nimesulide (nimesile) in acute gouty arthritis (GA). Twenty male patients (whose mean age was 51.1 +/- 8.4 years) with PA were examined. Seven patients were found to have monoarthritis of 1 metatarsophalangeal joint, oligoarthritis was present in 9 patients and 4 patients had polyarthritis. The history of arthritis was as long as 6 days in 16 patients and 21-30 days in 4. Nimesulide was given in a dose of 200 mg/day for at least 14 days. The time course of changes in the objective and subjective symptoms of arthritis was studied. The tolerability of the drug was evaluated by its effect on renal (the levels of creatinine and urea, creatinine clearance) and hepatic (alanine transferase (ALT), aspartate transferase (AST), gamma-glutamyltranspeptidase (gamma-GTP)) functions, and blood pressure (BP) [24-hour BP monitoring (24-h BPM) before and after treatment. There were clear positive changes in the major parameters of arthritis: the swelling index was 4.5 +/- 2.7 and 0.5 +/- 0.5 scores before and after treatment, respectively; hyperemia, 3.5 +/- 2.5 and 0.1 +/- 0. 1 scores; articular index, 3.6 +/- 2.0 and 0.7 +/- 0.6 scores; pain (visual analogue scale) when resting, 53.8 +/- 17.6 and 4.7 +/- 4.6 scores, and that when moving, 68.3 +/- 16.0 and 9.0 +/- 8.8 mm, respectively. Negative changes in the levels of creatinine and uric acid and a reduction in creatinine clearance were not observed. There were no increases in the levels of ACT, ALT, gamma-GTP. 24-h BPM did not reveal any significant changes in the mean 24-hour, mean diurnal and nocturnal variables of BP. The 24-hour BP profile became better in some patients. Thus, nimesulide is an effective and safe drug for the treatment of PA.