Objective: to study the frequency of hyperleptinemia in patients with systemic lupus erythematosus (SLE), its relationship with clinical and laboratory manifestations of the disease, drug therapy, and other metabolic disorders.Patients and methods. The cross-sectional study included 46 women with a definite diagnosis of SLE (median age 40 [31; 48] years) and disease duration 3.0 [0.9; 9.0] years. Glucocorticoids (GC) were received by 38 (83%) patients, hydroxychloroquine – by 35 (76%), immunosuppressants – by 10 (22%), biologic disease-modifying antirheumatic drugs – by 5 (11%). In all patients, fasting levels of glucose, leptin, apoliproprotein B (ApoB) and immunoreactive insulin were determined, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Concentration of leptin ≥11.1 ng/ml, ApoB – >1.6 mg/ml were considered an elevated level. HOMA-IR index ≥2.77 corresponded to the presence of insulin resistance (IR).Results and discussion. Hyperleptinemia was found in 34 (74%) patients with SLE, an increased level of ApoB – in 19 (41%), IR – in 10 (22%). In patients with hyperleptinemia, serositis, positivity for anti-double-stranded DNA (aDNA) and hypocomplementemia were less common, overweight and obesity were more frequent, the SLEDAI-2K index was lower, the aDNA level was lower, and the concentration of the C3 component of complement, insulin, HOMA-IR index, body mass index (BMI) and disease duration were higher (p<0.05 for all cases). BMI <25 kg / m2 had 26 (57%) women, 14 (54%) of whom had hyperleptinemia. In patients with BMI <25 kg / m2, we found a relationship between leptin concentration and disease duration (r=0.4, p=0.04), SLE activity according to SLEDAI-2K (r=-0.6, p=0.003), levels of aDNA (r=-0.6, p<0.001), C3 component of complement (r=0.5, p=0.01), maximum (r=0.7, p<0.001) and supporting (r=0,5, p=0.023) GC doses.In patients with BMI ≥25 kg/m2 (n=20), no such relationship was observed.Conclusion. Hyperleptinemia was found in the majority of women with SLE; elevated levels of ApoB and IR were much less common. Patients with hyperleptinemia are characterized by a longer duration and less activity of the disease, as well as the presence of overweight and obesity and an increase in the HOMA-IR index. In SLE patients with normal body weight, the concentration of leptin increased along with GC dose elevation.
Background Patients with Rheumatoid Arthritis (RA) have an increased risk for cardiovascular disease (CVD). Objectives To evaluate CVD prevalence and RA-related factors in RA patients participating in the prospective longitudinal (7 years duration) observational study. After the initial baseline visit, data will be collected every 6 months using the physician and patient questionnaires. Methods We studied 200 patients in a cross-sectional fashion: 165 (82,5%) females and 35 (17,5%) males, median (Me) age 55 [interquartile range (IR) 46;61] years who meet the 1987 ARA revised criteria for the classification of RA and enrolled in our cohort. Exclusion criteria: age less than 18 years or greater than 85 years at the time of enrollment into the registry, ACR functional class 4 RA. We considered the CVD (cardiovascular heart disease, cardiovascular revascularization procedure, myocardial infarction and stroke), traditional cardiovascular risk factors (smoking, family history of CVD, hypertension, dyslipidemia, menopausal status, body mass index (BMI), diabetes mellitus) and RA-related factors (duration of RA, disease activity score (DAS 28), seropositivity for IgM rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (ACCP), ACR functional class, treatment including both biologic and non-biologic disease modifying anti-rheumatic drugs (DMARDs) and steroids). Results The median disease duration of RA was 5 [1;10] years, early RA (≤ 1 year) was diagnosed in 60/200 (30%) patients, DAS 28 score was 3,9 [3,1;4,9], seropositive for IgM RF – 166/200 (83%) and/or ACCP – 151/200 (75,5%), 133/188 (73%) patients had erosions, ACR functional class I RA was 46/200 (23%), II RA – 129/200 (64,5), III RA – 25/200 (12,5%). Therapy: 87/200 (43,5%) patients received oral glucocorticoids, 141/200 (70,5%) – methotrexate, 18/200 (9%) – leflunomide, 6/200 (3%) – hydroxychloroquine, 2/200 (1%) – azathioprine, 43/200 (21,5%) - biologic DMARDs: rituximab – 13/200 (6,5%), adalimumab – 12/200 (6%), abatacept – 9/200 (6%), certolizumab pegol – 4/200 (2%), infliximab – 3/200 (1,5%), tocilizumab – 2/200 (1%). Ischemic heart disease was diagnosed in 38/200 (19%) patients, myocardial infarction – 3/200 (1,5%), cardiovascular revascularization procedure (coronary artery bypass graft) – 7/200 (3,5%), and stroke – 1/200 (0,5%). We observed the following frequency of traditional CVD risk factors: CVD family history – 58/200 (29%), dyslipidemia – 91/200 (46 %), BMI≥25 – 117/200 (58,5%), hypertension – 120/200 (60%), diabetes mellitus – 14/200 (7%), smoking status (ex-smoker+smoker) – 88/200 (44%), menopause – 110/165 (55%). Conclusions RA patients had a high frequency of CVD (20%). Ongoing observation of this cohort will further assess to assess the impact of chronic inflammation and specific therapy on CVD. Disclosure of Interest None Declared
Background The relationship between insulin resistance (IR) and inflammation in rheumatoid arthritis (RA) is poorly studied. Assume that an effective anti-inflammatory therapy may affect the IR. As IR markers currently used HOMA-IR index and the ratio of leptin/adiponectin (L/A). Objectives Evaluate the effect of combined treatment with methotrexate (MTX) and TNF-alpha inhibitors on IR in early RA. Methods In the study included 22 patients (15 female, 7 male) with RA eligible ACR, EULAR 2010, never receiving glucocorticoids and disease-modifying anti-rheumatic drugs. Average age of the patients - 57 [54, 60] years, mean duration of disease - 8 [6.0, 15.0] months, mean DAS28 - 5,9 [5,3; 6,9]. All patients were positive for RF and anti-CCP. The control group consisted of 30 subjects (23 women, 7 men) without rheumatic disease, matched by sex, age and body mass index (BMI) with RA patients. Baseline and after 24 weeks of observation, patients were evaluated by: RA activity (indices DAS, SDAI, CDAI), the index HOMA-IR, adiponectin and leptin concentration, the ratio of leptin/adiponectin (L/A). Level of adipokines was also examined in the control group by ELISA. Results At study entry adiponectin levels was higher in RA patients than in controls (20.0 [17.8, 34.0] vs 8,6 [5,6;12,2] ng/ml); leptin (25.4 [11.0, 32.0] vs 36,8 [19,0;46,2] ng/ml) and the ratio L/A (1.49 [0.2;1.9] vs 5,31[2,7;6,8]) is lower in RA patients than in controls vs (p<0.05 respectively). All patients with RA was assigned MTX, and after 12 weeks - an inhibitors of TNF-alpha (19 patients - adalimumab, 3 - certolizumab pegol). After 24 weeks of treatment decreased DAS28 (p=0,0001), SDAI (p=0,0006), CDAI (p=0,0003) and adiponectin levels (p=0,008). Leptin levels (p=0,005) and the ratio L/A (p=0,01) significantly increased, HOMA-IR did not change (p=0,2) (table1). Table 1 Baseline Week 24 Δ % Ð-value BMI 29,8 [25,8; 33,6] 30,0 [25,8; 33,6] 0,67 0,5 HOMA-IR 2,76 [1,5; 3,6] 3,34 [1,6; 5,1] 21 0,2 Adiponectin,ng/ml 20,0 [17,8; 34,0] 11,6 [6,7; 16,2] −42 0,008 Leptin, ng/ml 25,4 [11; 32] 32,8 [11,8; 49,8] 29,1 0,005 L/A 1,49 [0,2; 1,9] 4,28 [1,3; 4,2] 187,2 0,01 DAS28 6,0 [5,3; 6,9] 3,4 [2,4; 4,3] −43,3 0,0001 SDAI 41,2 [25,5; 56,6] 11,2 [7,0; 13,6] −69,7 0,0006 CDAI 36,3 [21,3; 48,4] 8,9 [5,1; 10] −72,7 0,0003 ESR, mm/h 45,7 [18,0; 56,0] 26,0 [9,0; 50,0] −43,1 0,02 CRP, mg/l 46,3 [18,3; 47,9] 10,2 [0,9; 11,0] −77,9 0,001 Data are presented as median (interquartile range). Conclusions The combination therapy of RA antiinflammatory (inhibitors of TNF-alpha, methotrexate) for 24 weeks decreases the activity of RA, but does not improve the performance of IR. The ratio L/A is preferably use at an early stage of the RA for the assessment of IR. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5239
Background Cardiovascular morbidity and mortality in patients with rheumatoid arthritis (RA) is associated with early atherosclerosis. A possible explanation could be the metabolic syndrome (MetS) and inflammation. Objectives To evaluate MetS prevalence and the preclinical atherosclerosis in patients with RA. Methods Two hundred twenty-five patients with RA (190 woman, 35 men) aged 18-59 years were included in this cross-sectional study, 79% of them had positive rheumatoid factor. MetS prevalence was assessed using NCEP ATPIII (2004) definitions (at least three of five characteristics: abdominal obesity, low level of high density lipoproteins cholesterol, elevated triglyceride and fasting glucose levels, high blood pressure). Carotid intima-media thickness was examined by high resolution B-mode ultrasound measurements. Atheromatous plaque was defined as a local intima-medial thickening ≥1,2mm. The levels of CRP and inflammatory cytokine (interleukin - 18) were determined in serum samples by the high sensitive particle-enhanced immunonephelometric assay. Results MetS was found in 49 (22%) patients with RA (obesity - 39%, low level of high density lipoproteins cholesterol - 56%, elevated triglyceride level - 10%, elevated fasting glucose level - 14%, hypertension - 54%). Patients with MetS were older (52 years versus 48 years without MetS, p=0,003) but had lower RA duration (54 months versus 120 months without MetS, p=0,02). No difference was observed in ESR, CRP levels and DAS28 in groups with and without MetS. Glucocorticoids use did not associate with MetS. Patients with MetS had significantly higher prevalence of carotid plaques (38% versus 20% in patients without MetS, p=0,01), maximal carotid intima-media thickness (1,0 (0,9-1,2)mm versus 0,9 (0,8-1,0)mm, p=0,007) and level of interleukin-18 (79,5 (0,01-213) pg/ml versus 40 (0,01-393) pg/ml, p=0,05). Conclusions Most frequently criteria of MetS in patients with RA are dyslipoproteinemia and hypertension. MetS is associated with preclinical atherosclerosis and higher level of proinflammatory interleukin-18. Disclosure of Interest None Declared
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