Objectives To prospectively investigate the effect of tofacitinib (TOFA), the first oral reversible inhibitor of JAK approved for RA treatment, on the levels of NT-proBNP, as a predictor of congestive heart failure (CHF) in patients (pt) with active RA. Methods Twenty six RA pt (median age 54 [40; 62] years, 81% female, disease duration 44 [24; 63,0] month (m), moderate to high activity (SDAI–27 (22; 35)), positive for ACCP (73%)/RF (77%), who were non-responders to methotrexate (MTX) at least 15 mg/week and other synthetic DMARDs) free of clinical overt cardiovascular disease were treated with TOFA and followed for 12 m. TOFA therapy was started in all pt in dose 5 mg BID per os with dose escalation to 10 mg BID in 8 (31%) pt. TOFA used in combination with MTX in 24 (92%) pt, leflunomide in 1 (4%). Low-dose oral corticosteroids (<10 mg/day prednisone or equivalent) were received by 9 (35%) pt. Remission was achieved in 38,5% (SDAI). Cardiovascular risk factors (CVRF) and the NT-proBNP levels were measured at baseline and after 12m. At baseline the most of pt had multiple CVRF and subclinical organ damage. Cardioprotective therapy received 16 (57%) pt (beta-AB–7, ARA/ACE inhibitors–11, statins–11, dihydropyridine CCB-7). Twenty controls matched for CVRF were included for comparison of normal NT-proBNP levels. Results The NT-proBNP level was significantly higher in RA pt than in the control group (median 62.2 (26.9–101.7) pg/mL vs 44.0 (34.0–54.3) pg/mL, p<0.05). At baseline NT-proBNP level was higher in female than in male (p=0,019). All 3 (11,5%) RA pt with a NT-proBNP level over 125 pg/mL were asymptomatic and exhibited normal echocardiography. Median SDAI were significantly reduced following TOFA treatment (from 26.8 to 4.7, p<0.001, respectively). During follow-up, no RA pt exhibited a cardiovascular event or CHF. NT-proBNP levels decreased by 63% over the 12-m of TOFA treatment (from 62.16 pg/mL to 14.8 pg/mL, p=0.011). The incidence rate of arterial hypertention (58% vs 65%), overweight (62% vs 62%), abdominal obesity (58% vs 62%), smokers (27% vs 27%), menopausal status (52% vs 52%), DM type 2 (7% vs 7%), mSCORE≥5% (23% vs 27%), subclinical carotid atherosclerosis (58% vs 58%) did not change significantly. An increase in body mass index (BMI) was observed from 26.5 [22.9; 29.0] to 26.9 [24.0; 30.1], p<0.001 and in HDL level from 1.37 [1.06; 1.87] to 1.90 [1.29; 2.16], p<0.01. The percentage change in the NT-proBNP level significantly correlated with the percentage change in the BMI (r=0,6, p=0,007), SDAI (r=0.51, p=0.009). Changes in NT-proBNP levels in RA pt with remission was greater than that observed in pt who didn't achieve remission (−87% vs −26%, p=0,005). The percentage change in the NT-proBNP level was not correlated with the percentage change in other CVRF. Conclusion TOFA decreased the NT-proBNP level in patients with RA without clinical overt cardiovascular disease and CHF. TOFA may have a cardioprotective effect in those with active RA.

ObjectivesTo compare the significance of the carotid ultrasound and the MDCT assessment of coronary calcification in the stratification of cardiovascular risk and the detection of indications for lipid-lowering therapy in patients with RA.MethodsNinety two patients with RA are included (ACR/EULAR, 2010), 74% are women, the median of age is 54 [41.5; 60] years, median of disease duration - 6 [5; 21] months, median of DAS28 (ESR) – 5.2 [5.0; 6.0], without cardiovascular diseases and diabetes mellitus, severe chronic renal failure (GFR <60 ml/min x 1.73m2). Arterial hypertension was detected in 57% of patients, dyslipidemia – in 50%, 63% of women were in postmenopause. Initially, the cardiovascular risk was assessed using the mSCORE scale, and then again, taking into account the results of carotid ultrasound and MDCT assessment of coronary calcification.ResultsAfter assessing the cardiovascular risk on the mSCORE scale 41.3% of patients with RA were classified as low risk (n = 38), medium risk – 38% (n = 35), high risk – 15.2% (n = 14), very high risk– 5.5% (n = 5). Non-target lipid levels were detected in 44.7% of low-risk patients, in 83% of medium risk patients, in 78.6% of high risk patients, in 100% of very high risk patient. Absolute indications for statin therapy were detected in 17.4%.Hemodynamically insignificant carotid plaques (stenosis <50%) was detected in 56.5% of patients with RA: in 23.7% of low risk category, in 74.3% of medium risk patients, in 85.7% of high risk patients, in 100% of very high risk patients. A sever calcification of the coronary arteries was detected in 25% (the coronary index is more than 300 U or > 75 percentile of the age- and sex-related reference values, in according to MESA): in 5.3% of low risk patients, in 37% of medium risk patients, in 28.6% of high risk patients, in 80% of very high risk.After carotid ultrasound 38% (34/92) of RA patients were reclassified from the category of low and medium cardiovascular risk on the mSCORE scale to the high risk category. The proportion of patients with high cardiovascular risk increased in 3.5 times (53.2%, p <0.001). There were 42 patients with non-target lipid levels in the high risk category. The proportion of patients with absolute indications for statins increased in 2.9 times compared with the results of the mSCORE evaluation (n = 47/92; 51%; p <0.001).After MDCT assessment of coronary calcification 16.3% (15/92) of RA patients were reclassified from the category of low and medium cardiovascular risk on the mSCORE scale to the high risk category. The proportion of patients with high cardiovascular risk increased in 2.1 times (31.5%, p <0.001). There were 24 patients with non-target lipid levels in the high risk category. The proportion of patients with indications for statins increased in 1.8 times compared with the results of the mSCORE evaluation (n = 29/92; 31.5%; p <0.001). Carotid ultrasound more often reveals indications for statin therapy, p <0.001.ConclusionThe use of the mSCORE scale is not sensitive enough for stratific...

Background:N-terminal pro-brain natriuretic peptide (NT-proBNP) is a recognized predictor of congestive heart failure (CHF) and cardiovascular death. Rheumatoid arthritis (RA) patients (pts) were shown to have higher NT-proBNP concentrations than in general population, but it remains unclear, whether NT-proBNP levels are related to RA duration, activity or treatment.Objectives:To investigate the effect of interleukin 6 receptor inhibitor - tocilizumab (TCZ) and JAK inhibitor - tofacitinib (TOFA) on NT-proBNP levels in RA pts during a 12-month (m) follow-up period.Methods:The study enrolled 60pts (50women/10men) with the lack of efficacy/resistance and/or intolerance of basic anti-inflammatory drugs (DMARDs); median age was 55[42;61] years, median disease duration 55[29;120]m, with moderate to high activity (DAS28-5,1[4,6;6,1], serum positivity for rheumatoid factor (RF)(85%)/ anti-cyclic citrullinated peptide antibodies (ACCP)(80%). The study did not include RA pts with CHF and clinically overt cardiovascular disease (CVD). Twenty nine RA pts received TCZ(8mg/kg) every 4 weeks: 61% received TCZ in combination with methotrexate (MTX), 35% - with low-dose glucocorticoids (GCs). Thirty one RA pts were prescribed oral TOFA at 5 mg BID with dose escalation to 10 mg BID in 8 (26%)pts. TOFA was used in combination with MTX in 90% pts, with GCs – in 29% pts. Pts treated with TCZ and TOFA were comparable in terms of age, sex, body mass index. RA activity rates (DAS28, SDAI, ESR, CRP) were higher in pts on TCZ -therapy compared with pts treated with TOFA. Echocardiography data and NT-proBNP levels using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland) were obtained at baseline and after 12m.Results:Significant positive changes in major disease activity, clinical and laboratory parameters were found in RA pts after 12 m of TCZ infusion and TOFA intake: remission (DAS28<2,6) was achieved in 54% and 39% pts, low activity levels (DAS28<3,2) – in 46% and 51% pts, respectively.The NT-proBNP levels were significantly higher in RA pts than in the control group (median 69,1 (37,9;105,8) pg/mL vs 55,3 (36,6;67,3) pg/mL,p<0.05).Six pts (10%) (three in each pts group) had NT-proBNP levels over 125pg/ml, but were asymptomatic and had unremarkable echocardiography.There was a good correlation between NT-proBNP level at baseline with age (r=0,55,p<0,001), SDAI (r=0,5, h=0,01), ACCP (r=0,23,p=0,01).Decrease of median NT-proBNP levels was documented after 12m of TCZ therapy (81,5[43,0;102,0]vs41,6[25,4;64,2]pg/ml (p<0,01) and after 12m TOFA therapy (66,1[30,5;105,0]vs16,8 [5,0;81,0]pg/ml,p=0,001).After 12m of TCZ correlations of ΔNT-proBNP were established with ΔESR (R=0,43;p<0,05], ΔСRP (R=0,46;p<0,05], ΔEe left ventricle (LV) (r=0,88,p=0,03).In the group of pts treated with TOFA ΔNT-proBNP level significantly correlated with the percentage change in DAS 28 (r=0,41,p=0,038), there was no direct correlation with changes in the parameters of the LV diastolic function.Conclusion:TCZ and TOFA treatment for 12 m reduced NT-proBNP levels in RA pts without clinically manifest CVD and CHF. Falling NT-proBNP concentrations are associated with positive dynamics of RA activity (DAS 28) and inflammatory markers (CRP, ESR), therefore allowing to suggest that increased NT-proBNP levels should be considered as a component of disease activity. Correlation between ΔNT-proBNP and ΔEeLF may be indicative as possible impact of these biomarkers on the LV diastolic function’s development in RA pts.Disclosure of Interests:None declared

BackgroundThe amino-terminal fragment of the B-type natriuretic peptide prohormone (NT-proBNP) is a marker for functional cardiac impairment and is increased in heart disease with or without symptoms of congestive heart failure (CHF)1.ObjectivesTo prospectively investigate the effect of tofacitinib (TOFA) on the levels of NT-proBNP, as a predictor of CHF in patients (pt) with active rheumatoid arthritis (RA).MethodsTwenty six RA pt (median age 54 [40;62] years, 81% female, disease duration 44[24;63,0] month (m), moderate to high activity (DAS28-5.1[4.6;6.1], SDAI–27(22;35)), positive for ACCP (73%)/RF (77%), who were non-responders to MTX at least 15 mg/week and/or other synthetic DMARDs and bDMARDs) free of clinical overt cardiovascular disease were treated with TOFA and followed for 12 m. TOFA therapy was started in all pt in dose 5 mg BID per os with dose escalation to 10 mg BID in 8 (31%) pt. TOFA used in combination with MTX in 24 (92%) pt, leflunomide in 1 (4%). Low-dose oral corticosteroids (<10 mg/day prednisone or equivalent) were received by 9 (35%) pt. Remission was achieved in 38,5% pt (DAS28), 38,5% (SDAI). Cardiovascular risk factors (CVRF) and the NT-proBNP levels were measured at baseline and after 12m. At baseline the most of pt had multiple CVRF and subclinical organ damage. Cardioprotective therapy received 16 (57%) pt (β-AB–7, ARA/ACE inhibitors–11, statins–11, dihydropyridine CCB-7). Twenty controls matched for CVRF were included for comparison of normal NT-proBNP levels with those of RA pt.ResultsThe NT-proBNP level was significantly higher in RA pt than in the control group (median 62.2(26.9-101.7) pg/mL vs 44.0 (34.0-54.3) pg/mL, p<0.05). At baseline NT-proBNP level was higher in female than in male (p=0,019). Its concentration correlated with DAS28 (r=0,41,p=0,036). Three pt (11,5%) had NT-proBNP level over 125 pg/mL. All RA pt with a NT-proBNP level over 125 pg/mL were asymptomatic and exhibited normal echocardiography. Median DAS28 and SDAI were significantly reduced following TOFA treatment (from 5.1 to 2.9, p < 0.001 and from 26.8 to 4.7, p < 0.001, respectively). During follow-up, no RA pt exhibited a cardiovascular event or CHF. NT-proBNP levels decreased by 63% over the 12-m of TOFA treatment (from 62.16 pg/mL to 14.8 pg/mL, p= 0.011). The incidence rate of arterial hypertention (58%vs65%), overweight (62%vs62%), abdominal obesity (58%vs62%), smokers (27%vs27%), menopausal status (52%vs52%), DM type 2 (7%vs7%), mSCORE≥5% (23%vs27%), subclinical carotid atherosclerosis (58%vs58%) did not change significantly. An increase in body mass index (BMI) was observed from 26.5[22.9;29.0] to 26.9[24.0;30.1],p<0.001 and in HDL level from 1.37[1.06;1.87] to 1.90[1.29;2.16],p<0.01. The percentage change in the NT-proBNP level significantly correlated with the percentage change in the BMI (r=0,6,p=0,007), DAS 28 (r = 0.41, p = 0.038) SDAI (r = 0.51, p = 0.009). Changes in NT-proBNP levels in RA pt with remission was greater than that observed in pt who didn’t achieve remission (-87% vs -26%, p=0,0...

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