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We-P12:308 Inflammation and platelet activation in patients with rheumatoid arthritis: Possible determinants of increased cardiovascular risk
P12
414
Wednesday, June 21, 2006: Poster Session Optimal atherosclerosis ,~:magement (2tM part)
q
W e - P 1 2 : 3 0 7 / E F F E C T OF A N T I - T N F A A D M I N I S T R A T I O N T H E LIPID P R O F I L E IN P A T I E N T S W I T H INFLAMMATORY DISEASES
ON
J.A. Papadakis 1, E.K. Spanakis 2 , G.E. Vrentzos 1, G. Katsikas 2, S.T. Kaxvounans-, H.D. K r m k o s - , P.I. Sldlropoulos-, E.S. Ganotakis , D.T. Boumpas 1'2. 1Dept of bttemal Medicine, Universi~ Hospital of
Heraklion, Heraklion, Greece: 2Dept of Rheumatology, Clinical Im,mnology arm Allergy, Universi~ Hospital of Heraklion, Heraklion, Greece B a c k g r o u n d : Tumor necrosis factor alpha (TNFa) is considered as one of the key cytokines in Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) pathophysiology. It has also multiple atherogenic effects, and increased levels of TNFa have been positively correlated with impaired insulin action. Objective: To access whether anti-TNFa therapy modifies the unfavorable lipid profile of patients with inflammatory diseases. M e t h o d s : The lipid profile and the inflammatory markers [high sensitivity C-reactive protein (hsCRP) and erythrocyte sedimedation rate (ESR)] were measured in 60 patients (24 with RA, 25 with AS and 11 with PsA) treated with anti-TNFa monoclonal antibodies, before and after 1, 3 and 6 months of treatment. Results: Serum high-density lipoprotein (HDL) levels were significantly increased at 1st, 3rd and 6th month after anti-TNFa administration [mean difference (95% CI): 4.7 (2.6-6.9)mg/dl; p<0.001, 3.5 (1.2-5.8)mg/dl; p<0.01, and 2.8 (0.6-5.0)mg/dl; p=0.01, respectively]. Serum cholesterol (TC) concentration was significantly increased only at 1st month [11.0 (4.4-17.5)mg/dl; p<0.01]. There were no significant differences either in triglycerides (TG) or in low-density lipoprotein (LDL) serum levels during subsequent visits. Atherogenic indexes TC/HDL and LDL/HDLwere significantly increased only at 1st month [0.26 (0.09-0.43); p<0.01 and 0.22 (0.07-0.36); p<0.01, respectively]. Conclusion: anti-TNFa administration increases serum HDL levels. This may improve the cardiovascular risk profile of patients with inflammatory diseases.
W e P 12:308 [ I N F L A M M A T I O N A N D P L A T E L E T A C T I V A T I O N IN PATIENTS WITH RHEUMATOID ARTHRITIS: POSSIBLE DETERMINANTS OF INCREASED CARDIOVASCULAR RISK I
C. Jurcut, R. Jurcut, S. Blaj, C. Tanasescu. Central Military Hospital,
Bucharest, Romania
W e - P 1 2 : 3 0 9 ] R H E U M A T H O I D A R T R I T H I S (RA) A N D A T H E R O S C L E R O S I S : O S T E O P O N T I N (OPN) A COMMON INFLAMMATORY MARKER ASSOCIATED WITH CARDIOVASCULAR RISK L. Bazzichi 1 , A. Mazzone 2 , A. Consensi 1 , T. Giuliano 1 , F. De Feo 3, M. Lanza I , C. Giacomelli 3 , S. Bombardieri I . 1Department ofb~temal
Medicine- Division of Rheumatology, Universi~ of Pisa, Pisa, Italy: 2bzstitute of Clinical Physiology, CNR of Pisa, Pisa, Italy: 3Deparment of Psychiatry, Neurobiology, Pharmacology arm Biothecnology, Universi~ of Pisa, Pisa, Italy Objectives: RA is a systemic inflammatory status, associated with the development of cardiovascular (CV) disease and CV mortality. OPN extracellular phosphorilathed glycoprotein with property cytokines, secreted by activated macrophages, leukocytes, T lymphocytes and stimulated by I L l , IL6 and TNF alpha, was found in inflamed joints and atherosclerotic plaque. Serum OPN was detected higher in coronary and carotid artery disease patients (pts) and in RA pts. We would estimate the link between RA and CV risk factors comparing ordinary and new inflammatory markers with lipidic profile. M e t h o d s : We studied clinically 32 pts, 23 with A R and 9 non case (2 A R 2 gout, 2 SSc, 1 Sj, 1 FM, 1 AS) without clinical signs of cardiovascular disease. In all pts, we detected a basal venous perhipheral blood sample for the measure of ordinary inflammatory markers 0ESV, CRR Fibrinogen, AB antiCCR RF), and OPN by enzyme immunometric assay EIA kit (Titer Zyme) (ref range 0-30 ng/ml). Moreover we detected atherosclerotic risk factors by systemic lipidic profile: Cholesterol Triglicerides, ApoA, ApoB, HomoCys. Results: In RA pts, plasma level of OPN are higher respect to non case (mean-l-SD) (117.5-4-82.1 vs 39.16-4-19.19; p=0.012); RA pts shown a significant correlation between serum levels of OPN and other inflammatory markers as ESR, CRR fibrinogen, RF (p<0.05), and between OPN and Cholesterol (p<0.05) and A p t A (p<0.05). Conclusions: Our results increase the hypothesis of an associated comorbidity between RA and atherosclerosis. Funding: The OPN could have an important role for the pathogenesis of RA also as marker disease.
I We-P12:310
I
I T N F A L P H A -1031 T > C P O L Y M O R P H I S M IS ASSOCIATED WITH ELEVATED MARKERS OF O X I D A T I O N A N D W I T H S M A L L E R L D L S I Z E IN SUBJECTS WITH RHEUMATOID ARTHRITIS
1
J.C. Vallv41 , J. Girona I , S. Paxedes I , E. Hurt-Camejo-, L. Masana 1 . 1 Umtat Recerca L{pids, h'cis, Hospital Univ. Sant Joan, Univ. Rovira i Virgili, Reus, Spain," 2Depart. Molecular Pharmacology. AstraZeneca, MOlndal, Sweden "
B a c k g r o u n d : Large epidemiological studies showed the great prevalence of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Moreover, this increased risk was not related to traditional cardiovascular risk factors and seems to be related to persistent inflammatory status existing in these patients. However, the predictors for the development of CVD in patients with RA were not clearly established, and, otherwise, the role of thrombosis mechanisms were inconsistent chaxacterized in these patients. M e t h o d s : In 22 pts with RA (mean age: 60.68 years), we performed standard biochemical workup and platelet histogram, including mean platelet volume (MPV) and platelet distribution width (PDW) as markers of platelet activation. We divided the study group in two subgroups: group A = 14 patients with RA without CVD and group B = 8 patients with RA and with CVD. Results: Patients from group B vs. group A had significantly higher levels of fibrinogen (544.00 vs. 415.37 mg/dl, p<0.05) and increased, erythrocyte sedimentation rate (47.25 vs. 31.00 ram, p=ns). Mean age was higher in group B vs. group A (73.85 vs. 54.53 years, p<0.05). Platelet histogram showed higher values for MPV (9.74 vs. 8.66 fL, p<0.01) and PDW (17.15 vs. 16.08, p<0.01) in patients with RA and CVD, reflecting great platelet activation in these patients. Conclusion: The presence of cardiovascular disease in patients with rheumatoid axthritis may be linked to an increased inflammatory and thrombosis activity (fibrinogen levels and platelet histogram indices).Age of the patients is also one of the determinants of CVD in rheumatoid arthritis.
~
.
Objective: To examine the association between the TNFa gene variants (-1031 C/T, -863 C/A, -857 T/C) with markers of oxidative stress and lipid profile in rheumatoid arthritis (RA) patients. M e t h o d s : we studied 30 RA patients and 30 matched controls. We analyzed plasma samples for lipids, inflammatory markers, susceptibility of LDL to oxidation and LDL size. We determined the TNFa polymorphisms (-1031 C/T, -863 C/A, -857 T/C) by PCR amplification and enzymatic restriction. LDL size was assessed by NMR. Results: The frequency of the rare alleles was not different between RA patients and controls. Although carriers of the -1031 C allele showed a 1.6 fold increased in plasma TNFa levels, we found no significant association between inflammatory parameters (CRR ESR, fibrinogen, sPLA2-IIA and TNFa) and the polymorphisms studied in RA patients. We found in the RA subjects a significant association between -1031C allele and lag phase, maximal rate and LDL size. More precisely, carriers of -1031C allele had significantly lower LDL lag phase (36,5%; p<0.03), higher maximal rate (19,2%; p<0.05), and smaller LDL particles (2,1%; p < 0,05) compared with carriers of the - 1031T allele. These results show, that RA subjects with the -1031C allele have a higher susceptibility to LDL oxidation and a more atherogenic LDL particle compared with RA subjects caxriers of the T allele. Conclusions: These results show that in RA patients, variability at the TNFa gene is associated with increased susceptibility to LDL oxidation and reduced LDL particle size. These results could help to detect RA patients with a higher cardiovascular risk.
XIV bzterTtational Symposium on Atherosclerosis, Rome, Italy, June 18-22, 2006
414
Wednesday, June 21, 2006: Poster Session Optimal atherosclerosis ,~:magement (2tM part)
q
W e - P 1 2 : 3 0 7 / E F F E C T OF A N T I - T N F A A D M I N I S T R A T I O N T H E LIPID P R O F I L E IN P A T I E N T S W I T H INFLAMMATORY DISEASES
ON
J.A. Papadakis 1, E.K. Spanakis 2 , G.E. Vrentzos 1, G. Katsikas 2, S.T. Kaxvounans-, H.D. K r m k o s - , P.I. Sldlropoulos-, E.S. Ganotakis , D.T. Boumpas 1'2. 1Dept of bttemal Medicine, Universi~ Hospital of
Heraklion, Heraklion, Greece: 2Dept of Rheumatology, Clinical Im,mnology arm Allergy, Universi~ Hospital of Heraklion, Heraklion, Greece B a c k g r o u n d : Tumor necrosis factor alpha (TNFa) is considered as one of the key cytokines in Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) pathophysiology. It has also multiple atherogenic effects, and increased levels of TNFa have been positively correlated with impaired insulin action. Objective: To access whether anti-TNFa therapy modifies the unfavorable lipid profile of patients with inflammatory diseases. M e t h o d s : The lipid profile and the inflammatory markers [high sensitivity C-reactive protein (hsCRP) and erythrocyte sedimedation rate (ESR)] were measured in 60 patients (24 with RA, 25 with AS and 11 with PsA) treated with anti-TNFa monoclonal antibodies, before and after 1, 3 and 6 months of treatment. Results: Serum high-density lipoprotein (HDL) levels were significantly increased at 1st, 3rd and 6th month after anti-TNFa administration [mean difference (95% CI): 4.7 (2.6-6.9)mg/dl; p<0.001, 3.5 (1.2-5.8)mg/dl; p<0.01, and 2.8 (0.6-5.0)mg/dl; p=0.01, respectively]. Serum cholesterol (TC) concentration was significantly increased only at 1st month [11.0 (4.4-17.5)mg/dl; p<0.01]. There were no significant differences either in triglycerides (TG) or in low-density lipoprotein (LDL) serum levels during subsequent visits. Atherogenic indexes TC/HDL and LDL/HDLwere significantly increased only at 1st month [0.26 (0.09-0.43); p<0.01 and 0.22 (0.07-0.36); p<0.01, respectively]. Conclusion: anti-TNFa administration increases serum HDL levels. This may improve the cardiovascular risk profile of patients with inflammatory diseases.
W e P 12:308 [ I N F L A M M A T I O N A N D P L A T E L E T A C T I V A T I O N IN PATIENTS WITH RHEUMATOID ARTHRITIS: POSSIBLE DETERMINANTS OF INCREASED CARDIOVASCULAR RISK I
C. Jurcut, R. Jurcut, S. Blaj, C. Tanasescu. Central Military Hospital,
Bucharest, Romania
W e - P 1 2 : 3 0 9 ] R H E U M A T H O I D A R T R I T H I S (RA) A N D A T H E R O S C L E R O S I S : O S T E O P O N T I N (OPN) A COMMON INFLAMMATORY MARKER ASSOCIATED WITH CARDIOVASCULAR RISK L. Bazzichi 1 , A. Mazzone 2 , A. Consensi 1 , T. Giuliano 1 , F. De Feo 3, M. Lanza I , C. Giacomelli 3 , S. Bombardieri I . 1Department ofb~temal
Medicine- Division of Rheumatology, Universi~ of Pisa, Pisa, Italy: 2bzstitute of Clinical Physiology, CNR of Pisa, Pisa, Italy: 3Deparment of Psychiatry, Neurobiology, Pharmacology arm Biothecnology, Universi~ of Pisa, Pisa, Italy Objectives: RA is a systemic inflammatory status, associated with the development of cardiovascular (CV) disease and CV mortality. OPN extracellular phosphorilathed glycoprotein with property cytokines, secreted by activated macrophages, leukocytes, T lymphocytes and stimulated by I L l , IL6 and TNF alpha, was found in inflamed joints and atherosclerotic plaque. Serum OPN was detected higher in coronary and carotid artery disease patients (pts) and in RA pts. We would estimate the link between RA and CV risk factors comparing ordinary and new inflammatory markers with lipidic profile. M e t h o d s : We studied clinically 32 pts, 23 with A R and 9 non case (2 A R 2 gout, 2 SSc, 1 Sj, 1 FM, 1 AS) without clinical signs of cardiovascular disease. In all pts, we detected a basal venous perhipheral blood sample for the measure of ordinary inflammatory markers 0ESV, CRR Fibrinogen, AB antiCCR RF), and OPN by enzyme immunometric assay EIA kit (Titer Zyme) (ref range 0-30 ng/ml). Moreover we detected atherosclerotic risk factors by systemic lipidic profile: Cholesterol Triglicerides, ApoA, ApoB, HomoCys. Results: In RA pts, plasma level of OPN are higher respect to non case (mean-l-SD) (117.5-4-82.1 vs 39.16-4-19.19; p=0.012); RA pts shown a significant correlation between serum levels of OPN and other inflammatory markers as ESR, CRR fibrinogen, RF (p<0.05), and between OPN and Cholesterol (p<0.05) and A p t A (p<0.05). Conclusions: Our results increase the hypothesis of an associated comorbidity between RA and atherosclerosis. Funding: The OPN could have an important role for the pathogenesis of RA also as marker disease.
I We-P12:310
I
I T N F A L P H A -1031 T > C P O L Y M O R P H I S M IS ASSOCIATED WITH ELEVATED MARKERS OF O X I D A T I O N A N D W I T H S M A L L E R L D L S I Z E IN SUBJECTS WITH RHEUMATOID ARTHRITIS
1
J.C. Vallv41 , J. Girona I , S. Paxedes I , E. Hurt-Camejo-, L. Masana 1 . 1 Umtat Recerca L{pids, h'cis, Hospital Univ. Sant Joan, Univ. Rovira i Virgili, Reus, Spain," 2Depart. Molecular Pharmacology. AstraZeneca, MOlndal, Sweden "
B a c k g r o u n d : Large epidemiological studies showed the great prevalence of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Moreover, this increased risk was not related to traditional cardiovascular risk factors and seems to be related to persistent inflammatory status existing in these patients. However, the predictors for the development of CVD in patients with RA were not clearly established, and, otherwise, the role of thrombosis mechanisms were inconsistent chaxacterized in these patients. M e t h o d s : In 22 pts with RA (mean age: 60.68 years), we performed standard biochemical workup and platelet histogram, including mean platelet volume (MPV) and platelet distribution width (PDW) as markers of platelet activation. We divided the study group in two subgroups: group A = 14 patients with RA without CVD and group B = 8 patients with RA and with CVD. Results: Patients from group B vs. group A had significantly higher levels of fibrinogen (544.00 vs. 415.37 mg/dl, p<0.05) and increased, erythrocyte sedimentation rate (47.25 vs. 31.00 ram, p=ns). Mean age was higher in group B vs. group A (73.85 vs. 54.53 years, p<0.05). Platelet histogram showed higher values for MPV (9.74 vs. 8.66 fL, p<0.01) and PDW (17.15 vs. 16.08, p<0.01) in patients with RA and CVD, reflecting great platelet activation in these patients. Conclusion: The presence of cardiovascular disease in patients with rheumatoid axthritis may be linked to an increased inflammatory and thrombosis activity (fibrinogen levels and platelet histogram indices).Age of the patients is also one of the determinants of CVD in rheumatoid arthritis.
~
.
Objective: To examine the association between the TNFa gene variants (-1031 C/T, -863 C/A, -857 T/C) with markers of oxidative stress and lipid profile in rheumatoid arthritis (RA) patients. M e t h o d s : we studied 30 RA patients and 30 matched controls. We analyzed plasma samples for lipids, inflammatory markers, susceptibility of LDL to oxidation and LDL size. We determined the TNFa polymorphisms (-1031 C/T, -863 C/A, -857 T/C) by PCR amplification and enzymatic restriction. LDL size was assessed by NMR. Results: The frequency of the rare alleles was not different between RA patients and controls. Although carriers of the -1031 C allele showed a 1.6 fold increased in plasma TNFa levels, we found no significant association between inflammatory parameters (CRR ESR, fibrinogen, sPLA2-IIA and TNFa) and the polymorphisms studied in RA patients. We found in the RA subjects a significant association between -1031C allele and lag phase, maximal rate and LDL size. More precisely, carriers of -1031C allele had significantly lower LDL lag phase (36,5%; p<0.03), higher maximal rate (19,2%; p<0.05), and smaller LDL particles (2,1%; p < 0,05) compared with carriers of the - 1031T allele. These results show, that RA subjects with the -1031C allele have a higher susceptibility to LDL oxidation and a more atherogenic LDL particle compared with RA subjects caxriers of the T allele. Conclusions: These results show that in RA patients, variability at the TNFa gene is associated with increased susceptibility to LDL oxidation and reduced LDL particle size. These results could help to detect RA patients with a higher cardiovascular risk.
XIV bzterTtational Symposium on Atherosclerosis, Rome, Italy, June 18-22, 2006