Proc. West. Pharmacol. Soc. 50: 119-122 (2007) Non-invasive Assessment of Arterial Stiffness Indices by Applanation Tonometry and Pulse Wave Analysis in Patients with Rheumatoid Arthritis Treated with TNF-α Blocker Remicade (infliximab) Alma Cypiene¹*, Aleksandras Laucevicius², Algirdas Venalis¹, Ligita Ryliskyte², Jolanta Dadoniene¹, Zaneta Petrulioniene², Milda Kovaite², Violetta Laskova 3 , and Jonas Gintautas³ ¹Institute of Experimental and Clinical Medicine at Vilnius University, Lithuania; ²Department of Cardiovascular Medicine, Vilnius University; Center of Cardiology and Angiology, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania; ³MediSys Health Network: Jamaica Hospital Medical Center, Brookdale University Hospital and Medical Center, and Flushing Hospital Medical Center, New York, USA *E-mail: alma.cypiene@santa.lt ABSTRACT Rheumatoid arthritis (RA) is accompanied by long lasting inflammation, which may lead to arterial dysfunction and premature aging of the arteries. The purpose of this clinical work was to determine the modification of carotid-radial pulse wave velocity (PWV) and aortic augmentation index (AIx) in young- aged RA patients and the influence of treatment with anti-TNF-α (infliximab) on these measures. We examined 68 RA patients (mean age 40.68 yrs) with moderate or high disease activity (DAS28 5.37±0.94) and 87 controls (mean age 38.10 yrs). PWV and AIx were assessed non-invasively by applanation tono- metry. A blood test included serum lipid profile, and high-sensitivity CRP measurements. We found that in RA patients, AIx (p<0.001) was significantly higher while PWV (p=0.315) did not differ as compared to control. Multiple regression analysis revealed the presence of RA is an independent predictor for AIx (R 2 =0.718, adjusted R 2 =0.707; p<0.001). Analysis (Mann–Whitney test) in 15 RA patients revealed lowering of PWV (p=0.004) under infliximab therapy with no change in AIx (p=0.573), suggesting the improvement of arterial wall function by anti-TNF-α therapy. We conclude that increased AIx is more prominent in RA patients as compared to the controls. PWV appears to be a less sensitive marker for the detection of enhanced development of arterial stiffness in relatively young-aged RA patients. However, PWV may serve as a good marker to discern effects of infliximab on artery elasticity. INTRODUCTION Rheumatoid arthritis (RA) is accompanied by long lasting inflammation, which is associated with endothelial dysfunction and may lead to functional stiffening of the large arteries. Previous studies have shown that endothelial dysfunction is associated with RA [1-3] as well as increase of arterial stiffness [4-9] and aortic pulse wave velocity (PWV) [1,10]. However, the mechanisms of the development of endothelial dysfunction and stiffening of arteries in RA patients remain unclear. Furthermore, the classic risk factors do not explain excess vascular disease in RA. Clinical epidemiology observations strongly suggest that mechanisms other than classic risk factors may play a role in accelerated atherogenesis in RA [11]. TNF-alpha is an important mediator of systemic and vascular wall inflammation, both in RA and in atherosclerotic vascular disease. However, the effect of circulating TNF-α on cardiovascular function is uncertain [2]. Clinical trials of anti-TNF-α therapy in RA patients have shown little benefit on carotid- femoral PWV [1], or endothelial function [1-3], but AIx has not been examined [1,9]. No existing study examined non-invasive carotid-radial (brachial) PWV, AIx and the effect of anti-TNF-α therapy on these measures in relatively young RA patients. These findings have led to the hypothesis that chronic inflammatory processes associated with RA may cause arterial wall dysfunction, which can lead to a subsequent increase of arterial stiffness and functional vascular damage that are closely related to the clinical course of RA in young patients. The aim of this study was to determine if carotid-radial pulse wave velocity (PWV) and aortic augmentation index (AIx) from applanation tonometry, were modified in young age RA patients and the influence of treatment with anti-TNF-α on these measures. METHODS Study population: We examined 68 consecutive patients with an established RA diagnosis (aged 40.68±10.07 yrs) and 87 controls (aged 38.10±8.69 yrs). Subjects were excluded from the study in cases of cardiovascular disease, hypertension (BP >140/90 mm Hg), diabetes mellitus, total cholesterol >6.2 mmol/L, renal disease and current smoking. Only premenopausal women were enrolled into the study. Approval was obtained from the Institutional Review Board, and a written informed consent was obtained from each participant. Non-invasive assessment of arterial stiffness: Subjects refrained from eating and drinking alcohol, coffee or tea for 12 hr prior to the study. The test of arterial stiffness was performed in the supine position in a quiet, temperature controlled room (22-24 o C) in the morning. Pulse wave velocity (PWV) was determined by measuring the carotid-to-radial pulse wave transit time. Carotid and radial pulse waves were obtained non-invasively by applanation tonometry using high-fidelity micromanometer (Sphygmocor v.7.01 AtCor Medical Pty. Ltd). Aortic augmentation index (AIx) was calculated from radial pulse waves of the non- 119