APPLICATION OF PHYSICAL METHODS FOR DETERMINATION OF FUNCTIONAL PARAMETERS OF ARTERIES IN RHEUMATIC PATIENTS Jolanta DADONIENE*, Alma CYPIENE**, Diana KARPEC***, Rita RUGIENE*, Sigita STROPUVIENE*, Aleksandras LAUCEVICIUS** *State Research Institute for Innovative medicine; Vilnius university, ** State Research Institute for Innovative medicine; Vilnius university hospital Santariskiu klinikos, Vilnius university, ***Vilnius University
BACKGROUND The inflammatory rheumatic diseases, including rheumatoid arthritis (RA) and systemic sclerosis (SSc) are associated with increased cardiovascular mortality and morbidity. The death rate is approximately higher 50% in RA and 20 30% in SSc patients. 1. Symmons DP, Gabriel SE. Epidemiology of CVD in rheumatic disease, with a focus on RA and SLE. Nat Rev Rheumatol 2011,7 (7):399-408. 2. Ward MM. Interpreting studies of cardiovascular mortality in rheumatoid arthritis: the importance of timing.arthrritis Rheum. 2008 Dec 15;59(12):1687-9. 3. Au K, Singh MK, Bodukam V et al. Atherosclerosis in systemic sclerosis: a systematic review and metaanalysis. Arthritis Rheum. 2011 Jul;63(7):2078-90.
ATHEROSCLEROSIS Chronic inflammatory autoimmune diseases accelerates the process of atherosclerosis. Endothelial dysfunction and the increase of arterial stiffness. Early diagnosis of these disorders might help to avoid serious complications. Roman MJ, Devereux RB, Schwartz JE, Lockshin MD, Paget SA, Davis A, et al. Arterial stiffness in chronic inflammatory diseases. Hypertension 2005;46:194-9.
THE GOAL To compare the stiffness of the arteries and endothelial function in rheumatoid arthritis and systemic sclerosis patient groups by using non invasive techniques.
METHODS Pulse wave velocity (PWV) measured between carotid and radial or carotid and femoral arteries is the index to estimate the stiffness of the arteries. Pulse waves were obtained non-invasively by applanation tonometry using high-fidelity micromanometer (SphygmoCor v.7.01 AtCor Medical Pty. Ltd.). O Rourke MF, Gallagher DE. Pulse wave analysis. J Hypertens Suppl 1996;14:147-57.
THE RADIAL ARTERY IS PUSHED TO THE SURFACE OF THE BONE
ARTERIAL STIFFNESS Test was performed in the supine position a quiet, temperature controlled room. Blood pressure was recorded in the left arm using automatic blood pressure monitor. Pulse waves obtained consecutively from the radial and carotid arteries were referenced to a simultaneously recorded ECG, and transit time was computed from the time difference between the carotid and radial waveforms.
PWV= D(M) / ΔT(SEC)
AORTIC AUGMENTATION INDEX The aortic augmentation index (AIx) as a derived marker of arterial wall dysfunction was calculated from radial pulse wave. AIx a measure of systemic arterial stiffness. Validated transfer function from peripheral pulse wave analysis was used to generate a corresponding central waveform. From this aortic AIx was calculated by using the integrated software. 1. Axtell AL, Gomari FA, Cooke JP. Assessing endothelial vasodilator function with the Endo-Pat 2000. J Vis Exp 2010, 15:2167 2. Roman MJ, Devereux RB, Schwartz JE, Lockshin MD, Paget SA, Davis A, et al. Arterial stiffness in chronic inflammatory diseases. Hypertension 2005;46:194-9
AIX = P2 P1/ PULSE PRESSURE (%) The difference between both pressure peaks reflects the degree to which central arterial pressure is augmented by wave reflection. Aix is calculated as the difference between the second and first systolic peaks expressed as a percentage of the pulse pressure.
ENDOTHELIAL FUNCTION Endothelial dysfunction is the earliest measure of functional abnormality in the blood vessels. The endothelial functioning was measured using a new device Itamar Medical Endo-PAT 2000.
ENDOPAT 2000 It is totally non-operator-dependent method. assessment Immediate automatically calculated test results. The device records endothelium-mediated changes in the digital pulse waveform known as the PAT (peripheral arterial tone) signal, measured with a pair of novel modified plethysmographic probes situated on the fingers of each hand. Endothelium-mediated changes in the PAT signal are elicited by creating a downstream hyperemic response, induced by occluding blood flow through brachial artery.
FINGERTIP PLETHYSMOGRAPH RECORDING PAT SIGNAL Hyperemia was induced by occluding blood flow through the brachial artery for 5 minutes using an inflatable cuff on one hand. A hyperemia induced ratio (HRI) is created using the post and pre occlusion waves. RHI in a level of 2 or more is considered as normal.
RESULTS One hundred and six patients at of age 59.3 (SD 8.59) - 96 women and 10 men, were enrolled into this study. 73 with established rheumatoid arthritis and 33 suffering with systemic sclerosis. Out off rheumatoid arthritis patients group 19 patients had experienced cardiovascular events and 4 patients out of systemic sclerosis group also had a cardiovascular event in the past. The data were analyzed with SPSS program
AIX AND RHI Rheumatoid arthritis group (n = 73) Systemic sclerosis group (n = 33) p value Standardized augmentation index, % (AIx) 31, 8 ± 7,5 28, 9 ± 7,1 0, 06 Reactive hyperemia index 2,06 ± 0,6 1, 5 ± 0,7 < 0, 001
PULSE WAVE VELOCITY 9,2 9 8,8 8,6 8,4 8,2 8 7,8 7,6 7,4 RA SSc Carotid - radial PWV (m/sec) Carotid - femoral PWV (m/sec)
RESULTS Carotid radial or carotid femoral pulse wave velocity and standardized augmentation index were increased in rheumatoid arthritis patients group showing arterial stiffness being more pronounced in this group. Though PWV not exceeded the critical level of 12 m/sec. Systemic sclerosis group of patients showed RHI significantly lower meaning the functioning of small arteries definitely worse than in rheumatoid arthritis group.
DISCUSSION The present cross sectional study is the first to show that vascular damage takes different ways to present in rheumatic patients: involving large and median arteries in rheumatoid arthritis and small arteries in systemic sclerosis. The study is lacking the comparable control group which is under investigation by now. The sample size of SSc group is small and the differences in artery stiffness may be even larger with the increase of the sample size.
DISCUSSION Several studies have shown that PWV and AIx are independent predictors of cardiovascular mortality in the elderly, hypertensive, diabetics, and patients with chronic renal failure as well as in general population. It should be recommended to assess these parameters using non- invasive techniques in rheumatic patients for the detection of early atherosclerosis. Roman MJ, Devereux RB, Schwartz JE, Lockshin MD, Paget SA, Davis A, et al. Arterial stiffness in chronic inflammatory diseases. Hypertension 2005;46:194-9.
CONCLUSIONS 1. In rheumatoid arthritis the most pronounced changes occur in conduitive arteries and aorta, consequently AIx and PWV are higher in this group showing the decreased elasticity of the arteries. 2. In systemic sclerosis group the changes occur in small vessels showing the endothelial functioning being damaged early in this disease.
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