Abstract
Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic inflammatory disease accompanied by increased cardiovascular morbidity and mortality. The aim of the present study was to investigate morphological and functional alterations of small and large vessels in patients with RA, and identify predisposing factors and potential associations with the estimated cardiovascular risk. In addition, hemodynamic parameters were non-invasively obtained and the role of a novel cardiac biomarker, galectin-3, was assessed.A total of 104 patients with RA and 52 volunteers free from any known health problems were studied. Aortic stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV) and central augmentation index. Carotid atherosclerosis was evaluated by measurement of carotid intima-media thickness (cIMT) and the detection of atherosclerotic plaques with ultrasound. Evaluation of small vessels included a) calculation of arteriolar and venular diameters, as well as thei ...
Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic inflammatory disease accompanied by increased cardiovascular morbidity and mortality. The aim of the present study was to investigate morphological and functional alterations of small and large vessels in patients with RA, and identify predisposing factors and potential associations with the estimated cardiovascular risk. In addition, hemodynamic parameters were non-invasively obtained and the role of a novel cardiac biomarker, galectin-3, was assessed.A total of 104 patients with RA and 52 volunteers free from any known health problems were studied. Aortic stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV) and central augmentation index. Carotid atherosclerosis was evaluated by measurement of carotid intima-media thickness (cIMT) and the detection of atherosclerotic plaques with ultrasound. Evaluation of small vessels included a) calculation of arteriolar and venular diameters, as well as their ratio, in retinal photographs, by use of specifically designed software, b) nailfold capillaroscopy, for the detection of microhemorrhages and the quantitative assessment of capillary rarefaction using semiautomated software, c) applanation tonometry for the assessment of myocardial perfusion with subendocardial viability ratio (SEVR), and d) 24hour urine collection for the estimation of microalbuminuria. In addition, 24hour ambulatory blood pressure measurement and impedance cardiography were applied. 10-year risk of general cardiovascular disease was estimated from the Framingham Heart Study. Galectin-3 levels were measured in serum samples with ELISA.Patients with RA, compared to controls, presented significantly higher levels of PWV and cIMT, and increased prevalence of atherosclerotic plaques in the carotid arteries. Patients with RA exhibited significantly narrower retinal arterioles and decreased retinal arteriovenous ratio; decreased dermal capillary density and increased prevalence of microhemorrhages, as well as lower SEVR, whereas microalbuminuria did not differ. Patients with RA free from cardiovascular comorbidities (n=47), compared to controls, presented statistically significant differences from the microvascular fields only, in particular, narrower retinal arterioles and wider retinal venules, more pronounced dermal capillary rarefaction and decreased SEVR. Inflammation was independently associated with retinal microvascular alterations and dermal capillary rarefaction. 24hour ambulatory blood pressure monitoring and impedance cardiography showed impaired nocturnal blood pressure fall and increased thoracic fluid content index, respectively, in patients compared to controls. Patients’ estimated cardiovascular risk was strongly associated (p≤0,001) with PWV, cIMT, the estimated retinal arteriolar diameter and the number of dermal capillaries. Finally, galectin-3 levels were significantly elevated among patients compared to controls, yet not in the subgroup of patients without cardiovascular comorbidities. Galectin-3 was independently associated with cardiac output and systemic vascular resistance.In conclusion, macrovascular involvement in patients with RA, who present low levels of systemic inflammation and adequately controlled disease in an outpatient setting, is primarily a consequence of classical cardiovascular risk factors. However, subclinical microvascular impairment is prominent even in the absence of cardiovascular comorbidities. Functional and morphological alterations of the microvasculature are associated with inflammation and cardiovascular risk and might be considered as more sensitive and earlier affected markers of angiopathy in RA.
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