CAROTID INTIMA MEDIA THICKNESS AND ENDOTHELIAL DYSFUNCTION- HALLMARKS OF MACROVASCULAR DISEASE IN SSC: A PROSPECTIVE STUDY

Background: Increased evidence suggest an accelerated macrovascular disease in SSc. Brachial artery flow-mediated vasodilation (FMD) and intima-media thickness (IMT) are currently used as non-invasive tests of vascular function and structure, as well as surrogate measures of subclinical atherosclerosis. Nitric oxide (NO) is one of the most important mediators of endothelial function; its release is on the base of FMD and it is impaired as a consequence of endothelial damage. Objectives: To evaluate the occurrence and significance of macrovascular involvement in SSc. Methods: We prospectively studied 35 SSc patients without history of cardiovascular and cerebrovascular events (6 males and 29 females; 11 with diffuse and 24 with limited disease) and 20 healthy controls. Brachial FMD, carotid IMT and circulating nitric oxide levels were assessed in all patients and controls. Clinical evaluation was performed in SSc patients at baseline and after 24 months. Results: FMD was significantly impaired in SSc patients compared to controls(3.41±4.56% vs. 7.66±4.24%; p<0.037). IMT was significantly increased in patients then in controls (0.93±0.29 mm vs. 0.± 0.13 mm; p<0.005). NO circulating levels were significantly reduced in SSc 8,99 mM/L; p±10,79 mM/L vs 32,39±compared to controls (22,56< 0,001). SSc patients with impaired FMD (defined as FMD<6%) had significantly lower circulating NO levels compared to those with conserved FMD. No correlation was found between FMD and IMT. No correlation was found between FMD, IMT and NO and disease duration, scleroderma subset, autoantibody pattern, capillaroscopy pattern, pulmonary involvement, presence of digital ulcers and traditional atherosclerotic risk factors. Out of 35 patients only 3 developed vascular events. One patient developed stroke and two myocardial infarction. The patients with myocardial infarction had impaired both FMD and IMT. The patients with a stroke had normal FMD and IMT values. Conclusion: The impairment of endothelial function and structural changes of large vessels are evident in SSc, but do not seem to be associated with SSc features and with traditional risk factors for atherosclerosis. Impaired FMD and IMT seem to be a risk factor for future cardiovascular, but not for cerebrovascular events. The prevention and prompt treatment of macrovascular complications is needed in SSc patients.