Arteriosclerosis subclínica y disfunción endotelial en pacientes con espondiloartropatía

Abstract

Background: Spondyloarthropathies (SpA) include a group of systemic inflammatory rheumatic diseases. Ankylosing Spondylitis (AS) and psoriatic arthritis (PsA) are the most prevalent entities and present an increase in mortality relative to general population, being the cardiovascular disease (CVD) the first cause of mortality in these patients. The main mechanism underlying the increased cardiovascular morbidity and mortality rate could be the accelerated atherosclerosis, probably related with chronic inflammation and different risk factors. Homocysteine is an emergent cardiovascular (CV) risk factor that increases the risk of peripheral arterial disease, cerebrovascular disease and coronary disease. However, there is a lack of information about homocysteine levels in SpA patients and its possible role in the development of accelerated atherosclerosis. Hypothesis: In patients with AS and PsA, subclinical atherosclerosis, defined by carotid atherosclerosis, endothelial dysfunction and peripheral arterial disease, could be related to higher prevalence of hyperhomocysteinemia. Objectives: Main objective: to estimate the prevalence of subclinical atherosclerosis (measured as carotid intima-media thickness and atherosclerotic plaques in carotid arteries, as well as the ankle-brachial index), and endothelial dysfunction (brachial artery flow-mediated vasodilatation) in AS and PsA patients and evaluate its relation with homocysteine serum levels. Secondary objectives: to describe classic CV risk factors prevalence in these patients, to study possible determinants of subclinical atherosclerosis and endothelial dysfunction related with clinical or biochemical characteristics of the rheumatic disease, and to assess possible differences in vascular involvement between AS and PsA patients. Patients and methods: Cross-sectional study of 78 consecutive patients, diagnosed with AS and PsA, according to New York and CASPAR criteria respectively, who underwent vascular study between July 2012 and January 2017. Patients with history of CVD, other systemic inflammatory diseases or comorbidities that compromise midterm survival, were excluded. Vascular study consisted of carotid intima-media thickness (IMT) measurement and atheroma plaques identification in carotid arteries, endothelial function assessed by brachial artery flow-mediated vasodilatation (FMD), and ankle-brachial index (ABI). The associations between subclinical atherosclerosis outcome variables and demographic data, clinical characteristics, and CV risk factors were evaluated. Results: The mean age of the study sample was 47±10 years, with higher proportion of males (63%). All patients presented some type of vascular involvement, without differences between both pathologies. Carotid atherosclerosis (atherosclerotic plaques and/or pathologic IMT) was observed in 43% of patients, while endothelial dysfunction was found in 76%, which was severe in 58%. Only 5 patients (6%) presented pathologic ABI. Up to 30% of patients showed hyperhomocysteinemia, with mean levels of 13±6 µmol/L, but there was no association between homocysteinemia and subclinical atherosclerosis. Age and hypertension were the main determinants of pathologic IMT and atheroma plaques. Endothelial dysfunction was significantly associated with corticosteroid therapy (OR 3.6; p 0.013) and C reactive protein levels (CRP) (OR 1.3; p 0.034). No association was found between biologic therapy and subclinical atherosclerosis. Conclusions: Patients with AS and PsA, without history of CVD, show a high prevalence of subclinical atherosclerosis and hyperhomocysteinemia. However, homocysteine serum levels are not related to subclinical atherosclerosis in this study. Similar to general population, age is the main determinant of carotid atherosclerosis (atheroma plaques and/or pathologic IMT). Corticoid therapy and CRP elevation are significantly associated with the presence of endothelial dysfunction. These results suggest the possibility of improving the risk profile of these patients by reducing CPR levels as well as limiting steroids intake. On the other hand, there has been no association between biologic therapy and subclinical vascular disease in this study. Finally, the results showed no significant difference in subclinical vascular involvement between patients with AS and PsA.