Dissertation committee:
Σφηκάκης Πέτρος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπων
Δαϊκος Γεώργιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τεντολούρης Νικόλαος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Βλαχόπουλος Χαράλαμπος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τεκτονίδου Μαρία, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Μακρυλάκης Κωνσταντίνος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Πρωτογέρου Αθανάσιος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Backgroung/Aim: Cardiovascular disease remains the main cause of morbidity and mortality worldwide. The development of arteriosclerosis and atheromatosis is the pathogenetic substrate of all cardiovascular diseases and is characterized by functional and morphological abnormalities in the wall of the arteries. Patients with Inflammatory Arthritis, such as Rheumatoid Arthritis (RA and Ankylosing Spondylitis (AS), present with increased prevalence of CVD, which leads to increased morbidity and mortality in these patients. In RA and AS, accelerated arterial disease is ascribed not only to classical CVD risk factors -namely arterial hypertension, glucose intolerance, smoking and dyslipidemia- which are known to be more prevalent in patients with CIRD, but also to the presence of chronic inflammation and perhaps to disease-related therapies. The aim of the present dissertation was to assess the prevalence as well as the acceleration of subclinical cardiovascular disease in patients with RA and AS and, in particular, define the degree, extent and type of arterial damage in each condition.
Methods: Overall, 227 RA patients (aged 57.8±12.4years, 17.6% men), 81 AS (aged 46.7±13.2 years, 85.4% men) and 674 controls (aged 52.2±12.7 years 53% men), without known CVD and/or Diabetes Mellitus, were enrolled. All subjects were assessed for subclinical cardiovascular disease, namely a) arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx), b)carotid hypertrophy, by intimal-medial thickness (IMT, adjacent to plaques when present) and cross sectional area (CSA) in both the right and left common carotid arteries and c) subclinical atheromatosis, i.e. the presence of atherosclerotic plaques in a total of 8 arterial beds both in carotid and femoral arteries (left and right common and internal carotid arteries and carotid bulb and both common femoral arteries). Re-assessment of all vascular indices was performed after a 3-year period in 177 patients with RA (aged 59.5±11.6 years, 17% men), 61 patients with AS (aged 49.6±12.8 years, 85.3% men) and 293 controls (aged 54.2±13.5 years, 48.8% men). Multivariate analysis of patients with RA or AS compared to controls was performed after adjusting for classical CVD risk factors and disease specific characteristics.
Results: Multivariate analysis of specifically selected RA and control populations characterized by the absence of hypertension, diabetes, dyslipidemia and smoking, revealed that RA patients had more than 2-fold higher prevalence of carotid and/or femoral atheromatic plaques than healthy controls (29% vs. 12%, p=0.039) and multi-arterial preclinical atheromatosis was more prevalent in RA. Interestingly plaque burden in the subgroup of RA patients with less than 5 years of disease duration was comparable to their matched controls. In contrast to atheromatosis, all indices indicative of either arterial stiffness or arterial wall hypertrophy were similar between RA and controls, even in patients with disease duration more than 5 years. In AS, strict 1:1 age-, gender- and risk factors-matching of 67 AS patients and controls showed that they had similar arterial hypertrophy and atherosclerosis indices, whereas atheromatosis was slightly increased in healthy controls, albeit not reaching significance. Moreover, none of the disease parameters, such as disease duration and activity or anti-TNF treatment, were associated to any of the studied vascular indices. Regarding evaluation of progression of subclinical CVD, comparison of RA patients in remission or low disease activity versus 1:1 demographically matched controls with comparable classical CVD risk factor burden, demonstrated no statistically significant differences for any of the evaluated markers of subclinical CVD. A further subgroup analysis between RA patients treated with biologic versus synthetic DMARDs showed that no difference was evident in any of the vascular indices examined between the two subgroups.
Conclusion: RA disease per se is sufficient to cause atheromatosis but not arterial stiffness or hypertrophy in the absence of classical CVD risk factors and this is evident in patients with more than 5 years disease duration. However, effective inflammation control, which may not be drug-specific, seems to de-accelerate the progression of atherosclerosis in RA to the rate observed in non-RA controls. Nevertheless, the current therapeutic strategy, based on the treat-to-target approach, should include prompt control of joint disease, as well as of cardiovascular risk factors. In contrast, subclinical arterial disease- in terms of atheromatosis, carotid hypertrophy and arterial stiffness- is not accelerated in well-controlled AS and thus, prompt and effective disease control can stop progression of arterial damage and improve arterial hypertrophy and stiffness in AS patients.
Keywords:
Cardiovascular disease, Arteriosclerosis, Atheromatosis, Rheumatoid arthritis, Ankylosing spondylitis
