E. Zampeli

A pilot study of endothelial dysfunction and aortic stiffness after interleukin-6 receptor inhibition in rheumatoid arthritis

Interleukin (IL)-6 is a pleiotropic proinflammatory cytokine involved in the pathogenesis of both atherosclerosis and rheumatoid arthritis. The role of the IL-6/IL-6 receptor pathway in the documented acceleration of atherosclerosis in rheumatoid arthritis has not been examined. In a non-randomized prospective pilot study we asked whether endothelial dysfunction, defined as impaired flow mediated dilatation (FMD), and aortic stiffness, assessed by pulse wave velocity (PWV) improve after 3 and 6 monthly therapeutic infusions of the anti-IL-6 receptor antibody tocilizumab for active rheumatoid arthritis. We found that FMD increased from 3.3 ± 0.8 to 4.4 ± 1.2 to 5.2 ± 1.9% (p = 0.003), whereas PWV decreased from 8.2 ± 1.2 to 7.7 ± 1.3 to 7.0 ± 1.0m/s (p < 0.001). Whether these beneficial arterial changes are direct effects of the IL-6/IL-6 receptor pathway inhibition, maintained over time and translate into better clinical outcome warrants further studies.

Myocardial ischaemia without obstructive coronary artery disease in rheumatoid arthritis: hypothesis-generating insights from a cross-sectional study

OBJECTIVE RA is associated with increased cardiovascular events, reportedly to equal diabetes mellitus (DM). The presence of myocardial ischaemia was assessed in asymptomatic high-risk RA patients and compared with patients with DM and a healthy control group. METHODS Eighteen consecutive non-diabetic RA patients without known cardiovascular disease who developed a new carotid atheromatic plaque during the last 3 years were matched 1:1 for traditional cardiovascular risk factors with asymptomatic type 2 DM patients and 1:2 with asymptomatic non-RA, non-DM control subjects. After dobutamine stress contrast echocardiography with wall-motion and perfusion evaluation, coronary angiography was performed in those with positive stress tests. RESULTS Ischaemia by echocardiography was found in 67% of RA patients; this was significantly higher than controls (31%, P = 0.019) but comparable to those with DM (78%, P = 0.71). Angiography performed in eight consenting RA patients was normal in four, revealed non-flow-limiting coronary atheromatic lesions in two and significant lesions in two patients. RA patients with ischaemia had CRP serum levels significantly higher by six-fold compared with those with normal stress echocardiography. CONCLUSION Asymptomatic RA patients may display myocardial ischaemia at similar levels to DM patients but with low prevalence of obstructive coronary artery disease. Microvascular abnormalities associated with increased inflammatory response may account for these findings. Their exact nature and significance require further evaluation.

The role of inflammation, the autonomic nervous system and classical cardiovascular disease risk factors on subendocardial viability ratio in patients with RA: a cross-sectional and longitudinal study.

IntroductionEvidence indicates that rheumatoid arthritis (RA) patients have increased susceptibility to myocardial ischaemia that contributes to myocardial infarction. The subendocardial viability ratio (SEVR) can be measured using pulse wave analysis and reflects myocardial oxygen supply and demand. The objective of the present study was to examine specific predictors of SEVR in RA patients, with a specific focus on inflammation and classical cardiovascular disease (CVD) risk factors.MethodsTwo patient cohorts were included in the study; a primary cohort consisting of 220 RA patients and a validation cohort of 127 RA patients. All patients underwent assessment of SEVR using pulse wave analysis. Thirty-one patients from the primary cohort who were about to start anti-inflammatory treatment were prospectively examined for SEVR at pretreatment baseline and 2 weeks, 3 months and 1 year following treatment. Systemic markers of disease activity and classical CVD risk factors were assessed in all patients.ResultsThe SEVR (mean ± standard deviation) for RA in the primary cohort was 148 ± 27 and in the validation cohort was 142 ± 25. Regression analyses revealed that all parameters of RA disease activity were associated with SEVR, along with gender, blood pressure and heart rate. These findings were the same in the validation cohort. Analysis of longitudinal data showed that C-reactive protein (P < 0.001), erythrocyte sedimentation rate (P < 0.005), Disease Activity Score in 28 joints (P < 0.001), mean blood pressure (P < 0.005) and augmentation index (P < 0.001) were significantly reduced after commencing anti-TNFα treatment. Increasing C-reactive protein was found to be associated with a reduction in SEVR (P = 0.02) and an increase in augmentation index (P = 0.001).ConclusionThe present findings reveal that the SEVR is associated with markers of disease activity as well as highly prevalent classical CVD risk factors in RA, such as high blood pressure and diabetes. Further prospective studies are required to determine whether the SEVR predicts future cardiac events in RA.

AB0333 Central Aortic Systolic Blood Pressure Measurements in Rheumatoid Arthritis: Towards the Optimization of the Blood Pressure-Associated Cardiovascular Risk Assessment

Background Rheumatoid Arthritis (RA) associates with increased risk of cardiovascular disease (CVD) and high prevalence of arterial hypertension [1]. Central aortic systolic blood pressure (SBP), assessed non-invasively, is a better predictor of CVD and a better guide for anti-hypertensive treatment compared to brachial SBP [2,3]. Data on the prevalence of central aortic SBP-based hypertension [3] are lacking in RA. Objectives Since abnormal/uncontrolled central aortic SBP might refine CVD risk classification in RA we aimed to describe its frequency in the presence or absence of, (i) abnormal/uncontrolled office brachial SBP, and (ii) “white coat” and masked systolic hypertension phenomena, which are frequently observed in these patients [1] Methods Consecutive RA patients referred to out cardiovascular laboratory for CVD risk stratification underwent office brachial SBP (triplicate oscillometric recording) and central aortic SBP (with Sphygmocor device) assessments, as well as out- of-office 24-hour ambulatory, or home monitoring of brachial SBP. Results Among 263 patients (median age 60 years IQR [52-67], women 80%), 27% and 30% had abnormal/uncontrolled brachial or central aortic measurements at office, respectively. Of all patients, 69% had both brachial and central aortic normal/controlled measurements, 25% had both brachial and central aortic abnormal/uncontrolled measurements, whereas the remaining 6% presented intermediate phenotypes (1.5% and 4.5% only brachial or only central aortic abnormal/uncontrolled measurements, respectively). Notably, abnormal central aortic measurements were noted in 100% of patients with systolic “white coat” hypertension phenomenon, as well as in 45% of patients with systolic masked hypertension phenomenon. Conclusions Given the fact that modern technologies provide the possibility to measure simultaneously office brachial and central aortic SBP, whereas the latter guides more efficiently blood pressure management, incorporation of central aortic measurement in clinical practice might help to optimize hypertension treatment in 6% of RA patients and particularly to detect the presence of masked hypertension almost in half of them without the use of out-of-office blood pressure monitoring. References Protogerou AD et al. Arterial hypertension assessed “out-of-office” in a contemporary cohort of rheumatoid arthritis patients free of cardiovascular disease is characterized by high prevalence, low awareness, poor control and increased vascular damage-associated “white coat” phenomenon. Arthritis Res Ther. 2013; 15(5):R142. Sharman JE, et al. Randomized trial of guiding hypertension management using central aortic blood pressure compared with best-practice care: principal findings of the BP GUIDE study. Hypertension. 2013; 62:1138-45. Cheng HM et al. Derivation and validation of diagnostic thresholds for central blood pressure measurements based on long-term cardiovascular risks. J Am Coll Cardiol. 2013; 62:1780-7. Disclosure of Interest None declared

SAT0109 Accelerated Subclinical Atheromatosis, but not Arterial Stiffness or Hypertrophy, in Rheumatoid Arthritis Patients Free of Classical Risk Factors

Background Several lines of evidence indicate that classical cardiovascular disease (CVD) risk factors, such as arterial hypertension, diabetes mellitus, smoking and dyslipidemia, are significantly increased in rheumatoid arthritis (RA), which, in turn, is associated with 1.5- to 2-fold increased prevalence of CVD. The exact contribution of the RA disease per se in this association, in terms of systemic inflammation, drugs, disease-related genetics and/or other factors, remains under study. Objectives We aimed to test the hypothesis that RA per se in patients free of classical CVD risk factors is associated with accelerated subclinical arterial disease. Methods Consecutive patients with RA (n=267) were comprehensively studied by ultrasound for, a) subclinical atheromatosis assessed by the presence of carotid artery and/or femoral artery plaques, b) stiffness of common carotid artery and aortic stiffness by pulse wave velocity, and, c) hypertrophy of common carotid artery assessed by intimal-medial thickness and cross sectional area (calculated adjacent to plaques, when plaques were present). Of all patients, we identified those who were CVD-free, non-smokers, without hypertension, diabetes and dyslipidemia (only 18%). Of them, 41 (aged 49±13 years, 36 women, median disease duration of 7 years, range 3-19 years) were compared to 41 healthy non-smokers, without hypertension, diabetes and dyslipidemia who were effectively matched 1:1 for age and gender and studied in parallel. Results Patients had more than 2-fold higher prevalence of carotid and/or femoral atheromatic plaques than healthy controls (29% vs. 12%, p=0.05). All patients with plaques had an acceptable functional status of class I or II. Moreover, body mass index, as well as family history of CVD, was similar between patients with plaques and their matched controls. Multi-arterial subclinical atheromatosis, defined as plaque presence at more than 1 of 8 arterial sites evaluated, was by far more prevalent in RA patients than controls (22% vs. 2%, p=0.007). Notably, plaque burden in the subgroup of RA patients with less than 5 years of disease duration was comparable to their matched controls. Either arterial stiffness or hypertrophy, however, was not significantly increased compared to controls, even in patients with long-standing RA. Conclusions These data directly show for the first time an acceleration of atheromatosis in RA, but not of arterial stiffness or hypertrophy, independently of the classical CVD risk factors. This phenomenon is not evidenced during the first 5 years after disease onset and seems to be chronic inflammation-dependent. Also, the dissociation between atheromatosis and arterial stiffness in this selected population suggests a minimal, if any, effect of chronic inflammation in arterial remodeling. Studies testing whether early and effective RA clinical disease control prevents the development of arterial damage in the long-term are ongoing. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5811