Traditional cardiovascular risk factors or inflammation: Which factors accelerate atherosclerosis in arthritis patients?

    Traditional cardiovascular risk factors or inflammation: Which factors accelerate atherosclerosis in arthritis patients? A. Dalbeni, A. Giollo, A. Tagetti, S. Atanasio, G. Orsolini, G. Cioffi, F. Ognibeni, M. Rossini, P. Minuz, C. Fava, O. Viapiana PII: DOI: Reference:

S0167-5273(16)33190-4 doi:10.1016/j.ijcard.2017.01.072 IJCA 24438

To appear in:

International Journal of Cardiology

Received date: Accepted date:

25 October 2016 6 January 2017

Please cite this article as: Dalbeni A, Giollo A, Tagetti A, Atanasio S, Orsolini G, Cioffi G, Ognibeni F, Rossini M, Minuz P, Fava C, Viapiana O, Traditional cardiovascular risk factors or inflammation: Which factors accelerate atherosclerosis in arthritis patients?, International Journal of Cardiology (2017), doi:10.1016/j.ijcard.2017.01.072

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ACCEPTED MANUSCRIPT Traditional cardiovascular risk factors or inflammation: which factors accelerate atherosclerosis in arthritis patients?

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Dalbeni A.1, Giollo A.2, Tagetti A.1, Atanasio S.1, Orsolini G.2, Cioffi G.3, Ognibeni F.3, Rossini M.2,Minuz P.1, Fava C.*1, Viapiana O.*2. 1

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* These authors contributed equally to this work.

Corresponding author:

p.le Scuro 10, 37124 Verona

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Andrea Dalbeni MD, PhD [email protected]

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Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy, 2 Division of Rheumatology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy 3 Department of Cardiology, Villa Bianca Hospital, Trento, Italy

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The authors have nothing to declare; in particular any financial support or other benefits from commercial sources for the work reported on in the manuscript, or any other financial interests that any of the authors may have, which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work.

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Abbreviations: ACE: angiotensin converting enzyme AS: ankylosing spondylitis ASDAS-CRP: ankylosing spondylitis disease activity score BMI: body mass index cDC: carotid distensibility cIMT: carotid intima-media thickness COX: cyclooxygenase CRP: C-reactive protein CVDs: cardiovascular diseases CVEs: cardiovascular events DAS28-CRP: disease activity score 28 DMARD: disease modifying anti-rheumatic drug ESR: erythrocyte sedimentation rate EULAR: European League Against Rheumatism NSAIDs: non-steroidal anti-inflammatory drugs PsA: psoriatic arthritis RA: rheumatoid arthritis SBP: systolic blood pressure SD: standard deviation SEM: standard error of the mean US: ultrasound examination

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ACCEPTED MANUSCRIPT ABSTRACT Patients with chronic inflammatory arthritis experience an increased incidence of

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cardiovascular (CV) events. In addition to visualizing atherosclerotic plaques, ultrasound

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examinations (USs) of the carotid arteries permit the measurement of subclinical markers of

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atherosclerosis, such as intima-media thickness (cIMT) and carotid segmental distensibility (cDC).

The aims of the study were to identify the determinants of atherosclerosis acceleration

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(plaques, cIMT and cDC) in a sample of patients suffering from chronic arthritis and to

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compare these patients with a control group of people with ≤ 1 traditional risk factor (TRF) for CV disease.

METHODS: We recruited 137 patients with rheumatoid arthritis (RA), 43 patients with

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psoriatic arthritis (PsA), 28 patients with ankylosing spondylitis (AS) and 48 healthy volunteers without histories of previous CV events. These patients underwent carotid artery

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US examinations using dedicated hardware. RESULTS: Regression and multivariate analyses demonstrated that only age (p<0.001) was

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consistently associated with cDC, cIMT and atherosclerotic plaques, both in the entire sample of patients with arthritis and in the subgroup of patients with RA. Among modifiable TRFs for cardiovascular disease, only hypertension, diabetes mellitus and smoking exhibited associations with some carotid phenotypes, with borderline significance. When patients with RA carrying ≤ 1 TRF were compared with control subjects carrying ≤ 1 TRF, only cDC was slightly lower in the RA group than in the control group. CONCLUSIONS: Age is the major determinant of subclinical atherosclerosis in patients with different types of arthritis, as the contributions of other TRFs and disease activity and duration indices to the disease seem to be limited.

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ACCEPTED MANUSCRIPT Key words: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, atherosclerotic

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plaques, intima-media thickness, carotid distensibility, traditional risk factors.

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ACCEPTED MANUSCRIPT INTRODUCTION Recent studies have shown that the prevalence of cardiovascular diseases (CVDs) is high in

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patients with inflammatory arthritis [1], particularly in patients with rheumatoid arthritis (RA)

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[2] and psoriatic arthritis (PsA) [3].

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The most update guidelines on cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders focus attention on screening, identification of CVD risk factors and CVD risk management because the risk of

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CV death is 1.5-fold higher among RA patients than among the general population [1,4]. A

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recent meta-analysis including a large cohort of patients from the United States showed that the risk of CVDs is 48% higher in patients with RA than in the general population (relative risk 1.48 CI 95% 1.36-1.62) [5]. The risk of non-fatal cardiovascular and cerebrovascular

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diseases resulting in disability-related care cost increases is also higher in patients with RA than in the general population [6].

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Also the 2016 European Guidelines on cardiovascular disease prevention in clinical practice underline that chronic systemic inflammation is now considered pivotal to the development of

arthritis [7].

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atherosclerosis and to increases in the incidence of cardiovascular events in patients with

Several studies have examined the prevalence of subclinical atherosclerosis in RA [9–11] using non-invasive but validated tools to assess vascular function and morphology. Most of these studies, but not all of them, noted abnormalities in endothelial function and increases in arterial stiffness and carotid intima-media wall thickness (cIMT) in RA patients compared to healthy controls [12,13]. Some of these abnormalities may be reversible. Very few studies have addressed how traditional CV risk factors (TRFs) and systemic inflammation contribute to vascular abnormalities in RA. In particular, cIMT, as determined via high-resolution B-mode ultrasound, is an easily 4

ACCEPTED MANUSCRIPT measurable and non-invasive marker of macrovascular atherosclerosis. Case-control and cross-sectional studies have shown that increased cIMT is associated with generalized

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atherosclerosis and coronary artery disease [14,15]. Longitudinal studies exploring IMT

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changes over time in RA have suggested that glucocorticoids also play a role in

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atherosclerosis progression [16,17], while other studies have suggested that newer drugs (such as biological drugs) may exert therapeutic effects on atherosclerosis [18,19]. The prevalence of TRFs (diabetes, hypertension, and obesity) are also increased in patients

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with RA compared to the general population [20]; thus, it is possible that these TRFs and

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specific RA characteristics (i.e., measures of clinical disease activity and laboratory measures of systemic inflammation) lead to more rapid increases in cIMT or increases in the prevalence of atherosclerotic plaques.

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It is also possible that the drugs currently used to treat these patients [21], particularly antiinflammatory drugs (NSAIDs) and corticosteroids, play roles in the association between

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arthritis and atherosclerosis.

The aim of the present study was to identify the determinants of atherosclerosis (plaques, cDC

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and cIMT) in a sample of patients suffering from chronic arthritis and to compare these patients with a control group of people with ≤ 1 traditional CV risk factor.

METHODS Between March 2014 and March 2016, 208 patients who visited the rheumatology outpatient clinic of the ―Azienda Ospedaliera Universitaria Integrata‖ of Verona were enrolled in this study. A total of 137 patients had a diagnosis of rheumatoid arthritis (RA), 43 patients had a diagnosis of psoriatic arthritis (PsA), and 28 patients had a diagnosis of ankylosing spondylitis (AS). None of these patients had histories of CV events. A sample of 48 volunteers without histories of previous CV events but with comparable numbers of CV risk factors were also enrolled in this study. The control patients were similar 5

ACCEPTED MANUSCRIPT to their counterparts with respect to age and sex and were enrolled in this study from the outpatient clinics of the General Medicine and Hypertension Division during the same period.

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DAS refers to the 'disease activity score', and the number 28 refers to the 28 joints that are

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examined during this assessment. This formula yields the overall disease activity score. A

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DAS28 greater than 5.1 implies active disease, while a DAS28 less than 3.2 implies low disease activity, and a DAS28 less than 2.6 implies disease remission [22].

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Patients with any type of known cardiomyopathy or atrial fibrillation were excluded from this study.

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This study was approved by the Institutional Ethics Committee of Verona (University

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Integrated Hospital of Verona), and all patients provided informed consent to participate.

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Ultrasound measurements

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All the measurements performed by ultrasound (LOGIQ P5 pro, GE, Indianapolis, USA) were processed with the aid of dedicated hardware (Multimedia Video Engine II (MVE2) DSP Lab., Pisa CNR, Italy), as described previously [23,24].

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Carotid intima-media thickness (cIMT) measurements were performed during evaluation of the distal common carotid artery, namely, the 1 cm long segment preceding the bulb [25]. The right and the left common carotid artery distensibility coefficients (cDCs) were determined in conjunction with brachial BP measurements and were calculated using the following formula: DC = (ΔA/A) / PPa, where ΔA is the stroke change (i.e., distension) in carotid artery cross-sectional area, which was normalized to the total diastolic carotid artery cross-sectional luminal area (A), and PPa is the pressure differential, assuming that the cross section of the artery is circular [26].

Statistics 6

ACCEPTED MANUSCRIPT All data were analysed using the SPSS statistical computer package (version 21.0; IBM Corporation, Armonk, NY, USA). Continuous variables are presented as the mean ± SD

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unless otherwise stated. Differences between subgroups were evaluated via ANOVA followed

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by Tukey’s post hoc test. Bivariate parametric and non-parametric correlations were estimated

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by Pearson’s coefficient r. Multiple linear regression was used in the multivariate model, which included sex, age, BMI, arthritis duration, family history of CVD, hypertension, diabetes, smoking, dyslipidaemia, NSAID use, cortisone and biological drug use, and the

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DAS28 (only in the RA group) as covariates. All tests were 2-sided, and p values <0.05 were

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considered statistically significant.

RESULTS

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The anthropometric, demographic and clinical characteristics of the investigated population are presented in Table 1. Of the 208 arthritis patients (median age ± SD, 57 ± 11.46 years),

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137 suffered from RA, 43 suffered from PsA, and 28 suffered from AS. Forty-eight non-arthritic subjects without histories of CVD (56.06±9.43 years) were enrolled

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in this study during the same period. There were no significant differences between the arthritis group and the control group with respect to BMI values or the incidence of diabetes. However, there were several significant differences between the two groups with respect to other TRFs for CV disease, which indicated that performing direct comparisons between the two groups was meaningless. We subsequently performed analyses to identify the determinants of subclinical atherosclerosis indices in the entire arthritis group and in the RA group (the group with the largest sample size) using a multivariate model. Regression analysis using either cDC or cIMT as the dependent variable and including sex, age, BMI, arthritis duration, family history of CVD, hypertension, diabetes, smoking, dyslipidaemia, NSAID use, and cortisone and biological drug use as covariates demonstrated that

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ACCEPTED MANUSCRIPT ). Hypertension was significantly associated with only

The same covariates were used in the logistic regression -

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analysis, which demonstrated that

p<0.01) were independently associated with the presence of

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-

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atherosclerotic plaques in the entire arthritis group.

Only patients with RA were included in the multivariate analysis (Table 2), which used the same covariates as above, as well as the DAS28. Only age remained significantly associated ) in the

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-

A

-

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multivariate analysis. Hypertension was not associated with either cDC (-

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p=0.01)

RA, as were

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were independently associated with the presence of atherosclerotic plaques in patients with -

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p=0.05) and

p=0.05), with borderline significance.

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smoking

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We compared a subgroup of RA patients with subgroups of patients with PsA and AS,

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evaluating only subjects <50 y of age to adjust for differences in age among the three groups, but we did not observe any differences in cDC, cIMT or plaque presence among the three groups.

significantly from age-matched control subjects carrying

s, RA patients vs controls,

respectively, p>0.05 for the difference in age) with respect to cIMT or plaque presence but exhibited a slight difference from their counterparts with respect to cDC (Table 3).

DISCUSSION The main result of the study was that age rather than TRFs, disease activity indices or drug use history was the major determinant of subclinical atherosclerosis in patients with different 8

ACCEPTED MANUSCRIPT types of arthritis. According to the most recent guidelines on cardiovascular disease prevention and on CVD risk management in patients with RA and other forms of

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inflammatory joint disorders, chronic arthritis (RA, PsA and AS) are systemic inflammatory

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population, especially CV disease-related mortality [4,7].

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diseases with progressive courses that lead to increased mortality compared with the general

However there are no conclusive evidence emerged regarding the precise CVD risk in patients with AS and PsA, different in RA patients.

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EULAR [4] give some indication recently regarding the CVD screening also of the other

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inflammatory joint disease, in which aetiology of atherogenesis seems to have specific mechanisms.

Atherosclerosis and RA have in common inflammatory mediators, and the synovial

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inflammation mechanisms are similar to those that have been found in unstable atherosclerotic plaque, including pronounced infiltration by macrophages and type 1 T helper (Th1) cells,

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collagen degradation and neovascularization. In RA inflammatory mediators such as CRP, tumour necrosis factor (TNF) [27], fibrinogen cytokines and interleukins (IL-s), in particular

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IL-6, IL-18 and IL-33, are abnormal and they promote proatherogenic activation and endothelial dysfunction, but are also associate with other CV risk factors, such as alteration in lipid levels, insulin resistance and oxidative stress that contribute to vascular damage [28]. Furthermore an impairment of the number and the activity of circulating proangiogenic haematopoietic cells (PHCs), including CD34+, has been shown in RA, demonstrating an endothelial dysfunction [29,30]. However, several other studies have identified alterations of the lipid profile, insulin sensitivity and other metabolic cardiovascular risk factors in all the other IJD documenting an increased mortality and morbidity due to cardiovascular disease. An array of vascular morphologic and functional abnormalities has also been reported in these diseases, supporting the hypothesis of accelerated atherosclerosis in inflammatory joint 9

ACCEPTED MANUSCRIPT disease [31]. It is believed that the main mechanism underlying the increased CV mortality and morbidity

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observed in patients with chronic arthritis is an atherosclerosis acceleration resulting from

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interactions between TRFs, which are usually more prevalent among these patients than

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among non-arthritis patients, and the inflammatory substrate of the arthritis itself. Our results are only partially consistent with this view. We noted close relationships between age and all the atherosclerosis indices, as measured by ultrasound; however, the other TRFs were not

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independently associated with atherosclerosis, with the exception of hypertension, which was

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associated with cIMT in the entire arthritis group; and diabetes, smoking habits and BMI, which were independently associated with the presence of plaques in the RA subgroup. We found that drugs (cortisone, NSAIDs and biological drugs, in particular) were not

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independently associated with atherosclerosis indices, nor were arthritis activity and duration. Tight disease control is thought to improve all outcomes in CIAs, including cardiovascular

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outcomes, and in RA anti-TNF therapy has been associated with cardiovascular risk reduction, compared with non-biologic DMARDs [32]. Data on cardiovascular risk reduction with anti-

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TNF therapy in PsA or AS are absent. Among non-biologic DMARDs, only methotrexate has been proved to be effective in reducing cardiovascular risk [33]. One possible reason to explain the similar prevalence of atherosclerosis in our patients with RA treated with and without anti-TNF drugs is that the two groups were substantially homogeneous for disease activity and traditional cardiovascular risk factors. Any small difference due to anti-rheumatic therapy could have been flattened by the presence of a long-standing disease with subsequent prolonged exposure to the inflammatory state – and subsequent cardiovascular damage - that was peculiar of most patients in our study. It should be stated that randomized trials investigating cardiovascular outcomes in RA, PsA or AS management approach are lacking in CIAs, and though in a small study of 27 patients with RA a significant increase in IMT in RA patients but not in controls was demonstrated after 18 months [34]. 10

ACCEPTED MANUSCRIPT Interestingly, when patients with RA were compared with age-matched patients with PsA and SA, no differences were noted. Moreover RA patients with ≤ 1 TRF exhibited no significant

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differences from control subjects with ≤ 1 TRF, apart from a mild difference in cDC.

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It is important to note, however, that the TRFs for CV appeared to be well-controlled by

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treatment in most of our patients. In addition to our study, many other studies have investigated the associations among carotid plaques, IMT and DC in arthritis patients compared with control subjects.

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Assessment of Carotid IMT, used as independent predictors of CV events [15] is a well

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known non-invasive imaging test for subclinical atherosclerosis, but in RA patients remain optional[4]. The other vascular test like cDC (used in this study) or flow mediated dilatation (FMD), nitric mediated dilatation (NMD), lumen diameter (LD), circumferential wall stress

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(CWS), circumferential wall tension (CWT), pulse wave velocity (PWV) and augmentation index (Aix) are also considered markers of subclinical atherosclerosis and a tool to determine

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the CV risk [35–37]. FMD and NMD are accepted as non-invasive methods to evaluate endothelial function in humans [24] while cDC, PWV and AIx are measures of peripheral and

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central arterial stiffness. PWV is recommended in the last ESH/ESC guideline in order to evaluate the extent of arterial damage and adapt the intensity of antihypertensive treatment [38]. Thus, these CV risk markers provide important prognostic data over and above traditional CV risk factors. At least three meta-analyses have previously attempted to summarize the results regarding this subject, especially those pertaining to cIMT, and have found that the mean difference in cIMT between RA patients and controls is approximately 0.1 mm [24–26] and that the prevalence of carotid plaques is increased in the former group compared with the latter group[11]. Regarding the factors associated with cIMT, meta-regression analyses and sensitivity analyses performed during a recent study pinpointed male gender and inflammation (also measured as disease activity with the DAS28) [11], whereas Van Sijl pinpointed TRFs, but not age [39], 11

ACCEPTED MANUSCRIPT and Tyrrell’s meta-analysis pinpointed pre-existing cardiovascular disease, rheumatic disease type, and disease duration [40].

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Consistent with our findings, several large studies were unable to find differences in carotid

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cIMT[41–43] or in prevalence of plaques [44–46] between patients with RA and control

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subjects or determined that age was the main factor contributing to disease progression. A recently published study enrolling 267 patients with RA observed that cIMT indices and cDC were similar between patients and controls without risk factors despite showing that more

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patients than controls had carotid plaques. This study also noted that the prevalence of plaques

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in patients with disease durations less than 5 years (who were younger) was equal to that in controls, suggesting that age is the main factor associated with the presence of plaques [47]. In the Arida study, RA disease, potentially a novel CVD risk factor in its own right, causes

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arterial damage mainly via potentially irreversible plaque formation but does not affect arterial stiffness or hypertrophy in the absence of classical CVD risk factors. These results

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seem to be different from our study, but we have to declare that two populations are quite different. In particular the lower DAS28 in our population and the absence of the TRF, in

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Arida population could explain the different results in the two studies [47]. In another study by Dehghan et al., cIMT was significantly increased in patients with RA compared with control subjects; however, as was the case in our study, age was the main variable associated with this subclinical atherosclerosis marker [10]. The explanations for the differences in the results of the above studies and meta-analyses remain controversial; however, most of the discrepancies may be attributed to differences among the control populations enrolled in the studies in question. It is also possible that the significant difference in cIMT of 0.1 mm that was identified by previous meta-analyses is not clinically relevant or that the accuracy of the measurement in the clinical setting is disproportionally low compared with that in clinical trials.

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ACCEPTED MANUSCRIPT The significant difference in cDC between RA patients and controls suggests that vascular elasticity is selectively impaired in RA patients; however, the clinical and pathophysiological

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importance of this finding remains to be clarified.

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Few studies have evaluated the issue of impaired elasticity in RA patients; most of these

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studies noted elasticity alterations in carotid and aortic segments, as measured via US and magnetic resonance, and observed that biological drugs exert favourable effects on vascular elasticity [48].

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The EULAR [4,21] recently issued a series of recommendations to reduce the risk of

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cardiovascular disease in patients with RA, AS and PsA. These recommendations include limiting corticosteroid and NSAID use as much as possible, quitting smoking and preferentially using statins and ACE inhibitors.

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However, NSAID, corticosteroid and biological drug use by the patients included in our study had no significant effect on atherosclerosis. A recent meta-analysis including patients with RA

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and PsA [32] determined that in addition to inflammatory diseases, NSAID use was associated with an increased risk of all events, albeit a very low relative risk (1.18) of all

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events. Moreover, this effect seemed to be driven mainly by COX-2 inhibitors rather than non-selective NSAIDs. Corticosteroids were also associated with an increased risk of CV events, whereas TNF inhibitors were associated with a decreased risk of CV events. In conclusion, our study noted no major differences in US atherosclerosis makers between arthritis patients and controls matched for age and numbers of TRFs. Moreover, only age rather than TRFs or disease activity and duration seems to be consistently associated with the same indices. Our study does not support the performance of US examinations of the carotid arteries in patients with arthritis; however, longitudinal studies may be better suited for evaluating this issue. Although our study findings indicate that US evaluations of the carotid arteries are not useful in arthritis patients, careful CV risk profile assessments should remain a fundamental aspect 13

ACCEPTED MANUSCRIPT of clinical practice to ensure that all preventative measures (lifestyle changes, weight loss, smoking cessation, physical activity, and drug therapy) necessary to control TRFs in this

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population are aggressively implemented.

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ACCEPTED MANUSCRIPT Table 1. Anthropometric, demographic and clinical characteristics of the investigated population Table 2: Carotid indices of atherosclerosis in arthritis patients with age <50y

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Table 3 Carotid indices of atherosclerosis in arthritis patients carrying

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Abbreviation: cIMT= common carotid intima media thickness; cDC= common carotid distensibility; n.s. not significant. Abbreviations: BMI= Body mass index; SBP= systolic blood pressure; ASDAS-CRP= ankylosing Spondylitis disease activity score DAS28-CRP= Disease Activity Score 28 ; CRP= C Reactive Protein, ESR= erythrocyte sedimentation rate *p ANOVA test between arthritic patients. cIMT= common carotid intima media thickness; cDC common carotid distensibility. p>0.05 by ANOVA n.s. not significant.

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ACCEPTED MANUSCRIPT Table 1. Anthropometric, demographic and clinical characteristics of the investigated population Arthritis Controls RA (137) PsA (43) AS (28) (208) (48) 75/133

33/104

22/21

57 ±11.45

60±11.3

55±9.03

0.001

51±12.31

0.001

26.76±4.92

ns

BMI, Kg/m2 ±SD

24.23±3.29

25.83 ±4.40

25.50±4.50

SBP, mmHg

129 ±17.20

137±17.82

139± 18.27

134± 16.78

135±16.67

0.007

Smoke, %

6.2

42.2

43.8

41.9

32.1

0.000

Hypertension, %

10.4

48.1

48.2

46.5

50.0

0.000

Dyslipidaemia, %

31.2

63.9

65.0

65.1

57.1

0.001

Diabetes, %

6.2

9.1

8.0

11.6

10.7

ns

-

207± 40.03

213±40.03

197±38.07

193±35.41

ns

-

3.55± 5.85

4.29±7.74

2.81±3.28

6.12±10.00

ns

-

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ESR (mm 1st hour)

26.26± 3.57

18.37 ±16.42 20.26±17.50 12.71±11.11 26.10±23.85 0.031

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Total cholesterol, mg/dl CRP, mg/L

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56 ±9.43

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Age, yrs ±SD

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25/23

Gender n M/F

p*

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ASDAS-CRP 1.81 ±1.08 2.08 ±1.17 1.41±0.78 (only for PsA and AS) DAS28-CRP 2.66 ±1.13 2.69±1.09 2.55±1.23 Only for RA and PsA) Duration of 14 ±10.58 15±10.65 10±8.17 14±11.83 arthritis Number of 12 ±9.42 13±9.92 10±6.85 6±7.95 articulations involved Abbreviations: BMI= Body mass index; SBP= systolic blood pressure; ASDAS-CRP= ankylosing Spondylitis disease activity score DAS28-CRP= Disease Activity Score 28 ; CRP= C Reactive Protein, ESR= erythrocyte sedimentation rate *p ANOVA test between arthritic patients.

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ns

ns 0.009 0.003

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Table 2: Carotid indices of atherosclerosis in arthritis patients with age <50y RA (n=30)

PsA (n=15)

AS (n=15)

p

cIMT, mm

0.62 0.13

0.65 0.11

0.56 0.9

n.s.

cDC

23.03 6.04

26.27 7.81

27.42 8.26

13

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Carotid plaques %

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Carotid phenotypes

7

n.s. n.s.

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Abbreviation: cIMT= common carotid intima media thickness; cDC common carotid distensibility. p>0.05 by ANOVA n.s. not significant.

22

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Table 3 Carotid indices of atherosclerosis in arthritis patients carrying 1 TRF Control (n=48)

cIMT, mm

0.67 0.12

0.66 0.12

cDC

19.31 6.66

22.75 8.17

n.s.

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Carotid plaque %

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RA (n=48)

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Carotid phenotypes

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0.027 n.s.

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Abbreviation: cIMT= common carotid intima media thickness; cDC= common carotid distensibility; n.s. not significant.

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