Skip Navigation



Rheumatology Advance Access published online on June 4, 2008
Rheumatology, doi:10.1093/rheumatology/ken198
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
47/8/1203    most recent
ken198v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Mathieu, S.
Right arrow Articles by Soubrier, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mathieu, S.
Right arrow Articles by Soubrier, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Trend towards increased arterial stiffness or intima–media thickness in ankylosing spondylitis patients without clinically evident cardiovascular disease

S. Mathieu1,2, H. Joly2,3, G. Baron4, A. Tournadre1,2, J.-J. Dubost1,2, J.-M. Ristori1,2, J.-R. Lusson2,3 and M. Soubrier1,2

1Rheumatology department, G. Montpied Teaching Hospital, 2Faculty of Medicine, Clermont 1 University, 3Cardiology department, G. Montpied Teaching Hospital, Clermont-Ferrand and 4Epidemiology, Biostatistics and Clinical Research department, Bichat Hospital, Paris, France.

Correspondence to: S. Mathieu, Service de Rhumatologie, 58, rue Montalembert, 63003 Clermont-Ferrand cedex 1, France. E-mail: smathieu11{at}yahoo.fr


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 References
 
Objectives. Increased incidence of cardiovascular disease (CVD) has been observed in AS. The reasons of this increase are not fully understood (greater prevalence of traditional cardiovascular risks, consequences of treatment (NSAID) or biological inflammation). The objectives of this study are to assess intima–media thickness (IMT) and arterial stiffness (i.e augmentation index AIx), markers of sub-clinical atherosclerosis in AS patients and to examine the effects of TNF-{alpha} inhibitors on arterial stiffness in active AS patients.

Methods. Sixty AS patients were enrolled with 60 healthy controls. Their BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) scores, ESR and CRP levels were recorded. Subclinical atherosclerosis was assessed by measurement of AIx by pulse wave analysis and IMT by carotid echography.

Results. We found significantly increased IMT in the AS group compared with healthy controls. After adjustment for confounding factors, an underlying trend towards increased IMT was still present (P = 0.06). No difference was found in arterial stiffness between the two groups. AS patients, treated or not with anti-TNF-{alpha} at baseline, had significantly increased IMT and AIx or a trend towards increase. IMT was positively correlated with tobacco use, WHR and blood pressure but not correlated with CRP level. Despite improvement in markers of disease activity, arterial stiffness was unchanged after 14 weeks of treatment with TNF antagonists.

Conclusion. This study shows a trend towards increased subclinical atherosclerosis in AS patients. TNF-{alpha} blockade does not seem to improve arterial stiffness in AS patients, but our results lack statistical power.

KEY WORDS: Ankylosing spondylitis, Intima–media thickness, Arterial stiffness, Tumour necrosis factor-{alpha} inhibitors


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 References
 
Increased cardiovascular morbidity and mortality have been observed in association with several inflammatory rheumatic diseases, including RA and SLE, and also in AS [1–7]. The causes underlying this increased incidence of cardiovascular disease (CVD) are not entirely understood. Traditional coronary risk factors such as hyperlipidaemia, smoking, hypertension and diabetes have been implicated, but cannot fully explain the increased risk of CVD in patients with SLE and RA [8, 9]. In RA, disease severity has consistently been associated with an increased risk of CVD, indicating that systemic inflammation is a major determinant of vascular comorbidity [10]. Mechanisms involved in inflammation and autoimmunity have been shown to contribute to atherosclerosis. These include factors such as inflammation-related dyslipidaemia and shared features of immune dysregulation [11]. Inflammatory biomarkers are good predictors for cardiovascular events in both the general population and inflammatory polyarthritis patients [12, 13]. Patients with AS are known to have an overall mortality of about 1.6–1.9 times that of the general population, and excess mortality from circulatory or CVD has been estimated at 20–40% [14–16]. In a recent survey, AS patients were more often smokers and had higher BMI compared with age-matched healthy controls. After adjusting for smoking status and BMI, these patients also had significantly increased CRP, IL-6 and fibrinogen [17]. This suggests an unfavourable risk profile associated with AS including systemic inflammation, which may predispose to CVD. However, the association between atherosclerosis and AS is still debated [18]. Arterial stiffness is a marker for vascular dysfunction and an independent risk factor for CVD [19]. Measurement of the intima–media thickness (IMT) of the far wall of the common carotid artery by high-resolution ultrasonography has been established as a clinically useful index for identifying early-stage atherosclerosis [20]. The common carotid artery IMT is strongly correlated with the presence of coronary artery diseases [21, 22].

In the present study, we used pulse wave analysis (PWA) and measurement of IMT to assess vascular health in AS patients and control subjects. In a sub-group of patients, we evaluated the effect of TNF blockers on arterial stiffness in AS.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 References
 
Between February 2006 and October 2006, we studied 60 patients with AS and 60 control subjects who were frequency matched for age, sex and smoking status. All patients met the New York diagnostic criteria [23]. Patients and controls with a history of CVD (previous stroke, myocardial infarction or angina, heart failure, peripheral vascular disease and transient ischaemic attack) or a family history of premature myocardial infarction (before 55 yrs of age in first-degree male relatives or before 65 yrs in female relatives) were excluded. We also excluded patients with diabetes mellitus (fasting blood glucose >7 mmol/l) and patients on anti-hypertensive medications or on lipid-lowering therapies. Eight patients were excluded (one for previous family history of myocardial infarction, one for previous stroke, three for hypertension, two for diabetes mellitus and one for New York diagnostic criteria not fulfilled). The study was approved by the local Research Ethics Committee of Gabriel Montpied Hospital and all subjects gave written informed consent.

Clinical assessment
Disease duration and medications were recorded. Disease activity was measured using the six-question patient-reported Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (where 0 = no disease activity and 100 = highest level of activity) [24]. Functional capacity was measured using the 10-question, patient-reported Bath Ankylosing Spondylitis Functional Index (BASFI) (where 0 = lowest level and 100 = highest level) [25]. Height, weight, waist and hip circumference and then waist-to-hip ratio (WHR) were recorded. BMI was calculated according to Quetelet's index as the ratio of weight (kilograms) to height (metres) squared (kilogram per square metres). Blood pressure was recorded with a mercury column sphygmomanometer.

Laboratory examinations
In the morning, after an overnight fast, venous blood was sampled for the measurement of serum concentrations of glucose, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TGs), atherogenic index (TC/HDL-C), CRP and ESR.

Radiographic examinations
Structural damage was scored on the radiographs of the lumbar and cervical spine, according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASS) by a single observer (S.M.) [26].

Non-invasive vascular assessment
To avoid interobserver variability, all measurements were performed by the same experienced examiner (H.J.), who was unaware of the clinical characteristics of the subjects.

PWA
The Sphygmocor apparatus (Atcor Medical, Sydney, Australia) was used to perform PWA. Blood pressure was recorded in the supine position. Radial artery waveforms were recorded from the wrist of the dominant arm with a tonometer. Data were acquired and stored directly into a portable computer. After acquisition of 10 sequential waveforms, an averaged peripheral waveform and the mathematically derived corresponding central aortic waveform were generated [27]. The augmentation index (AIx), a measure of systemic arterial stiffness, was calculated by the integral software as the difference between the second and first systolic peaks, expressed as a percentage of the pulse pressure.

IMT
IMT was measured in the left and right common carotid arteries (CCA) using high-resolution B-mode ultrasound (HP Sonos 5500, Soma Technology, Inc) with an electric linear transducer (mid-frequency 7.5 MHz). The subject lay supine with the neck extended and the chin turned controlateral to the side being examined. On a longitudinal, bi-dimensional ultrasound image of the carotid artery, the anterior (near) and posterior (far) walls of the carotid artery are displayed as two bright white lines separated by a hypoechogenic space. The distance between the leading edge of the first bright line (the lumen–intima interface) of the far wall and the leading edge of the second bright (collagen-containing upper layer of tunica adventitia) indicates the IMT [28]. IMT was measured at three points on the far walls of both the left and the right CCA as previously reported [29]. The three locations were then averaged to produce the mean IMT for each side. The number of subjects required to detect a difference between two groups has been calculated as 53 in RA [30].

Anti-TNF-{alpha} therapy was initiated in 18 patients (13 men and 5 women). Ten patients were started on infliximab (5 mg/kg on 0, 2, 6 and 14 weeks), four on adalimumab (40 mg every other week) and four on etanercept (25 mg twice weekly). At baseline and at 14 weeks, clinical assessment, laboratory examinations and PWA were recorded.

Statistical analysis
Median and interquartile range (IQR) for quantitative variables and number of patients (percentage) for categorical variables were calculated for cases and controls. The Wilcoxon signed rank test for paired data was used to compare the unmatched quantitative characteristics of case patients and control subjects. Multivariate regression was performed to estimate the effects on different variables when controlling for other variables. As the experimental design was a matched case–control study, we performed a conditional logistic regression analysis to estimate the odds ratios (ORs) and 95% CIs. Spearman's correlation test was used to determine the association between AIx and IMT and clinical parameters for AS. Multiple linear regression analysis was performed to identify the parameters accounting for IMT in AS. Quantitative variables between baseline and 14 weeks in the subgroup of patients who received TNF-antagonists were also compared by the Wilcoxon signed rank test. A P-value of <0.05 (two-tailed) was considered statistically significant. SAS software, version 9.1 (SAS Institute, Grégy-sur-Yerres, France) was used for statistical analysis.


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 References
 
The AS-related variables of the 60 AS patients are given in Table 1. The majority of AS patients had long-standing disease. The median BASDAI in AS group was 29.9 (11.5–57.7), which is consistent with active disease despite treatment. Twenty-two patients (36.6%) were on TNF antagonists, 20 patients (33.3%) on DMARD owing to peripheral arthritis and 3 patients (5.0%) were treated by prednisone with a median dose of 4 mg/day.


View this table:
[in this window]
[in a new window]

  		TABLE 1. Characteristics of AS patients

 
The demographic characteristics and cardiovascular risk factors for the 60 patients with AS and the 60 control patients are shown in Table 2. There were no significant differences in these variables between AS patients and controls except for WHR, glycaemia, TC and systolic blood pressure. AS patients had higher WHR [0.92 (0.88–0.98) vs 0.91 (0.85–0.97); P = 0.034], lower systolic blood pressure [120.0 (110.0–130.0) mmHg vs 130.0 (120.0–132.5) mmHg; P = 0.033], lower TC [4.6 (4.10–4.40) mmol/l vs 5.23 (4.70–5.80) mmol/l; P = 0.030] and lower glycaemia [4.40 (4.10–4.75) mmol/l vs 4.66 (4.35–5.00) mmol/l; P = 0.013].


View this table:
[in this window]
[in a new window]

  		TABLE 2. Demographic and cardiovascular characteristics of patients with AS and control subjects

 
The AS patients also had a significantly higher median CRP level [6.6 (1.1–15.6) mg/l vs 1.4 (1.0–3.9) mg/l; P < 0.001) than healthy controls, indicating active systemic inflammation. AIx was higher in the AS group but the difference was not significant [12.0 (2.0–24.0)% vs 7.5 (0.0–19.0)%; P = 0.164]. Increased carotid IMT was observed in AS patients [0.56 (0.51–0.62) mm vs 0.53 (0.48–0.59) mm; P = 0.023]. After adjustment for confounding factors [blood pressure, WHR, glycaemia, CRP and TC (P < 0.10 in bivariate analysis)], an underlying trend towards increased IMT was still present (P = 0.06). In the AS group, IMT was correlated to smoking (P = 0.006), WHR (r = 0.30; P = 0.019), systolic blood pressure (r = 0.41; P = 0.001) and diastolic blood pressure (r = 0.43; P < 0.001). No correlation was observed with CRP and mSASS. Linear regression showed that IMT could only be explained by high systolic blood pressure (P < 0.001) and smoking (P = 0.041) in AS.

Twenty-two patients were already being treated with TNF-{alpha} inhibitors at baseline. Sub-group analysis showed that AS patients treated or not with anti-TNF-{alpha} had significantly increased IMT and AIx or a trend towards increase compared with controls [AS patients treated with TNF-{alpha} inhibitors: AIx: 14.0 (2.0–26.0) vs 4.5 (–4.0 to 25.0), P = 0.037; IMT: 0.56 (0.51–0.63) vs 0.54 (0.49–0.57), P = 0.078; and treatment-naive patients: AIx: 12.0 (2.0–21.0) vs 10.5 (2.0–17.0), P = 0.939; IMT: 0.56 (0.51–0.62) vs 0.52 (0.47–0.60), P = 0.131]. In both groups, AS patients had significant higher CRP levels than matched controls [AS patients treated with TNF-{alpha} inhibitors: CRP: 5.90 (1.10–12.60) vs 1.50 (1.00–4.30), P = 0.04 and treatment-naive patients: CRP: 6.60 (1.40–21.50) vs 1.30 (1.00–3.60), P = 0.007] (Table 3).


View this table:
[in this window]
[in a new window]

  		TABLE 3. Comparison between AS patients and matching controls in step with presence or not of TNF-{alpha} treatment at baseline

 
As expected, after 14 weeks of treatment with TNF antagonists there was a significant improvement in markers of disease activity (BASDAI, ESR and CRP). There was no change in TC, TGs and LDL-C. In contrast, there was a significant increase in HDL-C [1.52 (1.30–1.97) vs 1.46 (1.10–1.79) mmol/l; P = 0.024) but no change in atherogenic index. However, despite this significant suppression of systemic inflammation, the median AIx value remained unchanged after 14 weeks of treatment with TNF antagonists (Table 4).


View this table:
[in this window]
[in a new window]

  		TABLE 4. Differences in parameters after 14 weeks of treatment by TNF antagonists in the subgroup of patients who received TNF antagonists (n = 18)

 

   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
References
 
In this study, a trend towards increased carotid IMT and arterial stiffness, markers of sub-clinical atherosclerosis, was observed in AS patients compared with healthy controls but not to a level of significance. TNF-{alpha} blockade does not seem to improve arterial stiffness in AS patients, but our results lack statistical power.

The control group had a worse cardiovascular profile with higher TC, higher glycaemia and higher systolic blood pressure. Only WHR was higher in the AS group than in controls. These results are at variance with those of Malesci et al. [31], Han et al. [32] or Divecha et al. [17], who reported respectively higher metabolic syndrome, higher hyperlipidaemia, higher hypertension and higher BMI in AS patients compared with controls, and with those of Sari et al. [33], who found no difference in traditional risk factors between AS and control groups. These discrepancies could be explained by the level of cardiovascular risk in our region of France, which is higher than that of the general population [34].

Despite this worse cardiovascular profile in controls, we found an underlying trend of increased IMT and AIx in the AS group. This finding is consistent with the idea that traditional risks by themselves, including cigarette smoking, hypertension and elevated lipid levels described in RA, were not sufficient to explain the increased CVD risk and increased incidence of sub-clinical atherosclerosis seen in RA patients [8, 30, 35–46].

In the AS group, IMT was correlated with traditional risk factors, such as smoking and systolic blood pressure, which was not reported elsewhere in AS. Several studies in RA demonstrated the correlation between IMT and age, TC, smoking or systolic and diastolic blood pressure [44, 47–49]. In contrast, we found no correlation of IMT with CRP, or mSASS, which is considered to be indicative of cumulative disease activity. Our findings are consistent with those of Malesci et al. [31], but their study, like ours, concerned only a small series of patients and lacks statistical power, and so there is no sufficient evidence to support a role of biological inflammation. In addition, atherosclerosis is an inflammatory disease, and there are striking parallels between the inflammatory and immunological mechanisms operating in atherosclerotic plaque formation and in rheumatoid synovitis [50, 51]. Several population studies of healthy men and women have shown a relationship between CRP and risk of future myocardial infarction [12]. In one study, CRP was a predictor of future CVD events in patients with inflammatory polyarthritis [13]. In our study, CRP level was always higher in AS patients, whether treated or not by TNF-{alpha} inhibitors. Inflammation might therefore be involved in increased subclinical atherosclerosis in AS.

We found no differences in baseline lipid profile between AS and control groups, unlike van Halm et al. [52], who reported decreased HDL-C. In patients in whom anti-TNF-{alpha} therapy was initiated, only HDL-C increased significantly, as observed elsewhere [53]. Despite improvements in atherogenic profile and CRP, arterial stiffness was not improved after 14 weeks of treatment with TNF antagonists. The same results were observed in RA patients and were interpreted as vasoconstriction induced by TNF antagonists [54].

The role of glucocorticoids in the occurrence of CVD in patients with RA and SLE has been a subject of debate for decades [55, 56]. Steroid therapy is known to adversely affect many metabolic factors such as body fat distribution, blood pressure and glucose metabolism. Steroids on the other hand may also be of benefit because of their anti-inflammatory effects [55, 56]. The absence of sub-clinical atherosclerosis in our patients could be explained by the quasi-absence of steroid exposure.

The major limitation of our study is its limited statistical power due to the small sample size. Multivariate analysis showed a trend towards increased sub-clinical atherosclerosis in AS. Future larger studies are needed to clearly demonstrate the presence of sub-clinical atherosclerosis and to define the role of systemic inflammation in the increased incidence of CV disease in AS.

Formula

Disclosure statement: The authors have declared no conflicts of interest.


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

  1. Lindqvist E, Eberhardt K. Mortality in rheumatoid arthritis patients with disease onset in the 1980s. Ann Rheum Dis (1999) 58:11–4.[Abstract/Free Full Text]
  2. Linos A, Worthington JW, O’Fallon WM, Kurland LT. The epidemiology of rheumatoid arthritis in Rochester, Minnesota: a study of incidence, prevalence, and mortality. Am J Epidemiol (1980) 111:87–98.[Abstract/Free Full Text]
  3. Sokka T, Mottonen T, Hannonen P. Mortality in early "sawtooth" treated rheumatoid arthritis patients during the first 8-14 years. Scand J Rheumatol (1999) 28:282–7.[CrossRef][Web of Science][Medline]
  4. Aranow C, Ginzler EM. Epidemiology of cardiovascular disease in systemic lupus erythematosus. Lupus (2000) 9:166–9.[Abstract/Free Full Text]
  5. Manzi S, Meilahn EN, Rairie JE, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham study. Am J Epidemiol (1997) 145:408–15.[Abstract/Free Full Text]
  6. Petri M, Perez-Gutthann S, Spence D, Hochberg MC. Risk factors for coronary disease in patients with systemic lupus erythematosus. Am J Med (1992) 93:513–9.[CrossRef][Web of Science][Medline]
  7. Roman MJ, Shanker BA, Davis A, et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med (2003) 349:2399–406.[Abstract/Free Full Text]
  8. Del Rincon I, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum (2001) 44:2737–45.[CrossRef][Web of Science][Medline]
  9. Asanuma Y, Oeser A, Shintani AK, et al. Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med (2003) 349:2407–15.[Abstract/Free Full Text]
  10. Turesson C, Jarenros A, Jacobsson L. Increased incidence of cardiovascular disease in patients with rheumatoid arthritis: results from a community based study. Ann Rheum Dis (2004) 63:952–5.[Abstract/Free Full Text]
  11. Sherer Y, Shoenfeld Y. Mechanisms of disease: atherosclerosis in autoimmune diseases. Nat Clin Pract Rheumatol (2006) 2:99–106.[CrossRef][Web of Science][Medline]
  12. Willerson JT, Ridker PM. Inflammation as a cardiovascular risk factor. Circulation (2004) 109:II2–10.[Medline]
  13. Goodson NJ, Symmons DP, Scott DG, Bunn D, Lunt M, Silman AJ. Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohort. Arthritis Rheum (2005) 52:2293–9.[CrossRef][Web of Science][Medline]
  14. Lautermann. Ankylosing spondylitis—cardiac manifestations. Clin Exp Rheumatol (2002) 20(Suppl):S11–5.
  15. Lehtinen K. Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis. Ann Rheum Dis (1993) 52:174–6.[Abstract/Free Full Text]
  16. Kaprove RE, Little AH, Graham DC, Rosen PS. Ankylosing spondylitis; survival in men with and without radiotherapy. Arthritis Rheum (1980) 23:57–61.[Web of Science][Medline]
  17. Divecha H, Sattar N, Rumley A, Cherry L, Lowe G, Sturrock R. Cardiovascular risk parameters in men with ankylosing spondylitis in comparison with non-inflammatory control subjects: relevance of systemic inflammation. Clin Sci (2005) 109:171–6.[CrossRef][Web of Science][Medline]
  18. Symmons DP. Men with ankylosing spondylitis have an increased risk of myocardial infarction. Arthritis Rheum (2004) 50:S477.
  19. Arnett DK, Evans GW, Riley WA. Arterial stiffness: a new cardiovascular risk factor? Am J Epidemiol (1994) 140:669–82.[Free Full Text]
  20. Wofford J, Kahl F, Howard G, McKinney W, Toole J, Crouse JI. Relation of extent of extracranial carotid artery atherosclerosis as measured by B-mode ultrasound to the extent of coronary atherosclerosis. Arterioscler Thromb (1991) 11:1786–94.[Abstract/Free Full Text]
  21. Lekakis JP, Papamichael CM, Cimponeriu AT, et al. Atherosclerotic changes of extracoronary arteries are associated with the extent of coronary atherosclerosis. Am J Cardiol (2000) 85:949–52.[CrossRef][Web of Science][Medline]
  22. Simons PC, Algra A, Bots ML, Grobbee DE, van der Graaf Y. Common carotid intima-media thickness and arterial stiffness: indicators of cardiovascular risk in high-risk patients. The SMART Study (Second Manifestations of ARTerial disease). Circulation (1999) 100:951–7.[Abstract/Free Full Text]
  23. Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum (1984) 27:361–8.[Web of Science][Medline]
  24. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol (1994) 21:2286–91.[Web of Science][Medline]
  25. Calin A, Garrett S, Whitelock H, et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol (1994) 21:2281–5.[Web of Science][Medline]
  26. Wanders AJ, Landewé RB, Spoorenberg A, et al. What is the most appropriate radiologic scoring method for ankylosing spondylitis? A comparison of the available methods based on the outcome measures in Rheumatology Clinical Trials filter. Arthritis Rheum (2004) 50:2622–32.[CrossRef][Web of Science][Medline]
  27. Booth AD, Wallace S, McEniery CM, et al. Inflammation and arterial stiffness in systemic vasculitis: a model of vascular inflammation. Arthritis Rheum (2004) 50:581–8.[CrossRef][Web of Science][Medline]
  28. Boutouyrie P, Tropeano AI, Asmar R, et al. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension (2002) 39:10–5.[Abstract/Free Full Text]
  29. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular health study collaborative research group. N Engl J Med (1999) 340:14–22.[Abstract/Free Full Text]
  30. Park YB, Ahn CW, Choi HK, et al. Atherosclerosis in rheumatoid arthritis: morphologic evidence obtained by carotid ultrasound. Arthritis Rheum (2002) 46:1714–9.[CrossRef][Web of Science][Medline]
  31. Malesci D, Niglio A, Mennillo GA, Buono R, Valentini G, La Montagna G. High prevalence of metabolic syndrome in patients with ankylosing spondylitis. Clin Rheumatol (2007) 26:710–4.[CrossRef][Web of Science][Medline]
  32. Han C, Robinson DW Jr, Hackett MV, Paramore LC, Fraeman KH, Bala MV. Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol (2006) 33:2167–72.[Web of Science][Medline]
  33. Sari I, Okan T, Akar H, et al. Impaired endothelial function in patients with ankylosing spondylitis. Rheumatology (2006) 45:283–6.[Abstract/Free Full Text]
  34. Cardio-vascular disease. Main cause of high mortality in Auvergne, France. (14 May 2008, date last accessed). http://www.auvergne.sante.gouv.fr/sante/santauve/crs/fiches/page9-1.pdf.
  35. Wolfe F, Freundlich B, Strauss W. Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid arthritis. J Rheumatol (2003) 30:3640.
  36. Maradit-Kremers H, Nicola PJ, Crowson CS, et al. Raised erythrocyte sedimentation rate signals heart failure in patients with rheumatoid arthritis. Ann Rheum Dis (2007) 66:76–80.[Abstract/Free Full Text]
  37. Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum (2005) 52:722–32.[CrossRef][Medline]
  38. Nicola PJ, Maradit-Kremers H, Roger VL, et al. The risk of congestive heart failure in rheumatoid arthritis: a population-based study over 46 years. Arthritis Rheum (2005) 52:412–20.[CrossRef][Web of Science][Medline]
  39. Nicola PJ, Crowson CS, Maradit-Kremers H, et al. Contribution of congestive heart failure and ischemic heart disease to excess mortality in rheumatoid arthritis. Arthritis Rheum (2006) 54:60–7.[CrossRef][Web of Science][Medline]
  40. Maradit-Kremers H, Crowson CS, Nicola PJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum (2005) 52:402–11.[CrossRef][Web of Science][Medline]
  41. Vaudo G, Marchesi S, Gerli R, et al. Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity. Ann Rheum Dis (2004) 63:31–5.[Abstract/Free Full Text]
  42. Bergholm R, Leirisalo-Repo M, Vehkavaara S, Makimattila S, Taskinen MR, Yki-Jarvinen H. Impaired responsiveness to NO in newly diagnosed patients with rheumatoid arthritis. Arterioscler Thromb Vasc Biol (2002) 22:1637–41.[Abstract/Free Full Text]
  43. Van Doornum S, McColl G, Wicks IP. Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum (2002) 46:862–73.[CrossRef][Web of Science][Medline]
  44. Kumeda Y, Inaba M, Goto H, et al. Increased thickness of the arterial intima media detected by ultrasonography in patients with rheumatoid arthritis. Arthritis Rheum (2002) 46:1489–97.[CrossRef][Web of Science][Medline]
  45. Del Rincon I, Williams K, Stern MP, Freeman GL, O’Leary DH, Escalante A. Association between atherosclerosis and markers of inflammation in rheumatoid arthritis and healthy subjects. Arthritis Rheum (2003) 48:1833–40.[CrossRef][Web of Science][Medline]
  46. Solomon DH, Goodson NJ, Katz JN, et al. Patterns of cardiovascular risk in rheumatoid arthritis. Ann Rheum Dis (2006) 65:1608–12.[Abstract/Free Full Text]
  47. Alkaabi JK, Ho M, Levison R, Pullar T, Belch JJF. Rheumatoid arthritis and macrovascular disease. Rheumatology (2003) 42:292–7.[Abstract/Free Full Text]
  48. Jonsson SW, Backman C, Johnson O, et al. Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis. J Rheumatol (2001) 28:2597–602.[Abstract/Free Full Text]
  49. Del Rincon I, Freeman GL, Haas RW, O’Leary DH, Escalante A. Relative contribution of cardiovascular risk factors and rheumatoid arthritis clinical manifestations to atherosclerosis. Arthritis Rheum (2005) 52:3413–23.[CrossRef][Web of Science][Medline]
  50. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med (1999) 340:115–26.[Free Full Text]
  51. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature (1993) 362:801–9.[CrossRef][Medline]
  52. Van Halm VP, van Denderen JC, Peters MJ, et al. Increased disease activity is associated with a deteriorated lipid profile in patients with ankylosing spondylitis. Ann Rheum Dis (2006) 65:1473–7.[Abstract/Free Full Text]
  53. Spanakis E, Sidiropoulos P, Papadakis J, et al. Modest but substained increase of serum high density lipoprotein cholesterol levels in patients with inflammatory arthritides treated with infliximab. J Rheumatol (2006) 33:12.
  54. Van Doornum S, McColl G, Wicks IP. Tumour necrosis factor antagonists improve disease activity but not arterial stiffness in rheumatoid arthritis. Rheumatology (2005) 44:1428–32.[Abstract/Free Full Text]
  55. Davis JM 3rd, Maradit-Kremers H, Crowson CS, et al. Glucocorticoids and cardiovascular events in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum (2007) 56:820–30.[CrossRef][Web of Science][Medline]
  56. Bruce IN. ‘Not only ... but also’: factors that contribute to accelerated atherosclerosis and premature coronary heart disease in systemic lupus erythematosus. Rheumatology (2005) 44:1492–502.[Abstract/Free Full Text]
Submitted 1 November 2007; Accepted 15 April 2008


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
47/8/1203    most recent
ken198v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Mathieu, S.
Right arrow Articles by Soubrier, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mathieu, S.
Right arrow Articles by Soubrier, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?