Skip Navigation



Rheumatology Advance Access published online on May 22, 2008
Rheumatology, doi:10.1093/rheumatology/ken155
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
47/7/1058    most recent
ken155v1
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 Sangle, S. R.
Right arrow Articles by D'Cruz, D. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sangle, S. R.
Right arrow Articles by D'Cruz, D. P.
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

Ankle-brachial pressure index: a simple tool for assessing cardiovascular risk in patients with systemic vasculitis

S. R. Sangle1, R. J. Davies1, M. Mora2, M. A. Baron1, G. R. V. Hughes1 and D. P. D'Cruz1

1The Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, London, UK and 2Internal Medicine Department, La Paz Universitary Hospital, Madrid, Spain.

Correspondence to: D. P. D’Cruz, Lupus Research Unit, The Rayne Institute, 4th Floor, Lambeth Wing, St Thomas’ Hospital, London SE1 7EH, UK. E-mail: david.d'cruz{at}kcl.ac.uk


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 Acknowledgements
 References
 
Objective. Cardiovascular disease may be increased in patients with systemic vasculitides (SV). The Ankle-Brachial Pressure Index (ABPI) is a non-invasive tool for the assessment of cardiovascular risk (CV). Our aim was to determine the prevalence of an abnormal ABPI in patients with SV and healthy controls and to correlate with clinical and serological parameters.

Methods. We studied 54 consecutive vasculitis patients (20 males) attending the vasculitis clinic and 49 healthy subjects. Patients were classified according to the ACR 1990 criteria and the Chapel Hill Consensus definitions. There were 18 patients with Wegener's granulomatosis, eight with Behcet's disease, seven with Churg—Strauss Syndrome, three with Henoch—Schonlein purpura, three with polyarteritis nodosa, three with Takayasu's disease, three with p-ANCA associated vasculitis, three with urticarial vasculitis, two with cutaneous leucocytoclastic angiitis, one with microscopic polyangiitis, one with primary central nervous system angiitis, one giant cell arteritis and one with cutaneous vasculitis secondary to Sjogren's syndrome. Traditional risk factors as well as glucose, lipid profile, CRP, hsCRP, ANCA and aPL were assessed. ABPI was measured according to a consensus statement on the methodology.

Results. The ABPI was abnormal in 11/54 (20.4%) of SV patients and 2/49 (4%) of the control group ({chi}2 with Yates correction = 4.8, P ≤ 0.03). CV events were more prevalent in the SV patients with abnormal ABPI (45.5% vs 11.6%, P ≤ 0.01).

Conclusions. There is an increased prevalence of an abnormal ABPI in patients with systemic vasculitides implying an increased risk of cardiovascular disease. This simple tool may be clinically useful in identifying systemic vasculitis patients at risk of accelerated atherosclerosis.

KEY WORDS: Ankle-brachial pressure index, Atherosclerosis, Systemic vasculitis, Antineutrophil cytoplasmic antibodies


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 Acknowledgements
 References
 
Vasculitis is characterized by inflammation of blood vessels often associated with necrosis and occlusion of vessels, resulting in diverse clinical manifestations. Both clinical and animal studies have shown that immunopathological mechanisms play a major role in the pathology of vasculitis [1]. Inflammation and endothelial abnormalities are associated with atherosclerosis [2]. There is increasing evidence that accelerated atherosclerosis may occur in systemic vasculitis (SV) patients in a similar way to patients with SLE. There are a variety of methods for detecting endothelial dysfunction, for example, flow-mediated dilatation (FMD) and carotid intima-media thickness (IMT) which require skilled technicians and expensive equipment. The ankle-brachial pressure index (ABPI) is simple to perform, can be done at the bedside and is relatively cheap. Our aim was to assess the prevalence of an abnormal ABPI in patients with SV.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 Acknowledgements
 References
 
We studied 54 consecutive patients (34 females under 60 yrs and 20 males under 55 yrs) attending our vasculitis clinic and 49 healthy subjects (32 females and 17 males under 55 yrs). Patients were classified according to the ACR 1990 criteria, the Chapel Hill Consensus definitions and the international study group for Behcet's disease. There were 18 patients with Wegener's granulomatosis, eight with Behcet's disease, seven with Churg—Strauss Syndrome, three with polyarteritis nodosa, three with Henoch—Schonlein pupura (HSP), three with Takayasu's disease, one each with microscopic polyangiitis and giant cell arteritis. Of the patients with vasculitis who did not meet any classification criteria but had clinical/serological and/or histological evidence of vasculitis: there were three with urticarial vasculitis, three with p-ANCA-associated vasculitis, two with cutaneous leucocytoclastic angiitis and one each with primary central nervous system angiitis and vasculitis secondary to Sjogren's syndrome (Table 1). All the patients were assessed for their Birmingham vasculitis activity score (BVAS) and vasculitis damage index (VDI), traditional atherosclerotic markers as well as glucose, lipid profile, hs CRP, ANCA and aPL. Hypertension was defined as blood pressure more than 140/90 mmHg or patients receiving antihypertensive therapy.


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

  		TABLE 1. Clinical characteristics of the Systemic Vasculitis patients (n = 54)

 
Study protocol
The ABPI was used to assess the peripheral arteries and was measured according to a consensus statement on methodology [3]. Ankle systolic pressures were measured in the posterior tibial and dorsalis pedis arteries in both ankles with a 8 MHz Doppler ultrasound probe (Maxi Dopplex 200, Huntleigh Healthcare Limited, Cardiff, UK) and a random zero a mercury sphygmomanometer attached to a contour wrapped 12 cm cuff positioned 5 cm proximal to the malleoli after at least 5 min of rest in the decubitus supine position with the head at 30° from horizontal. The pulse was located with the Doppler probe facing the direction of flow and then the cuff was inflated to 20 mmHg above the audible systolic pressure. The recorded systolic pressure was the pressure at which the Doppler probe sounds were first audible as the cuff was deflated. The same technique was used in both brachial arteries. The order of measurement of all pressures was the same in all the patients. All the measurements in each artery were done twice and the average considered. The highest pressure in anterior/posterior tibial arteries in each foot was divided by the highest systolic pressure in brachial artery to obtain the ABPI, as recommended in the consensus statement on methodology [3]. We took the lowest of the measurements as the definitive ABPI for each patient and a result <0.9 in any value was considered abnormal.

Ethics and informed consent
This study was approved by the Guy's and St Thomas’ Research Ethics Committee and all participating patients and healthy controls gave fully informed consent.

Statistical analysis
We used {chi}2 with Yates' correction test for statistical analysis of ABPI in the two groups. Statistical significance was accepted at the 0.05 level.


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 Acknowledgements
 References
 
The median age of the patients in the SV group was 39 (29–54) yrs and in the control group 40.9 (30–53) yrs. In the SV group the median disease duration was 37 (29–57) months. In the SV group, there were two Afro-Caribbean, six Indian and one far East-Asian and the rest Caucasian in origin. Antiphospholipid antibodies were detected in eight patients (14.8%). One patient had a CV event (brain stem infarction) with positive aPL (Table 1). Forty-six (90.7%) patients were on corticosteroids and/or immunosuppressive therapy. Table 2 shows the main significant differences between the vasculitis patients and the healthy controls. Hypertension, family history of CV events, the elevated BMI (>25) were significantly more common in vasculitis patients. There were no significant differences in the prevalence of smoking, diabetes and dyslipidaemia or menopausal status.


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

  		TABLE 2. Traditional risk factors, abnormal ABPI and CV events in patients with systemic vasculitis and healthy controls

 
The ABPI was abnormal in 11/54 (20.4%) of the SV patients and 2/49 (4%) of the control group; ({chi}2 with Yates correction = 4.8, P ≤ 0.03) (Table 2). Median age of the SV patients with abnormal ABPI was 45.5 yrs (SD 9.7). There were six patients with CV events in the SV group and of these five patients had an abnormal ABPI (P ≤ 0.001). The hs CRP was raised in 10 (18%) patients with vasculitis (six patients with abnormal ABPI and four had normal ABPI). There were four patients each (abnormal/normal ABPI) with aPL in the SV group. Nineteen of the 54 patients with SV had a family history of CV events. Eight of the 11 SV patients with abnormal ABPI had a family history of CV events, compared to 11 of the 43 SV patients with normal ABPI ({chi}2 with Yates correction = 6.6, P < 0.01) (Table 2). None of the patients or controls with an abnormal ABPI had symptomatic peripheral vascular disease.


   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
Acknowledgements
 References
 
Atherosclerosis is a disease of middle-aged and older individuals and is traditionally associated with diabetes mellitus, hypertension, obesity and hyperlipidaemia. Accelerated atherosclerosis is also widely observed in auto-immune diseases such as SLE, RA and more recently in the antiphospholipid syndrome [4, 5].

It is increasingly clear that endothelial dysfunction plays a central role in the pathogenesis of atherosclerosis, diabetic vasculopathy, graft rejections and various collagen vascular diseases. In ANCA-associated systemic vasculitis (AASV), the mechanism of neutrophil activation by ANCA includes the engagement of Fc gamma receptors, neutrophil-mediated tissue damage and neutrophil–endothelial interaction [6]. Earlier studies have demonstrated that antiendothelial cell antibodies are elevated in AASV, idiopathic ocular vasculitis and Behcet's disease [7–9]. Vascular endothelial cells have tissue-specific antigens that may be induced by cytokines triggering inflammation seen in systemic vasculitis. Interleukin-1 and TNF-{alpha} induce the expression of adhesion molecules [10–13]. There is a link between atherosclerosis and inflammation exemplified by the correlation between hs CRP and CV events in population studies [14]. hs CRP and its interaction with endothelium, monocytes, neutrophils, lipoproteins and complement leading to atherosclerosis is well described, and hs CRP may be an independent predictor of atherosclerosis [15, 16]. Atherosclerosis may be assessed by various non-invasive techniques such as Doppler ultrasound, intravascular ultrasound, helical and electron beam CT scan, cardiac stress test, magnetic resonance angiography and assessment of carotid plaque and intima-medial thickness [17]. Marked endothelial dysfunction has been demonstrated in ANCA and non-ANCA-associated SV compared with controls [10–12].

The ABPI is a non-invasive technique to assess peripheral arteries in the extremities that is easy to perform in the clinical setting. The high sensitivity (90%) and specificity (98%) of this test makes ABPI an ideal tool to detect peripheral arterial vascular disease (PAD) in the extremities [18]. It is an indicator of future risk of coronary arterial disease and strokes [19]. ABPI is a good instrument for this assessment, with high patient acceptability, which is quick and easy to measure. The use of the ABPI significantly improves the predictive value for fatal MI in population studies [20]. The specificity of ABPI in predicting coronary heart disease is 92.7% and for stroke 92.2% and for cardiovascular mortality was 87%. The corresponding positive likelihood ratios were 2.53 (95% CI, 1.76, 3.41) for coronary artery disease, and 5.61 (95 CI, 3.45, 9.13) for cardiovascular death [21]. Although an ABPI <0.90 is highly sensitive and specific for the presence of PAD, [22] the hand-held Doppler may not precisely detect ankle systolic pressures less than 30 mmHg. It is also important to note that ~5% of patients with PAD will have an ABPI greater than 0.90 due to calcification of arteries, resulting in falsely elevated lower-extremity pressures [23]. All patients were examined by a trained physician with extensive experience in the ABPI technique. We have used the ABPI to assess possible atherosclerosis because the patients with PAD, even in the absence of a history of myocardial infarction or ischaemic stroke, have approximately the same relative risk of death [20].

In our cohort an abnormal ABPI was more common in SV patients compared to healthy controls. Interestingly none of the patients or controls had symptomatic PAD. Abnormal ABPIs were observed at a much younger age [median age 45.5 yrs (S.D. 9.7)] than expected from population studies. In the SV group, as expected, the prevalence of hypertension, high BMI, dyslipidaemia and previous CV events were more common than the controls (Table 2). Although hs CRP were raised in the SV group, there was no significant difference in hs CRP levels between patients with abnormal/normal ABPI and the prevalence of traditional risk factors such as smoking, dyslipidaemia, high BMI and aPL was also similar. The most obvious difference in the SV group was that patients with abnormal ABPI had a high prevalence of previous CV events as compared to patients with normal ABPI (P ≤ 0.01). An abnormal ABPI directly correlated with previous CV events in this group. Furthermore, a family history of CV disease correlated with a high incidence of CV events in SV patients (P ≤ 0.05).

One might argue that the abnormal ABPI may be related to the arterial stenosis often seen in the large vessel SV (Takayasu) and not to atherosclerosis. In the SV group one patient with Takayasu's arteritis had an abnormal ABPI. Although this may be a possibility, there were seven small vessel disease patients with SV with an abnormal ABPI suggesting that atherosclerosis was more likely than vasculitic stenotic lesions.

The literature regarding ABPI in systemic vasculitis is scanty. Ooyanagi et al. found abnormal pulse wave velocity in Kawasaki's disease patients although there was no significant difference in ABPI between patients and the control group [24]. We could not find a correlation between damage as assessed by VDI or disease activity assessed by BVAS and previous cumulative prednisolone dose, possibly because of small numbers. It is possible that larger studies may be able to address this.

Our preliminary data suggests that ABPI is abnormal in SV patients as compared to healthy controls and occurs in relatively young patients. The traditional risk factors were more common in SV patients as compared to healthy controls. This could explain the increased CV episodes as there was a correlation between CV risk and abnormal ABPI. These findings support previous data of an increased prevalence of accelerated atherosclerosis in SV patients.

In contrast to other techniques such as FMD, our data suggests that the ABPI may be a simple and useful tool in the out-patient clinic setting.

Formula


   Acknowledgements
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Acknowledgements
References
 
We are grateful to the Hughes Syndrome Foundation for the Judith Maxfield Scholarship for Dr Sangle.

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


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Acknowledgements
 References
 

  1. Kamesh L, Harper L, Savage CO. ANCA positive vasculitis. J Am Soc Nephrol (2002) 13:1953–60.[Free Full Text]
  2. Verma S. C-reactive protein incites atherosclerosis. Can J Cardiol (2004) 20(suppl.):29B–31B.[Web of Science][Medline]
  3. Sacks D, Bakal CW, Beatty PT, et al. Position statement on the use of the Ankle Brachial Index in the evaluation of patients with peripheral vascular disease: a consensus statement developed by the standards division of the society of cardiovascular and interventional radiology. J Vasc Interv Radiol (2002) 13:353.[Web of Science][Medline]
  4. Petri M. Detection of coronary artery disease and the role of traditional risk factors in the Hopkins lupus Cohort. Lupus (2000) 9:170–5.[Abstract/Free Full Text]
  5. George J, Shoenfeld Y. The antiphospholipid "Hughes syndrome" syndrome: a cross roads of autoimmunity and atherosclerosis. Lupus (1997) 6:559–60.[Free Full Text]
  6. Reumaux D, Duthilleul P, Roos D. Pathogenesis of diseases associated with antineutrophil cytoplasm autoantibodies. Hum Immunol (2004) 65:1–12.[CrossRef][Web of Science][Medline]
  7. Ferraro G, Meroni PL, Tincani A, et al. Anti-endothelial cell antibodies in patients with Wegener's granulomatosis and micropolyarteritis. Clin Exp Immunol (1990) 79:47–53.[Web of Science][Medline]
  8. Edelsten C, D’Cruz D, Hughes GR, Graham EM. Anti-endothelial cell antibodies in retinal vasculitis. Curr Eye Res (1992) 11:203–8.[Medline]
  9. Aydintug AO, Togkoz C, D’Cruz D, et al. Endothelial cell antibodies in patients with Behcet's disease. Clin Immunol Immunopathol (1999) 67:157–62.[CrossRef]
  10. Buckley CD, Ed Rainger G, Nash GB, Raza K. Endothelial cells, fibroblasts and vasculitis. Rheumatology (2005) 44:860–3.[Abstract/Free Full Text]
  11. Bacon PA. Endothelial cell dysfunction in systemic vasculitis: new developments and therapeutic prospects. Curr Opin Rheumatol (2005) 17:49–55.[CrossRef][Web of Science][Medline]
  12. Filer AD, Gardner-Medwin JM, Thambyrajah J, et al. Diffuse endothelial dysfunction is common to ANCA associated with systemic vasculitis and polyarteritis nodosa. Ann Rheum Dis (2003) 62:162–7.[Abstract/Free Full Text]
  13. Raza K, Thambyrajah J, Townend JN, et al. Suppression of inflammation in primary systemic vasculitis restores vascular endothelial function: lessons for atherosclerotic disease. Circulation (2000) 102:1470–72.[Abstract/Free Full Text]
  14. Everett BM, Kurth T, Buring JE, Ridker PM. The relative strength of C-reactive protein and lipid levels as determinants of ischemic stroke compared with coronary heart disease in women. J Am Coll Cardiol (2006) 48:2235–42.[Abstract/Free Full Text]
  15. Mazer SP, Rabbani LE. Evidence for C-reactive protein's (CRP) role in vascular disease: atherothrombosis, immunoregulation and CRP. Thromb Thrombolysis (2004) 17:95–105.[CrossRef]
  16. Van Oostrom AJ, Van Wijk J, Cabezaz MC. Lipaemia, inflammation and atherosclerosis: novel opportunities in the understanding and treatment of atherosclerosis. Drugs (2004) 64:19–41.[CrossRef][Web of Science][Medline]
  17. Grundy SM, Howard B, Smith S, Eckel R, Redberg R, Borrow Ro. Prevention conference VI. Diabetes and cardiovascular disease. Executive summary. Conference proceeding of health care professionals from a special writing group of the American Heart Association (2002) 105:2231–9. Circulation.
  18. Greenland P, Abrams J, Aurigemma GP, et al. Prevention conference V, Beyond secondary prevention; identifying the high risk patients for primary prevention by non-invasive tests of atherosclerotic burden. Circulation (2000) 101:16–22.
  19. Lee AJ, Price JF, Russell MJ, Smith FB, van Wijk MC, Fowkes FG. Improved prediction of fatal myocardial infarction using the ankle brschial index in addition to conventional risk factors: the Edinburgh artery Study. Circulation (2004) 110:3075–80.[Abstract/Free Full Text]
  20. Doobay AV, Anand SS. Sensitivity and specificity of the ankle brachial index to predict future cardiovascular outcome: a systematicc review. Arterioscler Thromb Vasc Biol (2005) 25:1463–9.[Abstract/Free Full Text]
  21. Zheng G, Sharrett AR, Chambers IE, et al. Association of ankle-brachial index with clinical coronary heart disease, stroke and preclinical carotid and popliteal atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis (1997) 131:115–25.[CrossRef][Web of Science][Medline]
  22. Ouriel K, Zarins CK. Doppler ankle pressure: an evaluation of three methods of expression. (1982) 117:1297–300.
  23. Hiatt WR. Medical treatment of peripheral arterial disease and claudication. N Engl J Med (2001) 344:1608–21.[Free Full Text]
  24. Ooyanagi R, Fuse S, Tomita H, et al. Pulse wave velocity and ankle brachial index in patients with Kawasaki disease. Pediatr Int (2004) 46:398–402.[CrossRef][Web of Science][Medline]
Submitted 10 October 2007; revised version accepted 28 March 2008.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Rheumatology (Oxford)Home page
A. N. C. Santana
Circulating endothelial progenitor cells in ANCA-associated vasculitis: the light at the end of the tunnel?
Rheumatology, October 1, 2009; 48(10): 1183 - 1184.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
47/7/1058    most recent
ken155v1
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 Sangle, S. R.
Right arrow Articles by D'Cruz, D. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sangle, S. R.
Right arrow Articles by D'Cruz, D. P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?