Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

Open Badges Editorial

Peripheral arterial disease in polymyalgia rheumatica

Frances A Borg and Bhaskar Dasgupta*

Author Affiliations

Department of Rheumatology, Southend University Hospital, Prittlewell Chase, Westcliffe-on-Sea, Essex SS0 0RY, UK

For all author emails, please log on.

Arthritis Research & Therapy 2009, 11:111  doi:10.1186/ar2685

See related research article by Warrington et al.,

The electronic version of this article is the complete one and can be found online at:

Published:20 May 2009

© 2009 BioMed Central Ltd


Patients with polymyalgia rheumatica have been shown to have an increased risk of peripheral arterial disease on longitudinal follow-up. Possible explanations for this include premature atherosclerosis related to chronic inflammation, as with other inflammatory rheumatological conditions. Alternatively, polymyalgia rheumatica can be associated with vasculitis, even in the absence of clinical giant cell arteritis, and peripheral vascular disease may represent subclinical vasculitis. Further work is required to elucidate the reasons for this increased risk. Currently, it would remain reasonable to aggressively control modifiable atherosclerotic risk factors.


Warrington and colleagues report an increased risk of peripheral arterial disease (PAD) in patients with polymyalgia rheumatica (PMR) compared with matched controls [1]. They found that 38 out of 353 PMR patients developed PAD versus 28 out of 705 control subjects over a median follow-up of 11 years (hazard ratio adjusted for conventional cardiovascular risk factors = 2.5, 95% confidence interval = 1.53 to 4.08). The same centre previously reported an increased likelihood of coronary and cerebrovascular disease in PMR [2]. The authors speculate that possible explanations for this are premature atherosclerosis related to inflammation, or the presence of subclinical vasculitis.

Premature atherosclerosis and autoimmune inflammatory disease

An increased risk of cardiovascular disease is well established in inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis [3], over and above the risk explained by conventional cardiovascular risk factors. This increase appears to be related to chronic inflammation, with elevated levels of C-reactive protein associated with increased risk of cardiovascular disease, including PAD [4]. Atherosclerosis itself can be explained as an inflammatory process, with proinflammatory cytokines key in the development of endothelial dysfunction and the progression of atheromatous lesions.

Homocysteine has been implicated in the development of atherosclerotic disease in the general population, and in patients with systemic lupus erythematosus and rheumatoid arthritis. Levels of homocysteine have also been found to be elevated in PMR [5].

Although Warrington and colleagues found no correlation between PAD and PMR-related disease characteristics or the erythrocyte sedimentation rate at diagnosis, patients with PMR were at 2.5-fold increased risk even when adjusted for conventional risk factors for atherosclerosis [1]. This lack of association may simply reflect the limited statistical power of the study, which is acknowledged by the authors. Symptomatic PAD was an infrequent occurrence, seen in 38 out of 353 patients with PMR and in 28 out of 705 control patients. Atheroma mediated by chronic inflammation may still explain the elevated PAD risk since chronic inflammation in PMR would not be captured by the erythrocyte sedimentation rate at diagnosis. A previous study from the Mayo Clinic demonstrated an association between sustained elevation in the erythrocyte sedimentation rate (>3 recorded measurements >60 mm/hour at least 30 days apart) and cardiovascular death in rheumatoid arthritis. Measures such as this or the time spent with clinically active disease would better reflect chronic inflammation [6]. C-reactive protein may be a better marker of cardiovascular risk in PMR, as this association is well demonstrated in other chronic diseases, both rheumatological and non-rheumatological.

In the related condition of giant cell arteritis (GCA), increased cardiovascular mortality was associated with both the erythrocyte sedimentation rate and the steroid dose, suggesting proatherogenic effects of high-dose glucocorticoids and/or uncontrolled inflammation [7]. The higher PAD risk in PMR found by Warrington and colleagues may also be explained by steroid use, although lower doses and a smaller sample size may have led to the observed lack of association [1]. This lower steroid dose may explain why, in a previous study from the same centre, glucorticoid use was not associated with increased risk of coronary, peripheral vascular or cerebrovascular disease (hazard ratio = 0.58 to 0.85) [8].

Subclinical vasculitis

Arteritis has not been demonstrated in premature cardiovascular disease in systemic lupus erythematosus or rheumatoid arthritis on postmortem examination [3]. Arteritis remains a possibility, however, in PMR and GCA. A study of biopsyproven GCA demonstrated no increase in carotid intimal thickness, so atherosclerosis alone does not explain the increased cardiovascular mortality seen in GCA [9].

Although Warrington and colleagues did not find that the presence of clinical GCA correlated with PAD, the sample size was small. Cranial GCA has also been shown to be negatively associated with large vessel involvement [10]. Moosig and colleagues demonstrated large artery (aortic, subclavian, and axillary) uptake on positron emission tomography in 12 out of 13 patients with active PMR, but no clinical evidence of GCA [11]. Proinflammatory macrophage and T-cell-derived cytokine mRNA profiles similar to that of GCA have been found in histologically normal temporal artery specimens from patients with isolated PMR [12]. Subclinical ongoing large vessel vasculitis can therefore occur and may contribute to the increased risk of PAD in isolated PMR.


The interesting findings of Warrington and colleagues add further weight to the association between vascular disease and inflammatory rheumatological conditions. In PMR this possibly relates to inflammation-related atherosclerosis, or to subclinical arteritis. Further longitudinal observational cohort studies including structured documentation of disease activity, cumulative steroid dosages, and C-reactive protein levels are required to unravel the multiplicity of factors and interactions that may contribute to adverse vascular events in this condition.


GCR: giant cell arteritis; PAD: peripheral arterial disease; PMR: polymyalgia rheumatica.

Competing interests

The authors declare that they have no competing interests.


  1. Warrington KJ, Jarpa E, Crowson CS, Cooper LT, Hunder GG, Matteson EL, Gabriel SE: Increased risk of peripheral arterial disease in polymyalgia rheumatica: a population-based cohort study.

    Arthritis Res Ther 2009, 11:R50. PubMed Abstract | BioMed Central Full Text OpenURL

  2. Maradit Kremers H, Reinalda MS, Crowson CS, Zinsmeister AR, Hunder GG, Gabriel SE: Direct medical costs of polymyalgia rheumatica.

    Arthritis Rheum 2005, 53:578-584. PubMed Abstract | Publisher Full Text OpenURL

  3. Manzi S, Wasko MCM: Inflammation-mediated rheumatic diseases and atherosclerosis.

    Ann Rheum Dis 2000, 59:321-325. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  4. Ridker PM, Cushman M, Stamfer MJ, Tracy RP, Hennekens CH: Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease.

    Circulation 1998, 97:425-428. PubMed Abstract | Publisher Full Text OpenURL

  5. Martinez-Taboada VM, Bartolome MJ, Fernandez-Gonzalez MD, Blanco R, Rodriguez-Valverde V, Lopez-Hoyos M: Homocysteine levels in polymyalgia rheumatica and giant cell arteritis: influence of corticosteroid therapy.

    Rheumatology 2003, 42:1055-1061. PubMed Abstract | Publisher Full Text OpenURL

  6. Maradit Kremers H, Nicola LJ, Crowson CS, Ballman KV, Gabriel SE: Cardiovascular death in rheumatoid arthritis.

    Arthritis Rheum 2005, 52:722-732. PubMed Abstract | Publisher Full Text OpenURL

  7. Uddhammar A, Eriksson A-L, Nyström L, Stenling R, Rantapää-Dahlqvist S: Increased mortality due to cardiovascular disease in patients with giant cell arteritis in Northern Sweden.

    J Rheumatol 2002, 29:737-742. PubMed Abstract | Publisher Full Text OpenURL

  8. Maradit Kremers H, Reinalda MS, Crowson CS, Davis JM, Hunder GG, Gabriel SE: Glucocorticoids and cardiovascular and cerebrovascular events in polymyalgia rheumatica.

    Arthritis Rheum 2007, 57:279-286. PubMed Abstract | Publisher Full Text OpenURL

  9. Gonzalez-Juanatey C, Lopez-Diaz MJ, Martin J, Llorca J, Gonzalez-Gay MA: Atherosclerosis in patients with biopsy-proven giant cell arteritis.

    Arthritis Rheum 2007, 57:1481-1486. PubMed Abstract | Publisher Full Text OpenURL

  10. Nuenninghoff DM, Hunder GG, Christianson TJH, McClelland RL, Matteson EL: Incidence and predictors of large-artery complication (aortic aneurysm, aortic dissection, and/or large-artery stenosis) in patients with giant cell arteritis.

    Arthritis Rheum 2003, 48:3522-3531. PubMed Abstract | Publisher Full Text OpenURL

  11. Moosig F, Czech N, Mehl C, Hanze E, Zeuner RA, Kneba M, Schroder JO: Correlation between 18-fluorodeoxyglucose accumulation in large vessels and serological markers of inflammation in polymyalgia rheumatica: a quantitative PET study.

    Ann Rheum Dis 2004, 63:870-873. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  12. Weyand CM, Hicok KC, Hunder GG, Goronzy JJ: Tissue cytokine patterns in patients with polymyalgia rheumatica and giant cell arteritis.

    Ann Int Med 1994, 121:484-491. PubMed Abstract | Publisher Full Text OpenURL