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To the Editors:

We are grateful for the comments of Vizzardi et al, which emphasize the fact that in RA patients, alterations in arterial wall properties resemble those observed in DM patients. In conjunction, Stamatelopoulos et al also demonstrated that preclinical atherosclerosis appears to be of comparable frequency and severity in patients with RA and DM (1).

Inflammation is considered to be a key player in endothelial dysfunction (2). In addition, impaired endothelium-dependent vasodilatation has been shown at the microvascular level during active disease (flare), which improved after inflammatory suppression with disease-modifying antirheumatic drugs or anti–tumor necrosis factor α therapy (3). However, the extent to which endothelial dysfunction contributes to arterial stiffening is not clear. Stiffening of the aorta results in an increased pulse wave velocity and systolic augmentation of central blood pressure. The latter increases LV mass, as well as risk of stroke, coronary artery disease, congestive heart failure, and sudden cardiac death. The observations of Vizzardi and colleagues fit with the hypothesis that inflammation may contribute to arterial stiffening and subsequently to an increased ventricular load.

However, it should be acknowledged that systemic and local inflammation may also lead directly to arterial stiffening by a variety of different mechanisms. By implication, a proinflammatory environment may lead to an influx of inflammatory cells in the arterial wall, where they may damage structural components. Inflammation may promote deposition of calcium within the arterial wall, resulting in stiffening (4). Inflammation is also associated with higher levels of matrix metalloproteinase 9, an enzyme capable of digesting elastin, which is the main elastic element of large arteries (5).

The striking concurrence of RA and CVD, equivalent to DM as a known and established CVD risk factor, poses a major public health challenge and significant burden for RA patients. Therefore, the findings of Vizzardi and colleagues are important because they emphasize the need for further research to disentangle the complex interplay between inflammation and the vasculature.

  • 1
    Stamatelopoulos KS, Kitas GD, Papamichael CM, Chryssohoou E, Kyrkou K, Georgiopoulos G, et al. Atherosclerosis in rheumatoid arthritis versus diabetes: a comparative study. Arterioscler Thromb Vasc Biol 2009; 29: 17028.
  • 2
    Maki-Petaja KM, Cheriyan J, Booth AD, Hall FC, Brown J, Wallace SM, et al. Inducible nitric oxide synthase activity is increased in patients with rheumatoid arthritis and contributes to endothelial dysfunction. Int J Cardiol 2008; 129: 399405.
  • 3
    Datta D, Ferrel WR, Sturrock RD, Jadhav ST, Sattar N. Inflammatory suppression rapidly attenuates microvascular dysfunction in rheumatoid arthritis. Atherosclerosis 2007; 192: 3915.
  • 4
    Abedin M, Tintut Y, Demer LL. Vascular calcification: mechanisms and clinical ramifications. Atheroscler Thromb Vasc Biol 2004; 24: 116170.
  • 5
    Yasmin, McEniery CM, Wallace S, Dakham Z, Pulsalkar P, Maki-Petaja K, et al. Matrix metalloproteinase-9 (MMP-9), MMP-2, and serum elastase activity are associated with systolic hypertension and arterial stiffness. Arterioscler Thromb Vasc Biol 2005; 25: 3728.

Mike J. L. Peters MD*, Alexandre E. Voskuyl MD, PhD*, Yvo M. Smulders MD, PhD*, Ben A. C. Dijkmans MD, PhD†, Michael T. Nurmohamed MD, PhD†, * VU University Medical Center, Amsterdam, The Netherlands, † VU University Medical Center, Jan van Breemen Institute, Amsterdam, The Netherlands, On behalf of the authors.