European Heart Journal Advance Access originally published online on May 6, 2007
European Heart Journal 2007 28(15):1910; doi:10.1093/eurheartj/ehm147
Endothelial dysfunction and peripheral arterial disease
Division of Cardiology
Innsbruck Medical University
Anichstrasse 35
A-6020 Innsbruck
Austria
Division of Cardiology
Innsbruck Medical University
Innsbruck
Austria
Division of Cardiology
Innsbruck Medical University
Innsbruck
Austria
Division of Cardiology
Innsbruck Medical University
Innsbruck
Austria
Tel: +43 51250424118 Fax: +43 51250423264 E-mail address: matthias.frick{at}i-med.ac.at
We read with interest the study of Loffredo et al. investigating the association of oxidative stress and endothelial function in patients with peripheral arterial disease (PAD). The authors demonstrated that flow-mediated vasodilation (FMD) of the brachial artery was significantly lower in patients with PAD compared with controls, whereas 8-hydroxy-2-deoxy-2-deoxyguanosine (a marker of oxidative stress) was higher in PAD patients.1 In addition, infusion of propionyl-L-carnitine increased FMD in PAD patients. Despite a thorough study design, in our opinion, some important issues have not been addressed by the authors.
In the Framingham cohort (one of the largest population ever investigated using FMD), Benjamin et al.2 have reported a mean FMD value of 3.3 ± 3.0 and 2.4 ± 2.4% in women and men, respectively. In the present study, FMD was 6.7 ± 3.0% in PAD patients and even 10.3 ± 2.1% in controls. How do the authors explain these differences between FMD values? In our opinion, the present data support the variability in FMD values and the great overlap between groups.3
According to Table 1, arterial hypertension, diabetes mellitus, and the percentage of ex-smokers were higher in PAD patients. These risk factors have an important influence on FMD results. Therefore, on the basis of the present data and univariate statistical analyses, one cannot conclude that endothelial function is significantly reduced in PAD.
Additionally, not all studies have demonstrated a positive correlation between FMD and cardiovascular events. In fact, two studies with the greatest number of patients were not able to show a significant relation between peripheral endothelial function and cardiovascular events.4,5 Consequently, one could argue that an improvement in FMD using propionyl-L-carnitine has limited relevance.
The authors report that they have assessed intima-media thickness of the carotid artery. However, no results of these measurements are provided. It would be interesting to see whether intima-media thickness was different between controls and patients with PAD. If yes, it would further support the theory that FMD more closely reflects risk factor burden, whereas intima-media thickness is associated with prevalent atherosclerotic disease.
References
- Loffredo L, Marcoccia A, Pignatelli P, Andreozzi P, Borgia MC, Cangemi R, Chiarotti F, Violi F. Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease. Eur Heart J (2007) 28:608–612.
[Abstract/Free Full Text] - Benjamin EJ, Larson MG, Keyes MJ, Mitchell GF, Vasan RS, Keaney JF Jr, Lehman BT, Fan S, Osypiuk E, Vita JA. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study. Circulation (2004) 109:613–619.
[Abstract/Free Full Text] - Bots ML, Westerink J, Rabelink TJ, de Koning EJ. Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response. Eur Heart J (2005) 26:363–368.
[Abstract/Free Full Text] - Fathi R, Haluska B, Isbel N, Short L, Marwick TH. The relative importance of vascular structure and function in predicting cardiovascular events. J Am Coll Cardiol (2004) 43:616–623.
[Abstract/Free Full Text] - Frick M, Suessenbacher A, Alber HF, Dichtl W, Ulmer H, Pachinger O, Weidinger F. Prognostic value of brachial artery endothelial function and wall thickness. J Am Coll Cardiol (2005) 46:1006–1010.
[Abstract/Free Full Text]
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