European Heart Journal Advance Access originally published online on May 6, 2007
European Heart Journal 2007 28(15):1910-1911; doi:10.1093/eurheartj/ehm148
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Endothelial dysfunction and peripheral arterial disease: reply
IV Clinica Medica
Experimental Medicine
Policlinico Umberto I
Università La Sapienza
Viale del Policlinico
Roma 00185
Italy
IV Clinica Medica, Policlinico Umberto I
Università La Sapienza
Roma
Italy
IV Clinica Medica, Policlinico Umberto I
Università La Sapienza
Roma
Italy
Tel: +39 06 4461933 Fax: +39 06 4940594 E-mail address: francesco.violi{at}uniroma1.it
We would like to thank Frick et al. for the comments related to our recent paper on endothelial dysfunction in patients with peripheral arterial disease (PAD).1 We found that PAD patients have a reduced flow-mediated dilation (FMD) with an inverse correlation between FMD and oxidative stress. Short-term treatment with an antioxidant reduced oxidative stress and increased nitric oxide (NO) generation simultaneously with FMD restoration, so suggesting that oxidative stress may be implicated in arterial dysfunction via interference with NO biosynthesis/degradation. The values of FMD observed in our study were in the same order of magnitude of other studies performed in this clinical setting.2,3 Thus, in a previous study performed in 88 PAD patients, Brevetti et al.3 found a median value of 7.3% (inter-quartile range 5.1–9.5) and 11.4% (9.3–12.9) in PAD and control group, respectively.3 Furthermore, in other clinical settings such as coronary artery disease (CAD), FMD values did not seem much different compared with those observed in our study. For instance, in a population without CAD, Frick et al.4 showed values close to 8%, which are much higher than those found in the Framingham cohort.5 The surprisingly very low values of FMD observed in the Framingham study are not easy to explain, but we cannot exclude that some differences in the methodology may account for it. For instance, in the Framingham study, more than 50% of patients performed a 6-minute walking test before the brachial artery study.
As outlined in our paper, patients with PAD have several risk factors, such as hypertension, dyslipidaemia, diabetes, and smoking habit, that could contribute to lower FMD independently from PAD, but the sample size did not permit to solve this issue. Larger sample size is, therefore, necessary to explore if these risk factors, alone or in combination, are determinant of low FMD or if PAD per se is independently associated with reduced arterial dysfunction.
The aim of our study was not to investigate the clinical relevance of arterial dysfunction in PAD population; therefore, the FMD restoration after antioxidant treatment should be regarded as an element in favour of the key role played by oxidative stress in reducing arterial dilation. It is of note, however, that in PAD patients arterial dysfunction seems to be associated with adverse cardiovascular complications,2,6 but we believe that further studies are necessary to validate these data. We agree with Frick et al. that the intima-media thickness (IMT) may be another important information to stratify the atherosclerotic risk in the PAD population. In our study, when compared with controls, patients with PAD had a significant higher carotid IMT (0.61 ± 0.10 vs. 0.86 ± 0.18 mm; P < 0.001), thus suggesting that in this clinical setting, structural and functional changes of the arterial wall co-exist. Clinical and therapeutic implications of these findings should be explored in the future.
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] - Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO, Vita JA. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol. (2003) 41:1769–1775.
[Abstract/Free Full Text] - Brevetti G, Silvestro A, Di Giacomo S, Bucur R, Di Donato A, Schiano V, Scopacasa F. Endothelial dysfunction in peripheral arterial disease is related to increase in plasma markers of inflammation and severity of peripheral circulatory impairment but not to classic risk factors and atherosclerotic burden. J Vasc Surg (2003) 38:374–379.[CrossRef][ISI][Medline]
- 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] - 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] - Brevetti G, Silvestro A, Schiano V, Chiariello M. Endothelial dysfunction and cardiovascular risk prediction in peripheral arterial disease: additive value of flow-mediated dilation to ankle-brachial pressure index. Circulation (2003) 108:2093–2098.
[Abstract/Free Full Text]
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