We thank Zagura et al.1 for their research on the metabolomic signature of arterial stiffness in male patients with peripheral artery disease (PAD), which was reported recently in this journal. Aortic stiffness has commonly been estimated non-invasively using the carotid-femoral pulse wave velocity (cfPWV) after recording the pulse wave in these two vascular sites via tonometry. This method has been shown to be a reliable marker of aortic stiffness and a good prognostic marker for cardiovascular events in population studies.2, 3 However, we would like to warn the scientific community on the pitfalls of aortic stiffness estimation using this method in patients with PAD.

PAD patients frequently have aortic atherosclerotic disease, and aortic stiffness has been shown to be increased in these patients.4, 5 Patients with PAD are at an increased risk of cardiovascular events and mortality,6, 7 with a higher risk in case of proximal disease.8

However, patients with proximal (aorto-iliac) PAD may have an inaccurate estimation of aortic PWV.

Using the same sphygmocor machine (AtCor Medical, Sydney, New South Wales, Australia) as Zagura et al.,1 we studied the cfPWV in 76 patients hospitalized for PAD at our institution without clinical history of coronary artery disease and compared them with 86 patients hospitalized during the same period for severe coronary artery disease (CAD) requiring coronary bypass grafting. Patients with CAD were included after verifying that they had no PAD, as confirmed by a normal ankle-brachial index (>1.0). Our study sought to compare aortic stiffness in CAD patients with that in PAD patients and to investigate whether cfPWV was prognostic in the latter group by assessing mortality, cardiovascular events and limb amputations.

The general characteristics of the two patient groups are reported in the Table 1. Lower body mass index and higher rates of diabetes were observed in PAD patients; other general data did not significantly differ between groups. Peripheral pulse pressure was higher in patients with PAD, whereas central pressures were similar overall. A higher cfPWV and augmentation index were observed in patients with PAD compared with those with CAD, confirming previous reports on heart-femoral PWV.9

Table 1 Characteristics of patients with PAD and CAD in our study
Full size table

However, lower cfPWV was observed in PAD patients who had aorto-iliac disease (n=23, cfPWV=9.5±2.5 m s−1) compared with those without aorto-iliac disease (n=53, cfPWV=11.8±3.9 m s−1, P=0.03) based on imaging assessments. This difference remained significant after adjusting for risk factors and heart rate. In addition, after a follow-up of 10.5±4.5 months, no significant association between PWV and outcome in PAD patients was observed after univariate and multivariate analyses, whereas PWV was predictive of events in CAD patients.

Our results were initially surprising because when using a similar method, we found that cfPWV was a prognostic marker in CAD patients but not in PAD patients. However, these preliminary results require further confirmation with a larger cohort and a longer follow-up period. Nonetheless, the slower PWV in case of proximal PAD is counterintuitive because more stiffened arteries in the trajectory of pulse waves arriving at the femoral site would be expected in patients with aorto-iliac disease than in patients with more distal disease.

We believe that measuring cfPWV via tonometry is flawed as severe lesions disturb the physiological process leading to the propagation of PWV. As estimated by the Moens and Korteweg equation,10 PWV depends on not only arterial wall stiffness but also on arterial diameter, and arterial diameter is strongly affected by stenotic lesions and arterial remodeling. The presence of an abdominal aortic aneurysm is common and may affect cfPWV.11 In addition, collateral circulation may develop in these cases, with reinjection of the blood flow downstream of the stenotic lesion, which is also involved in PWV perturbation.

However, we advocate avoiding tonometric methods to assess cfPWV in patients with severe PAD and suggest other methods to estimate aortic stiffness that do record the lower-extremities pulse.12, 13