Peripheral Artery Disease and Aortic Stenosis: A Frequent and Challenging “Duo”

Aortic stenosis (AS) is the most common valvular heart disease in high-income countries, and its global burden is expected to rise with the aging of the population. ¹ The prognosis of AS is driven by the cardiac dysfunction^2,3 and by the associated clinical conditions, particularly in the early stages of cardiac damage. ⁴ Peripheral artery disease (PAD) has been frequently reported as a comorbidity in patients with severe AS and is independently associated with worse outcomes. ⁵ However, most available data come from studies of patients undergoing transcatheter aortic valve replacement (AVR), often involving older individuals at high surgical risk.^6,7

The study by Faure et al ⁸ addresses elegantly this gap of knowledge by focusing on patients with severe calcific AS referred for surgical AVR at Limoges University Hospital (France), over a 2-decade period (2000-2019). It provides long-term follow-up data (median 7.6 years). The prevalence of PAD in this cohort was reported at 8.9%, which is lower than the percentage derived from transcatheter AVR registries.^6,7 This discrepancy could be due to the younger age and lower comorbidity burden of the patients referred for surgical AVR, resulting in a lower prevalence of PAD compared to transcatheter AVR cohorts.

Interestingly, patients with PAD in this study exhibited less severe AS echocardiographic parameters compared to those without PAD. Specifically, the aortic valve area was larger (0.8 cm² [IQR: 0.70-0.90] vs 0.7 cm² [IQR: 0.60-0.80], P = .007) and the transvalvular mean gradient was lower (45.0 mm Hg [IQR: 39.0-55.0] vs 50.0 mm Hg [IQR: 42.0-60.0], P = .002). At first glance, this finding may seem counterintuitive, as one might expect PAD, with its association with higher atherosclerotic burden, to correlate with more severe calcific AS. However, the interplay between PAD and AS presents challenges (Figure 1).

Figure 1.

The complex interaction between PAD and AS.

First, the increased peripheral resistance typical of patients with PAD may lead to an underestimation of AS at echocardiography. This phenomenon has been observed in patients with altered peripheral resistances, where discordant echocardiographic AS severity parameters are more common—namely, a severely impaired aortic valve area despite gradients and velocities that fall within a nonsevere range, associated with preserved forward stroke volume.^9,10 Similarly, in patients with advanced PAD, as with those with uncontrolled hypertension, increased vascular stiffness may mask the true hemodynamic burden of stenosis, leading to an underestimation of AS severity. ⁹ Therefore, it is possible that patients with “very severe” AS might still be classified as having severe AS with slightly less impaired echocardiographic parameters.

Conversely, the significant symptomatic burden of severe AS may blunt clinical signs of PAD, particularly in patients with very severe AS. The reduced physical activity and limited mobility often seen in these patients may suppress typical PAD symptoms, such as intermittent claudication, contributing to the underdiagnosis of PAD in this population.

The association between PAD and less severe AS at the time of AVR might be due to patients being referred for surgery earlier, as symptoms may manifest sooner in the presence of PAD due to increased afterload from peripheral vascular disease. This additional vascular burden could also exacerbate adverse cardiac remodeling and extra-valvular cardiac damage.

Notably, the present study demonstrates a significant association between PAD and increased long-term mortality (adjusted hazard ratio, aHR = 1.62 [1.28-2.04], P < .0001). PAD was also associated with increased mortality within patients with coronary artery disease (HR = 1.92 [1.46–2.51], P < .0001).

AS, PAD, coronary artery disease, and cerebrovascular diseases could be all the clinical manifestations of atherosclerosis burden, despite being different in terms of pathophysiology. Thus, the more signs of atherosclerosis, the worse the burden and probably the worse the outcome, despite not all independently significant in the present study due to a small number of patients in certain groups.

The well-designed study by Faure et al ⁸ identifies PAD as a risk factor in patients with severe AS undergoing surgical AVR. It also reinforces the critical need for meticulous management of cardiovascular and modifiable risk factors associated with PAD and to intensify the medical surveillance in the follow-up following surgical AVR in these patients.