Hello, my name is Kim Smolderen. I'm an Associate Professor at Yale University with the section of cardiovascular medicine, and my background is Clinical Psychologist and Outcomes Researcher.

What is the estimated global prevalence of peripheral artery disease (PAD), and what is its defining characteristic in terms of pain presentation?

So, globally, PAD is prevalent in over 220 million individuals. And we know that its prevalence is increasing both in high, middle, and low-income countries, not only due to aging populations, but also due to the increased prevalence of obesity and diabetes.

Patients with PAD can present in its asymptomatic form — so they will notice that if they have reduced blood flow and a non-invasive test called the ankle-brachial index, if they develop symptoms, they might experience pain during walking that is resolved upon rest. Others may also experience atypical symptoms that do not follow that pattern. And in very advanced stages of PAD, people may also experience ischemic rest pain, meaning that they not only experience pain while walking, but also during the night and during the day more frequently.

What we often see in patients with PAD though is that this pain is not episodic, it has a chronic flavor often, and people are dealing with this pain more than six months before they really get the right treatment. And even if they get treatment, pain tends to come back and becomes a chronic issue in many cases.

What treatment options are available for pain management in PAD?

Right now, in early-stage PAD, the emphasis is on cardiovascular risk management and to resolve the pain. Supervised exercise is recommended, which means that people are instructed to walk through the pain and increase their walking regimen at least three times a week for at least 30 minutes, where they systematically try and walk through the pain and increase the pain-free walking distance, and the maximum walking distance is what we call that. And so we know this can improve the functioning and prolong the length or the distance that people can walk.

If such programmes are not successful, it can also be considered to offer an invasive procedure where an endovascular procedure is considered, and in some scenarios surgical bypass where the blockage can be removed and increased blood flow can be accomplished through that procedure. And that might also result in pain relief. There are medications for claudication pain: pletal. The success may depend on individual factors.

And then more and more, at least in the US, we notice that people do use a lot of pain medications and some of those medications include opioids. And that is a concerning evolution that we need to study more because we know that, of course, opioids are associated with increased risk of dependency, also increased risk of complications in this vascular population.

So given the chronic nature of the pain, we're really hoping with this paper to highlight non-pharmacological pain management options that are used in other chronic pain conditions too, such as there are exposure-based therapies, but also mindfulness-based interventions, or cognitive behavioral therapy interventions that really offer people strategies to modify their behaviors and come with problem-solving solutions for dealing with the pain as well as changing their cognitions associated with pain.

What are the key takeaways from the AHA scientific statement

Well, we really spend some time discussing how comorbidities in this population can make it difficult to assess pain in PAD. Oftentimes people also have diabetes, neuropathy or osteoarthritis and that really can change people's pain perception or mask symptoms.

Secondly, I think it is important to realize that psychological factors such as depression and anxiety can impact the experience of pain in this population. Pain is processed not at the level of where the ischemia is, so that's why the role of emotional factors in cognition play a big role in the intensity of the pain experience. So that's why we recommend a comprehensive assessment that takes a biopsychosocial approach and really opening our mindset for non-pharmacological solutions and taking the problem of pain from a multidisciplinary perspective so that people can have tailored solutions for the pain experience in PAD.

I think a lot of research mechanistically is still necessary in this population that can inform tailored treatment development for this population, as is the case for other chronic pain conditions.

Where are the knowledge or treatment gaps?

Yeah, I would say characterising the pain that people experience: who is most at risk? Are there subpopulations that are at risk? Is it predominantly younger, older? What is their risk profile? So we really don't have a good sense of that. And characterising the pain experience in a more longitudinal way requires more data collection as well.

We now have quality of life information but not detailed pain assessment information, so along with the phenotyping of the risk profiles, that would be necessary. And then mechanistically, I think we know very little about influences that impact the pain experience in this population. So that research needs to be further developed. And then following from that mechanistic research, mind-body interventions that could be used to address the pain and alleviate some of that pain. And how we can redirect people from using opioids as a resort to pain relief is also an area that requires more work in terms of research, but also intervention space, I would say.

What further research is required in order to address this?

I think that overlaps with the gaps. So the mechanistic research, I would imagine we would look at the role of inflammation, the role of the sympathetic nervous system and the overactivation and how that impacts the pain experience in this population. Also diagnostic methods to really further characterise the nature of the ischemic problem, whether microcirculation is involved and versus the role of macrocirculation and how those play a role in people's pain experience. I feel like that's an area that needs further work as well.

And then in the realm of implementation science, testing some of the evidence-based interventions for chronic pain management in a non-pharmacological way, such as mindfulness-based interventions, cognitive behavioral therapy interventions, and exposure-based methods are worthwhile translating to this population as well and tested out in the real world.