Thank you all very much for the opportunity to be here. It's honestly really exciting to be a vascular surgeon at a cardiology meeting and this is something that I really care about a lot and I appreciate you taking the time to invite me here. Now, as interventionalist, not one size fits all, I started preparing this talk to talk about the difference in actual interventions. But as you all know, disparities are much more complicated than that and PAD is always much more complicated than what meets the eye. So therefore, I'll spend some time going through prevention treatment and outcome disparities. So by way of prevention, and thank you for that really nice setup in the previous talk, awareness of PAD in both sexes is really low and I honestly think with more interest in cardiologists and doing peripheral work, there are a lot more providers who know about the disease and are paying attention to the disease and are advocating for the disease and that helps these patients. But in terms of gender, there's really poor epidemiologic data about gender and age-specific prevalence. There was a meta-analysis that's sponsored by the AHA that showed that women were more likely than men to have PAD. This should not be surprising because PAD increases with age and women live longer and are more likely to have PAD in post-menopausal years. That being said, we also think of PAD as being a men's smoking disease. Additionally, the cardiovascular morbidity and mortality has not really been studied by gender and so of course we know that most PAD patients end up dying an untimely death due to an MI or other cardiovascular event, but we don't really know the risk in women specifically. The second issue is that there's a huge knowledge gap in the risk factors and paying attention to patients who actually come into the clinic with complaints. There's been a slower decline in smoking rates among women and interestingly, there's more smoking-related PAD in women compared to men, but also women non-smokers are more likely to get PAD than men non-smokers. Also, diabetes, obesity, and age play an outsized role in development of PAD in women compared to men and when women present, it's usually at later stage with shorter walking speeds, slower walking distances, atypical symptoms or twice as more likely to be present and so perhaps there's a larger latent phase between the development of PAD and the actual symptoms in the presentation, so therefore, patients presenting with CLTI is much more common in women. Third issue, there's a real diagnostic dilemma. We know that women have a lower mean ABI and honest question here, should we have different diagnostic thresholds? I don't know. This hasn't been thought about. Women have smaller vessels. Does that mean that all of the other tests that we routinely do need different parameters for what normal is in women? And the vascular biology in general has just not really been examined. We don't really know about different risk factors for developing the inflammatory markers. We do know that hormone replacement therapy is not protective, but clearly there's a lot going on that's just beyond estrogen. And the other issue is that most basic and translational science is actually done in male lab animals and so the gender disparity is way upstream of the actual clinical trials and clinical patients that we see. So moving on to treatment, first issue here is that females get much less optimal medical therapy. They're less likely to get referred to vascular specialists and are less likely to be prescribed antiplatelets and statins. We know that aspirin has a less beneficial effect in preventing cardiac events in women compared to men, and women are more likely to have adverse events from statins, but on top of that, we're not even prescribing 1A guideline recommended medications, and this is something that's even worse amongst CLTI patients. And then supervised exercise therapy, of course, is extremely important, especially in atypical symptoms and claudicants, but there's no gender-based analysis in any of the recent randomized controlled trials supporting exercise. When we actually do make the diagnosis, we end up treating women less frequently than men, and interestingly, this is true for aneurysms as well, even though there's much more objective criteria about when aortic aneurysms ought to be treated. The incidence rate ratio of females versus males getting treated for PAD is only 0.69% in a national database, and this under treatment of women is consistent over time. Again, you can see for both aneurysms and PAD, the red bars here are women, and even as we've gotten more and more attention to the needs of these populations over time, we haven't really changed our treatment practices. So moving along to outcomes, this is where it gets really dicey, because most clinical trials have all of their results based on males. All of the RCTs from the last 12 years in PAD, there's 68 of them, which is pretty cool. Most of them industry-sponsored, but also some from the VA and the NIH. But overall, the number of females participating, so what the expected prevalence of PAD is in females, the PPR, or participation to prevalence ratio, is only 0.65, meaning that for every 100 men enrolled, there's only 65 women enrolled in clinical trials when it should be equal one-to-one. And of course, this has not improved over time. It's also no difference depending on the funding source, even though it's actually a law to have equal gender representation in clinical trials funded by the NIH. So we turn to single-center institutional studies, and there's very few that have actually done a gender-based analysis. This is an old paper, but it's one of the only ones that exist out there. This is a single-center study from UCLA that showed there's equivalent patency in femoral interventions despite women presenting with an increased severity of disease. A group out of New York also showed that percutaneous tibial interventions was actually better patency rates at a year in women compared to men. And then this is another. This is a couple of centers from Europe who presented this data. For pure metal stents, the patency was similar, and that would be what was reflected in that paper from 2008 that I shared with you, but women did much more poorly with drug-eluting stents. I went to the literature to try to suss this out a little bit better, and obviously all of you have been very involved in drug-eluting technology and bringing that to the peripheral space, but none of the trials that I could find actually had a specific gender-based analysis. So we don't actually know what's going on here. But when women do get treated, they get treated and they have reasonable patency, but they do have higher access complications. This is femoral punctures here, hematomas are more common, occlusions to the access site and complications requiring admission. I don't have the data to show you, but it's also been shown that women are less likely to have a successful fetal-first approach. And if you can get through the procedure and you get these patients on optimal medical therapy, women in the long term at one year are more likely to have bleeding complications. And this is mainly related to GI bleeds, but then also spontaneous hematomas. They're more likely to need blood transfusions compared to men, but interestingly, despite this, in this Medicare claims cohort, men are more likely to die at a year. Interestingly here, women are also more likely to have DVTs in the same Medicare cohort, and I want to draw attention to this because there's a really high incidence of DVT after percutaneous intervention in men and women. Up to 7% of these patients have a DVT at one year and 4% within 30 days of your procedure. I think this just indicates that we don't really know what's going on with vascular biology in men or women, but women are at higher risk of both bleeding and clotting, so surely there's something that we need to study more. And so in summary here, women's cardiovascular health program should always include PAD, and you guys are really helping tip the scales there. But on top of that, we've got to do a lot better work with diagnostic tool assessment that should include gender-based samples. We need to evaluate sensitivity and specificity for females in all of the tests we routinely use. We need to examine gender biases and gender-specific differences in biology and the basic science that leads up to the clinical trials, and we need trials that actually examine the efficacy of our drugs and devices for females specifically. And then somehow amazingly, despite presenting later, being on less optimal medical therapy, suffering more short- and long-term complications, pain C rates for percutaneous intervention are similar. And so whatever the secret sauce that's floating around in women's blood vessels is, we should figure it out, because then men may have good results too. So thank you very much.

vascular surgeon

peripheral artery disease

disparities

women's cardiovascular health

medical therapy