Intro: Welcome to UAB MedCast, a continuing education podcast for medical professionals. Providing knowledge that is moving medicine forward. Here's Melanie Cole.

Melanie Cole, MS (Host): Welcome to UAB MedCast. I'm Melanie Cole. And today, we're highlighting women and aortic disease. Joining me is Dr. Sasha Still. She's an Assistant Professor in the Division of Cardiothoracic Surgery at UAB Medicine. Dr. Still, it's a pleasure to have you join us today. I'd like you to start by telling us a little bit about aortic disease, what encompasses these disorders. Just give us an overview.

Sasha Still, MD: Great. Well, thank you for having me on to talk about and discuss this complex topic of women and aortic disease. What do we mean by aortic disease? There are two main problems involving the aorta, and one is aneurysm or an abnormal dilation or dissection or a tear within the layers of the aorta. These issues can involve any part of the aorta which extends from the heart, that area known as the aortic root, all the way down to the iliac artery bifurcation. As a cardiac surgeon, I manage mainly the aorta above the level of the diaphragm, that is the vessel within the chest cavity.

Because of aortic disease is multifactorial, causes may be congenital, so connective tissue diseases; degenerative, and what I mean by that is age-related wear and tear, also related to atherosclerosis, hypertension, smoking, inflammatory, and then infectious causes.

Now, regardless of the cause, aortic aneurysm rupture, dissection, so the emergency pathologies can be lethal. And in fact, in 2019, aortic disease led to almost 10,000 deaths nationwide. It's very likely that aortic disease overall affects women and men equally. However, historically, because of the underrepresentation of women in studies and clinical trials, it has been demonstrated to affect men more. However, it's probably more similar.

Melanie Cole, MS: So then, let's speak about how women specifically get diagnosed. What do you do differently for women as you're looking at the course of this disease?

Sasha Still, MD: This is a very interesting question. And that's because within the aortic surgery guidelines, there is nothing that is done differently in terms of women. I'm not talking about pregnant females, I'm talking about women with aortic disease who are not pregnant. That being said, it is well known that there are significant differences between men and women in terms of presentation, severity, as well as even surgical outcomes of aortic disease.

So, first, I'll talk about presentation. Women presenting with aortic disease are generally older on average. In fact, upwards towards 10 years older when they're diagnosed. They also exhibit higher rates of dilation, which has been shown in various studies up to two to three times more higher rate of expansion compared to men of those with either degenerative or heritable aortic disease.

In terms of aortic dissection, women also tend to present less frequently within the first six to 24 hours of symptom onset. And this is very important, a tear within the aorta, especially the ascending aorta, so an aortic dissection, it requires an emergency surgery to prevent death. So if women present later, they're likely going to have potentially a higher mortality rate regardless of the timing of the operation.

Melanie Cole, MS: Dr. Still, so tell us a little bit about some of the sex-based differences in the outcomes that you see.

Sasha Still, MD: First, I'll talk about published data and then we can talk about institutional outcomes that have been evaluated thus far. Nationally published studies demonstrate that women have upwards towards a 10% higher mortality of those who undergo repair of an acute type aortic dissection. Women have also been shown to have a three-fold increased risk of dissection or rupture compared to men. That's just in general.

In addition to that, both in the setting of repair of a type A or type B dissection, either using open or endovascular stenting, women have still demonstrated worse perioperative outcomes, including in-hospital mortality. So then, this begs the question, why do women have a higher risk of mortality? Is it because they have a higher, more aggressive pathology? Is it due to the fact that they have a higher rate of expansion? Is it because they percent with older age? We really don't know. We can only infer based on the multitude of longitudinal series that have been performed.

Undoubtedly, there is a biochemical basis of sex-based differences in aortic disease. First, we have to remember that our bodies are continually aging. There is normal vascular aging that occurs, which leads to an increase in the diameter of the aorta, in the length of the aorta, an increased level of stiffness, as well as decreased elasticity, in the setting of aging and oxidative stress, as well as altered metabolism.

Studies looking at the biochemical basis of aortic disease have demonstrated that women have higher rates of metalloproteinase activity as well as decreased activity of proteinase inhibitors. So, what this means is that women have a greater amount or a greater level of remodeling of their aorta, which can predispose them to worsening aortic disease at the time of presentation.

In addition to that, as women age, they go through menopause, which decreases the level of estrogen within the body. Estrogen itself has been associated with protective effects against atherosclerosis and overall endothelial dysfunction and, in addition to this, increases the level of elastin-to-collagen ratio in certain in vitro studies. This being said, once a woman has the normal hormonal changes moving through menopause, women may exhibit a higher risk of metalloproteinase activity and a decreased activity rate of proteinase inhibitors, meaning that there is more extracellular matrix remodeling that occur in women's blood vessels. This could ultimately predispose them to more aggressive pathology, as well as higher rates of endothelial dysfunction which predispose worse disease.

In addition to that, women have specific neurohormonal responses due to the fact that they have reproductive years. Increasing levels of estrogen are actually protective against atherosclerosis and endothelial dysfunction, as well as Increase the level of elastin within the blood vessels as demonstrated in in vitro studies. Once a woman undergoes menopause, decreasing levels of estrogen could adversely affect blood vessel remodeling leading to a higher rate of aortic disease requiring intervention later in life.

Melanie Cole, MS: So based on all this information, Dr. Still, what are some of the latest surgical and non-surgical treatment options available for women? How do you work with women to discuss these treatment options?

Sasha Still, MD: First and foremost, the best treatment is prevention. Abstaining from smoking, good blood pressure management, understanding when hypertension exists, regular doctor's visits in the setting of medical illness, all of those preventative measures help mitigate the risk of aortic disease.

In terms of surgical treatments, surgery for aortic disease is individualized patient by patient. Surgical management of aortic disease is individualized patient by patient. This is a reason why complex aortic disease should be treated in major aortic centers. Because there is no specific guideline in terms of managing the risk associated with the female sex, cardiac surgeons need to be mindful of the higher risk of more aggressive pathology and the higher risk of perioperative complications in order to improve outcomes over time.

Melanie Cole, MS: I'd like you to speak about the multidisciplinary approach that's really important for these women, these patients, because as we look at the lifestyle changes that a woman can implement to reduce their risk of developing aortic disease, Dr. Still, how do you work with other providers to help these women implement some of those lifestyle changes? Because I imagine there's plenty of providers involved.

Sasha Still, MD: When a woman is evaluated for aortic disease and is shown to have aortic disease, it is very important to ensure good surveillance. And by that, I mean, imaging surveillance of the aorta to monitor it for changes, expansion, as well as symptoms. Women, similar to the setting of a myocardial infarction or heart attack, may present with atypical symptoms that lead to a delayed diagnosis.

It is important to consider aortic disease, a chronic illness that requires multidisciplinary follow up and surveillance. Aortic disease never goes away. It requires communication, as well as communication with other providers, including primary care doctors and cardiologists, to ensure primary prevention is taking place, blood pressure is controlled, and other medical illnesses that could increase the risk of an aortic-related complication are being dealt with.

It is important to note that the most important aspect of managing a patient with aortic disease is to mitigate risk. There are three main ways to do that. One, focus on primary prevention at the primary care level. Two, ensure good surveillance and ongoing radiographic follow up to ensure there are no major changes that would require a surgical intervention be done sooner rather than later. And three, taking serious any new manifestation of patient symptoms.

Melanie Cole, MS: Thank you so much, Dr. Still, for joining us today and sharing your incredible expertise on this topic. Thank you again. And for more information, please visit our website at uabmedicine.org/physician. That concludes this episode of UAB MedCast. I'm Melanie Cole. Thanks so much for joining us today.