Cardiovascular Disease in Women From Pregnancy to Menopause

“I think that most cardiologists today are not asking their women patients any questions pertaining to their reproductive history. It is an important component and should be incorporated into our routine history and physical.”

Cath Lab Digest talks with Emily Lau, MD, MPH, about her ACC23/WCC presentation and research in women's cardiovascular disease risk. This episode of Cath Lab Conversations is also available on Spotify and Apple Podcasts!

The transcript below has been lightly edited for clarity.

Welcome to Cath Lab Conversations. I'm Cath Lab Digest 's Managing Editor, Rebecca Kapur. Today we're speaking with cardiologist Dr. Emily Lau, who is the Director of the Hormones & Cardiovascular Disease Clinic at Massachusetts General Hospital. Dr. Lau discusses her work in cardiovascular disease treatment needs in women from pregnancy to menopause. She presented her work at the American College of Cardiology's Annual Scientific Session together with the World Congress of Cardiology in New Orleans. Thank you for joining us.

Dr. Lau, what do you think about the current status of research into women's cardiovascular health?

I think that there's been such a growing recognition about the importance of women's cardiovascular disease that we really didn't even see just a handful of years ago. Women represent over 50% of our population and heart disease remains the number-one cause of death in women, and yet there's still so little awareness about this point. I'm just delighted that the ACC and the cardiovascular community at large is really beginning to recognize the importance of women's cardiovascular disease conditions that are unique to women in a lot of the topics that we're going to go through at this session.

How can we look at a woman's lifespan and relate it to her cardiovascular disease health?

I think what's really helpful is actually using a life course perspective. Really thinking about a woman's cardiovascular risk that begins early in life. We've come to realize that actually something that's very unique for women is that we have a reproductive lifespan, essentially, that starts at menarche, when we get our first menstrual period and really spans pregnancy, midlife, all the way to menopause when we stop our periods.

Each of these unique life points has been shown actually to confer some degree of cardiovascular risk later in life. If we even just start at the very beginning. When a girl undergoes menarche or has her first menstrual period has actually been shown to be associated with risk of cardiovascular disease and specifically with girls who undergo menarche at a younger age than average. The average age that most girls get their first period is about 12 years old. If they get their first period at age 10 or younger, or later age at greater than age 15 or so, both of those have been shown to be associated with greater later life cardiovascular disease risk.

Then as we just march along adolescence into early adulthood, there are a number of conditions like something called polycystic ovary syndrome, which is unique to women. It's characterized by insulin resistance, weight gain, obesity, and also irregular periods and potentially infertility. This is a condition that does affect a small proportion of women and has also been linked to greater risk of cardiovascular disease later in life.

Then again, just moving forward, pregnancy. There's a lot of attention this year at the ACC conference. I think because there's finally acknowledgement that pregnancy represents an important period in a woman's life. Pregnancy complications or adverse pregnancy outcomes like hypertensive disorders of pregnancy, preeclampsia, gestational diabetes, miscarriages have actually all been shown pretty consistently now to be linked to future risk of cardiovascular disease. Then even when we think about pregnancy, there are actually a number of women who are unable to get pregnant, so infertility itself has also been linked to both atherosclerotic cardiovascular disease and heart failure. Then finally moving all the way to the end of a woman's reproductive life, in her midlife, is menopause. That's what I'll be talking about at the [ACC 2023] session tomorrow. Menopause is actually a time of accelerating cardiovascular disease risk for women. Up until menopause, the prevalence of cardiovascular disease in women actually lag significantly behind that of men but after menopause, we really see those rates start to pick up. At some point, that trajectory is so steep that the rates of cardiovascular disease in women actually outpace that of men. That's I think a broad overview and sort of the approach that I like to take when I see my patients in the clinic in our women's heart health program.

How many of these conditions have a limited timeframe risk versus causing an increase in risk sometime in the future?

It's a great point. I think we're beginning to recognize, if I take for example, one pregnancy adverse outcome, hypertensive disorders of pregnancy, we actually know that hypertensive disorders pregnancy like pre-eclampsia are associated with short-term cardiovascular risks.

Right after the pregnancy, then the woman may have a heightened risk of heart failure, high blood pressure, other cardiovascular conditions, but separately, it has also been shown to be associated with cardiovascular risk decades later. I think that there are two important points here.

One is, first, that in that immediate acute setting, we really have to be mindful about, think about cardiovascular disease conditions, but once we were out of that postpartum period, a lot of times these are young, healthy women. They sort of go back to their primary care doctors or even don't seek medical care routinely and we lose them.

This is actually a really important period of time to be thinking about modifying their cardiovascular risk factors like high blood pressure, diabetes, weight, all of these things because we know that if you've had a history of preeclampsia early in your life during one of your pregnancies, that you are at much higher risk of developing heart disease maybe in your fifties, sixties, seventies and yet there's this whole window of time when we're not necessarily thinking about a woman's cardiovascular risk.

It sounds like with this information, you're hoping to reach primary care physicians?

Both primary care physicians and cardiologists, too. Certainly we think a lot about prevention and so that would be in the wheelhouse of our primary care colleagues. We need to be thinking about reproductive history in both the primary care setting and in the cardiovascular setting.

I think that most cardiologists today are not asking their women patients any questions pertaining to their reproductive history. It is an important component and should be incorporated into our routine history and physical. Then similarly for our primary care physicians, I think that we need to educate them to be aware that this otherwise healthy woman, because she had either a history of infertility, for example, or she had gestational diabetes, she's at heightened risk for developing heart disease later in life and so we need to be thinking about being aggressive about managing her blood pressure. A blood pressure of 150 is not going to be okay for her. We really need to be making sure that we treat her to our guideline targets.

How have the guidelines incorporated this information for physicians?

Well, I think that we're going to definitely see the guidelines continue to evolve in the coming years as there's been just sort of an exponential takeoff of data and literature in this space. The American Heart Association and American College of Cardiology have recognized adverse pregnancy outcomes in early age of menopause as risk enhancing factors for the development of atherosclerotic cardiovascular disease. What that really means is that you have a patient in front of you, you calculate their 10-year atherosclerotic cardiovascular disease risk like we do for every other patient, but if your patient has one of these risk-enhancing factors, it may make you think about starting statin therapy, for example, a little bit earlier than you might have otherwise.

Is there anything I didn't ask about that you wanted to mention?

I would just emphasize again, the importance of considering a woman's entire reproductive life as really a routine and integral part of their cardiovascular history. To emphasize just the need to continue to do rigorous research in this space.

What are some of the open questions?

One of the things my research group is particularly interested in understanding is what are the mechanisms that are driving menopause-related cardiovascular disease? As I mentioned, we see that heart disease rates really seem to accelerate after the menopause transition, but we really don't understand why.

For a long time we thought, well, after menopause, your ovaries stopped producing estrogen, and it must all be estrogen deficiency. We are beginning, we know now after a number of randomized trials in the late 1990s, early 2000s, that estrogen deficiency is probably just one part of the picture. It's a really complicated biologic story.

My group is doing a lot of work. We're enrolling a prospective study to try to understand molecular profiles and how they change across the menopause transition so we can maybe better understand the biology that is driving this observation, and then ultimately be able to provide preventive and therapeutic strategies. This has been the unanswered question in my mind that's really plagued women's health for the last half a century, and we still have not gotten that much closer to understanding the biologic underpinnings.