Highlights from the Presentation
On Novel Risk Factors for Cardiovascular Disease in Women
We know that women who have autoimmune disorders such as systemic lupus and rheumatoid arthritis have at least a threefold increased risk of heart disease. And these autoimmune disorders are five to 10 times more common in women than in men.
We also know that some complications of pregnancy, such as gestational diabetes, which confers a fourfold higher risk of subsequent diabetes and close to a 60% higher risk of heart attack, preeclampsia, and hypertension occurring during pregnancy--I'll be talking about in some detail--but again, a substantially increased risk of coronary disease.
And then early menopause, especially premature menopause occurring before the age of 40. But even early menopause before age 45 are risk factors for heart disease, and we really need more attention to the role of depression. There is a much higher prevalence of depression in women than men, and about a doubling in the risk of heart disease.
On What Ideal Cardiovascular Health Looks Like
It's defined by knowing your numbers and knowing that the numbers are in a good range, such as for total cholesterol, blood pressure, fasting glucose, body mass index, and also lifestyle factors--we're going to talk more about this--, a tremendously important role that behavioral and lifestyle factors can play in reducing risk.
Abstinence from smoking, following physical activity guidelines--which are for at least two and a half hours of moderate intensity exercise, brisk walking, other moderate intensity exercise per week, or at least hour and 50 minutes of vigorous exercise or a combination--and having a healthy diet/Mediterranean diet or similar dietary patterns. But fewer than 4% of women actually meet these criteria in the US, and it's no better in men.
…among the women who followed the lifestyle modifications that we've talked about--regular physical activity, not smoking, having a healthy body weight, having a healthy diet high in whole grains, fiber, fruits, vegetables, fish, low in saturated and trans fat--, and no more than moderate alcohol intake, there was fully an 83% lower risk of coronary heart disease. Compared to women who are not following these guidelines, close to an 80% reduction in stroke and a 91% lower risk of type two diabetes. So a very dramatic reduction in risk of these chronic disease outcomes among those following these healthy lifestyle factors.
Now, the American Heart Association has recently released what it calls the Life's Essential Eight factors. They previously had Life’s Simple Seven, which included all of the same factors except sleep. Adequate sleep has now been added because it's recognized that getting adequate sleep, such as seven to nine hours per night, is tremendously important to good health. And so, the four health behaviors in Life's Essential Eight are not smoking or vaping, having adequate sleep, healthy diet, regular physical activity, and then knowing your numbers and having your blood pressure, blood lipids, weight and blood glucose in the healthy range.
On the Menstraul Cycle’s Effect on Hearth Health
I really do think of menstrual cycles as being a vital sign for women in adolescence and adulthood during the reproductive adulthood years. This is menstrual cycle regularity when women are not taking birth control pills, not pregnant. Having irregular menses, this shows ages 20 to 35 reporting that their menstrual cycles were usually irregular, or especially those reporting very irregular or no cycles, had more than a 50% increased risk of total coronary heart disease, and especially a high risk of fatal coronary heart disease.
This is some research we did in the Nurses' Health study — Karen Solomon and colleagues more than 20 — about 20 years ago, where we've had a long interest in health implications of irregular menstrual cycles. And a number of studies now are documenting that there's an increased risk of cardiovascular disease in those who have irregular cycles. We also have seen that there's an increased risk of premature mortality before age 70. This is looking at the Nurses’ Health study to menstrual cycle regularity, ages 18 to 22, and also age more in midlife or early adulthood, 29 to 46 years.
And in both early adulthood and midlife, we found 30 to 40% higher risk of premature mortality among those with very irregular periods. And CVD death was increased by 59%. We also saw an increased risk with longer cycle length. Now, most women, like 80% or even more, reported their usual menstrual cycle was 26 to 31 days. And once women had a menstrual cycle length of 40 days or longer, this was associated with increased risk of CVD, CVD death, and all-cause mortality.
Now, why would this be? One reason is that the irregular menstrual cycles and longer menstrual cycle length may reflect underlying polycystic ovaries syndrome. And we know that PCOS, which affects fully 10% or more of women, is linked to insulin resistance. It's linked to an androgenic profile in terms of a higher testosterone to estrogen level.
It's linked to cardiovascular risk factors such as hypertension, type two diabetes, and abnormal lipids, but also in some recent studies--and this is a meta-analysis of multiple studies--it was linked to an increased risk of ischemic heart disease or coronary heart disease, almost a tripling in risk. It isn't clear how long this excess risk lasts or whether this persists well into the menopause, but at least in early adulthood, early menopause, there is this increased risk of CVD or CHD associated with polycystic ovary syndrome, which suggests that we need to pay more attention to this condition, do the testing for it, and also help women to lower their risk of cardiovascular disease. And I'll come back to that at the end.
Now, in some recent studies, some of the adverse outcomes of pregnancy, such as preeclampsia and hypertension occurring during pregnancy with what's called gestational hypertension--but not necessarily preeclampsia--, not having the protein in the urine and the edema. And it's not as severe a condition, but it's still linked to an increased risk of cardiovascular disease. So in some very elegant work published by Jen Stewart and colleagues in the Journal of the American College of Cardiology earlier this year, they looked at these hypertensive disorders of pregnancy.
Overall associated with about a 60% increase in CVD, while gestational hypertension without preeclampsia had about a 40% increase and preeclampsia about a 70% increase in CVD. But when you look specifically at coronary artery disease and coronary heart disease, then preeclampsia was linked to more than a doubling of subsequent risk of CHD. Gestational hypertension, a more modest risk, but stroke was actually more substantially increased with gestational hypertension than with preeclampsia. So this is these complications of pregnancy. Pregnancy is often considered a stress test for women's cardiometabolic health, but these complications of pregnancy predict future increased risk of cardiovascular disease.
And another analysis that was done in this study was to look at the percent of this excess risk of cardiovascular disease that was mediated by traditional risk factors such as the development of chronic hypertension after the pregnancy, development of high cholesterol type two diabetes, or increases in BMI/changes in BMI. And almost two-thirds of the risk was attributable to these traditional risk factors developing after the pregnancy, suggesting that we may be able to substantially reduce the risk of cardiovascular events among women who have preeclampsia or hypertensive disorders of pregnancy by monitoring and controlling these traditional risk factors.
On the Differences in Risk Factors for Women Who Have Had Surgical Versus Natural Menopause
Many studies do suggest that surgical menopause may confer even greater risk because it's completely — it very rapidly lowers the estrogen level. However, there's some interesting research lately, suggesting that an early natural menopause may itself be associated because it's often due to inflammatory conditions, maybe associated with a condition called clonal hematopoiesis of indeterminate potential. It's a long word, but that's been linked to an increased risk of cardiovascular disease, and the inflammatory state associated with early natural menopause may be a strong risk factor. So I think that overall the bilateral oophorectomy, surgical menopause, if the ovaries — both ovaries — are removed, has been more clearly linked to increased risk due to the sudden decline in in the estrogen levels.
On the Relative Cardiac Risk in Persons Born Biologically Female and Hormonally Transitioned to Men
We need more research on the effects of hormone therapy in transgender individuals. And, in fact, there has been some limited research suggesting that there may not be a substantial increase in cardiovascular risk, but I think much more research is needed. And also, whether the hormone therapy should be given orally versus transdermally — this is often higher doses. I think that this is an area that has not been really well researched, and we need more research on this topic.
On the Most Pressing Research Arenas in the Postmenopausal Age Group
I do think that having more research on the menopause and ways to reduce risk during the menopause transition and the post-menopausal phase of life is just tremendously important. And this has been a relatively neglected phase of life, even though I hope I've convinced you it's very strongly related to women's cardiometabolic risk. And you know, this increase, there's really an inflection point at which a lot of these risk factors increase.
I think we need more research on the FSH, the effects of estrogen — for example, in a woman who is having menopausal symptoms and disrupted sleep will hormone therapy — are those symptoms actually contributing to the gain in visceral adiposity? This was suggested by a recent study just presented at the North American Menopause Society Conference. And if you treat with estrogen, can you actually help to prevent some of those adverse changes? I think that's important.
We know about lifestyle modifications and diet. We have so much research showing the importance of lifestyle factors, physical activity, strength training, but it’s been very, very difficult to implement and disseminate this knowledge into actual practice and clinical practice of encouraging patients to make changes, and also in terms of population health. So I think much more research needs to be done in that area of affecting behavioral change.
On Her Being Named the 2022 Alma Dea Morani Renaissance Woman Awardee
I'm tremendously honored and truly humbled to receive this award. In fact, I'm almost speechless, which doesn't happen to me often.
When I look at the list of previous recipients, I'm awestruck. These are some of my greatest role models and the most inspiring trailblazers I've looked up to over the years. To be on the same list with such remarkable women is humbling, and I'm deeply grateful to the Women in Medicine Legacy Foundation, the New York Academy of Medicine, and the selection committee for this enormous honor.
