Welcome to the American College of Cardiology session on hypertension. Over the next 30 minutes, we'll focus on hypertension across a woman's life cycle, understanding the burden and impact. My name is Dr. Megan Coilwright, and I'm an interventional cardiologist at Essentia Health in Minnesota. Our learning objectives include describing the prevalence of hypertension throughout a woman's life cycle, and explaining the pathophysiology and the overlapping relationship between menopausal symptoms and hypertension as comorbidities and risk factors in women. Hypertension is a serious but silent disease process, and it is responsible for a large number of deaths among women, more so than many of the other cardiovascular risk factors that we think about. High blood pressure has deaths attributable in the almost 250 per 1,000 women, greater than smoking, physical inactivity, overweight, obesity, high LDL cholesterol, many of the other things that we focus on in our clinical encounters with our patients. In fact, hypertension accounts for one in five deaths among US women, and is greater in burden for women than for men. Looking at these five women pictured, one of them will die as a result of hypertension. Oftentimes, we don't necessarily see the focus on this disease process that matches the extent of its impact. More women than men develop adverse consequences from hypertension, such as diastolic dysfunction, left ventricular hypertrophy, heart failure, either with preserved or reduced ejection fraction, in addition to increased arterial stiffness. This really impacts the relationship between these risk factors and cardiovascular disease, and in fact, the relationship between hypertension and prior cardiovascular disease is the most prominent dyad among Medicare beneficiaries that are women. Control of hypertension can significantly improve quality of life, disability, and health care resource consumption related to hypertension. Today, we're going to be focusing on hypertension across a woman's life cycle, including teens and young adult age, through pregnancy and reproductive years, menopause, and an older age, thinking about medication issues, clinical trial data, and race and ethnicity issues while we weave primary prevention throughout today's discussion. First and foremost is the prevalence of hypertension by age. This is an important concept to think about. Oftentimes, we'll think about it being more common among men. And actually, what we see are differences in the prevalence of hypertension across women's life cycle. For example, if we look at the dark blue, which is the total of 18 and over, you're able to see the distribution by gender among men and women, slightly more prevalent among men. But when we break this down by age, we see significant differences. And when we reach 60 and over, we can see that hypertension is actually more prevalent in women than in men. Let's begin by focusing on teen and young adult age. This is the age where very important habits are developed. And in fact, physical inactivity is associated with a twofold increase in cardiovascular disease risk. Physically active women have a 50% risk reduction versus sedentary women. And regular mild to moderate exercise with aerobic activity in women is associated with a 5 to 8 millimeter mercury drop in blood pressure, regardless of weight loss. This matches the impacts that we're looking for in major clinical trials for interventions such as hypertensive medications or renal denervation. Obesity alone contributes to primary hypertension in adolescents, especially among racial and ethnic minorities. In teen and young adult age, it is important to develop the habits, particularly around physical activity. But we know that for young girls and women, this provides a particular challenge. Although we have an increasing focus on women's participation in sports, which has been fantastic, and can contribute to increased safety with regards to cardiovascular health, many young girls and women still worry about exercising. That is, can they be out walking, hiking, running on their own? We still live in an environment where this is challenging for women to have the freedom to do this without concern. In addition, joining a gym remains difficult for women, not necessarily the environment where women feel free to be engaged in aerobic activity. And yet this can be life-saving habits to develop early on in life. Thinking more about interventions in this space makes a lot of sense. When we think about considerations in the care of transgender and gender-expansive individuals, this also relates to early habits of physical activity. Transgender adults can have lower physical activity levels than their cisgender counterparts and are at increased risk for cardiovascular disease due in part to the use of gender-affirming hormones like estrogen. Considering issues specific to racial and ethnic minorities and LGBTQ plus communities, it remains essential in the management of hypertension across the lifespan, beginning with habits early on in life. Let's turn to the stage of potential reproductive health for women. Hypertension in pregnancy is a very serious disease that can be under-recognized and have a large impact on morbidity and maternal mortality. We think about hypertension in pregnancy in four categories, preeclampsia, chronic hypertension, chronic hypertension with superimposed preeclampsia, and gestational hypertension. Let's review a few of these definitions in an effort to continue to have all of our cardiovascular colleagues thinking critically about the detection and management of hypertension across women's lifespan, focusing on pregnancy. Preeclampsia is a syndrome of new-onset hypertension and proteinuria, or new-onset hypertension and end-organ dysfunction. We'll look for elevated liver enzymes, low platelet count, and renal insufficiency. Most often, this occurs after 20 weeks gestation in previously normotensive women. Eclampsia is diagnosed once seizures occur. Chronic hypertension, defined as a blood pressure of 140 systolic or more, or a diastolic pressure of 90 or more, predates pregnancy and is present before week 20 of gestation, or is defined as high blood pressure that persists greater than 12 weeks postpartum. Chronic hypertension with superimposed preeclampsia are women with chronic hypertension that develop increased blood pressure and new-onset proteinuria, or end-organ damage characteristic of preeclampsia. And gestational hypertension is when elevated blood pressure is first detected after 20 weeks gestation. These can have significant impacts on the health of women, as well as their children, and are important to detect and treat early on. Moving forward continuously here in women's lifespan, we can think about the relationship between work and hypertensive risk. Now, certainly, particularly in the United States, where there's very limited resources for supporting women as they go through their reproductive years and their work, oftentimes doing a double shift of working full-time and then coming home and being responsible for many of the work responsibilities at home. We live in a time where we still don't have equitable distribution of the labor that occurs at home with relation to running the house or caring for children, elderly relatives, or other needs in the community. It is certainly a goal, but it's something that takes a toll, not just on a woman's overall well-being, but on their cardiovascular health. This original research looked at a systematic review and meta-analysis of the association between long working hours and hypertension risk. And what was found was that diastolic blood pressure was higher among those with long working hours, but with a greater effect in women. Not just the work that we put in during the day in our roles as physicians or other clinicians, but the work that occurs when we go home as well can be detrimental to our cardiovascular health through the increased risk of hypertension. We're looking forward to think about the blood pressure effects specifically of gender-affirming hormone therapy. We talked previously about the need for physical activity as an early habit in all of our patients. But in our patients that are transgender or gender diverse, they may have higher rates of hypertension compared to the general population. Within two to four months of starting gender-affirming hormone therapy, transgender women had a lower average systolic blood pressure, but transgender men had a higher average systolic blood pressure. This highlights that clinicians should be asking whether their transgender or gender-diverse patients are receiving hormone replacement therapy, and if so, consistently monitor blood pressure before and after starting gender-affirming hormones to take hypertensive prevention measures if needed. Within two to four months of beginning hormone therapy specifically, in this study published in Hypertension in 2021, transgender women saw an average decrease of 4 million meters of mercury in their systolic pressure, but transgender men saw an increase of 2.6. The prevalence of stage 2 hypertension, defined of at least 140 over 90 millimeters of mercury, dropped from 19% to 10% in the transfeminine group within two to four months of beginning hormone therapy. The use of testosterone in transgender men could lead to an increased risk for heart attack or stroke if they also have untreated high blood pressure. Multiple research studies demonstrate that there are limitations in medical care for many of our patients that are transgender or gender-affirming because of a lack of welcoming and inclusion in the health care system. You may have patients that have not revealed their identity nor their use of hormone therapy, and in the treatment of hypertension, it is important to understand this as a potential risk factor and to align an individualized treatment plan to address. Let's continue to move forward in the lifespan and focus on menopause and older age. After age 60 years, the prevalence of hypertension becomes higher in women than in men, as we spoke about earlier, and this gap widens with aging related to the large proportion of older women and possibly medication access, side effects of medications, and ethnicity issues. Hypertension control rates remain higher in women than men in age 18 to 60, but in those greater than age 60 years, hypertensive control in women is poorer than in men. Debate does remain about optimal blood pressure targets, especially across the broad age spectrum, which makes management in some ways more challenging when we don't have the data to guide us. Remember that menopause signifies the permanent cessation of ovarian function and women's transition from a potential reproductive time to a post-potential reproductive time. It marks a critical stage that is characterized by dramatic changes for many women in hormonal and menstruation patterns, as well as physiologic and psychosocial symptoms. The experience of 12 consecutive months of amenorrhea, which is not the result of other causes, defines natural menopause. Now notably during this time, primarily driven by hypertension-related mortality, black women have life expectancies that are shorter than non-Hispanic white and Hispanic women. Hypertensive control disparities in women can be linked to access and affordability of care, as well as competing priorities related to socioeconomic differences within our country and other sociodeterminants of health in combination with overweight and obesity, driving home the point that hypertension is a significant risk factor for cardiovascular morbidity and mortality among women, and particularly among racial and ethnic minorities, necessitating a continued focus on this important disease condition. A scientific statement from the American Heart Association published in 2020 specifically talked about menopause transition and cardiovascular disease risk, talking about the timing of need for early prevention. Notably for women who utilize hormone replacement therapy, particularly for severe symptoms, there was a relationship between that therapy and hypertension. Women taking oral estrogen therapy had a 14% higher risk of developing high blood pressure compared to those using transdermal estrogen, and a 19% higher risk of developing high blood pressure compared to vaginal estrogen creams or suppositories. After accounting for age, there was a stronger association seen among women younger than 70 years than women older than 70 years. There certainly is an impact on hypertension with the use of hormones, and continuing to talk with patients about the evidence around this and screening patients for hypertension remains critical. Menopause symptoms and cardiovascular risk can also be related. Vasomotor symptoms may be associated with an abnormal lipid profile, the development of hypertension, and the onset of insulin resistance. This can occur as women go through menopause with them having no history of this in the past. These vasomotor symptoms are a good and early clue for women to talk to their doctor about some of the development of cardiovascular risk factors and ensure that they are being screened. These symptoms can disrupt sleep cycles and can significantly impact patients' lives in many ways. Menopause symptoms such as sleep disturbance are related to the development of metabolic syndrome and arterial stiffness and calcification. This isn't just a matter of hot flashes and not being able to sleep through the night. This is related to significant development of cardiovascular risk factors and should be taken very seriously and screened for women that are in the age range for menopause. Depression is also associated with an increased coronary artery calcium score and increased risk of cardiovascular death and all-cause mortality. Identifying and treating these important cardiovascular risk factors during menopause remains essential to improving the cardiovascular health of all of our patients. Now much of the information that I just provided does relate back to clinical trials. That is, how has women's lifespan been related to hypertension and cardiovascular risk? But we do have to point out that we are limited in some of the information around the way that hypertension impacts women across the lifespan. This is in part because we have not had a good track record in cardiovascular medicine for inclusion in our clinical trials. For example, in heart failure with reduced ejection fraction trials, and this is mirrored in coronary artery disease trials, we see that females represented only about a quarter of randomized controlled trial participants. We did note the proportion of female participants did not significantly change from 2000 to 2019, even as there were initiatives nationally to think about how we can include more women in clinical trials. Trial characteristics that were independently associated with the under-enrollment of females included men as first and last authors. We still have room to go for ensuring that our clinical trials are also representative. There are many, many talented women within the field of cardiovascular medicine that are interested in clinical trials and that have innovative and unique skill sets with regards to inclusion. This will be important so that we can understand how to be effective in the treatment of hypertension and the prevention of cardiovascular disease in women. Representation of women in contemporary clinical trials is significantly improved when there is the presence of diverse clinical trial leaders. More diverse enrollment occurred in women-led randomized controlled trials with a 50% increase in the women participants. Many trials, however, have no women investigators. This important study published in JAMA Internal Medicine looked at some of our major medical journals to see about the presence of female investigators and female leadership. Half of trials had no women at all on the leadership committees, and 4 in 10 trials had no women as site investigators. Forty percent of trials had no women on the ground talking to patients about these important clinical trials. It makes sense that we don't necessarily have the results that we're hoping for with representation. But if our trials are meant to be effective and efficient, we need to ensure that we're studying the population for whom those interventions are designed to help. There's room to grow in this area. The enrollment of older patients and women and racial and ethnic minority groups have been quite little. And as I mentioned, this is true in acute coronary syndrome clinical trials as well. Rates of about 25% for representation of women and many clinical trials have not even recorded race and ethnicity. In addition, we have not consistently recorded the difference between sex, meaning female or male, and gender, woman, man, non-binary, and other state-of-the-art categories that can impact the cardiovascular health as we've already discussed and will be important to continue to look for in the future in our Table 1. Gender and race-based disparities in clinical trials are significant. 460 acute coronary syndrome trials in this published study showed women at about a quarter, and the representation of women actually decreased over time. Only one in five trials reported race, but when reporting, non-white patients made up about 15% of the participants in these cardiovascular clinical trials, as opposed to their representation in the general population in the U.S., which is about 40%. One in five women will die of hypertensive-related conditions. And yet, we don't necessarily have the science to guide us in how to protect women and improve their quality of life, as well as prevent early mortality. Importantly, there isn't the intersectionality of race and ethnicity. A fascinating study was published recently in Jack, which looked at the relationship between race and ethnicity, social determinants of health, and their polygenic risk score. And what they found in the relationship was that sociodeterminants of health do vary with self-reported race and ethnicity, and specifically, they are highest in people who self-report as Black or Hispanic. That presence of sociodeterminants of health explained the increased odds of cardiovascular disease in people who self-reported as Black. Now, those factors that were associated with disease included lower income, food insecurity, neighborhood disorder, loneliness, and discrimination. These factors explained differences by race and ethnicity in heart disease more than any of the genetics did. Specifically, sociodeterminants of health for coronary heart disease were highest in self-reported Black and Hispanic and explained the increased odds of coronary heart disease more than genetics. Truly, this is important to understand, that we don't necessarily have differences in the patients between us other than their social circumstances. Talking with them about that, accessing resources, and considering this in the care of patients remains critically important. Let's review our take-home messages from today about the care of women across their lifespan as it relates to hypertension. The prevalence of hypertension is higher in women compared to men after menopause and should be a continued focus in our clinical encounters with women as they are more likely to develop detrimental effects such as left ventricular hypertrophy, diastolic and systolic dysfunction, and arterial stiffness. Symptoms of menopause, including vasomotor symptoms and sleep disturbances, are not to be dismissed in the clinical encounter. They can signify and are associated with increased cardiovascular risk and should be explored, treated, and those associated risks should be screened for and treated as well to improve the cardiovascular health of women after menopause. Clinical trials for hypertension continue to be needed and require diverse representation. We need to ensure the clinical trials, particularly of hypertension for medications or renal denervation or lifestyle modifications, that these trials include women and particularly diverse women such as our transgender and gender diverse patients as well as our racial and ethnically diverse patients, older patients, so that we understand the best way to improve the morbidity and mortality rates that we see among women. One in five women are dying of hypertension. This is a silent killer that necessitates a continued and renewed focus, not just in our clinical encounters but also in our clinical investigations. Thank you for your time.

hypertension

women's health

menopause

cardiovascular risks

clinical trials

healthcare barriers