Heart disease is the leading cause of death among women in the United States; responsible for about one in every five female deaths, according to the Centers for Disease Control and Prevention (CDC).

Research has shown that Black women are at greater risk for heart disease than white women, even when controlling for modifiable risk factors such obesity, high blood pressure and tobacco use. Why this occurs is unknown. But Melissa Witman, assistant professor in the Department of Kinesiology and Applied Physiology at the University of Delaware, may be on the path to solving the mystery.

Witman and her colleagues report new clues based on a recent study of vascular function — how healthy the arteries are throughout a person’s body.

The study, recently published in the Journal of Applied Physiology, found that while white and Black women experience no change in how well the body’s large arteries function across ovulation and menstruation, Black women do experience diminished function (i.e., blood flow) in the smaller blood vessels and capillaries that make up the body’s microvascular system.

Witman said the findings may have important clinical implications, particularly since reduced function of the body’s smaller vessels and capillaries is known to precede poorer performance in the body’s larger arteries and heart. This suggests that microvascular function could provide a useful tool for monitoring or identifying heart disease risk in otherwise healthy young women.

UDaily spoke with Witman and UD doctoral student Michele D’Agata, the paper’s lead author, to learn more about the study, which was funded in part by the National Institutes of Health.

Q: What is the vascular system, and what role does it play in the body?

Witman: The vascular system is a network of blood vessels that are responsible for receiving blood from the heart and efficiently delivering it throughout the body and then returning the blood to the heart again. You can think of it like a tree, consisting of large arteries near the heart that branch into smaller and smaller blood vessels throughout the body. The smaller blood vessels, known as the microvasculature, are extremely important in regulating the amount of oxygenated and nutrient-rich blood that is delivered to different areas of the body. For example, during exercise, the microvasculature near the working muscles dilate to increase the amount of blood flowing to the working muscles. By assessing vascular health, we can better understand cardiovascular disease risk as many of these assessments are predictive of future disease incidence and rates of hospitalization and death.

Q: Will you tell us about your study?

Witman: It is currently unclear if vascular function changes across the menstrual cycle with fluctuating sex hormones. This is because women are typically only studied during the early phase of the menstrual cycle, when estrogen is at its lowest and women are thought to be most "comparable" to men. Unfortunately, this only encompasses about five to seven days of each menstrual cycle and may not reflect how well the body’s arteries and blood vessels function for the remaining 20 to 30 days of a woman’s cycle. 

We recruited 26 healthy women between the ages of 18 and 35 with naturally occurring menstrual cycles to participate in a vascular screening at our research lab in UD’s STAR Health Sciences Complex in Newark, Delaware. We measured the women’s vascular response, or function, at three different time points across the menstrual cycle: when sex hormones were low at the beginning of their cycle, when estrogen was high around mid-cycle (i.e., around the time of ovulation), and when estrogen levels were moderate and progesterone was high, near the end of the cycle. This included using ultrasound to measure blood velocity and the diameter of each participant’s femoral artery during passive leg flexion and extension. The magnitude of the blood flow response from rest to movement gives us an indication of a person’s microvascular function.

Q: What did you find?

D’Agata: We found that microvascular function was lower in Black women relative to white women at all time points across the menstrual cycle. This means that regardless of “what time of the month” we tested participants, Black women had a lower blood flow response, indicating less dilation of the small blood vessels in their leg. This is likely one of the mechanisms contributing to higher cardiovascular risk and disease in Black women and this is important, as we detected these changes in young, apparently healthy women — a population generally thought to need little attention from a cardiovascular-risk perspective.

Q: Why are these findings important?

Witman: This is the first study to assess microvascular function across different phases of the menstrual cycle in Black and white women. In general, a lower increase in blood flow in response to a stimulus indicates that microvascular function may be impaired, which is one of the earliest signs of cardiovascular disease risk. If the microvasculature doesn’t work well, this can eventually lead to high blood pressure, thickening or hardening of the arteries, and other cardiovascular-related diseases, such as heart attack or stroke.

We recognize that race is not a biological variable but a social construct and yet this social construct is affecting the physiology of one group versus the other. Black women have some of the highest rates of cardiovascular disease morbidity and mortality and are also one of the most understudied groups. Before we can propose ways to help decrease this alarming racial disparity, we must first characterize the problem early in life, which is what our study aimed to achieve.

Q: Did you learn anything else that surprised you?

D’Agata: We also quantified estrogen and progesterone concentrations in over half of the study participants and found Black women exhibited less estrogen at all time points across the menstrual cycle, which may be contributing to the diminished blood flow in these tiny blood vessels. Prior research has provided evidence that estrogen benefits the vascular system by helping with blood vessel dilation, which leads to increased blood flow. More research is needed to investigate the association between estrogen and vascular function in a larger group of young Black women to determine how it may contribute to the increased cardiovascular disease risk in this population.

Q: Where do you hope this work will lead?

Witman: We need to better understand the physical processes in play so that we can develop strategies and interventions for reducing cardiovascular disease in Black adults. We hope this work will inspire other researchers to investigate potential causes for why we see reduced microvascular function earlier in life in young Black women. 

D’Agata: Meanwhile, we plan to continue studying the race disparity in vascular function identified among young, healthy Black women to identify achievable ways to preserve vascular health and ultimately decrease the development of cardiovascular disease. We want to identify ways to improve microvascular function in young Black women to limit the cardiovascular disease burden later in life.