When men have heart attacks, it’s often easily evident. It’s portrayed in media all the time: enormous chest pressure, shooting pains down the arm, nausea, shortness of breath. If you had to guess, I bet you’d think that women have the same reaction.
 
It’s true that some of the signs and symptoms overlap, but heart attacks and other cardiac events can be much more subtle in women, manifesting as extreme fatigue, pain in the upper abdomen, fainting, and/or indigestion, according to the American Heart Association (AHA). For this reason, many women delay seeking treatment—and that’s not good for survival. In a 2016 report, the American Heart Association stated that within a year of a heart attack, 26% of women died compared to just 19% of men. Five years after a heart attack, around half of the women died, compared to around a third of the men. This is a surprising gap, considering that men are twice as likely as women to have a heart attack (Albrektsen 2016). While there is no doubt that there are disparities in health education and medical equity, there is clearly a difference between the way that male and female heart and blood vessels function.
 
The coronary blood vessels that feed the heart tissue range in size. The largest ones, visible on the hearts’ exterior, are coronary arteries. About 4.5 millimeters in diameter, they bring blood from the aorta and deliver it en masse to feed the chambers that are constantly pumping. Obstructive coronary artery disease occurs in vessels of these size; these are the vessels that get bypassed in coronary bypass surgeries which occur more often in men. Small arteries and arterioles that control how much of the blood actually reaches the heart tissue are only about 200 micrometers in diameter. Read: tiny. So tiny that they become hard to image or evaluate clinically, and women have more microvascular dysfunction than men (Sara 2015).
 
Arterioles are very important to blood delivery: they dilate to increase flow or constrict to decrease flow, all depending on what the heart needs. If you are relaxed, your heart beats slowly so the arterioles delivering blood don’t need to dilate. However, once you get up and walk or run, or even watch the Aggies beat Alabama (Gig ‘em), your heart beats faster and it needs more blood. Your arterioles have to dilate to increase blood flow.
 
Sounds pretty important, right?
 
Right! As a result, your body has several redundant pathways to make sure that this process keeps happening with every beat of your heart. Unfortunately, this is one of the processes that gets messed up in the presence of disease, particularly cardiovascular disease, diabetes, or hypertension. It would be straightforward if the blood vessels of males and females became impaired in the same way, but recent research is suggesting otherwise.
 
In 2018, Pabbidi noted that the arterioles from healthy, female humans and animals are less sensitive to constrictors, suggesting that they are more readily able to increase blood flow. They also have been observed to respond more dramatically to shear stress. Shear stress is created when blood flows through a vessel. The blood flow stimulates the lining (the endothelium) to produce factors that cause dilation. Female microvessels constrict less to vasoconstrictors, and dilate more to dilators than male microvessels.
 
Some of the major groups of endothelial vasodilators include nitric oxide (NO) or hydrogen peroxide (H₂O₂) produced by the muscles that control vasodilation and constriction. Coronary artery disease decreases the availability and dilation effect of NO. In one study, males with decreased NO due to disease had increased H₂O₂ to replace the lack of NO and modulate dilation. Contrarily, females showed impaired H₂O₂-dilation (Davel 2018). This is interesting and concerning because Pabbidi 2018 suggested that females were more dependent on vasodilators like H₂O₂ rather than NO, and Wong 2014 observed that H₂O₂ played a role in female, not male, vasodilation.
 
The scientific community as a whole is still trying to understand the effects of disease on human vasculature, not to mention exploring the sex differences involved.* My current research is taking a look not only at the sex differences in signaling in ischemic heart disease, but also how exercise can also modulate blood vessel function in different, sex-dependent ways. There is so much we still need to learn, but the better we understand sex differences, the more we can shrink the mortality gap between women and men. We can find better, more specific treatments for men and women, so we can increase the survival rates for everyone.
 
*I recognize that while this blog post discusses the cisgender male and female physiology associated with my research project, I do not address the unique health concerns of those who undergo gender-affirming hormone therapy. Luckily, there is increasing research being conducted on cardiovascular health in transgender and gender diverse individuals. If you are interested, you can check out Streed 2021 to find out more.
 
— Kalen Johnson
 
Kalen is a doctoral candidate in the College of Veterinary Medicine and Biomedical Sciences.