Women and men are different, cardiovascular edition

It’s quite the task to photograph someone’s heart while they’re exercising. They have to lie on their back in a pressure-controlled chamber, riding a suspended stationary bike while an ultrasound imager points at their pumping heart — at least that’s how one group of researchers from the University of Calgary and Hong Kong went about it.

With this curious setup as part of their study, the researchers were looking for precise differences in men’s and women’s heart health.

“In any other body position or with any other camera system, it’s impossible nowadays to measure maximum cardiac output,” a key factor in assessing the heart’s ability to pump blood into the rest of the body, said David Montero, a co-author of the study and an assistant professor of medicine at the University of Hong Kong.

The results of their study, recently published in the journal Science Translational Medicine, show a striking difference: women’s lean body mass, composed mostly of skeletal muscle, correlates with a better-functioning heart, while men’s do not. For instance, women with more muscle in their arms and legs also tended to have hearts with larger inside diameters, which gives their hearts an advantage in the amount of oxygenated blood they can pump out to their bodies. With more arm and leg muscle, the walls of their hearts did not appear to be thickening, one characteristic that can prevent heart failure. There was no correlation between men’s lean body mass and these heart characteristics, even though men had significantly more lean body mass than women, as is commonly known.

This work is part of a larger body of literature that seeks to overcome previous bias in research favoring male subjects — both in mice and in people, said Candela Diaz-Cañestro, lead author of the study and postdoctoral researcher at the University of Hong Kong. As a researcher, she has been “trained to extrapolate these results to women, and as we have seen now in this study, for some details, we can’t do this extrapolation.”

Experts not involved in the study agreed that the research is a step toward finding new interventions, such as exercise prescriptions, tailored to women’s heart health needs. “This study helps us to begin to understand the mechanisms as to why men and women really develop cardiovascular disease differently and present differently,” said Emily Lau, a cardiologist at Massachusetts General Hospital and instructor of medicine at Harvard Medical School.

Women, for reasons largely still unknown, are more prone to certain heart conditions such as concentric hypertrophy, or heart wall thickening, and heart failure with preserved ejection fraction, “a disease of poor relaxation of the heart,” in which the muscle of the left ventricle stiffens, preventing the heart from filling properly with blood, said Tamara Horwich, a cardiologist and professor of medicine at the David Geffen School of Medicine at UCLA.

In the study, the researchers took X-rays of participants’ trunk, arms, and legs to measure their lean body mass and calculate their body composition. Using the supine bicycle setup, they measured their participants’ heart structure, function, and blood dynamics at rest and during exercise until they reached peak exercise over the course of 7- to 10-minute increments, taking ultrasounds of participants’ hearts in stages. The measurements and exercise regimen took about three hours each.

The study subjects were 70 healthy, white adults. Asked why other racial or ethnic groups weren’t included, Montero said the sophisticated physiological methods used did not allow the researchers to perform a large population study and “further studies are needed to assess the potential extrapolation of the present findings to other ethnicities.”

From participants’ exercise, the authors saw that women with higher lean body mass, exclusively, had blood vessels that showed less resistance to flowing out of the heart, allowing their hearts to work more efficiently. These women’s hearts could also fill up with more blood and pump out more blood than those with lower lean body mass.

The results “open the possibility that improving lean body mass, which can be improved with resistance training and other interventions, may be able to improve cardiovascular function and structure, and many strong diagnostic factors [related to] cardiac capacity and aerobic capacity in women,” Montero said.

Resistance training, or weight training to improve strength and endurance, is “not a type of exercise or type of recommendation that’s routinely given or thought about in preventive or primary or even cardiovascular care of women,” Horwich said. She also noted that total fat mass was not associated with any of the findings. The body mass index, commonly used to measure body fat based on height and weight, does not differentiate between a person’s fat mass and their lean body mass — the weight of everything else in the body apart from fat — which is why some athletes can have a high BMI but very little fat.

Women patients whose weight appears to be higher than would be expected for their height could be given medical advice to lose weight in order to improve their heart’s health. “Maybe that shouldn’t be the focus when it comes to women’s heart health,” given the study’s findings, Horwich said.

In other work, the authors found that women, with lower levels of lean body mass, who increased their lean body mass experienced improvements to their heart structure and function. In contrast, men, with higher levels of lean body mass, who increased theirs even more did not experience additional benefits to their heart. This suggests there may be a threshold above which an increase in the amount of lean body mass doesn’t correlate with cardiovascular factors. But where is that? “We don’t know exactly,” Montero said, “but it may be above 54 kg. [119 pounds] of lean body mass, which is among the lowest level in men and highest in women in our study.”

The authors said that after doing this observational study, they are now analyzing variables to further understand what it is specifically about women’s lean body mass that might be affecting these cardiovascular factors. They are also looking at how Asian populations are affected after initially testing white populations in North America. Another important step will be to understand these factors in patients who have heart disease.

Lau noted that it’s “challenging to make very large conclusions from a small sample size” of 70 participants in this case. Additionally, Horwich points out that “we’re not getting an exact measurement of the muscle, and … the quality of the muscle. There may be muscle that’s interlaced with fat, so it’s really a rough estimate.”

“For so long in medicine,” Lau said, “we’ve really treated men and women as essentially the same thing or if anything, we treat women as little men,” prioritizing women’s smaller size over other fundamental biological differences. It’s no surprise that there’s a “myth that heart disease is really a disease of men.”

When asked, “What’s the number one cause of death in women?” two-thirds of women in a 2009 American Heart Association survey were able to answer correctly: heart disease. Ten years later, in 2019, only 44% percent of women were able to say with confidence that heart disease is the leading cause of death in women.

These blind spots in women’s health persist. With this study and others like it, enough evidence is mounting, Montero said, that “we need to rewrite some sections of textbooks” to distinguish women’s cardiovascular system as markedly different from men’s.

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