What is the relationship between menarche at age 10 years or pregnancy outcome at age 30 years and cardiovascular (CV) risk at age 60 years? Canadian experts in women’s CV health are getting the word out about the fundamental pathophysiologic differences between men and women when it comes to CV disease (CVD). They are making inroads, but significant work still lies ahead.

Through her research, Colleen Norris, PhD, research lead of the CKHui/LHHW Women’s Heart Health Research Collaborative at the University of Alberta, has increased the understanding of how sex hormones affect women’s CV health as they age. Norris also is Cavarzan Chair in Women’s Health Research at the Women’s and Children’s Health Research Institute in Edmonton.

Her interest was piqued during her time as a postdoctoral student in epidemiology, when it was discovered that the outcomes of interventions for coronary artery disease differed between men and women no matter which variables were considered. Differences in care were one potential explanation for the diverging outcomes. “It was a battle in those days to [claim] that women were treated differently,” she told Medscape News Canada. “Everyone would say, ‘I treat women the same way I do men.’”

Physiological Sex Differences

But factors other than care also contribute to differences in outcome. Norris is lead author of a 2020 review on the state of the science on CVD in Canadian women, which summarized how sex hormones, particularly estrogen, affect physiologic and pathophysiologic CV response across women’s lifetimes. CV risk factors in women include events that affect hormone levels at any point in their lives, such as early menarche, amenorrhea due to intense exercise, or preeclampsia during pregnancy.

The review highlighted the crucial need for more research in this area, particularly in Canada. The problem is reflected in the lack of Canadian clinical guidelines that specifically address women. The lack of female representation in clinical trials for CVD is well-known, but the issue goes much further than that, said Norris. There is a need for research exclusively in women to better understand the influence of sex hormones on CV risk over women’s lifetimes.

In Canada, much of the research into sex differences in cardiology is spearheaded by the Canadian Women’s Heart Health Alliance (CWHHA), of which Norris is a member. Another CWHHA member, Paula Harvey, BMBS, PhD, physician in chief at Women’s College Hospital in Toronto, said that CV care for women in Canada has improved in recent years. “The more we study women and CVD, the more we realize what we don’t know, and the more we have to research and develop a body of evidence for implementation,” she said.

Presentation and Diagnosis

“We’ve learned that, yes, women are at risk for atherosclerotic disease of the major coronary arteries, particularly postmenopausal women, and the further away from onset of menopause, the [greater the] increase in risk,” said Harvey. “But there are also other conditions, like microvascular disease, where there is altered function of the smaller vessels in the heart that can cause lack of blood flow to the muscles. Women have increased risk for coronary artery spasm [ie, myocardial infarction with no obstructive coronary artery disease and ischemia with nonobstructive coronary artery disease]. Women are more likely to have spontaneous coronary artery dissection. Women are more likely to have takotsubo.

“All those things can cause a heart attack in a woman where you don’t have a positive coronary angiogram,” Harvey continued. “We know these conditions are not benign. If you survive the heart attack, you have an increased CV risk factor burden, and we need to understand the pathophysiology, so we know how to investigate and treat these conditions. Our diagnostic modalities are still pretty poor for microvascular disease and for spasm.”

Facilitating Change

A third CWHHA member is Sharon Mulvagh, MD, codirector of the Women’s Heart Health Clinic at the QEII Health Sciences Centre in Halifax. Mulvagh, the former director of the Women’s Heart Clinic at the Mayo Clinic in Rochester, Minnesota, came to Canada in 2016 to improve women’s CV care in this country. She described the situation at the time as “really bleak.” Only two clinics in the country focused on women’s heart health. Today, there are six. Mulvagh also helped establish the Wear Red Canada Day, which takes place annually on February 13, to help raise awareness about CVD in women.

“We’ve made major inroads in the last decade,” she said. In 2018, just as Mulvagh’s efforts were getting off the ground, the Heart and Stroke Foundation of Canada published a report titled “Ms. Understood: Women’s Hearts Are Victims of a System That Is Ill-Equipped to Diagnose, Treat and Support Them.” This report gave her efforts a big boost.

Resources for Clinicians

More research in women’s CV health is needed, and the current knowledge base is not always being implemented clinically. Norris, Harvey, and Mulvagh are coauthors of the CWHHA ATLAS, which was published in CJC Open in 2020. Its nine chapters provide in-depth information on the pathophysiologic underpinnings of sex differences in CVD, diagnostic and treatment considerations, socioeconomic considerations, knowledge gaps, and next steps.

Ultimately, all three experts agree that being a better cardiologist for female patients entails taking the time to listen and ask questions, not just about current symptoms, but also about stressors and lifespan risk factors such as pregnancy complications. Women may not use the same language as men, so it is important to read between the lines.

Recent research by Maneesh Sud, MD, interventional cardiologist at Sunnybrook Research Institute in Toronto, underscores the importance of understanding how to care for female cardiology patients. Sud found that while the absolute risk of CVD events is higher in men than women, as CV health declines, the relative impact of eight modifiable risk factors on CVD risk may be greater in women than men. In a poster presented at the 2025 Canadian Cardiovascular Congress, he showed, using the same Ontario Health Study database, that self-reported health status also appeared to have more of an impact on CVD risk in women than men. It may well be that addressing risk factors in female patients has powerful long-term effects.