The biology, the bias, and the evidence
By Harper Thomas
FOR DECADES, cardiovascular disease was framed as a “man’s disease.” That’s not because women are naturally protected, but because the science and clinical frameworks were built around male bodies. That legacy is finally shifting. Recent 2025 findings from large cohort studies and epidemiological research are reshaping how clinicians and the public understand women’s heart health. These studies underscore that women’s cardiovascular risk is not a watered-down version of men’s risk—it’s a distinct biological and social phenomenon.
BEYOND ESTROGEN
Traditional cardiovascular risk models focused on metrics like hypertension, cholesterol, and smoking. These are critical, but they miss important female-specific context. Pregnancy-related conditions, reproductive health, and psychosocial stressors all have measurable impacts on cardiovascular outcomes in women.
A landmark analysis presented at the American College of Cardiology’s 2025 annual meeting found that classic lifestyle and health risk factors (diet, physical activity, blood pressure, smoking, body mass index, glucose and lipid levels) had a stronger relative impact on cardiovascular outcomes in women than in men. Women with a poor risk profile experienced nearly five times the risk of heart disease compared to women with ideal health, whereas men with similar risk profiles had about 2.5 times the risk. This suggests that the same constellation of risk factors imposes a greater hazard in women, not just because of biology, but because of interactions among physiology, behavior, and health care access.
Such evidence challenges the 20th-century assumption that one risk model fits all sexes. Instead, it highlights that women’s aggregate risk isn’t a linear extension of men’s risk—it’s a distinct curve with its own peaks and inflection points.
Emerging research in 2025 is sharpening our understanding of how reproductive events intersect with long-term cardiovascular health. A major population study published in the Journal of the American Heart Association showed that women diagnosed with uterine fibroids—a common benign condition—had an 81-percent higher long-term risk of cardiovascular disease compared to women without fibroids. For women under age 40, the increased cardiovascular risk was more than 3.5-fold. While the mechanisms are still under investigation, this association suggests that reproductive system disorders may reflect underlying vascular or inflammatory pathways that also drive heart disease.
These disorders often go unmentioned during typical cardiovascular risk assessments, which are built around metabolic factors like LDL cholesterol or blood pressure.
THE STRESS/HEART RESPONSE
Another novel line of research highlights the link between psychological stress and heart health. A prospective analysis from the prestigious Harvard T.H. Chan School of Public Health found that women in the Nurses’ Health Study II who reported experiences of stalking or obtained restraining orders—a proxy for severe, chronic psychosocial stress—had a significantly higher risk of cardiovascular disease than women who did not have such experiences.
This tells us something critical about women’s cardiovascular biology: The heart responds to social and emotional stress in measurable physiological ways. Chronic stress activates inflammatory cascades, disrupts autonomic regulation, and impairs endothelial function—all pathways known to accelerate atherosclerosis.
LIFESTYLE MATTERS. BUT THE DOSE MAY VARY BY SEX
Lifestyle factors remain foundational to cardiovascular prevention. However, emerging evidence shows that women may derive significant cardiovascular benefit from levels of physical activity that differ from current broad guidelines. A study published in 2025 in The British Journal of Sports Medicine evaluated older women’s step counts and long-term outcomes. Women who recorded at least 4,000 steps on just one or two days per week had a 27-percent reduction in cardiovascular disease risk and a 26-percent reduction in mortality compared with women who never reached that threshold. More frequent stepping (three or more days per week) corresponded to even greater mortality benefits.
This study doesn’t mean that more activity isn’t better. But it does suggest that modest, achievable goals can confer meaningful protection in women, particularly older women whose risk escalates after menopause. Public health messaging that insists on “10,000 steps a day” may be demotivating; framing achievable thresholds can improve both adherence and outcomes.
This aligns with broader 2025 research highlighting that women may need different—and in some cases lower—exercise thresholds than men to achieve similar reductions in coronary disease risk. While guidelines still advocate for 150 minutes of moderate-to-vigorous activity weekly, differences in how exercise translates to risk reduction by sex justify more tailored prescriptions.
WHERE BIOLOGY AND SOCIETY CONVERGE
Sex differences in heart disease risk are biologically rooted, but they are also shaped by health care systems and social forces. Women are consistently underrepresented in clinical trials, despite evidence that sex-specific data improves care precision. This has real consequences: Women often present with atypical symptoms during myocardial infarction, leading to delayed diagnosis and higher mortality. Meanwhile, guideline-recommended therapies and diagnostics (e.g., statins, angiography) are less likely to be applied to women with comparable risk profiles.
Progress is visible but uneven. National campaigns like Go Red for Women and specialized cardiovascular programs are driving awareness and research inclusion, but systemic gaps remain.
THE PATH FORWARD DRIVEN BY PRECISION
The evolving scientific consensus is clear: Heart health in women demands precision, not approximation. Cardiovascular risk models must integrate sex-specific physiological markers, reproductive history, psychosocial stress, and more nuanced lifestyle metrics. Clinical care should anticipate that women may exhibit different pathways to disease and respond differently to interventions.
As research continues to unpack sex-specific mechanisms of heart disease, the future of women’s heart health will be defined not by male patterns scaled down, but by models built for women from the ground up. The science is here; the challenge now is translating it into practice.
