Cardiovascular disease has been seen as a man's disease for decades, yet it claims more women's lives than any other condition.
For generations, cardiovascular disease has been widely perceived as a predominantly male affliction, symbolized by the classic image of a middle-aged man clutching his chest. This perception has shaped decades of research, diagnosis, and treatment. The reality, however, tells a different story. Cardiovascular disease is now more common in women than in men, representing the leading cause of mortality for women globally 1 3 . This startling fact underscores a critical blind spot in medical science and highlights the urgent need to understand how heart disease manifests differently across sexes.
Recent research has revealed that these differences extend far beyond symptoms to encompass risk factors, disease progression, and treatment outcomes. The traditional one-size-fits-all approach to cardiovascular medicine is increasingly showing its limitations, leaving women vulnerable to underdiagnosis, undertreatment, and worse outcomes 3 . This article explores the revolutionary shift toward sex-specific cardiovascular research and what it means for the future of heart health for everyone.
For decades, women have been underrepresented in cardiovascular clinical trials, and the assumption persisted that risk factors affected men and women similarly 1 . We now know this is not the case. While traditional risk factors like high blood pressure, diabetes, and obesity impact both sexes, their relative strength and mechanisms can differ significantly.
Women with diabetes face a greater threat from heart disease than men with diabetes. Obesity, while impactful for both, is more stigmatized in women and they may respond differently to weight-loss interventions 3 .
High blood pressure often develops later in women, typically after menopause, and is less likely to be recognized and controlled 3 .
Women's lipid profiles change throughout their lifespan, becoming more atherogenic after menopause, yet dyslipidemia is often treated less aggressively in women 3 .
| Risk Factor | Impact in Women vs. Men | Key Disparities |
|---|---|---|
| Smoking | Higher relative risk for women 3 | Women have a harder time quitting; smoking has more severe CV consequences 3 |
| Diabetes | Higher relative risk for women 3 | Women are less likely to achieve care goals; higher risk of CV events post-diagnosis 3 |
| Hypertension | Develops later, post-menopause 3 | Less likely to be recognized and treated; poorer blood pressure control 3 |
| Mental Health | Conditions like depression and anxiety are more common and increase CVD risk 3 | Gender disparities in recognition and treatment lead to poorer cardiovascular outcomes 3 |
Perhaps the most significant advance in our understanding is the recognition of female-specific risk factors. A woman's reproductive history provides a unique window into her future cardiovascular health 1 .
Conditions like preeclampsia and gestational diabetes are not just temporary complications. They are powerful predictors of future cardiovascular risk, with women who have had preeclampsia facing a two- to four-times higher risk of cardiovascular disease later in life 3 .
Affecting 5-13% of women, PCOS heightens the risk of metabolic syndrome, type 2 diabetes, and hypertension, and is associated with a nearly 30% increased risk of CVD events 3 .
Early menarche, infertility, and spontaneous pregnancy loss have all been linked to increased risks of heart failure, coronary disease, and stroke 3 .
| Risk Factor | Description | Associated Cardiovascular Risk |
|---|---|---|
| Preeclampsia | Hypertensive disorder of pregnancy | 2-4 times higher risk of future CVD, stroke, and heart failure 3 |
| Early Menopause | Onset of menopause before age 45 | Higher incidence of coronary heart disease, stroke, and heart failure 3 |
| Polycystic Ovary Syndrome (PCOS) | A common hormonal disorder | ~30% increased risk of CVD events; higher rates of metabolic syndrome and hypertension 3 |
| Gestational Diabetes | Diabetes diagnosed during pregnancy | Increased risk of developing type 2 diabetes and cardiovascular disease later in life 3 |
While the physiological differences are clear, the fundamental biological mechanisms have remained elusive. A landmark 2025 international study published in Nature Communications, led by researchers from Queen Mary University of London, set out to change this by performing the largest-ever analysis of how sex regulates the human plasma proteome—the thousands of proteins circulating in our blood 9 .
The research team adopted a meticulous multi-step approach to unravel the complex links between genes, proteins, and sex. The study analyzed data from 56,000 males and females from the UK Biobank and the Fenland study, categorizing sex based on chromosomal information (XX or XY) 9 .
The core of their investigation involved conducting a genome-wide association study (GWAS) on approximately 6,000 blood proteins. This powerful method scans markers across the complete set of DNA to find genetic variations associated with particular traits—in this case, protein levels.
A critical step was performing these analyses separately for males and females. This allowed the scientists to directly compare how genetic variants influence protein levels in each sex and to identify which proteins showed baseline level differences 9 .
Analysis of 56,000 participants from UK Biobank and Fenland study 9
GWAS on approximately 6,000 blood proteins 9
Separate analysis for males and females to identify differences 9
Examination of sex-dependent genetic regulation of protein levels 9
of the 6,000 proteins studied showed significant differences between males and females 9
proteins had sex-dependent genetic regulation out of 6,000 studied 9
The findings were striking. The team discovered that for about two-thirds of the 6,000 proteins studied, circulating levels differed significantly between males and females 9 . This massive difference underscores the profound biological divergence at the molecular level.
When the researchers dug deeper, however, they found a surprise. They expected to see many differences in the genetic "switches" (the variants that regulate protein levels) between the sexes. Instead, they found that only a very small fraction—around 100 out of the 6,000 proteins—had sex-dependent genetic regulation 9 . This means that while protein levels are very different, the underlying genetic control of those levels is largely the same in men and women.
The lead author, Mine Koprulu, emphasized the implication: "what's causing these differences isn't solely down to differences in their genetics" 9 .
| Research Tool | Function in the Study |
|---|---|
| UK Biobank & Fenland Study Data | Large-scale, high-quality biomedical databases providing genetic, health, and biomarker data from hundreds of thousands of participants 9 . |
| Genome-Wide Association Study (GWAS) | A method to identify genetic variants across the genome that are associated with a specific trait (e.g., protein levels), allowing for unbiased discovery 9 . |
| Plasma Proteome Profiling | High-throughput technologies to measure the levels of thousands of proteins from a single blood sample, providing a snapshot of an individual's molecular state 9 . |
| Sex-Stratified Analysis | The process of separating and analyzing data for males and females independently, which is crucial for identifying sex-specific effects that would be masked in combined analyses 9 . |
Despite growing awareness, significant challenges remain. A 2025 analysis of over 94,000 COVID-19-related publications revealed that only 4% examined sex or gender-specific health considerations, highlighting a persistent gap in biomedical research 2 . This neglect has real-world consequences. In cardiology, women with heart attacks are less likely to receive timely interventions and are more likely to be misdiagnosed 3 .
of COVID-19 publications examined sex/gender-specific considerations 2
The future lies in precision medicine. As Professor Claudia Langenberg, a senior author of the proteome study, notes, "Our results clearly show that with very few exceptions... insights arising from studying these variants apply to both sexes." This provides a foundation for more equitable drug development 9 . The next frontier is integrating this biological understanding with gender-related factors—the social, cultural, and behavioral dimensions of health—to create truly personalized and effective cardiovascular prevention and treatment for all .