Nontraditional causes linked to many heart attacks in younger women

Researchers from Mayo Clinic have identified factors other than clogged arteries leading to heart attacks in women aged under 65 years, publishing their findings in the Journal of the American College of Cardiology.¹

Nontraditional factors were linked to over 50% of heart attacks in this population, including embolism, spontaneous coronary artery dissection (SCAD), and other conditions. While women presented with fewer heart attacks than men, these patients were more likely to have their primary causes of heart attack misdiagnosed.

“This research shines a spotlight on heart attack causes that have historically been under-recognized, particularly in women,” said Claire Raphael, MBBS, PhD, study author and interventional cardiologist at Mayo Clinic. “When the root cause of a heart attack is misunderstood, it can lead to treatments that are less effective—or even harmful.”

Differences between men and women

Frequent misdiagnoses were reported when SCAD, often presenting in younger, otherwise healthy women, was the cause of a heart attack. In these cases, plaque buildup was often cited as the source of a heart attack.

Both men and women presented with atherosclerosis as the most common source of heart attacks, but the rate of atherosclerosis was only 47% in women vs 75% in men. Additionally, despite having lower heart injury levels, patients with stressors such as anemia or infection leading to a heart attack had the greatest 5-year mortality rates.

Investigators highlighted other key findings, such as 68% of overall heart attacks being caused by typical plaque buildup, but the majority in women being linked to nontraditional causes. A 6-fold increase in the prevalence of SCAD was also reported in women vs men.

Stress-related triggers and mortality outcomes

Overall, stressors such as anemia or infection were the second-most common source of heart attacks. Additionally, the 5-year mortality rate from these sources was the most significant at 33%.

Under 3% of heart attack cases were unexplained, making it rare for a source to not be identified. Investigators concluded that this data may be used to guide the diagnosis and management of heart attacks in younger adults.

“Clinicians must sharpen their awareness of conditions like SCAD, embolism, and stress-related triggers, and patients should advocate for answers when something doesn’t feel right,” said Rajiv Gulati, MD, PhD, senior author and chair of the Division of Interventional Cardiology and Ischemic Heart Disease at Mayo Clinic.

Sex-specific risks

Sex-specific outcomes have also been reported following a heart attack.² At the European Society of Cardiology (ESC) Congress 2025, this data was highlighted alongside research indicating worse outcomes among women taking beta-blockers. These included increased mortality, reinfarction, and hospitalization for heart failure risks.

The trial was launched in 2018 and assessed the impact of beta-blocker therapy in patients with heart failure. Overall, the hazard ratio (HR) for adverse events in patients taking beta-blockers vs no beta-blockers was 1.04.

Notably, while the difference in incidence rates significantly differed among women with vs without beta-blockers, no significant difference was observed among men, with an HR of 0.94. This highlighted greater rates of the primary composite outcome among women vs men.

Implications

This increase in risk was primarily driven by increased mortality, most prominent in women with preserved left ventricular ejection fraction and those taking high doses of beta-blockers.

“Our findings suggest that a one-size-fits-all approach may not be appropriate and that sex-specific considerations are crucial for cardiovascular interventions prescriptions,” said Xavier Rosselló, MD, PhD, study investigator and cardiologist at University Hospital Son Espases in Mallorca.

References

1. Mayo Clinic study reveals hidden causes of heart attacks in younger adults, especially women. Mayo Clinic. September 15, 2025. Accessed September 17, 2025. https://www.eurekalert.org/news-releases/1098036.
2. Campbell P. Beta-blockers linked to worse outcomes in women following a heart attack. Contemporary OB/GYN. August 31, 2025. Accessed September 17, 2025. https://www.contemporaryobgyn.net/view/beta-blockers-linked-to-worse-outcomes-in-women-following-a-heart-attack.