Nov. 18, 2025
Mayo Clinic cardiovascular researchers found that the causes of a heart attack, also called myocardial infarction (MI), in patients age 65 and under — particularly women — are not often due to atherosclerosis. The study was published in JACC.
For more than half of women age 65 and under, MI was due to rarer causes including spontaneous coronary artery dissection (SCAD), embolism, and stress-related triggers such as anemia or infection.
"This is the first comprehensive epidemiologic study of MI in younger patients. We researched MI in patients age 65 and under and discovered that MI due to rarer causes is much more common than previously thought. There are also sex differences in MI causes. The findings can change how MI is diagnosed and managed in younger adults," says Rajiv Gulati, M.D., Ph.D., an interventional cardiologist and chair of Interventional Cardiology and Ischemic Heart Disease at Mayo Clinic in Rochester, Minnesota. Dr. Gulati is senior author of the study.
MI in Olmsted County
The JACC study focused on more than 15 years of data from the Rochester Epidemiology Project (REP). Medical records and cardiac imaging were examined of Olmsted County residents who had an abnormality of the heart blood test troponin. The REP allows researchers to study data of enrolled community members in Minnesota and Wisconsin who agreed to share their medical records to help improve health for people locally and globally.
The researchers found that MI occurred more in men (75%) than in women (47%). When women had MI, the underlying causes were often misdiagnosed.
Of the 1,474 events classified as index MI over a 15-year period, 68% were caused by atherothrombosis. In women, MI was mostly due to nontraditional causes. Less than 3% of the patients experienced unexplained heart attacks.
Seeing SCAD
SCAD was frequently missed and misclassified in women as MI caused by plaque buildup. "There is a critical need for heightened recognition of nonatherosclerotic causes of acute coronary syndrome in younger patients and younger women. Determining the underlying cause of MI can help avoid the wrong treatment, prevent recurrence and save lives," says Claire E. Raphael, M.B.B.S., Ph.D., an interventional cardiologist at Mayo Clinic in Rochester, Minnesota, and first author of the study.
Younger, relatively healthy women are often the patients affected by SCAD. The study revealed that SCAD was nearly six times more common in women than men. "It's important to perform careful angiography with consideration of intracoronary imaging where diagnosis is unclear. This can avoid misdiagnosis of nonatherothrombotic causes of MI," says Dr. Raphael.
Since younger women often do not show traditional cardiovascular risk factors, they may not receive a full cardiac workup. "We already knew that women were more likely to have nonatherothrombotic MI compared to men. What surprised us was how common this was: More than half of MI in women 65 and under was due to nonatherothrombotic causes," says Dr. Raphael. "It's essential that chest pain presentations in these patients prompt an ECG and troponin assessment regardless of baseline risk profile. This helps avoid underdiagnosis and delayed treatment."
Invasive coronary angiography is standard for establishing the diagnosis and meticulous technique is vital. "A key theme from our study is that accurate diagnosis is essential for guiding management decisions in SCAD. Achieving this requires deliberate, high-quality invasive imaging in most cases," says Dr. Gulati. "Awareness must drive evaluation strategies. Nontraditional presentations of acute coronary syndrome should be anticipated. With advancements in high-quality imaging and noninvasive modalities, we can now secure a definitive diagnosis in many of these cases."
Imaging and diagnostic tips:
- Maintain suspicion for nontraditional etiologies — not all MIs are atherosclerotic.
- Identify nontraditional causes with meticulous angiographic performance and scrutiny.
- Selectively using intravascular imaging may be key for diagnosis.
- MRI and adjunctive imaging can be crucial in getting a primary diagnosis.
Looking ahead
Continually seeking the hidden causes of MI is another way that Mayo Clinic cardiovascular specialists are finding solutions for patients.
"The study underscores the importance of correct diagnosis of the etiology of MI, since we know that treatments are different depending on the etiology. It will also allow benchmarking for future studies on treatment of these rarer causes of MI," says Dr. Raphael.
Most of the patients in this study were white Americans. Future research using large registries could help determine the cause of MI across different ethnic, racial and geographic populations.
"This discovery that there are many differences in the causes of MI between men and women will lead the way for new studies to understand sex differences," says Dr. Gulati. "Ultimately, our research shows a critical need to expand how to recognize MI in younger women. Improved recognition will enable more tailored management pathways to help patients."
For more information
Raphael CE, et al. Causes of myocardial infarction in younger patients: Troponin-elevation in persons ≤ 65 years old in Olmsted County. JACC. 2025;86:877.
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