Nontraditional Causes of MI Found Common in Younger Adults, Especially in Women

A new Mayo Clinic study challenges long-standing assumptions about myocardial infarction (MI) in adults under 65, showing that many heart attacks, and particularly for women, stem from causes other than atherosclerotic plaque.

The findings, published in the Journal of the American College of Cardiology, are based on 15 years of population data from the Rochester Epidemiology Project and represent one of the most comprehensive assessments of MI mechanisms in younger adults, according to the Mayo Clinic.

Researchers, led by Rajiv Gulati, MD, PhD, chair of the division of interventional cardiology in the department of cardiovascular medicine at Mayo Clinic, identified 1,474 index MIs between 2003 and 2018. While more than two-thirds (68%) overall were attributed to atherothrombosis, more than half of heart attacks in women under 65 were caused by nontraditional factors such as spontaneous coronary artery dissection (SCAD), embolism, or stressors like anemia and infection. In contrast, 75% of MIs in men were plaque-related.

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

Sex Differences in MI Etiology

Gulati, Raphael, and colleagues found that SCAD was nearly 6 times more common in women than men (3.2 vs 0.9 per 100,000 person-years [PY]) and was misclassified in more than 50% of cases at initial presentation.

Although women overall had lower rates of MI than men (48 vs 137 per 100,000 PY), nonatherothrombotic causes comprised the majority of cases in women:

• 47% atherothrombosis vs 75% in men
• 34% secondary MI due to supply/demand mismatch vs 19
• 11% SCAD vs 0.7%

Both men and women with atherothrombosis were of similar age (55 ± 8 years vs 54 ± 8 years), but women had a higher burden of cardiovascular risk factors despite similar disease extent on angiography, according to the results.

Stress-Related Triggers, Outcomes

The researchers reported that secondary MIs linked to systemic stressors such as infection or anemia were the second-most common cause overall and carried the highest mortality. Five-year all-cause mortality reached 33% in this group, compared with 8% after atherothrombosis, 8% after embolism, and 0% after SCAD.

“Understanding why a heart attack happened is just as important as treating it,” Raphael said. “It can mean the difference between recovery and recurrence.”

Clinical Implications

Gulati et al underscored that misdiagnosis of SCAD remains a key concern, as inappropriate interventions such as stenting can increase complications. They emphasized the need for heightened clinical vigilance and sex-specific management strategies.

“Our research highlights the larger need to rethink how we approach heart attacks in this patient population, and for younger adult women, in particular,” Gulati said in the Mayo statement. “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.”

Looking Ahead

Unexplained MIs were rare, accounting for fewer than 3% of cases after expert review. The authors note that the cause-specific findings provide a framework for individualized treatment and risk stratification.

"These cause-specific findings have implications for individualized management and risk stratification and provide epidemiologic benchmarking for future studies," they concluded.