Overview
A 15-year, population-based Mayo Clinic study (OCTOPUS: Olmsted Cardiac Troponin in Persons Under Sixty-six) found that heart attacks in people 65 and younger — especially women — often stem from causes other than the classic cholesterol-driven artery blockage. The investigators used a troponin-driven approach, including every troponin-positive event from Olmsted County, Minnesota, between 2003 and 2018, rather than limiting cases to typical chest‑pain presentations.
Methods
The study captured 4,116 troponin-positive events in 2,790 people. Each case was reviewed by two cardiologists (with additional experts resolving disagreements) using clinical records, imaging, and coronary angiograms. Events were classified into six causes: atherothrombosis (traditional arterial plaque rupture/thrombosis), spontaneous coronary artery dissection (SCAD), embolism (clot from elsewhere), coronary artery spasm, supply–demand mismatch (secondary ischemia), and unexplained causes.
Key findings
– Causes differed markedly by sex. About 75% of heart attacks in younger men were atherothrombotic, while only 47% of events in younger women were atherothrombotic. The majority (53%) of women’s events were non-atherothrombotic.
– SCAD was far more common in women: it caused 11% of women’s heart attacks versus under 1% in men. SCAD was frequently missed at first: 55% of SCAD cases were initially misdiagnosed as atherothrombosis or unexplained.
– Misdiagnosis is important because standard treatments for blocked arteries (angioplasty or stenting) can worsen SCAD when the arterial wall is torn.
– Overall incidence rates (per 100,000 person-years) were lower in women: 48 in women versus 137 in men. For atherothrombotic events the rates were 23 (women) versus 105 (men).
– When women did have atherothrombotic heart attacks, angiograms showed a similar burden of coronary disease as men, but women had higher rates of diabetes and hypertension, suggesting they may require more or different risk factors to reach comparable plaque burden.
– Secondary heart attacks (triggered by another serious illness, such as severe anemia or hypotension) carried the worst prognosis, with a five-year mortality of 33%. In contrast, SCAD patients in this cohort experienced no deaths during follow-up.
Clinical implications
The findings argue that emergency and cardiology teams should broaden diagnostic thinking for younger patients — particularly women — instead of defaulting to protocols based mainly on older men with atherothrombosis. Identifying SCAD, embolism, spasm, and supply–demand ischemia matters because management differs: some interventions used for atherothrombosis can be harmful when applied to non-atherothrombotic causes.
Practical advice for patients and clinicians
– Do not dismiss symptoms by age or sex. Young age or female sex does not rule out a heart attack.
– Know common presentations. Women may have atypical symptoms (shortness of breath, nausea, indigestion, upper abdominal pain, dizziness, or fainting) rather than classic crushing chest pain.
– Communicate clearly. Describe symptom quality and timing (for example: sudden neck/jaw ache with nausea and lightheadedness) and explicitly express concern about a possible heart attack.
– Ask for essential initial tests when appropriate: an electrocardiogram (ECG) and cardiac troponin measurements are key. If results or symptoms remain concerning, further imaging or coronary angiography should be considered with attention to SCAD and other non-atherothrombotic causes.
– If you feel your concerns are being minimized, request a second opinion or bring a trusted person to help advocate for a thorough evaluation.
Conclusion
This troponin-driven, population-based study shows that more than half of heart attacks in women under 65 arise from causes other than traditional atherothrombosis. Recognizing these differences can reduce misdiagnosis, prevent potentially harmful interventions, and help ensure patients receive the appropriate, potentially life-saving care.
