How can a 39-year-old premenopausal woman experience a myocardial infarction without diabetes mellitus or hypertension?

Myocardial Infarction in Young Premenopausal Women Without Traditional Risk Factors

A 39-year-old premenopausal woman can experience myocardial infarction through several distinct non-atherosclerotic mechanisms, most commonly spontaneous coronary artery dissection (SCAD), coronary vasospasm, microvascular dysfunction, or Type 2 MI from supply-demand mismatch—even in the complete absence of diabetes or hypertension. 1, 2, 3

Primary Mechanisms in Young Women

Spontaneous Coronary Artery Dissection (SCAD)

• SCAD accounts for 20-35% of all acute coronary syndromes in women under 60 years of age, making it the leading cause in this demographic despite representing only 4% of all MI cases overall 4, 1
• The pathophysiology involves spontaneous intramural hematoma formation within the coronary artery wall, with or without an intimal tear 1
• Over 90% of SCAD cases occur in women, with fibromuscular dysplasia present in up to 72% of patients—the strongest predisposing condition 1
• Precipitating factors include intense emotional stress, physical exertion, Valsalva-type activities, and the peripartum period 1
• Connective tissue disorders (systemic lupus erythematosus, Marfan syndrome) and hormonal fluctuations predispose to arterial wall weakening 4, 1

Coronary Vasospasm

• Focal coronary spasm can cause complete or near-complete epicardial artery occlusion, resulting in transmural ischemia and MI even with angiographically normal vessels 3
• The mechanism involves dysfunctional endothelium exposing smooth muscle to vasoconstrictors (catecholamines, thromboxane A2, serotonin) and an imbalance favoring vasoconstriction over vasodilation 3
• Attacks occurring in clusters with early morning predominance indicate higher MI risk, with cardiovascular death rate of 0.5% per year and MI risk of 1.2% per year during active disease phases 3
• Provocative testing with ergonovine is positive in up to 20% of patients with recent MI, suggesting vasospasm as a contributing mechanism 3

Coronary Microvascular Dysfunction

• Women have a higher proportion of acute coronary syndrome caused by coronary microvascular dysfunction, plaque erosion, and stress-related (Takotsubo) cardiomyopathy rather than classical plaque rupture 2, 3
• Microvascular spasm, impaired dilation, and extramural microvascular compression can all cause myocardial ischemia without epicardial obstruction 3
• A purely anatomical diagnostic approach using invasive angiography may fail to diagnose microvascular angina, leading to false reassurance when no obstructive lesions are identified 3

Type 2 Myocardial Infarction

• Type 2 MI occurs when myocardial necrosis results from oxygen supply-demand imbalance without coronary plaque instability 3
• Precipitants include increased oxygen demand (fever, tachycardia, thyrotoxicosis), reduced coronary blood flow (hypotension, dehydration), and reduced oxygen delivery (anemia, hypoxemia) 3
• Severe anemia (hemoglobin ≤5 g/dL) directly impairs myocardial oxygen delivery and can precipitate Type 2 MI 3

Clinical Recognition and Diagnostic Approach

Symptom Presentation

• Women frequently present with atypical symptoms beyond chest pain, including nausea, back pain, jaw pain, dyspnea, epigastric discomfort, fatigue, and diaphoresis, which are often misdiagnosed or dismissed 2, 5
• Chest pain remains the most common symptom but women describe it as pressure, tightness, heaviness, or burning rather than crushing pain 2
• 10% of women with ACS present with jaw pain versus 4% of men, and 61.9% of women ≤55 years report pain in jaw, neck, arms, or between shoulder blades 2

Risk Factors Beyond Diabetes and Hypertension

• Autoimmune/inflammatory disease, fibromuscular dysplasia, polycystic ovary syndrome, early menopause, and history of pre-eclampsia are risk factors preceding ACS among younger women 6
• Hypertensive disorders of pregnancy (gestational hypertension and pre-eclampsia) increase lifetime cardiovascular disease risk but are seldom considered in cardiovascular risk assessment 2
• Family history of premature coronary artery disease, hyperlipidemia, and smoking remain important even without diabetes or hypertension 2, 7

Diagnostic Workup

• Obtain immediate ECG looking for ST-segment elevation, ST-segment depression, T-wave abnormalities, or new Q waves 2
• Measure high-sensitivity troponin—elevation indicates myocardial necrosis requiring further evaluation 2, 3
• Coronary angiography is essential but may show no obstructive disease (MINOCA occurs in 5-25% of all MI presentations, particularly in women) 3
• Cardiac MRI identifies the underlying cause in up to 87% of MINOCA patients and should be pursued when angiography shows no obstructive disease 3
• Intracoronary imaging (intravascular ultrasound or optical coherence tomography) can be key to securing the diagnosis of SCAD 4, 1

Management Considerations

Acute Management

• Women with high-risk features (elevated troponin, ST-segment changes, hemodynamic instability) should receive an invasive strategy with coronary angiography similar to men 2
• Conservative management is preferred for stable SCAD patients, as revascularization attempts can worsen dissections 1
• For vasospastic angina, calcium channel blockers (diltiazem, nifedipine) alone or combined with long-acting nitrates prevent coronary arterial spasm in almost all patients 3
• For Type 2 MI, treat the underlying cause (aggressive rehydration for dehydration, transfusion for anemia) rather than pursuing reperfusion therapy 3

Secondary Prevention

• Beta-blockers are strongly recommended for long-term management of SCAD as they reduce recurrence risk 1
• Aggressive blood pressure control is essential as hypertension is an independent predictor of recurrent SCAD 1
• Women should receive the same pharmacological therapy as men (aspirin, P2Y12 inhibitors, anticoagulants, beta-blockers, ACE inhibitors, statins) with careful attention to weight-based and renal function-based dosing 2

Critical Pitfalls to Avoid

• Never dismiss atypical symptoms (jaw pain, epigastric pain, nausea) as non-cardiac without excluding cardiac causes first, especially in women over 35 2
• Traditional risk score tools and physician assessments often underestimate risk in women and misclassify them as having nonischemic pain 2
• Women are less likely to receive guideline-indicated medical and invasive care compared to men at similar risk, contributing to worse outcomes 2, 5
• Younger women (<50 years) face particularly poor long-term outcomes, with all-cause mortality significantly higher than younger men at 11.2 years follow-up 2
• Failing to obtain ECG in patients with epigastric pain or jaw pain, especially in high-risk populations (women, elderly, those with cardiovascular risk factors) 2
• Nearly 40% of women have persistent or worsening symptoms at 1-year post-discharge, highlighting the need for aggressive secondary prevention and close follow-up 2

Prognosis and Follow-Up

• The mortality rate after acute MI is greater for women than for men, though older age and diabetes account for much of this difference 4
• Despite having less obstructive coronary artery disease on angiography, women have worse cardiovascular outcomes even after adjustment for risk factors and imaging findings 2
• Participation in cardiac rehabilitation is associated with improved outcomes and must be strongly encouraged 5
• Attention to potential post-ACS depression and anxiety is an important aspect of holistic care, as women with ACS frequently suffer from depression 5, 6