What Causes a Heart Attack in a Healthy Woman? The Three Explanations That Fit When Risk Factors Don't

She was 44. Regular exerciser. LDL 108. Blood pressure 122/76. Nonsmoker. Her physician had told her a year earlier that her heart was in excellent shape. She had a STEMI. Her angiogram showed no obstructive plaque. The cardiology team told her family: we are not sure what caused this.

The cause was SCAD, spontaneous coronary artery dissection. Her left anterior descending artery’s inner lining had torn. The tear obstructed blood flow. The plaque that risk calculators and lipid panels were looking for was never there.

“Healthy” is a category that standard cardiovascular risk assessment defines by the absence of traditional risk factors. It does not mean no cardiovascular risk. For women, it often means risk factors that were never measured, risk mechanisms that are female-predominant, and a cardiovascular event that arrives with no prior warning from the tools that were supposed to prevent it.

The three mechanisms that standard screening misses in women

Mechanism 1: SCAD, Spontaneous Coronary Artery Dissection

SCAD is not caused by plaque accumulation, high cholesterol, or traditional cardiovascular risk factors. It is a tear in the arterial wall of a coronary artery, specifically, in the tunica media or the intima-media junction , that creates a false lumen alongside the true lumen. Blood entering this false lumen expands the tear, compressing the true lumen and obstructing blood flow.

SCAD accounts for approximately 35% of acute MIs in women under 50 and a meaningful proportion in women up to 60. It is rare in men (approximately 90% of SCAD cases occur in women). 5 / Solid

The demographics of SCAD patients: more often women, often athletic, often perimenopausal or postpartum, often with connective tissue abnormalities (fibromuscular dysplasia is found in approximately 86% of SCAD patients on coronary imaging). Many have no prior cardiovascular history, no elevated cholesterol, no hypertension, and no positive family history.

What triggers SCAD: severe physical exertion (particularly Valsalva-type, extreme weight lifting, labor contractions), severe emotional or psychosocial stress, hormonal changes (pregnancy, perimenopause, fertility treatments involving ovarian stimulation), and, in some cases, no identified precipitant.

The critical distinction for treatment: standard ACS treatment (stenting, antiplatelet therapy) is contraindicated or potentially harmful in SCAD. Stenting can propagate the dissection down the vessel. Medical management (anti-ischemic medications, beta-blockers) is the preferred approach for most SCAD cases. A woman presenting with STEMI whose angiogram shows a SCAD pattern needs a team experienced in SCAD management, not routine stenting.

Mechanism 2: Plaque erosion

The dominant mechanism in men’s heart attacks is plaque rupture: a large, lipid-rich, vulnerable plaque with a fibrous cap that ruptures under hemodynamic stress, exposing its necrotic core and triggering massive clot formation. The plaques that rupture are typically large, causing 50-70% stenosis that would be visible on angiography.

In women, a different mechanism is more common: plaque erosion. The surface endothelium of a plaque sheds, losing the smooth, non-thrombogenic endothelial layer , without the fibrous cap rupturing. The exposed collagen and underlying tissue activate the coagulation cascade and trigger localized thrombus formation over the eroded surface.

The erosion plaques are typically smaller: 20-40% stenosis, well below the threshold for clinical detection by angiography or coronary CT. A woman can have a STEMI from plaque erosion on a plaque that her angiogram would describe as “minimal atherosclerosis.” 5 / Solid

Plaque erosion is more common in younger women, in women with lower LDL, and in women with higher inflammatory markers (hs-CRP). This pattern is consistent with erosion being an inflammatory event at the endothelial surface rather than a mechanical rupture of a large, cholesterol-laden plaque.

The implication: a woman told after her heart attack that “the plaque was only 30% stenosis, so that’s not really the cause” may be told the wrong thing. A 30% stenosis with surface erosion is sufficient to cause a significant thrombus and a heart attack. Optical coherence tomography (OCT) during catheterization identifies the erosion morphology that standard angiography cannot see.

Mechanism 3: Coronary vasospasm

Vasospastic angina (Prinzmetal angina) can progress to MI in its most severe form, when the spasm is prolonged enough to cause complete occlusion and downstream myocardial injury. The mechanism: focal constriction of a segment of a coronary artery, reducing or eliminating blood flow through that vessel.

Vasospasm-related MI is distinctly more common in women. The angiogram, performed after the spasm has resolved, may show a completely normal coronary artery, producing a MINOCA diagnosis without an obvious mechanism. 4 / Promising

Vasospasm is more likely in: women under 55, women with connective tissue disorders, smokers, women with migraine with aura (shared vasospastic mechanism), and women with preceding cocaine or ergotamine use. Provocation testing with intracoronary acetylcholine or ergonovine during catheterization can confirm the diagnosis.

What “healthy” actually missed

For most women who have heart attacks without traditional risk factors, “healthy” was defined by:

• Normal LDL and total cholesterol (while Lp(a) was never measured)
• Normal blood pressure at clinic visits (while nocturnal hypertension was never assessed)
• Negative family history (while prior preeclampsia, in the woman herself , was not flagged as a risk modifier)
• No diabetes (while fasting insulin, which might have shown significant insulin resistance, was never ordered)
• No smoking, reasonable weight, reasonable exercise (while hs-CRP, which was elevated, was never checked)

The hidden contributors in many women presenting with MINOCA or unexplained early MI:

Lp(a). Genetically elevated Lp(a) promotes thrombosis through fibrinolytic inhibition, the precise mechanism underlying MINOCA events where thrombus forms on small, non-obstructive plaques. A woman with Lp(a) of 90 mg/dL who has a plaque erosion at a 25% stenosis is having an event that Lp(a)‘s pro-thrombotic effect contributed to, even though her LDL was “fine.”

Fibromuscular dysplasia (FMD). FMD affects the medium-sized arteries throughout the body, producing “string of beads” irregularity in the vessel wall. It is present in approximately 86% of SCAD patients and is often systemic, also present in the renal arteries and carotid arteries. Undiagnosed FMD is a substrate for SCAD. Women with SCAD should have systematic FMD screening across multiple arterial beds.

Prior preeclampsia. Doubles lifetime cardiovascular risk, predisposes to endothelial dysfunction and vascular vulnerability, and is absent from most standard risk calculators.

Subclinical thyroid disease. Untreated hypothyroidism and hyperthyroidism both increase cardiovascular risk through effects on lipids, blood pressure, and cardiac rhythm.

The MINOCA workup in a woman who had a “normal angiogram” heart attack

The diagnostic evaluation should not stop at a clean angiogram:

Cardiac MRI: Within 48 hours if possible, before edema resolves. CMR characterizes the myocardial injury pattern, ischemic vs. inflammatory (myocarditis), regional vs. diffuse, subendocardial vs. transmural. Detects SCAD-pattern late gadolinium enhancement, Takotsubo morphology, and myocarditis.

OCT (Optical Coherence Tomography): During catheterization or as a return procedure. Images the coronary wall at 10-15 micron resolution, compared to millimeter-scale angiography. Identifies SCAD, plaque erosion, plaque rupture, and intraluminal thrombus invisible on standard angiography.

Provocative vasospasm testing: Intracoronary acetylcholine or ergonovine during catheterization. Diagnoses epicardial or microvascular vasospasm.

Fibromuscular dysplasia screening: Renal artery duplex ultrasound and consideration of dedicated coronary FMD imaging in all SCAD patients.

Thrombophilia workup: If no mechanism is identified, coagulation panel, including antiphospholipid antibodies, lupus anticoagulant, Factor V Leiden, prothrombin gene mutation.

Lp(a) and inflammatory panel: Lp(a) should be measured in every MINOCA patient. Its prothrombotic effect is the most plausible biological mechanism by which a small, non-obstructive plaque becomes the site of a life-threatening thrombus. An hs-CRP and ApoB complete the picture of the risk factors that the standard “healthy” workup did not capture.

What the evidence shows: MINOCA is not a benign diagnosis

The reassurance that women with non-obstructive coronaries sometimes receive after a heart attack — “the arteries look clean, we are not sure what happened, but it may not be serious” — is not supported by outcomes data.

The Swedish MINOCA registries, including data from the SMINC-2 cohort, followed MINOCA patients prospectively and found 5-year major adverse cardiovascular event rates that rival those seen in MI with obstructive coronary artery disease. One-year death rates in MINOCA cohorts range from 3 to 7% depending on presentation and mechanism. 5 / Solid

The WISE study (Women’s Ischemia Syndrome Evaluation), an NHLBI-funded multicenter trial of women with chest pain and suspected ischemia, established that women with non-obstructive coronary disease on angiography had significantly higher rates of adverse cardiovascular outcomes than angiographically normal comparators. Microvascular dysfunction, plaque erosion physiology, and vasomotor abnormalities — all underdetected on standard angiography — were the drivers of ongoing risk.

The VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) found that women under 55 presenting with MI had worse 1-year physical function and higher readmission rates than age-matched men, despite lower overall atherosclerotic burden. The discordance between plaque burden and outcomes in women is consistent with MINOCA mechanisms operating independently of traditional plaque load.

For SCAD specifically, the Mayo Clinic SCAD registry — one of the largest prospective datasets in existence — reports recurrence rates of 10 to 17% at 5 years in SCAD survivors. Recurrence tends to affect a different coronary territory than the index event. This is not a one-time event for a significant proportion of patients.

What this means clinically: MINOCA is an explanation for how the heart attack occurred, not a reprieve from ongoing risk. The absence of obstructive plaque is an angiographic observation. It is not a prognostic one. These patients require mechanism-specific evaluation, mechanism-specific secondary prevention, and long-term surveillance — none of which they consistently receive.

Secondary prevention depends on the mechanism

This is the point most frequently missed in post-MINOCA discharge planning. The aspirin-and-statin protocol appropriate for atherosclerotic MI is not the right protocol for SCAD, is only partially applicable to plaque erosion, and is largely wrong for vasospasm-mediated MI.

After SCAD:

Stenting is contraindicated in most SCAD presentations. The catheter-based intervention that opens a plaque-obstructed artery can extend a dissection, propagating the tear further down the vessel. Conservative medical management is the guideline-preferred approach for hemodynamically stable SCAD.

Beta-blockers serve two roles: reducing myocardial oxygen demand after the index event, and reducing the contractile forces that stress the healing dissection site. Most SCAD-experienced centers continue beta-blockers for at least 2 to 5 years after the index event.

Dual antiplatelet therapy (aspirin plus clopidogrel) is commonly prescribed, though its mechanistic rationale is weaker than in atherosclerotic MI because SCAD involves a structural dissection rather than plaque-driven thrombus. Anticoagulation is generally avoided, as systemic anticoagulation can extend the intramural hematoma.

Exercise restriction in the first 3 to 12 months is standard. High-intensity isometric exercise and Valsalva-generating activities are the primary precipitants to avoid during the healing period.

After plaque erosion:

The EROSION trial demonstrated that OCT-identified plaque erosion lesions, managed conservatively with antithrombotic therapy and without stenting, showed significant thrombus resolution at 30 days in the majority of patients. This suggests that not every erosion STEMI requires stent implantation when the underlying vessel achieves adequate reperfusion. Statin therapy is relevant for erosion physiology because statins reduce endothelial inflammation — the upstream process that triggers endothelial shedding. Hs-CRP guided anti-inflammatory management should be part of the secondary prevention plan.

After vasospasm:

Calcium channel blockers — diltiazem, long-acting nifedipine, or amlodipine — are first-line for vasospastic angina and vasospasm-mediated MI. Long-acting nitrates provide supplemental protection. The critical behavioral elements are smoking cessation (smoking potently increases vasospastic activity), elimination of cocaine and amphetamines, and strict avoidance of ergot compounds. In women with coexisting migraine, the treatment plan requires review: triptans and ergotamine compounds are vasoconstrictors that can precipitate coronary vasospasm and should be replaced with alternative migraine therapies.

Recurrence and long-term monitoring

SCAD surveillance protocol:

All SCAD patients should have cardiac MRI at 3 to 6 months to assess dissection healing. Coronary angiography or coronary CTA at 6 to 12 months allows direct assessment of the healed segment. Given the 86% prevalence of fibromuscular dysplasia in SCAD patients, FMD screening of renal arteries by duplex ultrasound is standard in SCAD-specialty centers; consideration of carotid and vertebral FMD imaging follows in patients with evidence of systemic involvement.

Pregnancy counseling after SCAD requires individualized cardiovascular review before conception. Women who have had SCAD face elevated risk of recurrence in the peripartum period, and planned pregnancy requires preconception assessment of residual dissection healing, FMD extent, and cardiac function.

Monitoring after plaque erosion and MINOCA:

Repeat assessment of inflammatory markers, Lp(a) if not yet measured, and ApoB provides the mechanism-specific risk map. Women with elevated Lp(a) after a MINOCA event now have a specific therapeutic target: Lp(a)-lowering agents including olpasiran and pelacarsen are in late-phase clinical trials, with a first agent nearing regulatory submission for Lp(a) reduction specifically. Annual echocardiography in the first 2 to 3 years is appropriate for women who have not had full functional recovery of ejection fraction.

What the follow-up visit should include:

MINOCA patients face gaps in care because “normal angiogram” is misread by non-specialist physicians as “low risk.” Follow-up visits should include mechanism-specific secondary prevention review, blood pressure measurement (undertreated in MINOCA cohorts), repeat inflammatory and lipid panel, and explicit symptom review for recurrence signals: new chest pain, exertional limitation, palpitations that differ from the patient’s prior baseline.

A woman who survived a MINOCA event without a clear explanation does not have a clean bill of health. She has an incomplete diagnostic evaluation. The explanation exists. It requires cardiologists experienced in coronary OCT imaging, cardiac MRI interpretation, and provocative vasospasm testing. It requires asking about fibromuscular dysplasia, Lp(a), and pregnancy history. It requires a mechanism-specific secondary prevention plan rather than the same protocol applied to the patient in the next bed with a ruptured plaque and a stented LAD.

Related reading

For the SCAD mechanism in detail: SCAD: The Heart Attack That Tears the Artery Wall.

For the MINOCA diagnostic workup: MINOCA: The Heart Attack With Normal Arteries.

For the Lp(a) and ApoB that were missing from her “healthy” assessment: ApoB and Lp(a) in Women.