What is the primary recommendation for a premenopausal woman with multiple infarcts?

Multiple Infarcts in a Premenopausal Woman: Primary Recommendations

For a premenopausal woman presenting with multiple infarcts, the priority is to immediately investigate for spontaneous coronary artery dissection (SCAD), which accounts for 20-35% of acute coronary syndromes in women under 60 years, and to evaluate for underlying hypercoagulable states, connective tissue disorders, and pregnancy-related complications. 1

Immediate Diagnostic Workup

High-Priority Etiologies to Rule Out

Spontaneous Coronary Artery Dissection (SCAD)

• SCAD is a relatively rare cause of MI overall (up to 4% of all acute coronary syndromes) but disproportionately affects young women, representing 20-35% of all acute coronary syndrome cases in women aged <60 years 1
• SCAD is associated with connective tissue disorders, fibromuscular dysplasia, systemic lupus erythematosus, and is particularly prevalent in the peripartum period 1
• Intracoronary imaging such as intravascular ultrasound or optical coherence tomography can be key to securing the diagnosis 1
• Optimal management is challenging, with a conservative approach favored in stable, asymptomatic patients 1

Hypercoagulable States

• Antiphospholipid antibody syndrome must be evaluated, as women with prior pregnancy loss are at approximately 2-fold increased risk of myocardial infarction and cerebral infarction 1
• For pregnant women with ischemic stroke or TIA and high-risk thromboembolic conditions such as hypercoagulable state, adjusted-dose UFH or LMWH should be considered 1
• Women with antiphospholipid antibodies or syndrome should avoid hormone replacement therapy due to increased thrombotic risk 2, 3

Pregnancy-Related Complications

• Evaluate for history of preeclampsia, gestational hypertension, or pregnancy loss, as miscarriage is associated with a 1.45-fold increased risk of CVD, and more than 1 miscarriage is associated with a 2-fold risk 1
• Women with prior intrauterine growth restriction (IUGR) pregnancies are at increased risk for hyperlipidemia, hypertriglyceridemia, and insulin resistance 1

Advanced Cardiac Imaging

Cardiovascular Magnetic Resonance (CMR) or CT Coronary Angiography

• Non-invasive approaches such as cardiovascular magnetic resonance or computed tomography coronary angiography are the recommended initial tests for premenopausal women with suspected ischemic heart disease 1
• For premenopausal women at intermediate IHD risk who are functionally disabled, echocardiography or CMR should be performed, but MPI or CCTA may be used if an effective radiation dose of <3 mSv is possible 1
• CMR can distinguish between obstructive coronary disease and microvascular ischemia, which is critical as approximately half of women with myocardial ischemia have no flow-limiting coronary obstructive disease at angiography 1

Risk Factor Assessment and Management

Traditional and Emerging Risk Factors

Comprehensive Metabolic Evaluation

• Premenopausal women with CAD most commonly have single-vessel disease with the left anterior descending artery most commonly involved 4
• The prevalence of hypertension, diabetes, obesity, metabolic syndrome, family history of CAD, and 10-year risk score is higher in premenopausal females with CAD than controls 4
• Even after treatment with conventional therapies, premenopausal women with CAD have significantly elevated levels of ApoB, ApoB/ApoA1 ratio, hsCRP, lipoprotein (a), uric acid, fibrinogen, and total leukocyte count 4
• Low levels of Apo A1 and high levels of fibrinogen, hsCRP, and triglycerides drive vascular risk and should be considered as candidates for better diagnosis and early detection 4

Lipid Management

• Initiate LDL-C–lowering therapy (preferably a statin) simultaneously with lifestyle therapy in high-risk women with LDL-C ≥100 mg/dL 1
• Initiate statin therapy in high-risk women with an LDL-C <100 mg/dL unless contraindicated 1
• Initiate niacin or fibrate therapy when HDL-C is low, or non–HDL-C elevated in high-risk women 1

Antiplatelet and Anticoagulation Therapy

Aspirin and Antiplatelet Agents

• Aspirin therapy (75 to 162 mg), or clopidogrel if patient is intolerant to aspirin, should be used in high-risk women unless contraindicated 1
• β-blockers should be used indefinitely in all women who have had a myocardial infarction or who have chronic ischemic syndromes unless contraindicated 1

Warfarin for Atrial Fibrillation

• Among women with chronic or paroxysmal atrial fibrillation, warfarin should be used to maintain the INR at 2.0 to 3.0 unless they are considered to be at low risk for stroke (<1%/year) or high risk of bleeding 1

Critical Contraindications and Pitfalls

Hormone Replacement Therapy

Absolute Contraindication

• For women who have had ischemic stroke or TIA, postmenopausal hormone therapy (with estrogen with or without a progestin) is not recommended 1
• Combined estrogen plus progestin hormone therapy should not be initiated to prevent CVD in postmenopausal women 1
• HRT is contraindicated in women with established cardiovascular disease, regardless of the indication for its use 2, 3
• Women already taking HRT at the time of a cardiovascular event should discontinue therapy and not restart it for secondary prevention 3

Special Considerations

Takotsubo Cardiomyopathy

• Takotsubo cardiomyopathy is noteworthy for the absence of obstructive coronary artery disease, typical precipitation by intense psychological or emotional stress, and predominant occurrence in postmenopausal women 1
• Despite the presence of positive cardiac biomarkers and frequent hemodynamic compromise, almost all patients recover completely, typically with normal wall motion within 1 to 4 weeks 1

Microvascular Dysfunction

• Women with no or minimal obstructive disease had a total rate of death or MI of 9.4% by 4 years, indicating that normal coronary arteries on angiography do not guarantee benign prognosis 1
• Aggressive coronary risk factor reduction is appropriate even in the absence of obstructive coronary disease 1

Long-Term Management Strategy

Secondary Prevention

• Low sustained use of aspirin, beta-blockers, ACE inhibitors/AT2 receptor blockers and statins following a myocardial infarction represents a critical under-use gap that must be addressed 1
• Risk stratification is based on the extent and severity of inducible abnormalities noted on the stress examination 1
• CCTA can uniquely provide information on the obstructive and nonobstructive burden of CAD, which may be reasonable to guide posttest management approaches for women 1