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Embracing Differences to Advance a Contemporary Understanding of Symptom Phenotypes in Acute Myocardial Infarction.

Coronary heart disease affects ≈18 million American adults and remains the leading cause of mortality in the United States.1 Specifically, myocardial infarction (MI) affects 3% of US adults, and 14% of those with MI will die from it.1 While the incidence of MI has declined significantly over the past several decades, sub-population differences in that decline persist.1 An analysis of sex differences among young adults hospitalized with acute MI (AMI) in the ARIC (Atherosclerosis Risk in Communities) Community Surveillance Study found that AMI hospitalizations declined in all age groups except individuals younger than 55 years of age, for whom AMI hospitalizations increased. The most pronounced increase was among young women (35–54 years) with high comorbidity burden. Furthermore, women were less likely than men to receive guideline-based AMI therapies.2 Several critical sex differences in AMI have been described. Women have higher mortality post-AMI than men and are more likely than men to die within the first 12 months post-AMI.3 Pathophysiology and cause of AMI may differ among women as compared with men, and there are documented differences in clinical presentation.3 The presentation of AMI has long been classically characterized by the hallmark symptom of chest pain/discomfort. However, awareness of sex differences in clinical presentation, including symptom manifestation and time to presentation, among patients with AMI has increased. In this issue of Circulation: Cardiovascular Quality and Outcomes, Brush et al4 report on an analysis of sex differences in observed individual symptom phenotypes in men and women hospitalized with AMI, based on an analysis performed in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study. The authors found that women have more variation in unique symptom phenotypes, broader distribution of symptom phenotype subgroups, and higher number of symptoms per patient than men.4 These findings provide a unique contribution to the literature that has described sex differences in presentation by examining individual phenotypes rather than relying on population differences. In addition, the report generates hypotheses to elucidate determinants of poorer outcomes of AMI in women as compared with men. This report and its findings raise several key questions that provide future directions for further research: (1) Are sex differences in symptom phenotypes related to known sex differences in AMI presentation, management, and outcomes? (2) What exactly is the phenotype of atypical chest pain, why is it more common in women, and how can we refine our phenotyping to better define this symptom complex and improve the pace to diagnosis and treatment? Circulation: Cardiovascular Quality and Outcomes