Sex differences in clinical characteristics, phenotypes, management, and long-term outcomes of myocardial injury: an international cohort study

Abstract Background Several studies have demonstrated sex differences in patients presenting to the emergency department (ED) with myocardial infarction, heart failure or syncope. Whether sex-specific differences in chest pain patients with myocardial injury exist is unknown. Purpose To determine whether sex-specific differences in the clinical characteristics, phenotypes, management, and long-term outcomes of patients with myocardial injury exist. Methods Patients presenting to the ED with chest pain suggestive of MI were consecutively enrolled into a prospective multicenter international diagnostic study. Final diagnoses were centrally adjudicated by two independent cardiologists, applying the fourth universal definition of myocardial infarction, using all available medical records, including serial hs-cTn and cardiac imaging. Follow-ups were performed at 3 months, 1-, 2- and 5-years. The primary outcome was 5-year all-cause mortality. Secondary outcomes included 5-year cardiovascular mortality and non-cardiovascular mortality. Multivariable flexible parametric (Royston-Parmar) models assuming proportional hazards were fitted. Models were adjusted for age, history of coronary artery disease, history of malignancy, diabetes, hypertension, smoking status, history of liver disease, and renal function. Results Among 8046 chest pain patients presenting to the ED, 1158 (14.4%) had myocardial injury, of which 358 (31%) were females and 800 (69%) males. Women were older (79 years, vs. 73 years), had fewer cardiovascular risk factors and comparable non-cardiovascular comorbidities except for lung disease which was more commonly found in men. Myocardial injury phenotypes varied between sexes (Figure). The most common phenotype in both sexes was heart failure, yet it was more common in men (37.2%) than in women (22.3%). The second most common phenotype in women was hypertension (15.4%) and arrhythmia (15.4 %), while in men was myocarditis (17.8 %), followed by arrhythmia (15.8%). Women underwent less invasive coronary angiography (19.8% vs 26.9%) or stress testing (12% vs 21.5%). In the angiographic findings, women presented more often with normal findings (30.4% vs. 19.6%) or mild CAD (20.3% vs. 11.2%) whereas men displayed more frequently 3-vessel disease (14.5% vs. 36.4%), Table. After adjusting for known confounders, women were associated with a lower 5-years risk for all-cause mortality (HR 0.69; 95%CI: 0.56–0.83) and cardiovascular mortality (HR 0.61; 95%CI: 0.46–0.79). No statistically significant difference in non-cardiovascular mortality risk was found (HR 0.79; 95%CI: 0.59-1.04). Conclusions Women presenting with chest pain to the ED and having myocardial injury were less likely than men to undergo coronary angiography or non-invasive cardiac imaging. Long-term risk for all-cause or cardiovascular mortality was lower for women compared to men.Myocardial Injury phenotypesPatient management