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Background: Takotsubo stress cardiomyopathy (TSC) is a syndrome characterized by transient myocardial dysfunction with unknown etiology. Although recent studies have suggested that the syndrome is associated with comorbidity and has a dismal prognosis, there is a lack of comprehensive data describing the epidemiology and prognosis of TSC.Objectives: This study compared risk markers and mortality in patients with TSC with that of individuals with or without coronary artery disease (CAD).Methods: Patients with TSC and control subjects were identified from the Swedish Coronary Angiography and Angioplasty Register between 2009 and 2013 and linked with the Swedish national patient registry, cause of death registry, prescription drug registry, and education and income registries.Results: Patients with TSC were characterized by a low cardiovascular risk factor profile but with increased chronic obstructive pulmonary disease, migraine, and affective disorders. The use of beta-blockers was less common but use of β2-adrenergic agonist agents was more common in patients with TSC compared with either of the control groups. Being a patient with TSC was associated with a hazard ratio of 2.1 for death compared with the control subjects without CAD (95% confidence interval: 1.4 to 3.2). This was similar to the excess mortality risk seen among the CAD control subjects compared with control subjects without CAD (hazard ratio: 2.5; 95% confidence interval: 1.8 to 3.3). These associations remained significant after adjusting for CAD risk factors and risk markers for TSC.Conclusions: The findings of increased risk associated with β2-adrenergic agonist agents together with stress related to affective disorders emphasize the pathogenic role of sympathetic stimulation. The prognosis regarding mortality is worse than in control subjects without CAD and similar to patients with CAD emphasizing the urgent need for studies on optimal treatment of TSC. [ABSTRACT FROM AUTHOR]