Abstract
BACKGROUND: The burden and pathophysiologic mechanisms of myocardial infarction (MI) in younger patients remain understudied. Prior studies have been limited by selected cohorts and lack of awareness of nonatherothrombotic causes. OBJECTIVES: We sought to determine the incidence and outcomes of MI according to a unique pathophysiologic mechanism in a large community cohort aged ≤65 years, and to evaluate sex-differences in etiology METHODS: We identified all residents of Olmsted County, Minnesota, USA, age ≤65 years who experienced an event associated with a cardiac troponin T >99th percentile of upper reference range (≥0.01 ng/mL) from January 2003 to March 2018. Records and imaging were individually scrutinized. Patients classified as MI were assigned to 1 of 6 adjudicated pathophysiologic mechanisms: atherothrombosis, spontaneous coronary artery dissection (SCAD), embolism, vasospasm, myocardial infarction with nonobstructed coronary arteries not meeting another category (MINOCA-U), and supply/demand mismatch secondary myocardial infarction. We determined incidence and long-term all-cause and cardiovascular mortality for each group. RESULTS: There were 4,116 myocardial injury events in 2,780 patients (36% women) over 15 years. Excluding periprocedural MI, 1,474 events were classified as index MI, of which 68% were caused by atherothrombosis. The population incidence of MI was much lower in women, particularly in MI caused by atherothrombosis (48 vs 137 per 100,000 person years and 23 vs 105 per 100,000 person-years). Incidence of SCAD was much higher in women (3.2 vs 0.9 per 100,000 person-years) with 55% of cases misclassified as MINOCA or atherothrombosis at index presentation. Women with atherothrombosis were similar in age to men (55 ± 8 years vs 54 ± 8 years), with similar disease extent at angiography but greater burden of risk factors. Proportionately, nonatherothrombotic causes comprised the majority of MI in women (atherothrombosis 47% vs 75%, secondary myocardial infarction [SSDM] 34% vs 19%, SCAD 11% vs 0.7%, embolism 2% vs 2%, vasospasm 3% vs 1%, MINOCA-U 3% vs 2%). The 5-year all-cause mortality was highest after SSDM (SSDM 33%, atherothrombosis 8%, embolism 8%, SCAD 0%) with low cardiovascular mortality in all groups. CONCLUSIONS: This community-based study demonstrates nonatherothrombotic causes comprise an important burden of acute MI in persons age ≤65 years, particularly women. These cause-specific findings have implications for individualized management and risk stratification and provide epidemiologic benchmarking for future studies.