Circadian variation in patient characteristics and outcomes in ST-segment elevation myocardial infarction

Abstract

A morning peak in ST-segment elevation myocardial infarction (STEMI) has been described. The authors explored the relationship between variation of symptom onset, patient characteristics, and outcomes in two worldwide fibrinolytic trials. A total of 35 492 patients with STEMI were grouped into 8-h intervals by time of symptom onset: early (06:00 to 13:59 h), late-day (14:00 to 21:59 h), overnight (22:00 to 05:59 h). The authors correlated timing with patient characteristics and outcomes (adjusted for thrombolysis in myocardial infarction [TIMI] risk score) first in InTIME II-TIMI 17 trial (N = 15 031), and confirmed in the ExTRACT-TIMI 25 trial (N = 20 461). Timing was similar in the derivation (early 49%, late-day 30%, and overnight 21%; p < .001) and validation set (48%, 31%, and 21%, respectively; p < .001). Some patient characteristics consistently varied with time of symptom onset. Patients in the early cohort were older with poorer renal function. The late-day group had more smokers with higher initial heart rate and systolic blood pressure. Those with overnight symptom onset had higher rates of obesity, prior myocardial infarction, and treatment delays. Prior use of aspirin and beta-blockers was also highest in the overnight group. Relative to the early cohort, adjusted mortality was higher with late-day onset (derivation odds ratio [OR]: 1.19, p = .04; validation OR: 1.18, p = .01), but there was no excess in mortality overnight compared with early (derivation OR: .97, p = .72; validation OR: 1.01, p = .90). Composite endpoints followed similar patterns. This study indicates that circadian patterns in onset of STEMI continue to exist with patient characteristics differing by time of day. Despite a potential physiologic resistance to morning thrombolysis, outcomes were best in the early cohort, intermediate overnight, and worst with late-day symptom onset. Efforts to reduce smoking and improve control of blood pressure could reduce the number of patients with late-day onset of STEMI who experience the worst outcomes.