0008 The endogenous circadian system provides for enhanced coronary microvascular function in the morning

Abstract

Abstract Introduction Major adverse cardiovascular events occur most commonly in the morning compared to other times of the day or night. Evaluation of coronary microvascular reserve perfusion can be used to reflect the anatomic and functional status of the coronary vascular system, both of which contribute to major adverse cardiovascular events. Prior work suggests that coronary microvascular function is attenuated in the morning, but whether the circadian system contributes to this attenuation is unknown. Methods To determine if the circadian system drives the morning attenuation in coronary microvascular function, we studied 13 healthy participants (8 females, 5 males; 42+/-13 years [mean+/-SD]) in a 5-day forced desynchrony protocol in dim light, where all behaviors and measurements were distributed across the 24-hour cycle. Coronary microvascular function was evaluated by vasodilator myocardial contrast echocardiography, sequentially 16 hours apart, corresponding to each participant’s morning, evening and night. We analyzed time-intensity data to calculate microvascular flux rate (beta) at rest and during hyperemia for each measurement. Circadian phases were calculated based on individual dim-light melatonin onsets. We grouped data into three ~8-hour circadian bins corresponding to each participant’s morning, evening and night. Mixed model analyses were used to determine if there were significant differences between data collected in the circadian morning compared to the other times while controlling for the measurement schedule and between-subject variability. Results There were no significant time-dependent differences in echocardiographic indices of ventricular function, including stroke volume, cardiac output, or myocardial work. Contrary to our hypothesis, hyperemic perfusion was lowest in the evening rather than the morning (2.49 /s vs. 2.82 /s, p=0.042) but not different between morning and night (also 2.82 /s, p=0.96). Conclusion In healthy people, there is no circadian-system-driven morning attenuation in coronary microvascular function: indeed, the circadian system facilitates coronary vascular flow in the morning, possibly to accommodate the anticipated behaviorally driven increases in myocardial demand after awakening. Support (if any) NIH KL2TR002370, R01HL163232, R35HL155681, R01HL140577, R01HL130046, R01HL078610, R01HL156948, K01HL146992, K01HL151745, ULTR00128, Sleep Research Society Foundation, Oregon Institute of Occupational Health Sciences.