- This international study was the first to investigate the relationship between time of onset of ST-segment elevation myocardial infarction and the three most common pathologies, as detected by optical coherence tomography
- Marked circadian variation was evident for plaque rupture, with a peak during morning hours, that was not obvious for plaque erosion or calcified plaque
- The circadian pattern of plaque rupture was observed only on weekdays
- Risk factors for plaque rupture during the daytime were age greater than or equal to 60, male sex, nonsmoking status, hypertension, diabetes and hyperlipidemia
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It's long been known that circadian rhythms affect the time of onset of acute myocardial infarction (MI). Researchers at Massachusetts General Hospital recently became the first to study the mechanisms of that phenomenon in vivo, as they are pioneering the use of optical coherence tomography (OCT) to view coronary arteries. Makoto Araki, MD, PhD, research fellow in the Division of Cardiology, and Ik-Kyung Jang, MD, PhD, director of the Cardiology Laboratory for Integrative Physiology and Imaging at Mass General, and colleagues have observed marked circadian variation in plaque rupture, but not plaque erosion or calcified plaque. In the Journal of Thrombosis and Thrombolysis, they explain why acute MI caused by plaque rupture may be related to catecholamine surge.
Mass General researchers are leading an international, multicenter, longitudinal registry study of patients who undergo cardiac OCT. The current analysis involved 648 patients who presented with ST-segment elevation MI (STEMI) between October 2008 and January 2018 with an estimated onset time of:
- Midnight to 5:59 am (n=86)
- 6:00 am to 11:59 am(n=307)
- Noon to 5:59 pm (n=181)
- 6:00 pm to 11:59 pm(n=74)
OCT was performed before percutaneous coronary intervention. Plaque rupture was diagnosed in 60% of patients, plaque erosion in 30% and calcified plaque in 10%.
Circadian Variation by Mechanism
There was marked circadian variation in the incidence of plaque rupture, with a peak at 9:00 am. No circadian variation was observed in patients whose STEMI was due to plaque erosion or calcified plaque.
Weekday vs. Weekend
80% of patients presented with STEMI between Monday and Friday. On weekdays, the probability of plaque rupture more than doubled during the two daytime periods compared with midnight to 5:59 AM:
- 6:00 to 11:59 am—OR, 2.13; 95% CI, 1.30–3.49, P = .002
- Noon to 5:59 pm—OR, 2.10; 95% CI, 1.23–3.58, P = .005
Interestingly, this circadian pattern was not observed on Saturdays or Sundays.
Predefined subgroup analyses showed that risk factors for plaque rupture during the two daytime periods were age ≥60, male sex, nonsmoking status, hypertension, diabetes and hyperlipidemia. Thus, patients who already have a higher level of intrinsic vulnerability may be more susceptible to external triggers.
Implications for Therapy
Cortisol and catecholamine levels are high during the early morning and peak at the time of awakening. Systemic vascular tone, blood pressure and heart rate then increase. These changes lead to high local shear stress, which may trigger plaque rupture.
In addition, plasma fibrinolytic activity decreases in the morning, and platelet aggregation and blood viscosity increase. These procoagulant changes may allow even minor plaque disruption to form an occlusive thrombus.
In this study, the number of patients taking medications was small, so the effect of medication on circadian variation of plaque rupture wasn't analyzed. It would be interesting to find out whether adjusting the timing of medications that lower heart rate, blood pressure and platelet aggregation could prevent morning MI.
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