Research Article: Circadian onset and prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA)

Date Published: April 25, 2019

Publisher: Public Library of Science

Author(s): Anna M. Nordenskjöld, Kai M. Eggers, Tomas Jernberg, Moman A. Mohammad, David Erlinge, Bertil Lindahl, Giuseppe Andò.


Many acute cardiovascular events such as myocardial infarction (MI) follow circadian rhythms. Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a newly noticed entity with limited data on onset pattern and its impact on prognosis.

In this observational study of Swedish MINOCA patients registered in the SWEDEHEART registry between 2003–2013 and followed until December 2013 we identified 9,092 unique patients with MINOCA out of 199,163 MI admissions in total. Incidence rate ratios (IRR) were calculated for whole hours, parts of the day, weekdays, months, seasons and major holidays.

The mean age was 65.5 years, 62.0% were women and 16.6% presented with STEMI. The risk for MINOCA proved to be most common in the morning (IRR = 1.70, 95% CI [1.63–1.84]) with a peak at 08.00 AM (IRR = 2.25, 95% CI [1.96–2.59]) and on Mondays (IRR = 1.28, 95% CI [1.18–1.38]). No altered risk was detected during the different seasons, the Christmas and New Year holidays or the Swedish Midsummer festivities. There was no association between time of onset of MINOCA and short- or long-term prognosis.

The onset of MINOCA shows a circadian and circaseptan variation with increased risk at early mornings and Mondays, similar to previous studies on all MI, suggesting stress related triggering. However, during holidays were traditional MI increase, we did not see any increase for MINOCA. No association was detected between time of onset and prognosis, indicating that the underlying pathological mechanisms of MINOCA and the quality of care are similar at different times of onset but triggering mechanism may be more active early mornings and Mondays.

Partial Text

A majority of acute cardiovascular events such as myocardial infarction (MI) [1–6], sudden cardiac death [1, 5], rupture of aortic aneurysms [5], ischemic and hemorrhagic stroke [5] tend to be more common early mornings.

Table 1 present the baseline clinical characteristics which are previously reported [10, 14]. Women make up 62.0% of the cohort and the mean age was 65.5 years. Known risk factors were common among the patients and 13.6% suffered from diabetes, 48.2% had hypertension and 51.7% were current or previous smokers. A total of 1483 patients (16.6%) presented with STE-MINOCA at admission and the baseline characteristics are stratified according to the ECG finding (Table 1). A total of 31.2% of the patients were employed; 66.5% of patients <65 years and 3.9% of patients ≥65 years, respectively. This is the first large, nationwide, study investigating the presence of circadian, circaseptan and seasonal variations in the onset of MINOCA. With data from 9,092 unique MINOCA patients we were able to demonstrate a circadian onset of MINOCA, with a 70% increased risk for onset during the morning and a more than doubled risk at 8 AM. Furthermore, the onset of MINOCA was 27% higher on Mondays and considerably lower during the weekends. No monthly, seasonal or holiday related increased risk for MINOCA was detected. Our study has some limitations. Firstly, observational studies based on data from registries are not able to determine causality. Secondly, MINOCA patients form a heterogeneous group with several different underlying pathophysiological mechanisms such as plaque rupture, coronary artery spasm, coronary dissection, thrombosis with spontaneous thrombolysis, type 2 MI and clinically unrecognized myocarditis or Takotsubo syndrome [13]. Thirdly, any results of investigations after the initial hospitalization that may have changed the initial MINOCA diagnosis (e.g Cardiac Magnetic Resonance Imaging intracoronary imaging or computed tomography scan) are not registered in SWEDEHEART and therefore not possible to be considered. The knowledge about Takotsubo Syndrome was limited at the beginning of the study period and there may be a smaller number of Takotsubo Syndrome cases in the cohort, incorrectly diagnosed as having MI. Due to low number of adverse advents within 30 days of onset of MINOCA the present study has, due to low power, limited ability to detected associations between onset time and short- term prognosis. The limited number of onsets of symptoms during the holidays also limited the power to detect any holiday related associations. In this nationwide observational study of 9,092 patients with MINOCA a circadian and circaseptan variation in the onset of MINOCA was seen with higher risk early mornings and Mondays, similar to previous studies on all MI (mostly MI-CAD). However, during holidays were traditional MI increase, we did not see any increase for MINOCA.   Source:


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