Diurnal Variation in thrombolytic status in patients presenting with STEMI

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Prior studies mainly in healthy volunteers and patients with stable coronary artery disease (CAD) indicate circadian variation in spontaneous fibrinolytic activity. This is predominantly attributable to changes plasminogen activator inhibitor-1 (PAI-1) levels peaking between midnight and 06:00 hr, with a nadir at 18:00 hr. Whether circadian variation in spontaneous fibrinolysis exists amongst patients with ST-elevation myocardial infarction (STEMI) is unknown. Purpose It was our aim to assess circadian variation in fibrinolytic status in the acute setting in patients presenting with STEMI. Methods A prospective, observational study was conducted in patients presenting with STEMI for primary percutaneous coronary intervention (PPCI). Blood was tested on arrival pre-PPCI, after aspirin and P2Y12 inhibitor administration, but before any anticoagulant or antithrombotic agent administration in the cardiac cath lab. Venous blood was assessed to determine endogenous fibrinolysis using the Global Thrombosis Test, which utilises non-anticoagulated blood to assess the formation of an occlusive thrombus under high shear and the time taken for spontaneous restart of flow as a measure of endogenous fibrinolysis (lysis time, LT). Results A total of 527 patients were included, aged 64±13 years and 78% were male. 304 (58%) patients presented within working hours (08:00-17:00) with peak presentation between 11:00-12:00 and trough between 03:00 to 05:00 hrs. Lysis time was not related to time of presentation. Time of presentation was divided into 4 groups (A 00:00-05:59, B 06:00-11:59, C 12:00-17:59, D 18:00-23:59 hrs). There was no significant difference in LT between patients presenting at the 4 timepoints (median 1362s [interquartile range IQR 1077-1808] vs 1503s [1182-2056] vs 1440s [1164-1998] vs. 1420s [1125-1820], respectively, p=0.340). When comparing Group A to C, the LT was not significantly different (1362s [1077-1808] vs. 1440 [1164-1998], p=0.413). The presentation time of patients with impaired endogenous fibrinolysis (LT>3000 sec) did not differ significantly from patients with normal endogenous fibrinolysis. The hourly variation was similar in diabetics and non-diabetics, but the variation in lysis time appeared blunted in patients taking long term aspirin prior to presentation compared to non-aspirin takers. Conclusion In contrast to the known circadian variation in fibrinolysis in normal volunteers, and stable CAD, in our large cohort of STEMI patients, there appears to be no relationship between time of presentation/onset of STEMI and the effectiveness spontaneous fibrinolysis. This is reflected in our observation, supported by most contemporary studies, that peak time of STEMI presentation is during the late morning, and this does not relate to known circadian variation in fibrinolysis markers in CAD.