Nathan E K Procter1, Jocasta Ball2, Saifei Liu1, Nicola Hurst1, Vivek B Nooney3, Vincent Goh1, Irene Stafford1, Tamila Heresztyn1, Melinda Carrington2, Doan T M Ngo1, Elaine M Hylek4, Jeffrey S Isenberg5, Yuliy Y Chirkov1, Simon Stewart2, John D Horowitz6. 1. Basil Hetzel Institute, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia. 2. National Health and Medical Research Council (NHMRC), Centre of Excellence to Reduce Inequality in Heart Disease, Baker IDI Heart and Diabetes Institute, Australian Catholic University, Melbourne, Australia. 3. Basil Hetzel Institute, The Queen Elizabeth Hospital, University of South Australia, Adelaide, Australia. 4. Boston University School of Medicine, Boston, MA, USA. 5. Vascular Medicine Institute, University of Pittsburgh Department of Medicine, Pittsburgh, PA, USA. 6. Basil Hetzel Institute, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia. Electronic address: john.horowitz@adelaide.edu.au.
Abstract
BACKGROUND: Clinical factors associated with thromboembolic risk in AF patients are well characterized and include new onset AF. Biochemically, AF is associated with inflammatory activation and impairment of nitric oxide (NO) signalling, which may also predispose to thromboembolism: the bases for variability in these anomalies have not been identified. We therefore sought to identify correlates of impaired platelet NO signalling in patients hospitalized with atrial fibrillation (AF), and to evaluate the impact of acuity of AF. METHODS: 87 patients hospitalized with AF were evaluated. Platelet aggregation, and its inhibition by the NO donor sodium nitroprusside, was evaluated using whole blood impedance aggregometry. Correlates of impaired NO response were examined and repeated in a "validation" cohort of acute cardiac illnesses. RESULTS: Whilst clinical risk scores were not significantly correlated with integrity of NO signalling, new onset AF was associated with impaired NO response (6 ± 5% inhibition versus 25 ± 4% inhibition for chronic AF, p<0.01). New onset AF was a multivariate correlate (p<0.01) of impaired NO signalling, along with platelet ADP response (p<0.001), whereas the associated tachycardia was not. Platelet ADP response was predicted by elevation of plasma thrombospondin-1 concentrations (p<0.01). Validation cohort evaluations confirmed that acute AF was associated with significant (p<0.05) impairment of platelet NO response, and that neither acute heart failure nor acute coronary syndromes were associated with similar impairment. CONCLUSION: Recent onset of AF is associated with marked impairment of platelet NO response. These findings may contribute to thromboembolic risk in such patients.
BACKGROUND: Clinical factors associated with thromboembolic risk in AFpatients are well characterized and include new onset AF. Biochemically, AF is associated with inflammatory activation and impairment of nitric oxide (NO) signalling, which may also predispose to thromboembolism: the bases for variability in these anomalies have not been identified. We therefore sought to identify correlates of impaired platelet NO signalling in patients hospitalized with atrial fibrillation (AF), and to evaluate the impact of acuity of AF. METHODS: 87 patients hospitalized with AF were evaluated. Platelet aggregation, and its inhibition by the NO donorsodium nitroprusside, was evaluated using whole blood impedance aggregometry. Correlates of impaired NO response were examined and repeated in a "validation" cohort of acute cardiac illnesses. RESULTS: Whilst clinical risk scores were not significantly correlated with integrity of NO signalling, new onset AF was associated with impaired NO response (6 ± 5% inhibition versus 25 ± 4% inhibition for chronic AF, p<0.01). New onset AF was a multivariate correlate (p<0.01) of impaired NO signalling, along with platelet ADP response (p<0.001), whereas the associated tachycardia was not. Platelet ADP response was predicted by elevation of plasma thrombospondin-1 concentrations (p<0.01). Validation cohort evaluations confirmed that acute AF was associated with significant (p<0.05) impairment of platelet NO response, and that neither acute heart failure nor acute coronary syndromes were associated with similar impairment. CONCLUSION: Recent onset of AF is associated with marked impairment of platelet NO response. These findings may contribute to thromboembolic risk in such patients.
Authors: Gabriella Captur; Wendy E Heywood; Caroline Coats; Stefania Rosmini; Vimal Patel; Luis R Lopes; Richard Collis; Nina Patel; Petros Syrris; Paul Bassett; Ben O'Brien; James C Moon; Perry M Elliott; Kevin Mills Journal: Mol Cell Proteomics Date: 2019-06-26 Impact factor: 5.911
Authors: Nathan Ek Procter; Jocasta Ball; Doan Tm Ngo; Jeffrey S Isenberg; Elaine M Hylek; Yuliy Y Chirkov; Simon Stewart; John D Horowitz Journal: J Geriatr Cardiol Date: 2016-03 Impact factor: 3.327
Authors: Alessandra Borgognone; Eduard Shantsila; Sophie M Worrall; Eakkapote Prompunt; Thomas Loka; Brodie L Loudon; Myriam Chimen; G Ed Rainger; Janet M Lord; Ashley Turner; Peter Nightingale; Martin Feelisch; Paulus Kirchhof; Gregory Y H Lip; Steve P Watson; Michael P Frenneaux; Melanie Madhani Journal: Cardiovasc Res Date: 2018-08-01 Impact factor: 10.787
Authors: A Gundlund; Thomas Kümler; Anders Nissen Bonde; Jawad Haider Butt; Gunnar Hilmar Gislason; Christian Torp-Pedersen; Lars Køber; Jonas Bjerring Olesen; Emil Loldrup Fosbøl Journal: BMJ Open Date: 2019-09-20 Impact factor: 2.692