Anna P Pilbrow1, Lina Cordeddu2, Vicky A Cameron3, Chris M Frampton3, Richard W Troughton3, Robert N Doughty4, Gillian A Whalley5, Chris J Ellis4, Timothy G Yandle3, A Mark Richards6, Roger S-Y Foo7. 1. Christchurch Heart Institute, Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch 8011, New Zealand. Electronic address: anna.pilbrow@otago.ac.nz. 2. Division of Cardiovascular Medicine, ACCI Building, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. 3. Christchurch Heart Institute, Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch 8011, New Zealand. 4. Department of Medicine, Faculty of Medicine and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. 5. Faculty of Social and Health Sciences, Unitec, Private Bag 92025, Auckland 1142, New Zealand. 6. Christchurch Heart Institute, Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch 8011, New Zealand; Cardiovascular Research Institute, National University Health Systems, Centre for Translational Medicine, Medical Drive, 117599, Singapore. 7. Division of Cardiovascular Medicine, ACCI Building, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; Cardiovascular Research Institute, National University Health Systems, Centre for Translational Medicine, Medical Drive, 117599, Singapore.
Abstract
BACKGROUND: The prognostic utility of circulating plasma microRNA in patients with acute coronary syndromes (ACS) has been proposed but not yet demonstrated. We set out to investigate circulating microRNA levels in patients incurring recent ACS and examined associations with neurohormones, cardiac structure and function, and survival over 5 years of follow-up. METHODS: An initial screen of 375 microRNAs was performed in 35 ACS patients and 16 healthy controls. Candidates identified from the initial screen (miR-323-3p, miR-652, miR-27b, miR-103 and miR-208a) were validated in a further cohort of 200 patients at baseline (~ 30 days post-ACS) and at 4 and 12 months post-ACS, and compared with 100 controls. RESULTS: In the validation cohort, significantly higher levels in patients were replicated for miR-323-3p, miR-652 and miR-27b (10-fold, 2.3-fold and 2.3-fold, respectively, adjusted p<0.05). Lower levels of miR-103 were not replicated and miR-208a was undetectable. From baseline to 4 months post-admission, miR-323-3p and miR-652 remained elevated in patients compared to controls (adjusted p<0.01), with no further change in levels between 4 and 12 months; whereas miR-27b fell to control levels by 4 months. Baseline levels of miR-652 in the lowest tertile were significantly associated with readmission for heart failure (log-rank p<0.001). In combination with NT-proBNP and LVEF, miR-652 significantly improved risk stratification (p<0.001). CONCLUSIONS: Our study identifies miR-652 as a novel candidate biomarker for post-ACS prognosis beyond existing biomarkers of LVEF and NT-proBNP. Moreover circulating miR-323-3p was markedly elevated in patients for at least a year post-ACS and may be a stable biomarker for ACS.
RCT Entities:
BACKGROUND: The prognostic utility of circulating plasma microRNA in patients with acute coronary syndromes (ACS) has been proposed but not yet demonstrated. We set out to investigate circulating microRNA levels in patients incurring recent ACS and examined associations with neurohormones, cardiac structure and function, and survival over 5 years of follow-up. METHODS: An initial screen of 375 microRNAs was performed in 35 ACS patients and 16 healthy controls. Candidates identified from the initial screen (miR-323-3p, miR-652, miR-27b, miR-103 and miR-208a) were validated in a further cohort of 200 patients at baseline (~ 30 days post-ACS) and at 4 and 12 months post-ACS, and compared with 100 controls. RESULTS: In the validation cohort, significantly higher levels in patients were replicated for miR-323-3p, miR-652 and miR-27b (10-fold, 2.3-fold and 2.3-fold, respectively, adjusted p<0.05). Lower levels of miR-103 were not replicated and miR-208a was undetectable. From baseline to 4 months post-admission, miR-323-3p and miR-652 remained elevated in patients compared to controls (adjusted p<0.01), with no further change in levels between 4 and 12 months; whereas miR-27b fell to control levels by 4 months. Baseline levels of miR-652 in the lowest tertile were significantly associated with readmission for heart failure (log-rank p<0.001). In combination with NT-proBNP and LVEF, miR-652 significantly improved risk stratification (p<0.001). CONCLUSIONS: Our study identifies miR-652 as a novel candidate biomarker for post-ACS prognosis beyond existing biomarkers of LVEF and NT-proBNP. Moreover circulating miR-323-3p was markedly elevated in patients for at least a year post-ACS and may be a stable biomarker for ACS.