Francesco Radico1,2, Marco Zimarino1, Fabio Fulgenzi1, Fabrizio Ricci2, Marta Di Nicola3, Lasse Jespersen4, Su Min Chang5, Karin H Humphries6, Mario Marzilli7, Raffaele De Caterina1. 1. Institute of Cardiology and Center of Excellence on Aging, "G. d'Annunzio" University, C/o Ospedale SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy. 2. Department of Neurosciences, Imaging and Clinical Sciences, Institute for Advanced Biomedical Technologies, University G. d'Annunzio, Via Luigi Polacchi, 66100, Chieti, Italy. 3. Department of Medical, Oral and Biotechnological Sciences, Laboratory of Biostatistics, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 66100, Chieti, Italy. 4. Department of Cardiology, Bispebjerg University Hospital, Bispebjerg Bakke 23, Copenhagen 2400, Denmark. 5. Department of Cardiology, Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, 6565 Fannin Street, Houston, TX 77030, USA. 6. Division of Cardiology, Department of Medicine, BC Centre for Improved Cardiovascular Health, St Paul's Hospital, 1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada. 7. Department of Cardiology, University of Pisa, Via Paradisa 2, 56100, Pisa, Italy.
Abstract
Aims: The long-term prognosis of angina in patients without obstructive coronary artery disease (CAD) is uncertain. To assess the incidence of long-term adverse outcomes in such patients. Methods and results: We searched PubMed, Cochrane Library, the Embase database, and the Clinical Trials Registry for studies published in English until January 2017, assessing the composite primary outcome of all-cause death and non-fatal myocardial infarction using random-effects models to estimate pooled incidences. We identified 54 studies, reporting outcomes in overall 35 039 patients (mean age 56, male/female ratio 0.51, 99 770 person-years) with angina and no obstructive CAD. After a median follow-up of 5 years (interquartile range 3-7 years), the pooled incidence of the primary outcome was 0.98/100 person-years [95% confidence interval (CI) 0.77-1.19%], with considerable heterogeneity among studies (I2 = 91%, P < 0.001). The primary outcome was associated with prevalent dyslipidaemia (P = 0.016), diabetes (P = 0.035), and hypertension (P = 0.016). Studies enrolling patients with less-than-obstructive CAD showed a higher incidence of the primary outcome (1.32/100 person-years, 95% CI 1.02-1.62) compared with studies including only patients with 'entirely normal' coronary arteries (0.52/100 person-years, 95% CI 0.34-0.79, respectively; P < 0.01). The incidence of the primary outcome did not differ significantly between studies enrolling only patients with documented myocardial ischaemia and those studies enrolling patients regardless of presence of ischaemia. However, ischaemia documented by non-invasive imaging techniques was associated with a higher incidence of events (P = 0.02). Overall, these patients, however, suffered from a high incidence of recurrent hospitalization. Conclusion: Angina without obstructive CAD has a heterogeneous prognosis. A main determinant of major adverse events is the presence of 'some' coronary atherosclerosis, with unequivocal myocardial ischaemia being associated with worse clinical outcomes. Patients' quality of life is also worsened by the high incidence of hospitalization, angina recurrence, and repeated coronary angiography.
Aims: The long-term prognosis of angina in patients without obstructive coronary artery disease (CAD) is uncertain. To assess the incidence of long-term adverse outcomes in such patients. Methods and results: We searched PubMed, Cochrane Library, the Embase database, and the Clinical Trials Registry for studies published in English until January 2017, assessing the composite primary outcome of all-cause death and non-fatal myocardial infarction using random-effects models to estimate pooled incidences. We identified 54 studies, reporting outcomes in overall 35 039 patients (mean age 56, male/female ratio 0.51, 99 770 person-years) with angina and no obstructive CAD. After a median follow-up of 5 years (interquartile range 3-7 years), the pooled incidence of the primary outcome was 0.98/100 person-years [95% confidence interval (CI) 0.77-1.19%], with considerable heterogeneity among studies (I2 = 91%, P < 0.001). The primary outcome was associated with prevalent dyslipidaemia (P = 0.016), diabetes (P = 0.035), and hypertension (P = 0.016). Studies enrolling patients with less-than-obstructive CAD showed a higher incidence of the primary outcome (1.32/100 person-years, 95% CI 1.02-1.62) compared with studies including only patients with 'entirely normal' coronary arteries (0.52/100 person-years, 95% CI 0.34-0.79, respectively; P < 0.01). The incidence of the primary outcome did not differ significantly between studies enrolling only patients with documented myocardial ischaemia and those studies enrolling patients regardless of presence of ischaemia. However, ischaemia documented by non-invasive imaging techniques was associated with a higher incidence of events (P = 0.02). Overall, these patients, however, suffered from a high incidence of recurrent hospitalization. Conclusion:Angina without obstructive CAD has a heterogeneous prognosis. A main determinant of major adverse events is the presence of 'some' coronary atherosclerosis, with unequivocal myocardial ischaemia being associated with worse clinical outcomes. Patients' quality of life is also worsened by the high incidence of hospitalization, angina recurrence, and repeated coronary angiography.
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