Maria Tomasdottir1, Claes Held2, Nermin Hadziosmanovic3, Johan Westerbergh3, Johan Lindbäck3, Philip E Aylward4, Andrzej Budaj5, Christopher P Cannon6, Johan Engdahl7, Christopher B Granger8, Wolfgang Koenig9, Athanasios J Manolis10, Jonas Oldgren2, Ralph A H Stewart11, Emma Svennberg12, Dragos Vinereanu13, Harvey D White11, Agneta Siegbahn14, Lars Wallentin2, Ziad Hijazi15. 1. Department of Medical Sciences, Cardiology, Uppsala University, Sweden. 2. Department of Medical Sciences, Cardiology, Uppsala University, Sweden; Uppsala Clinical Research Center, Uppsala University, Sweden. 3. Uppsala Clinical Research Center, Uppsala University, Sweden. 4. South Australian Health and Medical Research Institute, Flinders University and Medical Centre, Adelaide, SA, Australia. 5. Centre of Postgraduate Medical Education, Grochowski Hospital, Warsaw, Poland. 6. Cardiovascular Innovation, Brigham and Women's Hospital, Boston, MA. 7. Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden. 8. Duke Clinical Research Institute, Duke Medicine, Durham, NC. 9. Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany. 10. Cardiology Department, Asklepeion Hospital, Athens, Greece. 11. Green Lane Cardiovascular Service, Auckland City Hospital and University of Auckland, Auckland, New Zealand. 12. Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden; Department of Cardiology, Karolinska Hospital, Stockholm, Sweden. 13. University of Medicine and Pharmacy Carol Davila, University and Emergency Hospital, Bucharest, Romania. 14. Uppsala Clinical Research Center, Uppsala University, Sweden; Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden. 15. Department of Medical Sciences, Cardiology, Uppsala University, Sweden; Uppsala Clinical Research Center, Uppsala University, Sweden. Electronic address: Ziad.Hijazi@ucr.uu.se.
Abstract
BACKGROUND: In patients with coronary heart disease (CHD), atrial fibrillation (AF) is associated with increased morbidity and mortality. We investigated the associations between clinical risk factors and biomarkers with incident AF in patients with CHD. METHODS AND RESULTS: Around 13,153 patients with optimally treated CHD included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial with plasma samples obtained at randomization. Mean follow-up time was 3.5 years. The association between clinical risk factors and biomarkers with incident AF was estimated with Cox-regression models. Validation was performed in 1,894 patients with non-ST-elevation acute coronary syndrome included in the FRISC-II trial. The median (min-max) age was 64 years (range 26-92) and 2,514 (19.1%) were women. A total of 541 patients, annual incidence rate of 1.2%, developed AF during follow-up. In multivariable models, older age, higher levels of NT-proBNP, higher body mass index (BMI), male sex, geographic regions, low physical activity, and heart failure were independently associated with increased risk of incident AF with hazard ratios ranging from 1.04 to 1.79 (P ≤ .05). NT-proBNP improved the C-index from 0.70 to 0.71. In the validation cohort, age, BMI, and NT-proBNP were associated with increased risk of incident AF with similar hazard ratios. CONCLUSIONS: In patients with optimally treated CHD, the incidence of new AF was 1.2% per year. Age, NT-proBNP as a marker of impaired cardiac function, and BMI were the strongest factors, independently and consistently associated with incident AF. Male sex and low physical activity may also contribute to the risk of AF in patients with CHD.
BACKGROUND: In patients with coronary heart disease (CHD), atrial fibrillation (AF) is associated with increased morbidity and mortality. We investigated the associations between clinical risk factors and biomarkers with incident AF in patients with CHD. METHODS AND RESULTS: Around 13,153 patients with optimally treated CHD included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial with plasma samples obtained at randomization. Mean follow-up time was 3.5 years. The association between clinical risk factors and biomarkers with incident AF was estimated with Cox-regression models. Validation was performed in 1,894 patients with non-ST-elevation acute coronary syndrome included in the FRISC-II trial. The median (min-max) age was 64 years (range 26-92) and 2,514 (19.1%) were women. A total of 541 patients, annual incidence rate of 1.2%, developed AF during follow-up. In multivariable models, older age, higher levels of NT-proBNP, higher body mass index (BMI), male sex, geographic regions, low physical activity, and heart failure were independently associated with increased risk of incident AF with hazard ratios ranging from 1.04 to 1.79 (P ≤ .05). NT-proBNP improved the C-index from 0.70 to 0.71. In the validation cohort, age, BMI, and NT-proBNP were associated with increased risk of incident AF with similar hazard ratios. CONCLUSIONS: In patients with optimally treated CHD, the incidence of new AF was 1.2% per year. Age, NT-proBNP as a marker of impaired cardiac function, and BMI were the strongest factors, independently and consistently associated with incident AF. Male sex and low physical activity may also contribute to the risk of AF in patients with CHD.