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  3. Trends in excess mortality associated with atrial fibrillation over 45 years (Framingham Heart Study): community based cohort study
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Research

Trends in excess mortality associated with atrial fibrillation over 45 years (Framingham Heart Study): community based cohort study

BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m2724 (Published 11 August 2020) Cite this as: BMJ 2020;370:m2724
  1. Nicklas Vinter, doctoral student1 2,
  2. Qiuxi Huang, doctoral student3,
  3. Morten Fenger-Grøn, senior researcher4,
  4. Lars Frost, associate professor1,
  5. Emelia J Benjamin, professor5 6,
  6. Ludovic Trinquart, associate professor3 6
  1. 1Diagnostic Centre, University Research Clinic for Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg, Denmark and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  2. 2Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
  3. 3Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA 02118, USA
  4. 4Research Unit for General Practice, Aarhus, Denmark
  5. 5Department of Medicine, School of Medicine and Department of Epidemiology School of Public Health, Boston University, Boston, MA, USA
  6. 6National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA
  1. Correspondence to: L Trinquart ludovic{at}bu.edu (or @l_trinquart on Twitter)
  • Accepted 23 June 2020

Abstract

Objective To assess temporal trends in the association between newly diagnosed atrial fibrillation and death.

Design Community based cohort study.

Setting Framingham Heart Study cohort, in 1972-85, 1986-2000, and 2001-15 (periods 1-3, respectively), in Framingham, MA, USA.

Participants Participants with no atrial fibrillation, aged 45-95 in each time period, and identified with newly diagnosed atrial fibrillation (or atrial flutter) during each time period.

Main outcome measures The main outcome was all cause mortality. Hazard ratios for the association between time varying atrial fibrillation and all cause mortality were calculated with adjustment for time varying confounding factors. The difference in restricted mean survival times, adjusted for confounders, between participants with atrial fibrillation and matched referents at 10 years after a diagnosis of atrial fibrillation was estimated. Meta-regression was used to test for linear trends in hazard ratios and restricted mean survival times over the different time periods.

Results 5671 participants were selected in time period 1, 6177 in period 2, and 6174 in period 3. Adjusted hazard ratios for all cause mortality between participants with and without atrial fibrillation were 1.9 (95% confidence interval 1.7 to 2.2) in time period 1, 1.4 (1.3 to 1.6) in period 2, and 1.7 (1.5 to 2.0) in period 3 (Ptrend=0.70). Ten years after diagnosis of atrial fibrillation, the adjusted difference in restricted mean survival times between participants with atrial fibrillation and matched referents decreased by 31%, from −2.9 years (95% confidence interval −3.2 to −2.5) in period 1, to −2.1 years (−2.4 to −1.8) in period 2, to −2.0 years (−2.3 to −1.7) in period 3 (Ptrend=0.03).

Conclusions No evidence of a temporal trend in hazard ratios for the association between atrial fibrillation and all cause mortality was found. The mean number of life years lost to atrial fibrillation at 10 years had improved significantly, but a two year gap compared with individuals without atrial fibrillation still remained.

Footnotes

  • Contributors: NV, LF, and LT developed the hypothesis and study design. QH and LT did the statistical analysis. NV and LT wrote the first and successive drafts of the manuscript. All authors contributed to the study concept and design, interpretation of the data, and drafting or critical revision of the manuscript for important intellectual content or additionally to data acquisition. QH and LT had full access to the data and take responsibility for the integrity of the data and the accuracy of the data analysis. LT is the guarantor. We thank the participants and staff of the Framingham Heart Study for their valuable contributions.

  • Funding: This work was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI), Framingham Heart Study (NHLBI/NIH contract No HHSN268201500001I), and the Boston University School of Medicine. This work was also supported by the American Heart Association (18SFRN34110082, 18SFRN34150007, and 1RC1HL101056) and the NIH/NHLBI (R01 HL128914, R01 HL092577, and R01 HL126136). The Framingham Heart Study is supported by 75N92019D00031. The funding sources had no role in the design, analysis, and reporting of the study.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI), Framingham Heart Study, and the Boston University School of Medicine for the submitted work; LF reports grants from the Health Research Foundation of Central Denmark Region, personal fees from Bristol-Myers Squibb, personal fees from Pfizer, personal fees from Bayer, and personal fees from Merck Sharp and Dohme, outside of the submitted work. EJB serves as an uncompensated member of the MyHeartLab Steering Committee. The MyHeartLab Study is a principal investigator initiated study from the University of California San Francisco (UCSF): principal investigator Jeffrey Olgin, through a research grant to UCSF from Samsung. NV, QH, MF-G, and LT have no competing interests.

  • Ethical approval: The Framingham Heart Study was approved by the Boston Medical Center and Boston University Medical Campus institutional review board (protocol No H-32132). Participants signed informed consent at study examinations.

  • Data sharing: Participant level data are available at the database of Genotypes and Phenotypes (https://www.ncbi.nlm.nih.gov/gap/) and BioLINCC (https://biolincc.nhlbi.nih.gov/home/).

  • LT affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned (and, if relevant, registered) have been explained.

  • Dissemination to participants and related patient and public communities: Results from the Framingham Heart Study are routinely disseminated to participants by the study website and newsletters as well as social media outlets. Findings will be disseminated by the media departments of the authors’ institutes. Results of the study will also be linked in the Framingham Heart Study website and shared by social media outlets for participants and relevant patient and public communities.

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This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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