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Temporal Relations of Atrial Fibrillation and Congestive Heart Failure and Their Joint Influence on Mortality: The Framingham Heart Study
Abstract
Background— Atrial fibrillation (AF) and congestive heart failure (CHF) frequently occur together, but there is limited information regarding their temporal relations and the combined influence of these conditions on mortality. Methods and Results— We studied participants in the Framingham Study with new-onset AF or CHF. Multivariable Cox proportional hazards models with time-dependent variables were used to evaluate whether mortality after AF or CHF was affected by the occurrence and timing of the other condition. Hazard ratios (HRs) were adjusted for time period and cardiovascular risk factors. During the study period, 1470 participants developed AF, CHF, or both. Among 382 individuals with both conditions, 38% had AF first, 41% had CHF first, and 21% had both diagnosed on the same day. The incidence of CHF among AF subjects was 33 per 1000 person-years, and the incidence of AF among CHF subjects was 54 per 1000 person-years. In AF subjects, the subsequent development of CHF was associated with increased mortality (men: HR 2.7; 95% CI, 1.9 to 3.7; women: HR 3.1; 95% CI, 2.2 to 4.2). Similarly, in CHF subjects, later development of AF was associated with increased mortality (men: HR 1.6; 95% CI, 1.2 to 2.1; women: HR 2.7, 95% CI, 2.0 to 3.6). Preexisting CHF adversely affected survival in individuals with AF, but preexisting AF was not associated with adverse survival in those with CHF. Conclusions— Individuals with AF or CHF who subsequently develop the other condition have a poor prognosis. Additional studies addressing the pathogenesis, prevention, and optimal management of the joint occurrence of AF and CHF appear warranted.
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“In adjusted models, AF is associated with increased morbidity, especially stroke and heart failure, as well as increased mortality.2–5”
From Worldwide Epidemiology of Atrial Fibrillation: A Global Burden of Disease 2010 Study (2014) · cites this paper as [5]
In the citing paper
“The plasma concentrations of the inflammatory marker C-reactive protein143 and of fibroblast growth factor-23144 have been found to be higher in women than in men in epidemiological studies.”
From Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis (2016) · cites this paper as [143]
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“AF and CHF are common conditions that predispose each other, share risk factors, and are associated with morbidity and mortality [19].”
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“Preexisting AF, occurring before HF, is less associated with mortality.(2,14)”
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“Comparing the temporal relations of AF and HF with risk of mortality, the Framingham Heart Study demonstrated that coexisting AF and HF were associated with a higher hazard ratio of mortality, but only in patients who developed HF first.(1) In concordance, the present study showed a stronger association with mortality…”
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“A 4–5 fold risk of systemic embolism (SE) [3] and a higher risk of heart failure (HF) development [4].”
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“An estimated 40% of individuals with either AF or HF will develop the other condition.(4) Thus, the aphorism: “HF begets AF, and AF begets HF.”
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“It is also known that patients with HF tend to develop AF.(11) As such, it is possible that transient AF may have developed in our patients, as has been noted in patients with unknown cause of stroke, and that embolic events from occult AF may have been prevented by effective anticoagulation.”
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“cardiac and extra-cardiac caused by AF significantly increase morbidity and mortality [13, 14].”
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“In the Framingham Heart Study, 1470 subjects developed either new AF or HF from 1948 to 1995, with 383 (26%) developing both.(6) In addition, lifetime risks for developing AF in men and in women who are 40 years or older is 1 in 6 in patients without congestive HF or myocardial infarction (MI), and 1 in 4 in the same…”
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“The exclusion criteria include: (1) paroxysmal or persistent AF, (2) Class I indication for pacing (including AVJ ablation for poor rate control), (3) ability to walk ≥450 m in 6 minutes, (4) musculoskeletal disorders that prohibit the completion of a 450 m walk, (5) NYHA Class I or IV at the time of enrollment, (6) a…”
BackgroundArrhythmias in Dilated Cardiomyopathy
Kumar, S., Stevenson, W. G., & John, R. M. (2015) · Cardiac Electrophysiology Clinics · doi:10.1016/j.ccep.2015.03.005 · Cited by 26
Carotid Atherosclerosis and Incident Atrial Fibrillation
Willeit, K., Pechlaner, R., Egger, G., Weger, S., Oberhollenzer, M., Willeit, J., & Kiechl, S. J. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.302272 · Cited by 26
Dukes, J. W., Dewland, T. A., Vittinghoff, E., Olgin, J. E., Pletcher, M. J., Hahn, J. A., Gladstone, R. A., & Marcus, G. M. (2016) · BMJ · doi:10.1136/bmj.i2714 · Cited by 26
Bajaj, N. S., Bhatia, V., Sanam, K., Ather, S., Hashim, T., Morgan, C. J., Fonarow, G. C., Nanda, N. C., Prabhu, S. D., Adamopoulos, C., et al. (2014) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2014.05.045 · Cited by 25
Kwiecinski, W., Provost, J., Dubois, R., Sacher, F., Haı̈ssaguerre, M., Legros, M., Nguyen‐Dinh, A., Dufait, R., Tanter, M., & Pernot, M. (2014) · Medical Physics · doi:10.1118/1.4896820 · Cited by 25
Pan, K., Wu, Y., Lee, M., & Ovbiagele, B. I. (2021) · International Journal of Medical Sciences · doi:10.7150/ijms.52257 · Cited by 25
Lau, D., Sandhu, R. K., Andrade, J. G., Ezekowitz, J. A., So, H., & Klarenbach, S. W. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.019599 · Cited by 25
Wang, X., Zhao, Q., Deng, H., Wang, X., Guo, Z., DAI, Z., Xiao, J., Wan, P., & Huang, C. (2014) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.12429 · Cited by 26
“1 kg were divided into three groups: (1) the control group (three males and three females), (2) the HF group (four males and four females), and (3) the HF + RSD group (three males and five females).”
MethodRillig, A., Makimoto, H., Wegner, J., Lin, T., Heeger, C.-H. H., Lemeš, C., Fink, T., Metzner, A., Wißner, E., Mathew, S., et al. (2015) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.12765 · Cited by 25
“(1) After 6 years, single-procedure success rates after PVI in patients with reduced LVEF ( 45%) were as low as 35.”
BackgroundMethodLin, T., Yang, Y., Liao, M., Tsai, C., Hwang, J., Chiang, F., Chen, P., Lin, J.-L., & Lin, L. (2015) · Kidney International · doi:10.1038/ki.2015.96 · Cited by 25
Adachi, T., Sato, A., Baba, M., Hiraya, D., Hasegawa, T., Kuroki, K., Hoshi, T., & Aonuma, K. (2013) · Heart and Vessels · doi:10.1007/s00380-013-0377-3 · Cited by 25
“The largest studies suggest that patients with HF and supraventricular tachyarrhythmias (SVTs) in general, and AF in particular, have increased rates of HF exacerbation, hospitalisation for HF, and death [5, 6].”
BackgroundGabrielli, L., Marincheva, G., Bijnens, B. H., Doltra, A., Tolosana, J. M., Borràs, R., Castel, M., Berruezo, A., Brugada, J., Mont, L., et al. (2014) · EP Europace · doi:10.1093/europace/euu023 · Cited by 25
Bekwelem, W., Norby, F. L., Agarwal, S. K., Matsushita, K., Coresh, J., Alonso, Á., & Chen, L. Y. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.117.007452 · Cited by 25
Schrage, B., Geelhoed, B., Niiranen, T., Gianfagna, F., Vishram‐Nielsen, J. K. K., Costanzo, S., Söderberg, S., Ojeda, F., Vartiainen, E. A., Donati, M. B., et al. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.119.015218 · Cited by 25
“3 The subsequent disease onset may be an indicator of disease deterioration.”
EARLY: a pilot study on early diagnosis of atrial fibrillation in a primary healthcare centre
Benito, L., Coll‐Vinent, B., Gomez, E., Marti, D., Mitjavila, J., Torres, F., Miró, Ò., Sisó‐Almirall, A., & Mont, L. (2015) · EP Europace · doi:10.1093/europace/euv146 · Cited by 25
Lee, M., Saver, J., Hong, K., Wu, H.-C., & Ovbiagele, B. (2013) · Circulation: Heart Failure · doi:10.1161/circheartfailure.112.971697 · Cited by 21
An Argument for Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation
ZIMETBAUM, P. J. (2005) · Circulation · doi:10.1161/circulationaha.104.537175 · Cited by 24
Unsupervised deep learning of electrocardiograms enables scalable human disease profiling
Friedman, S. F., Khurshid, S. S., Venn, R. A., Wang, X., Diamant, N., Achille, P. D., Weng, L.-C. C., Choi, S. H., Reeder, C., Pirruccello, J. P., et al. (2025) · npj Digital Medicine · doi:10.1038/s41746-024-01418-9 · Cited by 30
Atrial fibrillation in heart failure: stroke risk stratification and anticoagulation
Abraham, J. M., & Connolly, S. J. (2014) · Heart Failure Reviews · doi:10.1007/s10741-014-9420-4 · Cited by 24
“Indeed, of those with a diagnosis of atrial fibrillation, about 40 % will develop a concomitant diagnosis of heart failure and the reverse is true as well [1, 2].”
BackgroundCardiac arrhythmia and heart failure: From bench to bedside
Yong-Fu, X. (2011) · 老年心脏病学杂志:英文版 · doi:10.3724/sp.j.1263.2011.00131 · Cited by 24
Smer, A. M., Salih, M., Darrat, Y., Saadi, A., Guddeti, R. R., Haddad, T. M., Kabach, A., Ayan, M., Saurav, A., Abuissa, H. S., et al. (2018) · Clinical Cardiology · doi:10.1002/clc.23068 · Cited by 24
“The presence of AF and HF is associated with increased morbidity, mortality, and healthcare costs.(2,3) Restoration and maintenance”
BackgroundVergara, P., Solimene, F., D’Onofrio, A., Pisanò, E., Zanotto, G., Pignalberi, C., Iacopino, S., Maglia, G., Bella, P. E. D., Calvi, V. I., et al. (2019) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2019.06.018 · Cited by 24
New‐onset atrial fibrillation in critically ill patients with coronavirus disease 2019 (COVID‐19)
Ergün, B., Ergan, B., Sözmen, M. K., Küçük, M., Yakar, M. N., Cömert, B., Gökmen, A. N., & Yaka, E. (2021) · Journal of Arrhythmia · doi:10.1002/joa3.12619 · Cited by 24
Yue, Y., Chen, C., Liu, P., Xing, Y., & Zhou, X. (2021) · Sensors · doi:10.3390/s21165302 · Cited by 24
“AF has strong associations with other CVDs, such as myocardial infarction (MI) and chronic heart failure (CHF) [6].”
BackgroundLiu, X., Liu, H., Wang, L., Zhang, L., & Xu, Q. (2022) · PLoS ONE · doi:10.1371/journal.pone.0263131 · Cited by 26
Aulin, J., Hijazi, Z., Lindbäck, J., Alexander, J. H., Gersh, B. J., Granger, C. B., Hanna, M., Horowitz, J. D., Lópes, R. D., McMurray, J. J. V., et al. (2022) · American Heart Journal · doi:10.1016/j.ahj.2022.03.009 · Cited by 24
The relationship between atrial fibrillation and NLRP3 inflammasome: a gut microbiota perspective
Xing, Y., Yan, L., Li, X., Xu, Z., Wu, X., Gao, H., Chen, Y., Ma, X., Liu, J., & Zhang, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1273524 · Cited by 29
Themistoclakis, S., Raviele, A., China, P., Pappone, C., Ponti, R. D., Revishvili, A. S., Aliot, E., Kück, K., Hoff, P. I., Shah, D. C., et al. (2014) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.12462 · Cited by 24
Taillandier, S., Bernard, A. B., Lallemand, B., Siméon, E., Pericart, L., Clémenty, N., Babuty, D., & Fauchier, L. (2014) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2013.12.024 · Cited by 24
Atrial Fibrillation and Cardiovascular Outcomes in the Elderly
O’Neal, W. T., Salahuddin, T., Broughton, S. T., & Soliman, E. Z. (2016) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.12907 · Cited by 24
Metadata
- Authors
- Wang, T. J., Larson, M. G., Levy, D., Vasan, R. S., Leip, E. P., Wolf, P. A., D’Agostino, R. B., Murabito, J. M., Kannel, W. B., & Benjamin, E. J.
- Affiliations
- Boston University (US)
- ORCID
- Venue
- Circulation
- Published
- 2003-06-17
- Volume
- 107
- Issue
- 23
- Pages
- 2920-2925
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1998083759
- Cited by
- 1,970
- References
- 28
- Citations by year
- 2026: 49 · 2025: 65 · 2024: 114 · 2023: 93 · 2022: 117 · 2021: 137 · 2020: 109 · 2019: 103 · 2018: 120 · 2017: 107 · 2016: 111 · 2015: 115 · 2014: 112 · 2013: 101 · 2012: 84
- FWCI
- 27.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01hc25195-41-0-1)
- National Heart, Lung, and Blood Institute (K24-HL-04334-01A1, N01‐HC25195, K24HL004334)
- National Institute of Neurological Disorders and Stroke (5-RO1-NS-17950, R01NS017950)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Keywords
- atrial fibrillation, congestive heart failure, mortality, comorbidities, prognosis, Framingham Heart Study
- MeSH terms
- Aged, Atrial Fibrillation, Female, Follow-Up Studies, Heart Failure, Humans, Male, Massachusetts, Middle Aged, Prognosis, Risk Factors, Cohort Studies, Comorbidity, Incidence, Multivariate Analysis, Proportional Hazards Models, Survival Analysis, Disease Progression
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