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Editorial |

Atrial Fibrillation and Aging: Risky Mutual Relationships FREE TO VIEW

Giuseppe Boriani, MD, PhD
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FINANCIAL/NONFINANCIAL DISCLOSURES: None delcared.

CORRESPONDENCE TO: Giuseppe Boriani, MD, PhD, Cardiology Department, University of Modena and Reggio Emilia, Policlinico di Modena, Viale del Pozzo, 71, 41124 Modena, Italy


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(2):301-302. doi:10.1016/j.chest.2015.08.018
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Atrial fibrillation (AF) and aging have several mutual relationships. As known from many epidemiological studies, both the prevalence and incidence of AF increase sharply after 65 years of age and more than 10% of patients aged at least 85 years (so-called “oldest-old” patients) have clinical AF., However, all of these epidemiological surveys underestimate the real prevalence and incidence of AF since a substantial proportion of elderly patients are asymptomatic, with AF often discovered at a routine check or only at the time of stroke, or even after stroke occurrence.,

The age-dependency of AF was initially highlighted by epidemiological studies performed in Europe and North America, but more recently, reports from Asia also confirmed that in consideration of the progressive aging of the population, the epidemiological burden of AF is an emerging global threat.,,

In the current issue of CHEST (see page 401), Yamashita et al report on interesting data from the Fushimi AF registry, a study performed in Japan, which represents one of the largest community-based prospective studies on elderly Asian patients with AF. Japan has the highest average expected longevity in the world, corresponding to 84 years (87 for women and 80 for men), followed by Australia, Italy, and Singapore with 83 years, whereas in the United States average life expectancy at birth is lower, corresponding to 79 years (81 for women and 76 for men). As shown in the Fushimi AF registry, management of AF is challenging in oldest-old patients since people aged ≥ 85 years have complex clinical features such as a high prevalence of heart failure (43% of patients) and chronic kidney disease (estimated glomerular filtration rate, < 60 mL/min/1.73 m2 in 58% of patients). The negative prognostic implication of impairment in kidney function and the complexity of decision-making when AF is associated with worsening renal function are of great clinical significance.

In oldest-old patients with AF, decision-making regarding antithrombotic prophylaxis is difficult, like navigating between Scylla and Charybdis, in view of the risk of thromboembolism coupled with that of hemorrhage. For the patients aged ≥ 85 years enrolled in the Fushimi AF registry, the thrombotic risk is quite evident since the CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke [doubled]) and the CHA2DS2-VASc (congestive heart failure or left ventricular dysfunction, hypertension, age ≥75 years [doubled], diabetes, stroke [doubled], vascular disease, age 65 -74 years, sex category [female]) scores were high and 29% of patients had a history of stroke. With regard to the risk of bleeding, according to many studies, the risk of intracranial hemorrhages is particularly high in Asian patients, with a twofold increase in the risk of intracerebral hemorrhages compared with white people, and increasing up to fourfold with warfarin treatment. The difficulties of decision-making in this setting are reflected in the Fushimi registry, in which the use of oral anticoagulants appears to drop above age 84, with a weak association with score for congestive heart failure, hypertension, age 75 years, diabetes mellitus, and stroke.

In the Fushimi AF registry, outcomes in the oldest-old patients (aged ≥ 85 years) were characterized, compared with younger patients, by a higher incidence of stroke or systemic embolism as well as mortality, but not of major bleeding. According to the findings of this registry and of the literature, it is clear that aging profoundly influences AF management, because it is associated with complex comorbidities, frailty, adverse outcomes, and relatively short life expectancy.

The relationship between AF and aging is indeed bidirectional, since AF causes a series of injuries that worsen biological aging, specifically at the level of the brain. Since the first description by Gerhardt van Swieten (1700-1772), it has been known that embolism can occlude the arteries of the brain and thereby cause an ischemic stroke with major loss of cerebral function. The damage of acute ischemic stroke is impressive, with an average loss per hour of cerebral ischemia corresponding to 120 million neurons, 830 billion synapses, and 714 km (447 miles) of myelinated fibers. It has been calculated that there are 21.5 billion neurons in the typical human neocortex and that the neocortex loses around 31 million neurons per year in normal aging. Compared with the normal rate of neuron loss in brain aging, ischemia-related accelerated aging corresponds to 3.6 years per hour of acute ischemia without treatment, resulting in accelerated aging for the brain of around 36 years for an untreated stroke, with 10-h duration of evolution. Well-known evidence that AF-related ischemic strokes are even more severe and disabling than ischemic strokes unrelated to AF further stresses the adverse implications of AF in the setting of aging of the elderly.,

Apart from injuries related to acute cerebral ischemia, AF may cause cognitive impairment or aggravate a previous cognitive dysfunction, with more rapid decline compared with sinus rhythm, up to an overt state of dementia. Even though the cause-effect relationship between AF and cognitive impairment is difficult to evaluate, a semi-systematic review showed that a series of studies reported an association between cognitive decline and AF, and among cross-sectional studies, patients with AF had a 1.7 to 3.3 greater risk of cognitive impairment and a 2.3-fold increased risk of dementia compared with patients in sinus rhythm, although with marked heterogeneity in design, size, and quality of the analyzed studies. Cerebral hypoperfusion, microembolization, lower than optimal anticoagulation, silent cerebral infarct, inflammation, and other factors have been evoked to explain the impairment in cognitive function that may develop in patients with AF, resulting in accelerated aging.,

Cognitive impairment is a key component of frailty syndrome, a geriatric syndrome characterized by decreased reserves in multiple organ systems, with increased vulnerability to sudden health state changes triggered by relatively minor stressor events. There is a statistical association between AF and frailty, although it is unclear whether the frailty state represents a trigger for AF onset or whether chronic AF can worsen the frailty state.

In summary, the relationships between AF and aging are mutual and risky because aging promotes AF, but AF also induces and aggravates a series of degenerative processes typical of aging, with profound effects on patient health status and on the resources that health care providers have to dedicate to the care of very elderly patients. Care of these patients is a great challenge for the individual physician, the community, and health care systems since it includes increased risks of adverse events and great complexity with increased risk of errors and non-adherence. This is coupled with a huge financial burden involved in taking care of these extremely old patients, which suggests the need for organizational changes, taking into account some change in the models of care delivery.

References

Boriani G. .Diemberger I. .Martignani C. .Biffi M. .Branzi A. . The epidemiological burden of atrial fibrillation: a challenge for clinicians and health care systems. Eur Heart J. 2006;27:893-894 [PubMed]journal. [PubMed]
 
Andrade J. .Khairy P. .Dobrev D. .Nattel S. . The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms. Circ Res. 2014;114:1453-1468 [PubMed]journal. [CrossRef] [PubMed]
 
Boriani G. .Laroche C. .Diemberger I. .et al Asymptomatic atrial fibrillation: clinical correlates, management, and outcomes in the EORP-AF Pilot General Registry. Am J Med. 2015;128:509-518 [PubMed]journal. [CrossRef] [PubMed]
 
Boriani G. .Glotzer T.V. .Santini M. .et al Device-detected atrial fibrillation and risk for stroke: an analysis of >10,000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices). Eur Heart J. 2014;35:508-516 [PubMed]journal. [CrossRef] [PubMed]
 
Tse H.F. .Wang Y.J. .Ahmed Ai-Abdullah M. .et al Stroke prevention in atrial fibrillation—an Asian stroke perspective. Heart Rhythm. 2013;10:1082-1088 [PubMed]journal. [CrossRef] [PubMed]
 
Boriani G. . The epidemiologic threat of atrial fibrillation: need for secondary, primary, and primordial prevention. Chest. 2015;147:9-10 [PubMed]journal. [CrossRef] [PubMed]
 
Yamashita Y. .Hamatani Y. .Esato M. .et al Clinical characteristics and outcomes in extreme elderly (age ≥85 years) Japanese patients with atrial fibrillation: the Fushimi AF Registry. Chest. 2016;149:401-412 [PubMed]journal
 
  2015;:- [PubMed] World Health Statistics Geneva, Switzerland  :- [PubMed]journal
 
Boriani G. .Savelieva I. .Dan G.A. .et al Chronic kidney disease in patients with cardiac rhythm disturbances or implantable electrical devices: clinical significance and implications for decision making—a position paper of the European Heart Rhythm Association endorsed by the Heart Rhythm Society and the Asia Pacific Heart Rhythm Society. Europace. 2015;17:1169-1196 [PubMed]journal. [CrossRef] [PubMed]
 
Boriani G. .Diemberger I. .Biffi M. .Martignani C. . Balancing the risk of hemorrhage vs thromboembolism in patients with atrial fibrillation: how to navigate between Scylla and Charybdis? Chest. 2010;138:1032-1033 [PubMed]journal. [CrossRef] [PubMed]
 
Chiang C.E. .Wang K.L. .Lip G.Y. . Stroke prevention in atrial fibrillation: an Asian perspective. Thromb Haemost. 2014;111:789-797 [PubMed]journal. [CrossRef] [PubMed]
 
Saver J.L. . Time is brain—quantified. Stroke. 2006;37:263-266 [PubMed]journal. [CrossRef] [PubMed]
 
Thacker E.L. .McKnight B. .Psaty B.M. .et al Atrial fibrillation and cognitive decline: a longitudinal cohort study. Neurology. 2013;81:119-125 [PubMed]journal. [CrossRef] [PubMed]
 
Udompanich S. .Lip G.Y. .Apostolakis S. .Lane D.A. . Atrial fibrillation as a risk factor for cognitive impairment: a semi-systematic review. QJM. 2013;106:795-802 [PubMed]journal. [CrossRef] [PubMed]
 
Polidoro A. .Stefanelli F. .Ciacciarelli M. .et al Frailty in patients affected by atrial fibrillation. Arch Gerontol Geriatr. 2013;57:325-327 [PubMed]journal. [CrossRef] [PubMed]
 
Boriani G. .Maniadakis N. .Auricchio A. .et al Health technology assessment in interventional electrophysiology and device therapy: a position paper of the European Heart Rhythm Association. Eur Heart J. 2013;34:1869-1874 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

Boriani G. .Diemberger I. .Martignani C. .Biffi M. .Branzi A. . The epidemiological burden of atrial fibrillation: a challenge for clinicians and health care systems. Eur Heart J. 2006;27:893-894 [PubMed]journal. [PubMed]
 
Andrade J. .Khairy P. .Dobrev D. .Nattel S. . The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms. Circ Res. 2014;114:1453-1468 [PubMed]journal. [CrossRef] [PubMed]
 
Boriani G. .Laroche C. .Diemberger I. .et al Asymptomatic atrial fibrillation: clinical correlates, management, and outcomes in the EORP-AF Pilot General Registry. Am J Med. 2015;128:509-518 [PubMed]journal. [CrossRef] [PubMed]
 
Boriani G. .Glotzer T.V. .Santini M. .et al Device-detected atrial fibrillation and risk for stroke: an analysis of >10,000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices). Eur Heart J. 2014;35:508-516 [PubMed]journal. [CrossRef] [PubMed]
 
Tse H.F. .Wang Y.J. .Ahmed Ai-Abdullah M. .et al Stroke prevention in atrial fibrillation—an Asian stroke perspective. Heart Rhythm. 2013;10:1082-1088 [PubMed]journal. [CrossRef] [PubMed]
 
Boriani G. . The epidemiologic threat of atrial fibrillation: need for secondary, primary, and primordial prevention. Chest. 2015;147:9-10 [PubMed]journal. [CrossRef] [PubMed]
 
Yamashita Y. .Hamatani Y. .Esato M. .et al Clinical characteristics and outcomes in extreme elderly (age ≥85 years) Japanese patients with atrial fibrillation: the Fushimi AF Registry. Chest. 2016;149:401-412 [PubMed]journal
 
  2015;:- [PubMed] World Health Statistics Geneva, Switzerland  :- [PubMed]journal
 
Boriani G. .Savelieva I. .Dan G.A. .et al Chronic kidney disease in patients with cardiac rhythm disturbances or implantable electrical devices: clinical significance and implications for decision making—a position paper of the European Heart Rhythm Association endorsed by the Heart Rhythm Society and the Asia Pacific Heart Rhythm Society. Europace. 2015;17:1169-1196 [PubMed]journal. [CrossRef] [PubMed]
 
Boriani G. .Diemberger I. .Biffi M. .Martignani C. . Balancing the risk of hemorrhage vs thromboembolism in patients with atrial fibrillation: how to navigate between Scylla and Charybdis? Chest. 2010;138:1032-1033 [PubMed]journal. [CrossRef] [PubMed]
 
Chiang C.E. .Wang K.L. .Lip G.Y. . Stroke prevention in atrial fibrillation: an Asian perspective. Thromb Haemost. 2014;111:789-797 [PubMed]journal. [CrossRef] [PubMed]
 
Saver J.L. . Time is brain—quantified. Stroke. 2006;37:263-266 [PubMed]journal. [CrossRef] [PubMed]
 
Thacker E.L. .McKnight B. .Psaty B.M. .et al Atrial fibrillation and cognitive decline: a longitudinal cohort study. Neurology. 2013;81:119-125 [PubMed]journal. [CrossRef] [PubMed]
 
Udompanich S. .Lip G.Y. .Apostolakis S. .Lane D.A. . Atrial fibrillation as a risk factor for cognitive impairment: a semi-systematic review. QJM. 2013;106:795-802 [PubMed]journal. [CrossRef] [PubMed]
 
Polidoro A. .Stefanelli F. .Ciacciarelli M. .et al Frailty in patients affected by atrial fibrillation. Arch Gerontol Geriatr. 2013;57:325-327 [PubMed]journal. [CrossRef] [PubMed]
 
Boriani G. .Maniadakis N. .Auricchio A. .et al Health technology assessment in interventional electrophysiology and device therapy: a position paper of the European Heart Rhythm Association. Eur Heart J. 2013;34:1869-1874 [PubMed]journal. [CrossRef] [PubMed]
 
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