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      Impact of Frailty on Mortality and Hospitalization in Chronic Heart Failure: A Systematic Review and Meta‐Analysis

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          Abstract

          Background

          Although frailty has been associated with increased risks for hospitalization and mortality in chronic heart failure, the precise average effect remains uncertain. We performed a systematic review and meta‐analysis to summarize the hazards for mortality and incident hospitalization in patients with heart failure and frailty compared with those without frailty and explored the heterogeneity underlying the effect size estimates.

          Methods and Results

          MEDLINE, EMBASE, and Cochrane databases were queried for articles published between January 1966 and March 2018. Predefined selection criteria were used. Hazard ratios ( HRs) were pooled for meta‐analyses, and where odds ratios were used previously, original data were recalculated for HR. Overlapping data were consolidated, and only unique data points were used. Study quality and bias were assessed. Eight studies were included for mortality (2645 patients), and 6 studies were included for incident hospitalization (2541 patients) during a median follow‐up of 1.82 and 1.12 years, respectively. Frailty was significantly associated with an increased hazard for mortality ( HR, 1.54; 95% confidence interval, 1.34–1.75; P<0.001) and incident hospitalization ( HR, 1.56; 95% confidence interval, 1.36–1.78; P<0.001) in chronic heart failure. The Fried phenotype estimated a 16.9% larger effect size than the combined Fried/non‐Fried frailty assessment for the end point of mortality ( HR, 1.80; 95% confidence interval, 1.41–2.28; P<0.001), but not for hospitalization ( HR, 1.57; 95% confidence interval, 1.30–1.89; P<0.001). Study heterogeneity was found to be low (I 2=0%), and high quality of studies was verified by the Newcastle‐Ottawa scale.

          Conclusions

          Overall, the presence of frailty in chronic heart failure is associated with an increased hazard for death and hospitalization by ≈1.5‐fold.

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          Most cited references49

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          Outcome of heart failure with preserved ejection fraction in a population-based study.

          The importance of heart failure with preserved ejection fraction is increasingly recognized. We conducted a study to evaluate the epidemiologic features and outcomes of patients with heart failure with preserved ejection fraction and to compare the findings with those from patients who had heart failure with reduced ejection fraction. From April 1, 1999, through March 31, 2001, we studied 2802 patients admitted to 103 hospitals in the province of Ontario, Canada, with a discharge diagnosis of heart failure whose ejection fraction had also been assessed. The patients were categorized in three groups: those with an ejection fraction of less than 40 percent (heart failure with reduced ejection fraction), those with an ejection fraction of 40 to 50 percent (heart failure with borderline ejection fraction), and those with an ejection fraction of more than 50 percent (heart failure with preserved ejection fraction). Two groups were studied in detail: those with an ejection fraction of less than 40 percent and those with an ejection fraction of more than 50 percent. The main outcome measures were death within one year and readmission to the hospital for heart failure. Thirty-one percent of the patients had an ejection fraction of more than 50 percent. Patients with heart failure with preserved ejection fraction were more likely to be older and female and to have a history of hypertension and atrial fibrillation. The presenting history and clinical examination findings were similar for the two groups. The unadjusted mortality rates for patients with an ejection fraction of more than 50 percent were not significantly different from those for patients with an ejection fraction of less than 40 percent at 30 days (5 percent vs. 7 percent, P=0.08) and at 1 year (22 percent vs. 26 percent, P=0.07); the adjusted one-year mortality rates were also not significantly different in the two groups (hazard ratio, 1.13; 95 percent confidence interval, 0.94 to 1.36; P=0.18). The rates of readmission for heart failure and of in-hospital complications did not differ between the two groups. Among patients presenting with new-onset heart failure, a substantial proportion had an ejection fraction of more than 50 percent. The survival of patients with heart failure with preserved ejection fraction was similar to that of patients with reduced ejection fraction. Copyright 2006 Massachusetts Medical Society.
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            Frailty: emergence and consequences in women aged 65 and older in the Women's Health Initiative Observational Study.

            To define frailty using simple indicators; to identify risk factors for frailty as targets for prevention; and to investigate the predictive validity of this frailty classification for death, hospitalization, hip fracture, and activity of daily living (ADL) disability. Prospective study, the Women's Health Initiative Observational Study. Forty U.S. clinical centers. Forty thousand six hundred fifty-seven women aged 65 to 79 at baseline. Components of frailty included self-reported muscle weakness/impaired walking, exhaustion, low physical activity, and unintended weight loss between baseline and 3 years of follow-up. Death, hip fractures, ADL disability, and hospitalizations were ascertained during an average of 5.9 years of follow-up. Baseline frailty was classified in 16.3% of participants, and incident frailty at 3-years was 14.8%. Older age, chronic conditions, smoking, and depressive symptom score were positively associated with incident frailty, whereas income, moderate alcohol use, living alone, and self-reported health were inversely associated. Being underweight, overweight, or obese all carried significantly higher risk of frailty than normal weight. Baseline frailty independently predicted risk of death (hazard ratio (HR)=1.71, 95% confidence interval (CI)=1.48-1.97), hip fracture (HR=1.57, 95% CI=1.11-2.20), ADL disability (odds ratio (OR)=3.15, 95% CI=2.47-4.02), and hospitalizations (OR=1.95, 95% CI=1.72-2.22) after adjustment for demographic characteristics, health behaviors, disability, and comorbid conditions. These results support the robustness of the concept of frailty as a geriatric syndrome that predicts several poor outcomes in older women. Underweight, obesity, smoking, and depressive symptoms are strongly associated with the development of frailty and represent important targets for prevention.
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              The prevalence of frailty in heart failure: A systematic review and meta-analysis.

              There is a growing interest in the intersection of heart failure (HF) and frailty; however, estimates of the prevalence of frailty in HF vary widely. The purpose of this paper was to quantitatively synthesize published literature on the prevalence of frailty in HF and to examine the relationship between study characteristics (i.e. age and functional class) and the prevalence of frailty in HF.
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                Author and article information

                Contributors
                e.fung@cuhk.edu.hk
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                22 November 2018
                04 December 2018
                : 7
                : 23 ( doiID: 10.1002/jah3.2018.7.issue-23 )
                : e008251
                Affiliations
                [ 1 ] Department of Medicine and Therapeutics Faculty of Medicine The Chinese University of Hong Kong Hong Kong, SAR
                [ 2 ] Laboratory for Heart Failure and Circulation Research Li Ka Shing Institute of Health Sciences Prince of Wales Hospital Hong Kong, SAR
                [ 3 ] Cardiology Department Hospital Universitari Germans Trias i Pujol Badalona Spain
                [ 4 ] Department of Medicine Universitat Autonòma de Barcelona Spain
                [ 5 ] CIBERCV Instituto de Salud Carlos III Madrid Spain
                [ 6 ] Department of Geriatrics Instituto de Investigación IiSGM and CIBERFES Hospital General Universitario Gregorio Marañón Madrid Spain
                [ 7 ] Universidad Complutense de Madrid Spain
                [ 8 ] Western Sydney Nursing and Midwifery Research Centre Western Sydney University and Western Sydney Local Health District Sydney Australia
                [ 9 ] Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol Badalona Spain
                [ 10 ] Heart and Lung Transplant Unit St Vincent's Hospital University of New South Wales Sydney Australia
                [ 11 ] Transplantation Research Laboratory Victor Chang Cardiac Research Institute Sydney Australia
                [ 12 ] Centro Nacional de Investigaciones Cardiovasculares Madrid Spain
                [ 13 ] Instituto de Investigación i+12 and Cardiology Department Hospital Universitario 12 de Octubre Madrid Spain
                [ 14 ] CUHK Jockey Club Institute of Ageing The Chinese University of Hong Kong Hong Kong, SAR
                [ 15 ] School of Public Health Imperial College London London United Kingdom
                [ 16 ] CARE Programme Lui Che Woo Institute of Innovative Medicine Faculty of Medicine The Chinese University of Hong Kong Hong Kong, SAR
                [ 17 ] Gerald Choa Cardiac Research Centre Faculty of Medicine The Chinese University of Hong Kong Hong Kong, SAR
                Author notes
                [*] [* ] Correspondence to: Erik Fung, MB, ChB, PhD, Division of Cardiology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, 9/F, Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, 30–32 Ngan Shing St, Shatin, New Territories, Hong Kong SAR. E‐mail: e.fung@ 123456cuhk.edu.hk
                Article
                JAH33686
                10.1161/JAHA.117.008251
                6405567
                30571603
                96b026b3-18b6-4562-b9e4-33ee7f959a49
                © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 02 December 2017
                : 12 October 2018
                Page count
                Figures: 2, Tables: 1, Pages: 11, Words: 8187
                Funding
                Funded by: Ministerio de Educación y Ciencia
                Award ID: SAF2014‐59892
                Funded by: Generalitat de Catalunya
                Award ID: SLT002_16_00209
                Funded by: Fundació La MARATÓ de TV3
                Award ID: 201502‐30
                Award ID: 201516‐10
                Funded by: Red de Terapia Celular–TerCel
                Award ID: RD16/0011/0006
                Funded by: Centro de Investigación en Red en Enfermedades Cardiovasculares
                Award ID: CB16/11/00403
                Funded by: Instituto de Salud Carlos III–Sudirección General de Evaluación y el Fondo Europeo de Desarrollo Regional
                Funded by: Ministerio de Economía, Industria y Competitividad
                Funded by: Pro‐CNIC Foundation
                Funded by: Severo Ochoa Center of Excellence
                Award ID: SEV‐2015‐0505
                Funded by: University of Technology Sydney
                Funded by: Chancellor's Postdoctoral Research Fellowship
                Award ID: 2015001232
                Funded by: Faculty of Medicine
                Funded by: Chinese University of Hong Kong
                Funded by: Food and Health Bureau of the Hong Kong Special Administrative Region
                Funded by: Hong Kong Jockey Club
                Funded by: Research Grants Council
                Categories
                Systematic Review and Meta‐analysis
                Systematic Review and Meta‐analysis
                Custom metadata
                2.0
                jah33686
                04 December 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.3 mode:remove_FC converted:04.12.2018

                Cardiovascular Medicine
                chronic heart failure,frailty,hospitalization,meta‐analysis,mortality,heart failure

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