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      Frailty assessment and risk prediction by GRACE score in older patients with acute myocardial infarction

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          Abstract

          Background

          Risk prediction after myocardial infarction is often complex in older patients. The Global Registry of Acute Coronary Events (GRACE) model includes clinical parameters and age, but not frailty. We hypothesised that frailty would enhance the prognostic properties of GRACE.

          Methods

          We performed a prospective observational cohort study in two independent cardiology units: the Royal Infirmary of Edinburgh, UK (primary cohort) and the South Yorkshire Cardiothoracic Centre, Sheffield, UK (external validation). The study sample included 198 patients ≥65 years old hospitalised with type 1 myocardial infarction (primary cohort) and 96 patients ≥65 years old undergoing cardiac catheterisation for myocardial infarction (external validation). Frailty was assessed using the Clinical Frailty Scale (CFS). The GRACE 2.0 estimated risk of 12-month mortality, Charlson comorbidity index and Karnofsky disability scale were also determined for each patient.

          Results

          Forty (20%) patients were frail (CFS ≥5). These individuals had greater comorbidity, functional impairment and a higher risk of death at 12 months (49% vs. 9% in non-frail patients, p < 0.001). The hazard of 12-month all-cause mortality nearly doubled per point increase in CFS after adjustment for age, sex and comorbidity (Hazard Ratio [HR] 1.90, 95% CI 1.47–2.44, p < 0.001). The CFS had good discrimination for mortality by Receiver Operating Characteristic (ROC) curve analysis (Area Under the Curve [AUC] 0.81, 95% CI 0.72–0.89) and enhanced the GRACE estimate (AUC 0.86 vs. 0.80 without CFS, p = 0.04). At existing GRACE thresholds, the CFS resulted in a Net Reclassification Improvement (NRI) of 0.44 (95% CI 0.28–0.60, p < 0.001), largely through reductions in risk estimates amongst non-frail patients. Similar findings were observed in the external validation cohort (NRI 0.46, 95% CI 0.23–0.69, p < 0.001).

          Conclusions

          The GRACE score overestimated mortality risk after myocardial infarction in these cohorts of older patients. The CFS is a simple guided frailty tool that may enhance prediction in this setting. These findings merit evaluation in larger cohorts of unselected patients.

          Trial registration

          Clinicaltrials.gov; NCT02302014 (November 26th 2014, retrospectively registered).

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          Most cited references19

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          Frailty assessment instruments: Systematic characterization of the uses and contexts of highly-cited instruments.

          The medical syndrome of frailty is widely recognized, yet debate remains over how best to measure it in clinical and research settings. This study reviewed the frailty-related research literature by (a) comprehensively cataloging the wide array of instruments that have been utilized to measure frailty, and (b) systematically categorizing the different purposes and contexts of use for frailty instruments frequently cited in the research literature. We identified 67 frailty instruments total; of these, nine were highly-cited (≥ 200 citations). We randomly sampled and reviewed 545 English-language articles citing at least one highly-cited instrument. We estimated the total number of uses, and classified use into eight categories: risk assessment for adverse health outcomes (31% of all uses); etiological studies of frailty (22%); methodology studies (14%); biomarker studies (12%); inclusion/exclusion criteria (10%); estimating prevalence as primary goal (5%); clinical decision-making (2%); and interventional targeting (2%). The most common assessment context was observational studies of older community-dwelling adults. Physical Frailty Phenotype was the most used frailty instrument in the research literature, followed by the Deficit Accumulation Index and the Vulnerable Elders Survey. This study provides an empirical evaluation of the current uses of frailty instruments, which may be important to consider when selecting instruments for clinical or research purposes. We recommend careful consideration in the selection of a frailty instrument based on the intended purpose, domains captured, and how the instrument has been used in the past. Continued efforts are needed to study the validity and feasibility of these instruments.
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            Representation of elderly persons and women in published randomized trials of acute coronary syndromes.

            Elderly persons and women were underrepresented in randomized controlled trials (RCTs) prior to 1990. Since then, efforts have been made to correct these biases, but their effect is unclear. To determine whether the percentage of elderly persons and women in published clinical trials of acute coronary syndromes has increased and how this enrollment compared with disease prevalence. The MEDLINE and Cochrane databases were searched for English-language articles from January 1966 to March 2000 regarding myocardial infarction, unstable angina, or acute coronary syndromes. Additional data sources included meta-analyses, review articles, and cardiology textbooks. Estimates of community-based myocardial infarction rates came from the National Registry of Myocardial Infarction and the Worcester Heart Study. Published RCTs of acute coronary syndrome patients were included and trials enrolling 50 patients or fewer, those without clinical end points, papers published in a language other than English, and unpublished manuscripts were excluded. Of 7645 studies identified, 593 RCTs were selected for review. The RCTs were abstracted by 2 of the authors for year of publication, source of support (ie, funding), pharmacotherapy, study phase, number of study sites, trial location, number of patients, mean age of the study population, and any age exclusion criteria for enrollment. The number of published RCTs with explicit age exclusions has declined from 58% during 1966-1990 to 40% during 1991-2000. Trial enrollment of patients aged 75 years or older increased from 2% for studies published during 1966-1990 to 9% during 1991-2000, but remains well below their representation among all patients with myocardial infarction (37%) in the United States. Enrollment of women has risen from 20% for studies published between 1966-1990 to 25% during 1991-2000, but remains well below their proportion of all patients with myocardial infarction (43%) in the United States. Attempts at making cardiovascular RCTs more inclusive appear to have had limited success; thus, women and elderly persons remain underrepresented in published trial literature relative to their disease prevalence. Because safety and efficacy can vary as a function of sex and age, these enrollment biases undermine efforts to provide evidence-based care to all cardiac patients.
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              Impact of age on management and outcome of acute coronary syndrome: observations from the Global Registry of Acute Coronary Events (GRACE).

              Evidence-based cardiac therapies are underutilized in elderly patients. We assessed differences in practice patterns, comorbidities, and in-hospital event rates, by age and type of acute coronary syndrome (ACS). We studied 24165 ACS patients in 102 hospitals in 14 countries stratified by age. Approximately two-thirds of patients were men, but this proportion decreased with age. In elderly patients (> or = 65 years), history of angina, transient ischemic attack/stroke, myocardial infarction(MI), congestive heart failure, coronary artery bypass graft (CABG) surgery, hypertension or atrial fibrillation were more common, and delay in seeking medical attention and non-ST-segment elevation MI were significantly higher. Aspirin, beta-blockers, thrombolytic therapy, statins and glycoprotein IIb/IIIa inhibitors were prescribed less, while calcium antagonists and angiotensin-converting enzyme inhibitors were prescribed more often to elderly patients. Unfractionated heparin was prescribed more often in young patients, while low-molecular-weight heparins were similarly prescribed across all age groups. Coronary angiography and percutaneous intervention rates significantly decreased with age. The rate of CABG surgery was highest among patients aged 65-74 years (8.1%) and 55-64 years (7.7%), but reduced in the youngest (4.7%) and oldest (2.7%) groups. Major bleeding rates were 2-3% among patients aged 6% in those > or = 85 years. Hospital-mortality rates, adjusted for baseline risk differences, increased with age (odds ratio: 15.7 in patients > or = 85 years compared with those < 45 years). Many elderly ACS patients do not receive evidence-based therapies, highlighting the need for clinical trials targeted specifically at elderly cohorts, and quality-of-care programs that reinforce the use of such therapies among these individuals.
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                Author and article information

                Contributors
                atul.anand@ed.ac.uk
                Journal
                BMC Geriatr
                BMC Geriatr
                BMC Geriatrics
                BioMed Central (London )
                1471-2318
                13 March 2020
                13 March 2020
                2020
                : 20
                : 102
                Affiliations
                [1 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, BHF Centre for Cardiovascular Science, , University of Edinburgh, ; Room SU.305 Chancellor’s Building, Edinburgh, EH16 4SB UK
                [2 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Geriatric Medicine Research Group, , University of Edinburgh, ; Edinburgh, UK
                [3 ]GRID grid.418716.d, ISNI 0000 0001 0709 1919, Department of Cardiology, Edinburgh Heart Centre, , Royal Infirmary of Edinburgh, ; Edinburgh, UK
                [4 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Edinburgh Clinical Trials Unit, , Usher Institute for Population Health Sciences and Informatics University of Edinburgh, ; Edinburgh, UK
                [5 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Primary Palliative Care Research Group, Usher Institute for Population Health Sciences and Informatics, , University of Edinburgh, ; Edinburgh, UK
                [6 ]GRID grid.412937.a, ISNI 0000 0004 0641 5987, South Yorkshire Cardiothoracic Centre, , Northern General Hospital, ; Sheffield, UK
                Author information
                http://orcid.org/0000-0002-6428-4554
                Article
                1500
                10.1186/s12877-020-1500-9
                7069195
                32164580
                9c8e74ba-a8fd-49b1-8864-cb1ef9590402
                © The Author(s). 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 20 May 2019
                : 28 February 2020
                Funding
                Funded by: Marie Curie Research
                Award ID: A15867
                Funded by: Chief Scientist Office
                Award ID: PCL/18/05
                Award Recipient :
                Funded by: British Heart Foundation
                Award ID: FS/16/14/32023
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Geriatric medicine
                frailty,risk prediction,myocardial infarction,acute coronary syndrome
                Geriatric medicine
                frailty, risk prediction, myocardial infarction, acute coronary syndrome

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