Abstract
Background: Frailty is a state of vulnerability and a decreased physiological response to stressors. As the population ages, the prevalence of frailty is expected to increase. Thus, identifying tools and resources that efficiently predict frailty among the Saudi population is important. We aimed to describe the prevalence and predictors of frailty among Saudi patients referred for cardiac stress testing with nuclear imaging. Methods: We included 876 patients (mean age 60.3 ± 11 years, women 48%) who underwent clinically indicated cardiac nuclear stress testing between January and October 2016. Fried Clinical Frailty Scale was used to assess frailty. Patients were considered frail if they had a score of four or higher. Multivariate adjusted logistic regression models were used to determine the independent predictors of elderly frail patients. Results: In this cohort, the median age of the included patients was 61 years, and the prevalence of frailty was 40%. The frail patients were older, more frequently women, and had a higher body mass index. Additionally, frailty was associated with a higher prevalence of cardiovascular risk factors: hypertension (85% vs. 70%) and diabetes (75% vs. 60%). In a fully adjusted logistic regression model, women, hypertension, and obesity (BMI ≥ 30 kg/m2) were independent predictors of elderly frail patients. Conclusions: With the aging of the Saudi population, frailty prevalence is expected to increase. Elderly, obesity, hypertension, and female gender are risk factors of frailty. Interventions to reduce frailty should be focused on this high-risk population.
Keywords: Fried clinical frailty scale, frail elderly, cardiac nuclear stress testing, cardiovascular predictors
Introduction
Rapid progression of medical knowledge has allowed investigators to address many gaps in cardiac sciences1–2 through improving cardiac care provided and achieving higher standards of management.3–6 Targeted medical therapies and focused care reduced major adverse cardiac event rates in the last decade.7–10 As a result, global life expectancy has increased significantly, and the number of elderly patients in need of cardiac care increased dramatically.3 However, these elderly patients are underrepresented in the vast majority of recent cohort studies and randomized clinical trials. Many were excluded because of significant physical and cognitive disability as well as associated comorbidities.11–12
Frailty assessment is often a difficult task.13 Multiple assessment tools are used to assess the physical, social, and psychological status of this population.14–15 However, frailty prevalence is influenced by developmental and financial factors of nations,16–17 which might affect its distribution based upon variations in cardiovascular risk factors.14 Additionally, frailty evaluation and quantification is a complex task that is only partially related to conventional coronary artery risk assessment. However, frailty has a significant impact on therapeutic clinical decisions in coronary artery disease.18–19
Saudi Arabia, as a developing country, stated a goal to increase its life expectancy by 5 years within the coming decade.20 As the population ages, the prevalence of frailty and comorbid conditions, including coronary artery disease and other cardiac pathologies, are expected to increase. Therefore, identifying tools and resources that efficiently detect frailty among Saudi elderly patients is important. Thus, this study aims to describe the prevalence and predictors of frailty among Saudi patients referred for cardiac stress testing with nuclear imaging.
Methods
Data collection and patients characteristics
This is a cross-sectional study that included all consecutive patients who underwent a clinically indicated cardiac positron emission tomography (PET) at a tertiary care center between January and October 2016. This center provides advanced cardiovascular care, including advanced imaging techniques for cardiac patients.21 Prior to the cardiac PET assessment, patients’ baseline characteristics, cardiovascular risk factors, laboratory results, and medications used were collected. Patients were excluded if he or she refused to be enrolled in the study.
Frailty assessment and evaluation
The frailty assessment was completed at the time of the PET procedure by a trained nurse using the Canadian Study of Health and Ageing Clinical Frailty Scale or in short “Fried Scale.”22 This scale is a semi-objective scale describing patients’ frailty status according to quick and direct questions about patients’ activities of daily living (ADLs) and interaction with surroundings. Patients were asked about their life dependence, need for assistance on any ADLs, instrumental ADLs, outside home activity, frequency of exercise, and current medical problems. Then, their level of frailty was established (Figure 1). Demented and terminally ill patients were excluded. Patients were considered to be frail if they had a score of four or higher on the Fried scale.
Figure 1.

Canadian Study of Health and Aging Clinical Frailty Scale, adapted from Moorhouse and Rockwood35.
Study definitions
Patients using antihyperglycemic medications or with a prior history of diabetes were reported as diabetics. Hypertension was defined as prior hypertension history or the use of any blood pressure-lowering medications. Patients with a prior diagnosis of lipid abnormality or using lipid-lowering therapies were considered to have dyslipidemia.
Statistical analysis
Continuous data were presented as mean with standard deviation and categorical data as percent frequencies. Students’ t-test and chi-square or Fisher's exact tests were used for group comparison, as appropriate. Multivariate logistic regression models were used to predict frail patients. The regression model consisted of patients’ baseline characteristics, conventional cardiovascular risk factors, and cardiac-related medications. All analyses were conducted using Stata 14 software (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP).23 Statistical significance was considered if p ≤ 0.05.
Results
A total of 876 patients (mean age 60.3 ± 11 years; 48.3% were women) were included. The prevalence of frailty was 40%. The prevalence of conventional cardiovascular risk factors including hypertension, diabetes, dyslipidemia, and smoking were 76%, 66%, 46%, and 9.6%, respectively. Many patients had a previous cardiac history: stroke 4.1%, percutaneous coronary intervention 18.4%, coronary artery bypass grafting 8.9%, and chronic heart failure 4.8%. Cardiac-related medications and angiotensin-related medications were used in every other patient, while beta-blockers and calcium channel blockers were used in one-third of the study cohort, and a quarter of the cohort were using diuretics (Table 1).
Table 1.
Baseline characteristics of the study cohort.
| Overall population (n = 876) | Frailty status | |||
| Nonfrail (60.05%) | Frail (39.95%) | p | ||
|
| ||||
| Age (years) | 60.28 ± 11.45 | 57.04 ± 11.09 | 65.14 ± 10.22 | < 0.001 |
|
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| Female | 423 (48.29%) | 41.25% | 58.86% | 0.002 |
|
| ||||
| Height (cm) | 161.29 ± 9.76 | 163.43 ± 9.38 | 158.22 ± 9.49 | < 0.001 |
|
| ||||
| Weight (kg) | 83.32 ± 17.72 | 83.45 ± 17.15 | 83.15 ± 18.55 | 0.851 |
|
| ||||
| BMI (kg/m2) | 31.81 ± 7.14 | 30.91 ± 6.40 | 33.18 ± 7.94 | < 0.001 |
|
| ||||
| Cardiovascular risk factor | ||||
|
| ||||
| Hypertension | 664 (75.80%) | 69.58% | 85.14% | < 0.001 |
|
| ||||
| Diabetes | 574 (65.53%) | 59.51% | 74.57% | < 0.001 |
|
| ||||
| Dyslipidaemia | 405 (46.23%) | 46.39% | 46.00% | 0.910 |
|
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| Asthma | 74 (8.45%) | 7.03% | 10.57% | 0.065 |
|
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| Smoking | 84 (9.59%) | 10.84% | 7.71% | 0.124 |
|
| ||||
| Previous TIA/stroke | 36 (4.11%) | 3.04% | 5.71% | 0.051 |
|
| ||||
| Chronic renal failure | 133 (15.18%) | 12.93% | 18.57% | 0.023 |
|
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| Chronic heart failure | 42 (4.79%) | 3.80% | 6.29% | 0.092 |
|
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| Previous PCI | 161 (18.38%) | 19.58% | 16.57% | 0.260 |
|
| ||||
| Previous CABG | 78 (8.90%) | 8.56% | 9.43% | 0.657 |
|
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| Medications | ||||
|
| ||||
| Angiotensin-related medications | 469 (53.54%) | 50.57% | 58.00% | 0.031 |
|
| ||||
| Beta blockers | 391 (44.63%) | 42.40% | 48.00% | 0.102 |
|
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| Calcium channel blockers | 294 (33.56%) | 30.42% | 38.29% | 0.016 |
|
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| Diuretics | 219 (25.00%) | 18.44% | 34.86% | < 0.001 |
|
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BMI, body mass index; TIA, transient ischemic attack; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting.
All the data were presented as frequencies or mean ( ± standard deviation), as appropriate. Chi-square test and student's t-test were used as indicated.
Frail patients were older, more often women, and had a higher body mass index (Table 1). In addition, they had a higher prevalence of hypertension (85.1% vs. 69.6%; p < 0.001), diabetes (74.6% vs. 59.5%; p < 0.001), previous stroke (5.7% vs. 3.0%; p = 0.051), and chronic kidney disease (6.3% vs. 3.8%; p = 0.023). They were more often on beta-blockers, angiotensin-converting enzymes, and diuretics (Table 1). Furthermore, frailty prevalence increased with increasing age across male and female groups (Figure 2). Surprisingly, patients younger than 60 years old had a high prevalence of frailty. Every other female patient older than the sixth decade was frail, and almost one-third of male patients in the same age group were frail, too.
Figure 2.

Prevalence of frailty across different age groups.
Using a multivariate logistic regression model within the study cohort, we found that age, female gender, body mass index, diabetes, renal disease, and diuretics use were independently predictive of frail patients (Table 2).
Table 2.
Multivariate logistic regression predict frail patients among study cohort.
| Odds ratio | p | 95% confidence interval | |
|
| |||
| Age | 1.09 | < 0.001 | (1.08–1.11) |
|
| |||
| Female | 2.19 | < 0.001 | (1.56–3.08) |
|
| |||
| Body mass index | 1.05 | < 0.001 | (1.03–1.08) |
|
| |||
| Diabetes | 1.57 | 0.011 | (1.11–2.22) |
|
| |||
| Renal disease | 3.09 | < 0.001 | (1.90–5.03) |
|
| |||
| Diuretics | 1.57 | 0.017 | (1.08–2.27) |
|
| |||
The model consists of baseline characteristics (age, gender [female], and body mass index), cardiac risk factors (hypertension, diabetes, stroke, and kidney disease), and medications (angiotensin-related medications, calcium channel blockers, and diuretics).
Subgroup analysis for patients 65 years and older
Since frailty impacts clinical decisions mainly in older patients, we analyzed the older cohort separately. Among patients older than 65 years, frail patients were older (72 vs. 70 years, p < 0.001), more often women (53% vs. 30%, p < 0.001), and with higher body mass index (32.1 vs. 29.6 kg/m2, p < 0.001). Despite that, no apparent differences between frail and nonfrail patients in cardiovascular risk factors and cardiac-related medications were noted (Table 3). A multivariate logistics regression model was used to define possible frailty predictors in this subgroup. Patients’ age, gender, and body mass index were independently associated with frailty (Table 4).
Table 3.
Baseline characteristics for subgroup (65 years and older).
| Overall population (n = 332) | Frailty status | |||
| Nonfrail (40.66%) | Frail (59.34%) | p | ||
|
| ||||
| Age (years) | 71.34 ± 5.42 | 70.15 ± 4.54 | 72.16 ± 5.82 | < 0.001 |
|
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| Female | 144 (43.37%) | 29.63% | 52.79% | < 0.001 |
|
| ||||
| Height (cm) | 160.55 ± 9.22 | 163.65 ± 7.59 | 158.68 ± 9.63 | < 0.001 |
|
| ||||
| Weight (kg) | 79.74 ± 15.60 | 78.68 ± 13.91 | 80.38 ± 16.55 | 0.453 |
|
| ||||
| BMI (kg/m2) | 31.06 ± 6.35 | 29.60 ± 5.16 | 32.06 ± 6.88 | < 0.001 |
|
| ||||
| Cardiovascular risk factor | ||||
|
| ||||
| Hypertension | 275 (82.83%) | 80.00% | 84.77% | 0.257 |
|
| ||||
| Diabetes | 237 (71.39%) | 67.41% | 74.11% | 0.184 |
|
| ||||
| Dyslipidaemia | 166 (50.00%) | 52.59% | 48.22% | 0.434 |
|
| ||||
| Asthma | 29 (8.73%) | 8.15% | 9.14% | 0.754 |
|
| ||||
| Smoking | 27 (8.13%) | 5.19% | 10.15% | 0.104 |
|
| ||||
| Previous TIA/stroke | 17 (5.12%) | 2.96% | 6.60% | 0.140 |
|
| ||||
| Chronic renal failure | 45 (13.55%) | 12.59% | 14.21% | 0.672 |
|
| ||||
| Chronic heart failure | 17 (5.12%) | 5.19% | 5.08% | 0.965 |
|
| ||||
| Previous PCI | 62 (18.67%) | 19.26% | 18.27% | 0.821 |
|
| ||||
| Previous CABG | 45 (13.55%) | 15.56% | 12.18% | 0.378 |
|
| ||||
| Medications | ||||
|
| ||||
| Angiotensin-related medications |
199 (59.94%) | 59.26% | 60.41% | 0.834 |
|
| ||||
| Beta blockers | 165 (49.70%) | 52.59% | 47.72% | 0.383 |
|
| ||||
| Calcium channel blockers | 141 (42.47%) | 41.48% | 43.15% | 0.763 |
|
| ||||
| Diuretics | 100 (30.12%) | 25.93% | 32.99% | 0.168 |
|
| ||||
BMI, body mass index; TIA, transient ischemic attack; PCI: percutaneous coronary intervention; CABG, coronary artery bypass grafting.
All the data were presented as frequencies or mean ( ± standard deviation), as appropriate. Chi-square test and student's t-test were used as indicated.
Table 4.
Multivariate logistic regression predict frail patients older than 65 years.
| Odds ratio | p | 95% confidence interval | |
|
| |||
| Age | 1.12 | < 0.001 | (1.05–1.20) |
|
| |||
| Female | 2.64 | < 0.001 | (1.30–5.45) |
|
| |||
| Body mass index | 1.06 | 0.017 | (1.01–1.16) |
|
| |||
The model consists of baseline characteristics (age, gender [female], and body mass index), cardiac risk factors (hypertension, diabetes, stroke, and kidney disease), and medications (angiotensin-related medications, calcium channel blockers, and diuretics).
Discussion
Our study described the frailty prevalence in Saudi Arabia among patients who were referred for cardiac risk assessment by nuclear stress testing. Furthermore, we identified the predictors of elderly frail patients.24–26
Frailty assessment tools are numerous, and most of these are time consuming, which might have limited acceptance in a busy daily clinical practice. The Canadian Study of Health and Aging clinical frailty scale or in short Fried scale has been shown to have good diagnostic and prognostic values.9,22 It was developed over 25 years ago15,24,27 and was essential to describe the epidemiology of cognitive impairment and other important clinical factors among this target population.
The frailty prevalence in our study cohort was 40%, which is a little higher than other international published reports.14,28–29 Few published literature have stated that frailty is not a geriatric-related problem. Some younger patients could be frail while they are chronologically young. Results from our study population come in agreement with the previous observation. One could argue that frail patients younger than 65 years share some phenotypical characteristics with older frail patients. The impacts of these findings on management decisions and outcomes of these young frail patients warrant further study.
In addition, the heterogeneity of aging was seen in our study. Many elderly patients are not frail despite advanced chronological age. Van Kan et al.,15 suggested that frailty is a predisability stage. This implies that disability is not the cause but rather a consequence of frailty. Disability should not be included in the definition nor used as a tool for the assessment.15,30 Thus, frailty is considered to be a separate pathophysiological condition that has its own predisposing factors.
On the other hand, cardiovascular risk predictors are essential for clinical decision making and assessment for better patients’ outcomes. Identifying patients who may benefit from any cardiac-specific treatments such as major procedures and critical interventions is the pillar for survival improvement and better quality of life.31–32 Despite that, traditional cardiac risk scores have their own limits. All these scores comprehend age as the main contributor without discrimination between actual and biological ages. Additionally, the generalizability of these risk scores is restricted since they always have an upper age limit. Thus, using simple frailty tools to assist in the prediction of major cardiac events might improve the predictability of coronary artery disease, management decisions, resource utilization, and hard outcomes.23,33–34 One should note that congestive heart failure and chronic kidney disease were associated with frailty status. This suggests that frailty is a clinical condition that can be detected across the spectrum of cardiovascular diseases.
Limitations
This study has several limitations. Although the clinical frailty scale is easy to implement, it has some subjective aspects that are predisposed to interobserver variability. Also, there might be an inherent selection bias. Patients with life-limiting diseases such as stroke, cancer, and end-stage renal failure have a short life expectancy. Thus, these conditions were not noted as predictors of frailty. Lastly, we did not assess the prognostic impacts of frailty on major cardiac events such as cardiac mortality, hospitalization, and revascularization.
Conclusions
With the aging of the Saudi population, frailty prevalence is expected to increase. Elderly, obesity, hypertension, and female gender are risk factors to develop frailty. Interventions to reduce frailty should be focused on this high-risk population.
Acknowledgements
We would like to extend our great thanks and appreciation to our nuclear cardiology nurses for their unrivaled support; Katrina Billanes, Swee Meen Kan, Ria Andres, Reniebelle Tomas, Haiya Al Beshi, Norazrin Jamaludin, Normaliza Kamarudin, Ashwag Al-Heggi, Amal Al Anazi and Fatima Al Mutairi.
References
- 1.Lauer MS. Advancing cardiovascular research. Chest. 2012;141(2):500–505. doi: 10.1378/chest.11-2521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Williams KJ, Feig JE, Fisher EA. Rapid regression of atherosclerosis: insights from the clinical and experimental literature. Nat Clin Pract Cardiovasc Med. 2008;5:91–102. doi: 10.1038/ncpcardio1086. [DOI] [PubMed] [Google Scholar]
- 3.Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J et al. From vulnerable plaque to vulnerable patient a call for new definitions and risk assessment strategies: part I. Circulation. 2003;108:1664–1672. doi: 10.1161/01.CIR.0000087480.94275.97. [DOI] [PubMed] [Google Scholar]
- 4.Task Force Members. Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C et al. ESC guidelines on the management of stable coronary artery disease. Eur Heart J. 2013;34(38):2949–3003. doi: 10.1093/eurheartj/eht296. [DOI] [PubMed] [Google Scholar]
- 5.Authors/Task Force Members. Hamm CW, Bassand J-P, Agewall S, Bax J, Boersma E et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2011;32(23):2999–3054. doi: 10.1093/eurheartj/ehr236. [DOI] [PubMed] [Google Scholar]
- 6.Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH et al. ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147–e239. doi: 10.1016/j.jacc.2013.05.019. [DOI] [PubMed] [Google Scholar]
- 7.Graham DJ, Reichman ME, Wernecke M, Zhang R, Southworth MR, Levenson M et al. Cardiovascular, bleeding, and mortality risks in elderly medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation. Circulation. 2015;(131):157–164. doi: 10.1161/CIRCULATIONAHA.114.012061. [DOI] [PubMed] [Google Scholar]
- 8.Cannon CP, Harrington RA, James S, Ardissino D, Becker RC, Emanuelsson H et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet. 2010;375(9711):283–293. doi: 10.1016/S0140-6736(09)62191-7. [DOI] [PubMed] [Google Scholar]
- 9.Heidenreich PA, Lee TT, Massie BM. Effect of beta-blockade on mortality in patients with heart failure: a meta-analysis of randomized clinical trials 1. J Am Coll Cardiol. 1997;30(1):27–34. doi: 10.1016/s0735-1097(97)00104-6. [DOI] [PubMed] [Google Scholar]
- 10.Fonarow GC, Wright RS, Spencer FA, Fredrick PD, Dong W, Every N et al. Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality. Am J Cardiol. 2005;96(5):611–616. doi: 10.1016/j.amjcard.2005.04.029. [DOI] [PubMed] [Google Scholar]
- 11.Lakoski S, Cushman M, Siscovick D, Blumenthal R, Palmas W, Burke G et al. The relationship between inflammation, obesity and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA) J Hum Hypertens. 2011;25:73–79. doi: 10.1038/jhh.2010.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Kim F, Nichol G, Maynard C, Hallstrom A, Kudenchuk PJ, Rea T et al. Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial. JAMA. 2014;311(1):45–52. doi: 10.1001/jama.2013.282173. [DOI] [PubMed] [Google Scholar]
- 13.Cleveland JC. Frailty, aging, and cardiac surgery outcomes: the stopwatch tells the story. J Am Coll Cardiol. 2010;56(20):1677–1678. doi: 10.1016/j.jacc.2010.07.021. [DOI] [PubMed] [Google Scholar]
- 14.Afilalo J, Alexander KP, Mack MJ, Maurer MS, Green P, Allen LA et al. Frailty assessment in the cardiovascular care of older adults. J Am Coll Cardiol. 2014;63(8):747–762. doi: 10.1016/j.jacc.2013.09.070. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Van Kan GA, Rolland Y, Bergman H, Morley J, Kritchevsky S, Vellas B, The IANA. Task Force on frailty assessment of older people in clinical practice. J Nutr Health Aging. 2008;12(1):29–37. doi: 10.1007/BF02982161. [DOI] [PubMed] [Google Scholar]
- 16.Casale-Martínez RI, Navarrete-Reyes AP, Ávila-Funes JA. Social determinants of frailty in elderly Mexican community-dwelling adults. J Am Geriatr Soc. 2012;60(4):800–802. doi: 10.1111/j.1532-5415.2011.03893.x. [DOI] [PubMed] [Google Scholar]
- 17.Bunt S, Steverink N, Olthof J, van der Schans C, Hobbelen J. Social frailty in older adults: a scoping review. Eur J Ageing. 2017;14(3):323–334. doi: 10.1007/s10433-017-0414-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Hulten E, Bittencourt MS, Ghoshhajra B, O'Leary D, Christman MP, Blaha MJ et al. Incremental prognostic value of coronary artery calcium score versus CT angiography among symptomatic patients without known coronary artery disease. Atherosclerosis. 2014;233(1):190–195. doi: 10.1016/j.atherosclerosis.2013.12.029. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Fukushima K, Javadi MS, Higuchi T, Lautamaki R, Merrill J, Nekolla SG et al. Prediction of short-term cardiovascular events using quantification of global myocardial flow reserve in patients referred for clinical 82Rb PET perfusion imaging. J Nucl Med. 2011;52(5):726–732. doi: 10.2967/jnumed.110.081828. [DOI] [PubMed] [Google Scholar]
- 20.Government of Saudi Arabia. Saudi Vision 2030 [Internet]. 2016 (cited 21 May 2019). Available from: https://vision2030.gov.sa/download/file/fid/417.
- 21.Dilsizian V, Bacharach SL, Beanlands RS, Bergmann SR, Delbeke D, Dorbala S et al. ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. J Nucl Cardiol. 2016;23(5):1187–1226. doi: 10.1007/s12350-016-0522-3. [DOI] [PubMed] [Google Scholar]
- 22.Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J et al. Frailty in older adults evidence for a phenotype. J Gerontol A: Biol Sci Med Sci. 2001;56(3):M146–M156. doi: 10.1093/gerona/56.3.m146. [DOI] [PubMed] [Google Scholar]
- 23.McNallan SM, Singh M, Chamberlain AM, Kane RL, Dunlay SM, Redfield MM et al. Frailty and healthcare utilization among patients with heart failure in the Community. JACC Heart Fail. 2013;1(2):135–141. doi: 10.1016/j.jchf.2013.01.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I et al. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173(5):489–495. doi: 10.1503/cmaj.050051. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Murali-Krishnan R, Iqbal J, Rowe R, Hatem E, Parviz Y, Richardson J et al. Impact of frailty on outcomes after percutaneous coronary intervention: a prospective cohort study. Open Heart. 2015;2(1):e000294. doi: 10.1136/openhrt-2015-000294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Song X, Mitnitski A, Rockwood K. Prevalence and 10-year outcomes of frailty in older adults in relation to deficit accumulation. J Am Geriatr Soc. 2010;58(4):681–687. doi: 10.1111/j.1532-5415.2010.02764.x. [DOI] [PubMed] [Google Scholar]
- 27.Rockwood K, Stadnyk K, MacKnight C, McDowell I, Hebert R, Hogan DB. A brief clinical instrument to classify frailty in elderly people. Lancet. 1999;353(9148):205–206. doi: 10.1016/S0140-6736(98)04402-X. [DOI] [PubMed] [Google Scholar]
- 28.Lupón J, González B, Santaeugenia S, Altimir S, Urrutia A, Más D et al. Prognostic implication of frailty and depressive symptoms in an outpatient population with heart failure. Rev Esp Cardiol. 2008;61(8):835–842. [PubMed] [Google Scholar]
- 29.Pittman JG, Cohen P. The pathogenesis of cardiac cachexia. N Engl J Med. 1964;271:403–409. doi: 10.1056/NEJM196408202710807. [DOI] [PubMed] [Google Scholar]
- 30.von Haehling S, Anker SD, Doehner W, Morley JE, Vellas B. Frailty and heart disease. Int J Cardiol. 2013;168(3):1745–1747. doi: 10.1016/j.ijcard.2013.07.068. [DOI] [PubMed] [Google Scholar]
- 31.Goff JDC, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino SRB, Gibbons R et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014;63(25 Part B):2935–2959. doi: 10.1016/j.jacc.2013.11.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Selvarajah S, Kaur G, Haniff J, Cheong KC, Hiong TG, van der Graaf Y et al. Comparison of the Framingham Risk Score, SCORE and WHO/ISH cardiovascular risk prediction models in an Asian population. Int J Cardiol. 2014;176:211–218. doi: 10.1016/j.ijcard.2014.07.066. [DOI] [PubMed] [Google Scholar]
- 33.Sergi G, Veronese N, Fontana L, De Rui M, Bolzetta F, Zambon S et al. Pre-frailty and risk of cardiovascular disease in elderly men and women: the Pro.V.A. study. J Am Coll Cardiol. 2015;65(10):976–983. doi: 10.1016/j.jacc.2014.12.040. [DOI] [PubMed] [Google Scholar]
- 34.Uchmanowicz I, Łoboz-Rudnicka M, Szeląg P, Jankowska-Polańska B, Łoboz-Grudzień K. Frailty in heart failure. Curr Heart Fail Rep. 2014;11(3):266–273. doi: 10.1007/s11897-014-0198-4. [DOI] [PubMed] [Google Scholar]
- 35.Moorhouse P, Rockwood K. Frailty and its quantitative clinical evaluation. J R Coll Physicians Edinb. 2012;42:333–340. doi: 10.4997/JRCPE.2012.412. [DOI] [PubMed] [Google Scholar]
