Frailty: from clinical syndrome to epidemiological construct?
Authors: Martin Gulliford, Rathi Ravindrarajah
Journal: The Lancet Public Health (2018)

More people now live to advanced ages. The health and social care needs of the growing population with age-related frailty are becoming important public health and health policy concerns. Frailty has been described as “a distinctive health state related to the ageing process in which multiple body systems gradually lose their in-built reserves,”1British Geriatrics SocietyWhat is frailty?. British Geriatrics Society, London2018http://www.bgs.org.uk/frailty-explained/resources/campaigns/fit-for-frailty/frailty-what-is-itDate accessed: June 5, 2018Google Scholar rendering frail individuals susceptible to adverse outcomes such as falls, fractures, hospital admissions, and mortality. The notion of frailty has potential for risk stratification, but how can it be defined and recognised and what are the causes of frailty? A qualitative study,2Korenvain C Famiyeh I-M Dunn S et al.Identifying frailty in primary care: a qualitative description of family physicians' gestalt impressions of their older adult patients.BMC Family Practice. 2018; 19: 61Crossref PubMed Scopus (17) Google Scholar published earlier this year, found that physicians can generally recognise frailty when they see it in their patients but clinicians acknowledge uncertainty and lack of reliability in classifying their patients' frailty status in the absence of clear definitions and diagnostic criteria. Many researchers have tried to operationalise definitions of frailty, of which the most widely accepted is the frailty phenotype proposed by Fried and colleagues.3Fried LP Tangen CM Walston J et al.Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M157Crossref PubMed Google Scholar This model is based on the co-occurrence of at least three of five apparently non-specific features including unintentional weight loss, self-reported exhaustion, weakness (low grip strength), slow walking speed, and low physical activity.3Fried LP Tangen CM Walston J et al.Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M157Crossref PubMed Google Scholar Another approach to the classification of frailty draws on the cumulative deficit model leading to the calculation of a quantitative frailty index. The Frailty Index developed by Rockwood and colleagues.4Rockwood K Mitnitski A Frailty in relation to the accumulation of deficits.J Gerontol A Biol Sci Med Sci. 2007; 62: 722-727Crossref PubMed Scopus (1563) Google Scholar considers the number of possible deficits in an individual. Recent exemplars of this approach include the e-Frailty Index5Clegg A Bates C Young J et al.Development and validation of an electronic frailty index using routine primary care electronic health record data.Age Ageing. 2016; 45: 353-360Crossref PubMed Scopus (575) Google Scholar and the Hospital Frailty Risk Score.6Gilbert T Neuburger J Kraindler J et al.Development and validation of a Hospital Frailty Risk Score focusing on older people in acute care settings using electronic hospital records: an observational study.Lancet. 2018; 391: 1775-1782Summary Full Text Full Text PDF PubMed Scopus (491) Google Scholar The construction of these indices shows considerable overlap with the concept of multiple morbidity.7Barnett K Mercer SW Norbury M et al.Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study.Lancet. 2012; 380: 37-43Summary Full Text Full Text PDF PubMed Scopus (3701) Google Scholar Frailty indices are generally strongly associated with mortality5Clegg A Bates C Young J et al.Development and validation of an electronic frailty index using routine primary care electronic health record data.Age Ageing. 2016; 45: 353-360Crossref PubMed Scopus (575) Google Scholar and this finding suggests that some patients with frailty might be approaching a stage of terminal decline.8Diehr P Williamson J Burke GL et al.The aging and dying processes and the health of older adults.J Clin Epidemiol. 2002; 55: 269-278Summary Full Text Full Text PDF PubMed Scopus (83) Google Scholar Two papers, one by Eric Brunner and colleagues9Brunner EJ Shipley MJ Ahmadi-Abhari S et al.Midlife contributors to socioeconomic differences in frailty during later life: a prospective cohort study.Lancet Public Health. 2018; (published online June 13.)http://dx.doi.org/10.1016/S2468-2667(18)30079-3Summary Full Text Full Text PDF PubMed Scopus (40) Google Scholar and the other by Peter Hanlon and colleagues,10Hanlon P Nicholl BI Jani BD et al.Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participants.Lancet Public Health. 2018; (published online June 13.)http://dx.doi.org/10.1016/S2468-2667(18)30091-4Summary Full Text Full Text PDF PubMed Scopus (349) Google Scholar in this issue of The Lancet Public Health, explore the epidemiology of frailty in the context of two well-known UK cohort studies, the Whitehall II and UK Biobank studies, respectively. Both reports assessed relatively young populations. The Whitehall II study assessed participants at a mean age of 69 years, with a minority of women, whereas the analysis of UK Biobank study included participants aged 37–73 years. Both reports used Fried's phenotype to assess frailty, classifying participants as pre-frail if they showed one or two features, and frail if they showed three or more. In the Whitehall II study,9Brunner EJ Shipley MJ Ahmadi-Abhari S et al.Midlife contributors to socioeconomic differences in frailty during later life: a prospective cohort study.Lancet Public Health. 2018; (published online June 13.)http://dx.doi.org/10.1016/S2468-2667(18)30079-3Summary Full Text Full Text PDF PubMed Scopus (40) Google Scholar fewer than 2% showed evidence of frailty under the age of 65, increasing to more than 10% at 75 years or older. There were substantial inequalities in the occurrence of frailty, which was more frequent in women, ethnic minority groups and those with low employment grade. Low employment grade at age 50 years was associated with 2·60 times higher odds of later frailty (95% CI 1·89–3·58). Participants who had long-term conditions or lifestyle risk factors for long-term conditions at the age of 50 years were more likely to develop frailty in later life, and these characteristics largely accounted for inequalities in frailty. These findings are consistent with those of a recent international study,11Stringhini S Carmeli C Jokela M et al.Socioeconomic status, non-communicable disease risk factors, and walking speed in older adults: multi-cohort population based study.BMJ. 2018; 360: k1046Crossref PubMed Scopus (70) Google Scholar which explored inequalities in walking speed in old age and support the view that social inequality has a major negative effect on healthy ageing.12Cooper R Socioeconomic adversity—an important barrier to healthy aging.BMJ. 2018; 360: k1288Crossref PubMed Scopus (2) Google Scholar In the UK Biobank study,10Hanlon P Nicholl BI Jani BD et al.Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participants.Lancet Public Health. 2018; (published online June 13.)http://dx.doi.org/10.1016/S2468-2667(18)30091-4Summary Full Text Full Text PDF PubMed Scopus (349) Google Scholar 16 538 (3%) of 493 737 participants met the criteria for frailty, with more than a third of the sample (185 360 [38%] of 493 737) meeting the criteria for pre-frailty. Multiple morbidity was strongly associated with frailty in the UK Biobank data with participants with four or more long term conditions having 27 times higher odds of frailty than those with no long-term conditions (OR 27·1, 95% CI 25·3–29·1). Of all individual long-term conditions, frailty was most frequently observed in patients with multiple sclerosis and chronic fatigue syndrome. Obesity at midlife was associated with frailty in both studies, suggesting that targeting modifiable risk factors at midlife might reduce the occurrence of frailty at later ages. These new analyses advance our understanding of the association between long-term conditions, multiple morbidity, and frailty. These studies show that long-term conditions and their risk factors are often antecedents of frailty; multiple morbidity and frailty often co-exist. The data also raise questions concerning our present epidemiological definitions of frailty. The high proportion of participants classified as pre-frail in the UK Biobank study could suggest that the definition lacks specificity; however, pre-frailty was associated with mortality in the UK Biobank data with hazard ratios for mortality at age 65–73 years compared with the non-frail group of 1·45 in men (95% CI 1·34–1·57) and 1·50 in women (1·34–1·68). Other recent studies have assessed the associations of low walking speed11Stringhini S Carmeli C Jokela M et al.Socioeconomic status, non-communicable disease risk factors, and walking speed in older adults: multi-cohort population based study.BMJ. 2018; 360: k1046Crossref PubMed Scopus (70) Google Scholar or low grip strength13Celis-Morales CA Welsh P Lyall DM et al.Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants.BMJ. 2018; 361: k1651PubMed Google Scholar with mortality without invoking the concept of frailty. There is a lack of consensus on the definition of frailty; the classification of individuals as frail depends on the theoretical construct incorporated in the frailty model,14Mitnitski A Fallah N Rockwood MR et al.Transitions in cognitive status in relation to frailty in older adults: a comparison of three frailty measures.J Nutrition, Health & Aging. 2011; 15: 863-867Crossref PubMed Scopus (109) Google Scholar raising a possibility that there might be more than one kind of frailty. At present, the term frailty might be viewed as describing one phase of an ageing continuum and this continuum is perhaps not readily dichotomised. We declare no competing interests. Midlife contributors to socioeconomic differences in frailty during later life: a prospective cohort studyBehavioural and cardiometabolic risk factors in midlife account for more than a third of socioeconomic differences in frailty. Our findings suggest that interventions targeting physical activity, obesity, smoking, and low-grade inflammation in middle age might reduce socioeconomic differences in later-life frailty. Full-Text PDF Open AccessFrailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participantsEfforts to identify, manage, and prevent frailty should include middle-aged individuals with multimorbidity, in whom frailty is significantly associated with mortality, even after adjustment for number of long-term conditions, sociodemographics, and lifestyle. Research, clinical guidelines, and health-care services must shift focus from single conditions to the requirements of increasingly complex patient populations. Full-Text PDF Open Access