Transitions from health to disease in older populations
Authors: Jean-Pierre Michel
Journal: The Lancet Healthy Longevity (2022)

The original results of the longitudinal, multicentre ASPREE trial, which was conducted in 50 sites in Australia and the USA, have been a source of very important and valid information regarding healthy older adults.1McNeil JJ Woods RL Nelson MR et al.Effect of aspirin on disability-free survival in the healthy elderly.N Engl J Med. 2018; 379: 1499-1508Crossref PubMed Scopus (252) Google Scholar, 2McNeil JJ Wolfe R Woods RL et al.Effect of aspirin on cardiovascular events and bleeding in the healthy elderly.N Engl J Med. 2018; 379: 1509-1518Crossref PubMed Scopus (510) Google Scholar, 3McNeil JJ Nelson MR Woods RL et al.Effect of aspirin on all-cause mortality in the healthy elderly.N Engl J Med. 2018; 379: 1519-1528Crossref PubMed Scopus (399) Google Scholar Secondary analyses of ASPREE trial data have led to the publication of more than 100 scientific papers, including the Article by Johannes T Neumann and colleagues,4Neumann JT Thao LTP Callander E et al.A multistate model of health transitions in older people: a secondary analysis of ASPREE clinical trial data.Lancet Healthy Longev. 2022; 3 (e87): e89Summary Full Text Full Text PDF Scopus (1) Google Scholar which focuses on health transitions. Their secondary analysis fills a knowledge gap, tracing the path from health to intermediate disease states (ie, cancer events, stroke events, cardiac events, and physical disability or dementia) and to death in healthy older adults aged 70 years or older (≥65 years for Black and Hispanic people in the USA). Eligible participants were able to perform the Katz activities of daily living with minimal difficulty, were cognitively unimpaired, and did not have any life-threatening illness that shortened their life expectancy to less than 5 years. Neumann and colleagues4Neumann JT Thao LTP Callander E et al.A multistate model of health transitions in older people: a secondary analysis of ASPREE clinical trial data.Lancet Healthy Longev. 2022; 3 (e87): e89Summary Full Text Full Text PDF Scopus (1) Google Scholar showed that, after a median follow-up of 4·7 years (IQR 3·6–5·7), 15 398 (80·6%) of 19 114 older participants (median age 74·0 years [IQR 71·6–77·7]) were alive and had not transitioned to the investigated disease states. Healthy 75-year-old men were estimated to remain in the healthy state for 4·40 years (90·3%) of their 4·87 years of expected total life remaining and healthy 85-year-old men were estimated to remain in the healthy state for 3·89 years (84·7%) of their 4·59 years of expected total life remaining. For women, the percentages were even higher. Healthy 75-year-old women were estimated to remain in the healthy state for 4·60 years (93·3%) of their 4·93 years of expected total life remaining and healthy 85-year-old women were estimated to remain in the healthy state for 4·20 years (88·4%) of their 4·75 years of expected total life remaining. This result is unusual because previous studies have suggested that women tend to live with longer periods of disability than do men.5Hoogendijk EO van der Noordt M Onwuteaka-Philipsen BD et al.Sex differences in healthy life expectancy among nonagenarians: a multistate survival model using data from the Vitality 90+ study.Exp Gerontol. 2019; 116: 80-85Crossref PubMed Scopus (14) Google Scholar This finding could suggest a healthy survivor bias, probably driven by the study entry criteria. From an initial healthy state, the rate of transition was highest to cancer, followed by disability or dementia, cardiac events, and then stroke events and death. The rate of transition from a healthy state to cancer was significantly lower for women than for men (hazard ratio 0·59). The rate of transition was highest from cancer to death, followed by the rate of transition to death from stroke and cardiac events. Of the 1849 participants who transitioned to incident cancer, 27·1% subsequently transitioned to death. This finding contrasts with death registries that suggest that deaths from cancers represent around 15% of global deaths.6Lozano R Naghavi M Foreman K et al.Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.Lancet. 2012; 380: 2095-2128Summary Full Text Full Text PDF PubMed Scopus (9517) Google Scholar, 7Mathers CD Loncar D Projections of global mortality and burden of disease from 2002 to 2030.PLoS Med. 2006; 3: e442Crossref PubMed Scopus (7282) Google Scholar Classically, leading causes of death worldwide include ischaemic heart disease, cerebrovascular diseases, trachea, bronchus, and lung cancers, diabetes, bronchopulmonary obstructive diseases, and lower respiratory tract infections, a situation unlikely to change until at least 2030.7Mathers CD Loncar D Projections of global mortality and burden of disease from 2002 to 2030.PLoS Med. 2006; 3: e442Crossref PubMed Scopus (7282) Google Scholar Disability or dementia occurred in 4·8% of participants, and stroke and cardiac events were the leading causes of transition to disability or dementia. Cardiac and stroke events represented fewer than 5% of registered events and represented 12·1% of deaths in this study cohort. This low rate contrasts with the high mortality from cancers. When interpretating the results of this Article by Neumann and colleagues,4Neumann JT Thao LTP Callander E et al.A multistate model of health transitions in older people: a secondary analysis of ASPREE clinical trial data.Lancet Healthy Longev. 2022; 3 (e87): e89Summary Full Text Full Text PDF Scopus (1) Google Scholar some shortcomings need to be considered. For example, the authors' choice to combine dementia and permanent physical disability into a single composite outcome is difficult to support from the geriatrician's standpoint. Age-related disability has a myriad of causes, such as sarcopenia, frailty, mobility disorders, cardiovascular diseases, neurovascular diseases, diabetes, and respiratory diseases, and does not necessarily co-occur with dementia. Hence, merging dementia and permanent disability seems hazardous. Moreover, in the analysis by Neumann and colleagues,4Neumann JT Thao LTP Callander E et al.A multistate model of health transitions in older people: a secondary analysis of ASPREE clinical trial data.Lancet Healthy Longev. 2022; 3 (e87): e89Summary Full Text Full Text PDF Scopus (1) Google Scholar disability or dementia, a surrogate of loss of independence, occurred in 4·8% of participants, but only 12·3% of deaths were preceded by disability or dementia. Furthermore, there were 295 deaths in the study cohort for which the specific cause was not reported, and no attention was given to multimorbidity or polypharmacy in the context of mortality. The study also does not report on how common disease risk factors, education, socioeconomic inequities, lifestyle behaviours, comorbidities (eg, depression and diabetes), and medications affected health transitions, although the importance of these factors for healthy transitions has recently been expounded by longitudinal studies.8Dugravot A Fayosse A Dumurgier J et al.Social inequalities in multimorbidity, frailty, disability, and transitions to mortality: a 24-year follow-up of the Whitehall II cohort study.Lancet Public Health. 2020; 5: e42-e50Summary Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 9Gil-Salcedo A Dugravot A Fayosse A et al.Healthy behaviors at age 50 years and frailty at older ages in a 20-year follow-up of the UK Whitehall II cohort: a longitudinal study.PLoS Med. 2020; 17e1003147Crossref PubMed Scopus (20) Google Scholar Nevertheless, this Article considerably enriches our knowledge around health transitions in older people, affirming that healthy ageing was the dominant state in the ASPREE cohort. The surprising finding of this analysis was that higher proportions of 75-year-old and 85-year-old women remained in a healthy state for longer than men of the same age. I declare no competing interests. A multistate model of health transitions in older people: a secondary analysis of ASPREE clinical trial dataWe describe a multistate model in a healthy older population in whom the most common transition was from a healthy state to cancer. Our findings provide unique insights into the frequency of events, their transition rates, and the impact of age and sex. These results have implications for preventive health interventions and planning for appropriate levels of residential care in healthy ageing populations. Full-Text PDF Open Access