Prediction of disability-free survival in healthy older people
Franz–Josef Neumann, Lê Thị Phương Thảo, Anne M. Murray, Emily Callander, Prudence R. Carr, Mark Nelson, Rory Wolfe, Robyn L. Woods, Christopher M. Reid, Raj C. Shah, Anne B. Newman, Jeff D. Williamson, Andrew Tonkin, John J. McNeil, on behalf of the ASPREE investigators, John McNeil, Anne M. Murray, Lawrie Beilin, Andrew K. Chan, Jamehl Demons, Michael E. Ernst, Sara Espinoza, Matthew P. Goetz, Colin I. Johnston, Brenda Kirpach, Danny Liew, Karen L. Margolis, Frank L. Meyskens, Mark Nelson, Chris Reid, Raj Shah, Elsdon Storey, Andrew Tonkin, Rory Wolfe, Robyn Woods, John Zalcberg, Mark Nelson, Diane G. Ives, Michael Berk, Wendy Bernstein, Donna J. Brauer, Christine Burns, Trevor Chong, Geoffrey Cloud, Jamehl Demons, Geoffrey Donnan, Charles Eaton, Paul B. Fitzgerald, Peter Gibbs, Andrew Haydon, Michael Jelinek, Finlay Macrae, Suzanne E. Mahady, Mobin Malik, Karen Margolis, Catriona McLean, Anne M. Murray, Anne Newman, Luz M. Rodriguez, Suzanne Satterfield, Raj C. Shah, Elsdon Storey, Jeanne Tie, Andrew Tonkin, Gijsberta van Londen, Stéphanie Ward, Jeff Williamson, Erica M. Wood, John Zalcberg, Jay P. Mohr, Garnet L. Anderson, Stuart J. Connolly, Larry J. Friedman, JoAnn E. Manson, Mary Sano, Sean J. Morrison, E. Magnus Ohman, John McNeil, Robyn Woods, Walter P. Abhayaratna, Lawrie Beilin, Geoffrey Donnan, Peter Gibbs, Colin I. Johnston, Danny Liew, Trevor Lockett, Mark Nelson, Chris Reid, Nigel Stocks, Elsdon Storey, Andrew Tonkin, Rory Wolfe, John Zalcberg, Anne M. Murray, Chris Reid, Walter P. Abhayaratna, Michael Ernst, Colin I. Johnston, Beth Lewis, Danny Liew
Abstract
Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6-77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people.Trial registration Clinicaltrials.gov (NCT01038583).