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

Autoři: Andres Gil-Salcedo aff001;  Aline Dugravot aff001;  Aurore Fayosse aff001;  Julien Dumurgier aff001;  Kim Bouillon aff002;  Alexis Schnitzler aff001;  Mika Kivimäki aff003;  Archana Singh-Manoux aff001;  Séverine Sabia aff001
Působiště autorů: Université de Paris, Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases, France aff001;  Département d’Information Médicale, Centre Hospitalier de Saint-Brieuc, Saint-Brieuc, France aff002;  Department of Epidemiology and Public Health, University College London, London, United Kingdom aff003;  Helsinki Institute of Life Sciences, University of Helsinki, Helsinki, Finland aff004
Vyšlo v časopise: 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 17(7): e32767. doi:10.1371/journal.pmed.1003147
Kategorie: Research Article



Frailty is associated with increased risk of various health conditions, disability, and death. Health behaviors are thought to be a potential target for frailty prevention, but the evidence from previous studies is based on older populations with short follow-ups, making results susceptible to reverse causation bias. We examined the associations of healthy behaviors at age 50, singly and in combination, as well as 10-year change in the number of healthy behaviors over midlife with future risk of frailty.

Methods and findings

In this prospective cohort study of 6,357 (29.2% women; 91.7% white) participants from the British Whitehall II cohort, healthy behaviors—nonsmoking, moderate alcohol consumption, ≥2.5 hours per week of moderate to vigorous physical activity, and consumption of fruits or vegetables at least twice a day—were measured at age 50, and change in behaviors was measured between 1985 (mean age = 44.4) and 1997 (mean age = 54.8). Fried’s frailty phenotype was assessed in clinical examinations in 2002, 2007, 2012, and 2015. Participants were classified as frail if they had ≥3 of the following criteria: slow walking speed, low grip strength, weight loss, exhaustion, and low physical activity. An illness–death model accounting for both competing risk of death and interval censoring was used to examine the association between healthy behaviors and risk of frailty. Over an average follow-up of 20.4 years (standard deviation, 5.9), 445 participants developed frailty. Each healthy behavior at age 50 was associated with lower risk of incident frailty: hazard ratio (HR) after adjustment for other health behaviors and baseline characteristics 0.56 (95% confidence interval [CI] 0.44–0.71; p < 0.001) in nonsmokers, 0.73 (95% CI 0.61–0.88; p < 0.001) for moderate alcohol consumption, 0.66 (95% CI 0.54–0.81; p < 0.001) for ≥2.5 hours of physical activity per week, and 0.76 (95% CI 0.59–0.98; p = 0.03) for consumption of fruits or vegetables at least twice a day. A greater number of healthy behaviors was associated with reduced risk of frailty, with the HR for each additional healthy behavior being 0.69 (95% CI 0.62–0.76; p < 0.001) and the HR for having all versus no healthy behaviors at age 50 being 0.28 (95% CI 0.15–0.52; p < 0.001). Among participants with no or 1 healthy behavior in 1985, those who increased the number of healthy behaviors by 1997 were at a lower risk of frailty (mean follow-up = 16 years) compared with those with no such increase: the HR was 0.64 (95% CI 0.44–0.94; p = 0.02) for change to 2 healthy behaviors and 0.57 (95% CI 0.38–0.87; p < 0.001) for change to 3–4 healthy behaviors in 1997. The primary limitation of this study is potential selection bias during the follow-up due to missing data on frailty components.


Our findings suggest that healthy behaviors at age 50, as well as improvements in behaviors over midlife, are associated with a lower risk of frailty later in life. Their benefit accumulates so that risk of frailty decreases with greater number of healthy behaviors. These results suggest that healthy behaviors in midlife are a good target for frailty prevention.

Klíčová slova:

Alcohol consumption – Behavior – Behavioral and social aspects of health – Ethnic epidemiology – Frailty – Morbidity – Physical activity – Socioeconomic aspects of health


1. Beard JR, Officer AM, Cassels AK. The World Report on Ageing and Health. Gerontologist. 2016;56 Suppl 2:S163–6. doi: 10.1093/geront/gnw037 26994257

2. Prince MJ, Wu F, Guo Y, Gutierrez Robledo LM, O'Donnell M, Sullivan R, et al. The burden of disease in older people and implications for health policy and practice. Lancet. 2015;385(9967):549–62. doi: 10.1016/S0140-6736(14)61347-7 25468153

3. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. The journals of gerontology Series A, Biological sciences and medical sciences. 2001;56(3):M146–56. doi: 10.1093/gerona/56.3.m146 11253156

4. Hoogendijk EO, Afilalo J, Ensrud KE, Kowal P, Onder G, Fried LP. Frailty: implications for clinical practice and public health. Lancet. 2019;394(10206):1365–75. doi: 10.1016/S0140-6736(19)31786-6 31609228

5. Borges MK, Canevelli M, Cesari M, Aprahamian I. Frailty as a Predictor of Cognitive Disorders: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2019;6:26. doi: 10.3389/fmed.2019.00026 30838210

6. Li G, Thabane L, Papaioannou A, Ioannidis G, Levine MA, Adachi JD. An overview of osteoporosis and frailty in the elderly. BMC Musculoskelet Disord. 2017;18(1):46. doi: 10.1186/s12891-017-1403-x 28125982

7. Kojima G. Frailty as a predictor of disabilities among community-dwelling older people: a systematic review and meta-analysis. Disabil Rehabil. 2017;39(19):1897–908. doi: 10.1080/09638288.2016.1212282 27558741

8. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62. doi: 10.1016/S0140-6736(12)62167-9 23395245

9. Chang SF, Lin PL. Frail phenotype and mortality prediction: a systematic review and meta-analysis of prospective cohort studies. Int J Nurs Stud. 2015;52(8):1362–74. doi: 10.1016/j.ijnurstu.2015.04.005 25986959

10. Gomez M, García-Sánchez I, Carta A, Antunes J. Prevention and Early Diagnosis of Frailty and Functional Decline, Both Physical and Cognitive, in Older People. Netherlands: European Commission; July-August 2013 [cited 7 May 2020].

11. Cesari M, Prince M, Thiyagarajan JA, De Carvalho IA, Bernabei R, Chan P, et al. Frailty: An Emerging Public Health Priority. J Am Med Dir Assoc. 2016;17(3):188–92. doi: 10.1016/j.jamda.2015.12.016 26805753

12. Buchner DM, Wagner EH. Preventing frail health. Clin Geriatr Med. 1992;8(1):1–17.

13. World Health Organization [Internet]. Report of the global survey on the progress in national chronic diseases prevention and control Geneva: World Health Organization; 2007 [cited 7 May 2020].

14. Loef M, Walach H. The combined effects of healthy lifestyle behaviors on all cause mortality: a systematic review and meta-analysis. Prev Med. 2012;55(3):163–70. doi: 10.1016/j.ypmed.2012.06.017 22735042

15. Kojima G, Iliffe S, Jivraj S, Liljas A, Walters K. Does current smoking predict future frailty? The English longitudinal study of ageing. Age Ageing. 2018;47(1):126–31. doi: 10.1093/ageing/afx136 28985256

16. Kojima G, Iliffe S, Walters K. Smoking as a predictor of frailty: a systematic review. BMC Geriatr. 2015;15:131. doi: 10.1186/s12877-015-0134-9 26489757

17. Blodgett J, Theou O, Kirkland S, Andreou P, Rockwood K. Frailty in relation to sedentary behaviours and moderate-vigorous intensity physical activity. Rev Clin Gerontol. 2014;24(4):239–54. doi: 10.1017/S0959259814000124

18. da Silva VD, Tribess S, Meneguci J, Sasaki JE, Garcia-Meneguci CA, Carneiro JAO, et al. Association between frailty and the combination of physical activity level and sedentary behavior in older adults. BMC Public Health. 2019;19(1):709. doi: 10.1186/s12889-019-7062-0 31174515

19. Blodgett J, Theou O, Kirkland S, Andreou P, Rockwood K. The association between sedentary behaviour, moderate-vigorous physical activity and frailty in NHANES cohorts. Maturitas. 2015;80(2):187–91. doi: 10.1016/j.maturitas.2014.11.010 25542406

20. Garcia-Esquinas E, Rahi B, Peres K, Colpo M, Dartigues JF, Bandinelli S, et al. Consumption of fruit and vegetables and risk of frailty: a dose-response analysis of 3 prospective cohorts of community-dwelling older adults. Am J Clin Nutr. 2016;104(1):132–42. doi: 10.3945/ajcn.115.125781 27194305

21. Kojima G, Avgerinou C, Iliffe S, Walters K. Adherence to Mediterranean Diet Reduces Incident Frailty Risk: Systematic Review and Meta-Analysis. J Am Geriatr Soc. 2018;66(4):783–8. doi: 10.1111/jgs.15251 29322507

22. Kojima G, Liljas A, Iliffe S, Jivraj S, Walters K. A systematic review and meta-analysis of prospective associations between alcohol consumption and incident frailty. Age Ageing. 2018;47(1):26–34. doi: 10.1093/ageing/afx086 28541395

23. Kojima G, Iliffe S, Liljas A, Walters K. Non-linear association between alcohol and incident frailty among community-dwelling older people: A dose-response meta-analysis. Biosci Trends. 2017;11(5):600–2. doi: 10.5582/bst.2017.01237 29021422

24. Ortola R, Garcia-Esquinas E, Leon-Munoz LM, Guallar-Castillon P, Valencia-Martin JL, Galan I, et al. Patterns of Alcohol Consumption and Risk of Frailty in Community-dwelling Older Adults. The journals of gerontology Series A, Biological sciences and medical sciences. 2016;71(2):251–8. doi: 10.1093/gerona/glv125 26297937

25. Perez-Tasigchana RF, Sandoval-Insausti H, Donat-Vargas C, Banegas JR, Rodriguez-Artalejo F, Guallar-Castillon P. Combined Impact of Traditional and Nontraditional Healthy Behaviors on Frailty and Disability: A Prospective Cohort Study of Older Adults. J Am Med Dir Assoc. 2019. doi: 10.1016/j.jamda.2019.08.025 31636035

26. Poortinga W. The prevalence and clustering of four major lifestyle risk factors in an English adult population. Prev Med. 2007;44(2):124–8. doi: 10.1016/j.ypmed.2006.10.006 17157369

27. Artaud F, Sabia S, Dugravot A, Kivimäki M, Singh-Manoux A, Elbaz A. Trajectories of Unhealthy Behaviors in Midlife and Risk of Disability at Older Ages in the Whitehall II Cohort Study. The journals of gerontology Series A, Biological sciences and medical sciences. 2016;71(11):1500–6. doi: 10.1093/gerona/glw060 27034508

28. Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. The journals of gerontology Series A, Biological sciences and medical sciences. 2004;59(3):255–63. doi: 10.1093/gerona/59.3.m255 15031310

29. Marmot MG, Smith GD, Stansfeld S, Patel C, North F, Head J, et al. Health inequalities among British civil servants: the Whitehall II study. Lancet. 1991;337(8754):1387–93. doi: 10.1016/0140-6736(91)93068-k 1674771

30. UK Chief Medical Officers’ Alcohol Guidelines Review. United Kingdom: UK Department of Health; January 2016. [cited 18 June 2020].

31. World Health Organization [Internet]. Physical Activity and Adults. [cited 7 May 2020]. Geneva: World Health Organization; 2011.

32. Khaw KT, Wareham N, Bingham S, Welch A, Luben R, Day N. Combined impact of health behaviours and mortality in men and women: the EPIC-Norfolk prospective population study. PLoS Med. 2008;5(1):e12. doi: 10.1371/journal.pmed.0050012 18184033

33. Sabia S, Elbaz A, Rouveau N, Brunner EJ, Kivimäki M, Singh-Manoux A. Cumulative associations between midlife health behaviors and physical functioning in early old age: a 17-year prospective cohort study. J Am Geriatr Soc. 2014;62(10):1860–8. doi: 10.1111/jgs.13071 25283337

34. Bouillon K, Sabia S, Jokela M, Gale CR, Singh-Manoux A, Shipley MJ, et al. Validating a widely used measure of frailty: are all sub-components necessary? Evidence from the Whitehall II cohort study. Age (Dordr). 2013;35(4):1457–65. doi: 10.1007/s11357-012-9446-2 22772579

35. Boyd CM, Xue QL, Simpson CF, Guralnik JM, Fried LP. Frailty, hospitalization, and progression of disability in a cohort of disabled older women. Am J Med. 2005;118(11):1225–31. doi: 10.1016/j.amjmed.2005.01.062 16271906

36. Leffondre K, Touraine C, Helmer C, Joly P. Interval-censored time-to-event and competing risk with death: is the illness-death model more accurate than the Cox model? Int J Epidemiol. 2013;42(4):1177–86. doi: 10.1093/ije/dyt126 23900486

37. Brunner EJ, Shipley MJ, Ahmadi-Abhari S, Valencia Hernandez C, Abell JG, Singh-Manoux A, et al. Midlife contributors to socioeconomic differences in frailty during later life: a prospective cohort study. Lancet Public Health. 2018;3(7):e313–e22. Epub 2018/06/18. doi: 10.1016/S2468-2667(18)30079-3 29908857

38. Chiuve SE, McCullough ML, Sacks FM, Rimm EB. Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and antihypertensive medications. Circulation. 2006;114(2):160–7. doi: 10.1161/CIRCULATIONAHA.106.621417 16818808

39. Sabia S, Nabi H, Kivimäki M, Shipley MJ, Marmot MG, Singh-Manoux A. Health behaviors from early to late midlife as predictors of cognitive function: The Whitehall II study. Am J Epidemiol. 2009;170(4):428–37. doi: 10.1093/aje/kwp161 19574344

40. Bayan-Bravo A, Perez-Tasigchana RF, Sayon-Orea C, Martinez-Gomez D, Lopez-Garcia E, Rodriguez-Artalejo F, et al. Combined Impact of Traditional and Non-Traditional Healthy Behaviors on Health-Related Quality of Life: A Prospective Study in Older Adults. PLoS ONE. 2017;12(1):e0170513. doi: 10.1371/journal.pone.0170513 28122033

41. Artaud F, Dugravot A, Sabia S, Singh-Manoux A, Tzourio C, Elbaz A. Unhealthy behaviours and disability in older adults: three-City Dijon cohort study. BMJ (Clinical research ed). 2013;347:f4240. doi: 10.1136/bmj.f4240 23881930

42. Brien SE, Ronksley PE, Turner BJ, Mukamal KJ, Ghali WA. Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies. BMJ (Clinical research ed). 2011;342:d636. doi: 10.1136/bmj.d636 21343206

43. Kokkinos PF, Fernhall B. Physical activity and high density lipoprotein cholesterol levels: what is the relationship? Sports Med. 1999;28(5):307–14. doi: 10.2165/00007256-199928050-00002 10593643

44. Mensink RP, Zock PL, Kester AD, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003;77(5):1146–55. doi: 10.1093/ajcn/77.5.1146 12716665

45. Ozguner F, Koyu A, Cesur G. Active smoking causes oxidative stress and decreases blood melatonin levels. Toxicol Ind Health. 2005;21(1–2):21–6. doi: 10.1191/0748233705th211oa 15986573

46. Harasym J, Oledzki R. Effect of fruit and vegetable antioxidants on total antioxidant capacity of blood plasma. Nutrition. 2014;30(5):511–7. doi: 10.1016/j.nut.2013.08.019 24698344

47. Clarkson PM, Thompson HS. Antioxidants: what role do they play in physical activity and health? Am J Clin Nutr. 2000;72(2 Suppl):637S–46S. doi: 10.1093/ajcn/72.2.637S 10919970

48. Lecomte E, Herbeth B, Pirollet P, Chancerelle Y, Arnaud J, Musse N, et al. Effect of alcohol consumption on blood antioxidant nutrients and oxidative stress indicators. Am J Clin Nutr. 1994;60(2):255–61. doi: 10.1093/ajcn/60.2.255 8030604

49. Navab M, Anantharamaiah GM, Fogelman AM. The role of high-density lipoprotein in inflammation. Trends Cardiovasc Med. 2005;15(4):158–61. doi: 10.1016/j.tcm.2005.05.008 16099381

50. Landi F, Russo A, Pahor M, Capoluongo E, Liperoti R, Cesari M, et al. Serum high-density lipoprotein cholesterol levels and mortality in frail, community-living elderly. Gerontology. 2008;54(2):71–8. doi: 10.1159/000111381 18025809

51. Batty GD, Shipley M, Tabak A, Singh-Manoux A, Brunner E, Britton A, et al. Generalizability of occupational cohort study findings. Epidemiology. 2014;25(6):932–3. doi: 10.1097/EDE.0000000000000184 25265141

52. Aguayo GA, Vaillant MT, Donneau AF, Schritz A, Stranges S, Malisoux L, et al. Comparative analysis of the association between 35 frailty scores and cardiovascular events, cancer, and total mortality in an elderly general population in England: An observational study. PLoS Med. 2018;15(3):e1002543. doi: 10.1371/journal.pmed.1002543 29584726

53. Sabia S, van Hees VT, Shipley MJ, Trenell MI, Hagger-Johnson G, Elbaz A, et al. Association between questionnaire- and accelerometer-assessed physical activity: the role of sociodemographic factors. Am J Epidemiol. 2014;179(6):781–90. doi: 10.1093/aje/kwt330 24500862

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