Original article
Vol. 151 No. 3536 (2021)
Does the frailty phenotype at the age of 66 to 71 predict death? A 14-year survival analysis of the Lc65+ study
- Sarah Fustinoni
- Brigitte Santos-Eggimann
- Yves Henchoz
Summary
BACKGROUND: Frailty is a health characteristic resulting from the loss of physiological reserve of multiple organs, leading to exposure to adverse outcomes, and is possibly reversible in its earliest stages. It is identified by a specific phenotype that contributes to the practice of geriatric medicine, where it is considered a potential target for preventive action. This phenotype has recently attracted interest in other medical specialties for risk assessment before stressful interventions in older adults. Whereas frailty is unusual in sexagenarians, pre-frailty is common. This longitudinal study aimed to evaluate the significance of fulfilling at least one criterion of the frailty phenotype in the late sixties as a predictor of short- and long-term mortality in males and females.
METHODS: Data came from the first sample of the Lc65+ cohort, representative of the community-dwelling Lausanne population born between 1934 and 1939 (n = 1315). After baseline assessment of the five criteria of Fried’s frailty phenotype (shrinking, exhaustion, muscular weakness, motor slowness and low physical activity) in 2005 (age 66–71 years), deaths were recorded over 14 years. We separated individuals into non-frail (fulfilling 0 criterion) and (pre-)frail (1+ criteria). The relationship between the phenotype and mortality was investigated graphically using Kaplan-Meier survival curves and quantified in Cox models. Multivariable analyses incrementally controlled age, socioeconomic and health characteristics. The prediction of fully adjusted models was evaluated using the Harrell’s C index.
RESULTS: Overall, 401 persons (30.5%) were (pre-)frail at baseline. A quarter of the 1315 participants died over 14 years (n = 336, 25.6%). The mortality rate was significantly higher in males in the (pre-)frail subgroup only. Survival curves showed a significant effect of (pre-)frailty on the risk of dying for both sexes. The effect of (pre-)frailty on mortality was stronger during the first 4 years of the follow-up. In males, it was significant both in short (0–4 years) and longer (>4–14 years) terms. In females, it was significant in the short term only. In all models, the estimated effect was stronger in males. The fully adjusted model was fairly predictive of death in the short term both in males (Harrell’s C 0.79) and females (0.75).
CONCLUSIONS: The significantly higher mortality of individuals presenting 1+ frailty criteria supports the appropriateness of a systematic assessment of the frailty phenotype at the age of 66–71 years. In both females and males, early identification of pre-frailty has the potential to limit or reverse the development of frailty and extend lifespan through adequate individual management.
References
- World Health Organization. Decade of healthy ageing: baseline report. Geneva, Switzerland, 2020
- Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al.; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146–56. https://doi.org/10.1093/gerona/56.3.M146
- Dent E, Kowal P, Hoogendijk EO. Frailty measurement in research and clinical practice: a review. Eur J Intern Med. 2016 Jun;31:3–10. https://doi.org/10.1016/j.ejim.2016.03.007
- Walston JD, Bandeen-Roche K. Frailty: a tale of two concepts. BMC Med. 2015 Aug;13(1):185. https://doi.org/10.1186/s12916-015-0420-6
- Collard RM, Boter H, Schoevers RA, Oude Voshaar RC. Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc. 2012 Aug;60(8):1487–92. https://doi.org/10.1111/j.1532-5415.2012.04054.x
- O’Caoimh R, Sezgin D, O’Donovan MR, Molloy DW, Clegg A, Rockwood K, et al. Prevalence of frailty in 62 countries across the world: a systematic review and meta-analysis of population-level studies. Age Ageing. 2021 Jan;50(1):96–104. https://doi.org/10.1093/ageing/afaa219
- Boakye D, Rillmann B, Walter V, Jansen L, Hoffmeister M, Brenner H. Impact of comorbidity and frailty on prognosis in colorectal cancer patients: a systematic review and meta-analysis. Cancer Treat Rev. 2018 Mar;64:30–9. https://doi.org/10.1016/j.ctrv.2018.02.003
- Houghton JS, Nickinson AT, Morton AJ, Nduwayo S, Pepper CJ, Rayt HS, et al. Frailty factors and outcomes in vascular surgery patients: a systematic review and meta-analysis. Ann Surg. 2020 Aug;272(2):266–76. https://doi.org/10.1097/SLA.0000000000003642
- Tjeertes EK, van Fessem JM, Mattace-Raso FU, Hoofwijk AG, Stolker RJ, Hoeks SE. Influence of frailty on outcome in older patients undergoing non cardiac surgery - a systematic review and meta-analysis. Aging Dis. 2020 Oct;11(5):1276–90. https://doi.org/10.14336/AD.2019.1024
- Dent E, Martin FC, Bergman H, Woo J, Romero-Ortuno R, Walston JD. Management of frailty: opportunities, challenges, and future directions. Lancet. 2019 Oct;394(10206):1376–86. https://doi.org/10.1016/S0140-6736(19)31785-4
- Walston J, Buta B, Xue QL. Frailty screening and interventions: considerations for clinical practice. Clin Geriatr Med. 2018 Feb;34(1):25–38. https://doi.org/10.1016/j.cger.2017.09.004
- Santos-Eggimann B, Cuénoud P, Spagnoli J, Junod J. Prevalence of frailty in middle-aged and older community-dwelling Europeans living in 10 countries. J Gerontol A Biol Sci Med Sci. 2009 Jun;64(6):675–81. https://doi.org/10.1093/gerona/glp012
- Kojima G, Taniguchi Y, Iliffe S, Jivraj S, Walters K. Transitions between frailty states among community-dwelling older people: a systematic review and meta-analysis. Ageing Res Rev. 2019 Mar;50:81–8. https://doi.org/10.1016/j.arr.2019.01.010
- Santos-Eggimann B, Karmaniola A, Seematter-Bagnoud L, Spagnoli J, Büla C, Cornuz J, et al. The Lausanne cohort Lc65+: a population-based prospective study of the manifestations, determinants and outcomes of frailty. BMC Geriatr. 2008 Aug;8(1):20. https://doi.org/10.1186/1471-2318-8-20
- Whooley MA, Avins AL, Miranda J, Browner WS. Case-finding instruments for depression. Two questions are as good as many. J Gen Intern Med. 1997 Jul;12(7):439–45. https://doi.org/10.1046/j.1525-1497.1997.00076.x
- Harrell FE Jr, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996 Feb;15(4):361–87. https://doi.org/10.1002/(SICI)1097-0258(19960229)15:4<361:AID-SIM168>3.0.CO;2-4 https://doi.org/10.1002/(SICI)1097-0258(19960229)15:4<361::AID-SIM168>3.0.CO;2-4
- Chang SF, Lin PL. Frail phenotype and mortality prediction: a systematic review and meta-analysis of prospective cohort studies. Int J Nurs Stud. 2015 Aug;52(8):1362–74. https://doi.org/10.1016/j.ijnurstu.2015.04.005
- Ding YY. Predictive validity of two physical frailty phenotype specifications developed for investigation of frailty pathways in older people. Gerontology. 2017;63(5):401–10. https://doi.org/10.1159/000471803
- Langholz PL, Strand BH, Cook S, Hopstock LA. Frailty phenotype and its association with all-cause mortality in community-dwelling Norwegian women and men aged 70 years and older: the Tromsø Study 2001-2016. Geriatr Gerontol Int. 2018 Aug;18(8):1200–5. https://doi.org/10.1111/ggi.13447
- von Renteln-Kruse W, Minder CE. It is time to detect preclinical signs of incipient frailty. J Am Geriatr Soc. 2016 Oct;64(10):2166–7. https://doi.org/10.1111/jgs.14419
- Zasadzka E, Trzmiel T, Roszak M, Pawlaczyk M. Is the outcome of frailty syndrome gender dependent? J Women Aging. 2020 May-Jun;32(3):349–60. https://doi.org/10.1080/08952841.2019.1593797
- Fan Y, Huang J, Zhou Y, Gu X, Gong D. Does the impact of frailty on all-cause mortality in older persons differ between women and men? A meta-analysis. J Am Med Dir Assoc. 2021 Mar;22(3):606.e1–6. https://doi.org/10.1016/j.jamda.2020.05.059
- Gordon EH, Hubbard RE. Do sex differences in chronic disease underpin the sex-frailty paradox? Mech Ageing Dev. 2019 Apr;179:44–50. https://doi.org/10.1016/j.mad.2019.02.004
- Thompson MQ, Theou O, Tucker GR, Adams RJ, Visvanathan R. Recurrent measurement of frailty is important for mortality prediction: findings from the North West Adelaide Health Study. J Am Geriatr Soc. 2019 Nov;67(11):2311–7. https://doi.org/10.1111/jgs.16066
- Zucchelli A, Vetrano DL, Marengoni A, Grande G, Romanelli G, Calderón-Larrañaga A, et al. Frailty predicts short-term survival even in older adults without multimorbidity. Eur J Intern Med. 2018 Oct;56:53–6. https://doi.org/10.1016/j.ejim.2018.06.012
- Gill TM, Gahbauer EA, Allore HG, Han L. Transitions between frailty states among community-living older persons. Arch Intern Med. 2006 Feb;166(4):418–23. https://doi.org/10.1001/archinte.166.4.418
- Turusheva A, Frolova E, Korystina E, Zelenukha D, Tadjibaev P, Gurina N, et al. Do commonly used frailty models predict mortality, loss of autonomy and mental decline in older adults in northwestern Russia? A prospective cohort study. BMC Geriatr. 2016 May;16(1):98. https://doi.org/10.1186/s12877-016-0276-4
- Hanlon P, Nicholl BI, Jani BD, Lee D, McQueenie R, Mair FS. 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 Jul;3(7):e323–32. https://doi.org/10.1016/S2468-2667(18)30091-4
- Kusumastuti S, Gerds TA, Lund R, Mortensen EL, Westendorp RG. Discrimination ability of comorbidity, frailty, and subjective health to predict mortality in community-dwelling older people: population based prospective cohort study. Eur J Intern Med. 2017 Jul;42:29–38. https://doi.org/10.1016/j.ejim.2017.05.016
- Gonzalez-Colaço Harmand M, Meillon C, Bergua V, Tabue Teguo M, Dartigues JF, Avila-Funes JA, et al. Comparing the predictive value of three definitions of frailty: results from the Three-City study. Arch Gerontol Geriatr. 2017 Sep;72:153–63. https://doi.org/10.1016/j.archger.2017.06.005
- Grabovac I, Haider S, Mogg C, Majewska B, Drgac D, Oberndorfer M, et al. Frailty status predicts all-cause and cause-specific mortality in community dwelling older adults. J Am Med Dir Assoc. 2019 Oct;20(10):1230–1235.e2. https://doi.org/10.1016/j.jamda.2019.06.007
- Graham JE, Snih SA, Berges IM, Ray LA, Markides KS, Ottenbacher KJ. Frailty and 10-year mortality in community-living Mexican American older adults. Gerontology. 2009;55(6):644–51. https://doi.org/10.1159/000235653
- Lohman MC, Sonnega AJ, Resciniti NV, Leggett AN. Frailty phenotype and cause-specific mortality in the United States. J Gerontol A Biol Sci Med Sci. 2020 Sep;75(10):1935–42. https://doi.org/10.1093/gerona/glaa025
- Papachristou E, Wannamethee SG, Lennon LT, Papacosta O, Whincup PH, Iliffe S, et al. Ability of self-reported frailty components to predict incident disability, falls, and all-cause mortality: results from a population-based study of older British men. J Am Med Dir Assoc. 2017 Feb;18(2):152–7. https://doi.org/10.1016/j.jamda.2016.08.020
- Pereira AA, Borim FS, Aprahamian I, Neri AL. Comparison of two models of frailty for the prediction of mortality in Brazilian community-dwelling older adults: the FIBRA study. J Nutr Health Aging. 2019;23(10):1004–10. https://doi.org/10.1007/s12603-019-1264-0
- Ravindrarajah R, Lee DM, Pye SR, Gielen E, Boonen S, Vanderschueren D, et al.; European Male Aging Study Group. The ability of three different models of frailty to predict all-cause mortality: results from the European Male Aging Study (EMAS). Arch Gerontol Geriatr. 2013 Nov-Dec;57(3):360–8. https://doi.org/10.1016/j.archger.2013.06.010
- Shi GP, Ma T, Zhu YS, Wang ZD, Chu XF, Wang Y, et al. Frailty phenotype, frailty index and risk of mortality in Chinese elderly population- Rugao longevity and ageing study. Arch Gerontol Geriatr. 2019 Jan - Feb;80:115–9. https://doi.org/10.1016/j.archger.2018.11.001