Standard laboratory tests to identify older adults at increased risk of death

BMC Medicine

Kenneth Rockwood²  Arnold Mitnitski¹  Michael RH Rockwood¹  Susan E Howlett³ 

[1]Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada

[2]Department of Geriatric Medicine and Institute of Brain, Behaviour and Neurosciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK

[3]Department of Physiology, Institute of Cardiovascular Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK

关键词: Aging;    Biomarkers;    Deficit accumulation;    Deficit index;    Frailty index;    Frailty;   

Others  :  1121409
DOI  :  10.1186/s12916-014-0171-9

 received in 2014-07-17, accepted in 2014-09-03,  发布年份 2014

【 摘 要 】

Background

Older adults are at an increased risk of death, but not all people of the same age have the same risk. Many methods identify frail people (that is, those at increased risk) but these often require time-consuming interactions with health care providers. We evaluated whether standard laboratory tests on their own, or added to a clinical frailty index (FI), could improve identification of older adults at increased risk of death.

Methods

This is a secondary analysis of a prospective cohort study, where community dwelling and institutionalized participants in the Canadian Study of Health and Aging who also volunteered for blood collection (n = 1,013) were followed for up to six years. A standard FI (FI-CSHA) was constructed from data obtained during the clinical evaluation and a second, novel FI was constructed from laboratory data plus systolic and diastolic blood pressure measurements (FI-LAB). A combined FI included all items from each index. Predictive validity was tested using Cox proportional hazards analysis and discriminative ability by the area under receiver operating characteristic (ROC) curves.

Results

Of 1,013 participants, 51.3% had died by six years. The mean baseline value of the FI-LAB was 0.27 (standard deviation 0.11; range 0.05 to 0.63), the FI-CSHA was 0.25 (0.11; 0.02 to 0.72), and the combined FI was 0.26 (0.09; 0.06 to 0.59). In an age- and sex-adjusted model, with each increment in the FI-LAB, the hazard ratios increased by 2.8% (95% confidence interval 1.02 to 1.04). The hazard ratios for the FI-CSHA and the combined FI were 1.02 (1.01 to 1.03) and 1.04 (1.03 to 1.05), respectively. The FI-LAB and FI-CSHA remained independently associated with death in the face of the other. The areas under the ROC curves were 0.72 for FI-LAB, 0.73 for FI-CSHA and 0.74 for the combined FI.

Conclusions

An FI based on routine laboratory data can identify older adults at increased risk of death. Additional evaluation of this approach in clinical settings is warranted.

【 授权许可】

   
2014 Howlett et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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【 参考文献 】

• [1]Clegg Al, Young J, Iliffe S, Rikkert MO, Rockwood K: Frailty in elderly people. Lancet 2013, 381:752-762.
• [2]Vellas B, Cestac P, Morley JE: Implementing frailty into clinical practice: we cannot wait. J Nutr Health Aging 2012, 16:599-600.
• [3]Rodríguez-Mañas L, Féart C, Mann G, Viña J, Chatterji S, Chodzko-Zajko W, Gonzalez-Colaço Harmand M, Bergman H, Carcaillon L, Nicholson C, Scuteri A, Sinclair A, Pelaez M, Van der Cammen T, Beland F, Bickenbach J, Delamarche P, Ferrucci L, Fried LP, Gutiérrez-Robledo LM, Rockwood K, Rodríguez Artalejo F, Serviddio G, Vega E: Searching for an operational definition of frailty: a Delphi method based consensus statement: the frailty operative definition-consensus conference project. J Gerontol A Biol Sci Med Sci 2013, 68:62-67.
• [4]Dent E, Chapman I, Howell S, Piantadosi C, Visvanathan R: Frailty and functional decline indices predict poor outcomes in hospitalised older people. Age Ageing 2014, 43:477-484.
• [5]Evans SJ, Sayers M, Mitnitski A, Rockwood K: The risk of adverse outcomes in hospitalized older patients in relation to a frailty index based on a comprehensive geriatric assessment. Age Ageing 2014, 43:127-132.
• [6]Krishnan M, Beck S, Havelock W, Eeles E, Hubbard RE, Johansen A: Predicting outcome after hip fracture: using a frailty index to integrate comprehensive geriatric assessment results. Age Ageing 2014, 43:122-126.
• [7]Ellis G, Whitehead MA, Robinson D, O’Neill D, Langhorne P: Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials. BMJ 2011, 343:d6553.
• [8]de Vries NM, Staal JB, van Ravensberg CD, Hobbelen JS, Olde Rikkert MG, van der Nijhuis SM: Outcome instruments to measure frailty: a systematic review. Ageing Res Rev 2011, 10:104-114.
• [9]Kulminski AM, Ukraintseva SV, Kulminskaya IV, Arbeev KG, Land K, Yashin AI: Cumulative deficits better characterize susceptibility to death in elderly people than phenotypic frailty: lessons from the Cardiovascular Health Study. J Am Geriatr Soc 2008, 56:898-903.
• [10]Mitnitski AB, Mogilner AJ, Rockwood K: Accumulation of deficits as a proxy measure of aging. Sci World 2001, 1:323-336.
• [11]Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K: A standard procedure for creating a frailty index. BMC Geriatr 2008, 8:24. BioMed Central Full Text
• [12]Parks RJ, Fares E, Macdonald JK, Ernst MC, Sinal CJ, Rockwood K, Howlett SE: A procedure for creating a frailty index based on deficit accumulation in aging mice. J Gerontol A Biol Sci Med Sci 2012, 67:217-227.
• [13]Teng EL, Chui HC: The modified mini-mental state (3MS) examination. J Clin Psychiatry 1987, 48:314-318.
• [14]Canadian Study of Health and Aging: study methods and prevalence of dementia CMAJ 1994, 150:899-913.
• [15]Canadian Study of Health and Aging Working Group: Canadian Study of Health and Aging.Int Psychogeriatr 2001, Suppl 1:1–237.
• [16]Rockwood K, Rockwood MR, Mitnitski A: Physiological redundancy in older adults in relation to the change with age in the slope of a frailty index. J Am Geriatr Soc 2010, 58:318-323.
• [17]Rockwood MR, Howlett SE, Rockwood K: Orthostatic hypotension (OH) and mortality in relation to age, blood pressure and frailty. Arch Gerontol Geriatr 2012, 54:e255-e260.
• [18]Henry JB: Clinical Diagnosis and Management by Laboratory Methods. Saunders, Philadelphia; 1991.
• [19]Jones D, Kho A, Francesco L: Hypotension. In Principles and Practice of Hospital Medicine. Edited by McKean SC, Ross JJ, Dressler DD, Brotman DJ, Ginsberg JS. New York: McGraw-Hill; 2012:Chapter 91.
• [20]Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, Jones DW, Kurtz T, Sheps SG, Roccella EJ: Recommendations for blood pressure measurement in humans and experimental animals: Part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension 2005, 45:142-161.
• [21]Howlett SE, Rockwood K: New horizons in frailty: ageing and the deficit-scaling problem. Age Ageing 2013, 42:416-423.
• [22]Mitnitski A, Song X, Rockwood K: Assessing biological aging: the origin of deficit accumulation. Biogerontology 2013, 14:709-717.
• [23]Liu Z, Que S, Xu J, Peng T: Alanine aminotransferase-old biomarker and new concept: a review. Int J Med Sci 2014, 11:925-935.
• [24]Mitchell SJ, Hilmer SN, Murnion BP, Matthews S: Hepatotoxicity of therapeutic short-course paracetamol in hospital inpatients: impact of ageing and frailty. J Clin Pharm Ther 2011, 36:327-335.
• [25]Le Couteur DG, Blyth FM, Creasey HM, Handelsman DJ, Naganathan V, Sambrook PN, Seibel MJ, Waite LM, Cumming RG: The association of alanine transaminase with aging, frailty, and mortality. J Gerontol A Biol Sci Med Sci 2010, 65:712-717.
• [26]Streiner D, Norman G: Health Measurement Scales: A Practical Guide to Their Development and Use. Oxford University Press, Oxford; 2008.
• [27]Abdel-Rahman EM, Mansour W, Holley JL: Thyroid hormone abnormalities and frailty in elderly patients with chronic kidney disease: a hypothesis. Semin Dial 2010, 23:317-323.
• [28]Chaves PH, Semba RD, Leng SX, Woodman RC, Ferrucci L, Guralnik JM, Fried LP: Impact of anemia and cardiovascular disease on frailty status of community-dwelling older women: the Women’s Health and Aging Studies I and II. J Gerontol A Biol Sci Med Sci 2005, 60:729-735.
• [29]Hubbard RE, Sinead O’Mahony M, Woodhouse KW: Erythropoietin and anemia in aging and frailty. J Am Geriatr Soc 2008, 56:2164-2165.
• [30]Landi F, Russo A, Pahor M, Capoluongo E, Liperoti R, Cesari M, Bernabei R, Onder G: Serum high-density lipoprotein cholesterol levels and mortality in frail, community-living elderly. Gerontology 2008, 54:71-78.
• [31]Collerton J, Martin-Ruiz C, Davies K, Hilkens CM, Isaacs J, Kolenda C, Parker C, Dunn M, Catt M, Jagger C, von Zglinicki T, Kirkwood TB: Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study. Mech Ageing Dev 2012, 133:456-466.
• [32]Darvin K, Randolph A, Ovalles S, Halade D, Breeding L, Richardson A, Espinoza SE: Plasma protein biomarkers of the geriatric syndrome of frailty. J Gerontol A Biol Sci Med Sci 2014, 69:182-186.
• [33]Fernández-Garrido J, Ruiz-Ros V, Buigues C, Navarro-Martinez R, Cauli O: Clinical features of prefrail older individuals and emerging peripheral biomarkers: a systematic review. Arch Gerontol Geriatr 2014, 59:7-17.
• [34]Tajar A, Lee DM, Pye SR, O’Connell MD, Ravindrarajah R, Gielen E, Boonen S, Vanderschueren D, Pendleton N, Finn JD, Bartfai G, Casanueva FF, Forti G, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean ME, Punab M, Wu FC, O’Neill TW: The association of frailty with serum 25-hydroxyvitamin D and parathyroid hormone levels in older European men. Age Ageing 2013, 42:352-359.
• [35]Goggins WB, Woo J, Sham A, Ho SC: Frailty index as a measure of biological age in a Chinese population. J Gerontol A Biol Sci Med Sci 2005, 60:1046-1051.
• [36]Mitnitski A, Rockwood K: Biological age revisited. J Gerontol A Biol Sci Med Sci 2014, 69:295-296.
• [37]López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G: The hallmarks of aging. Cell 2013, 153:1194-1217.
• [38]Howlett SE, Rockwood K: Ageing: develop models of frailty. Nature 2014, 512:253.
• [39]Kulminski AM, Culminskaya IV, Ukraintseva SV, Arbeev KG, Land KC, Yashin AI: Sex-specific health deterioration and mortality: the morbidity-mortality paradox over age and time. Exp Gerontol 2008, 43:1052-1057.