Serum Il-6 and IGF-1 improve clinical prediction of functional decline after hospitalization in older patients

Background and aims: Although inflammatory and hormonal markers have been associated with further functional adverse outcomes in community-dwelling seniors, these markers have not been studied from this perspective in acutely ill older patients. This prospective study was designed to determine whether biological markers can improve the predictive value of a clinical screening tool to assess the risk of functional decline in hospitalized older patients. Methods: Patients aged 75 years and over admitted for hip fracture, acute heart failure or infection (n=118) were recruited. The clinical screening tool SHERPA was filled in on admission, with concomitant measurement of interleukin-6 (IL-6), insulin-like growth factor 1 (IGF-1), C-reactive protein (CRP), white blood cells, urea, albumin, pre-albumin and total cholesterol. Functional decline was defined as a decrease of one point in the activities of daily living scale between pre-admission and 3-month post-discharge status. We compared the discrimination calibration of SHERPA vs SHERPA+, a logistic regression model including SHERPA and selected biomarkers. Results: Three months after discharge, functional decline had occurred in 46 patients. Interleukin-6 (IL-6) and insulinlike growth factor 1 (IGF-1) were selected, since their levels were significantly different between decliners and non-decliners, and were included in the new logistic regression model SHERPA+. Areas under the ROC curve [95% CI] for functional decline prediction were 0.73 [0.63–0.81] for SHERPA vs 0.79 [0.69–0.86] for SHERPA+ (p=0.14). However, SHERPA+ was better calibrated, as the average predicted risk of functional decline within subgroups matched the proportion which actually underwent functional decline (Brier score=0.185). Since functional decline was higher in patients with hip fracture, the SHERPA+ model was challenged by including the diagnosis. Only SHERPA, IGF-1 and diagnosis were significantly associated with functional decline. Conclusions: Selected biological markers may marginally improve the clinical prediction of post-discharge functional decline in hospitalized patients, and to stratify them appropriately. The predictive value of these biomarkers is not fully independent of disease status. Further studies are needed to confirm these results in a cohort representative of older patients admitted through the emergency department.

[1]  S. Katz Studies of illness in the aged , 1963 .

[2]  Sati Mazumdar,et al.  Rating chronic medical illness burden in geropsychiatric practice and research: Application of the Cumulative Illness Rating Scale , 1992, Psychiatry Research.

[3]  Muhammad Jalaluddin,et al.  Hospital Admission Risk Profile (HARP): Identifying Older Patients at Risk for Functional Decline Following Acute Medical Illness and Hospitalization , 1996, Journal of the American Geriatrics Society.

[4]  L. Rubenstein,et al.  Comprehensive geriatric assessment: a meta-analysis of controlled trials , 1993, The Lancet.

[5]  A. E. El Solh,et al.  Determinants of short and long term functional recovery after hospitalization for community-acquired pneumonia in the elderly: role of inflammatory markers , 2006, BMC geriatrics.

[6]  Suzanne G. Leveille,et al.  Change in Muscle Strength Explains Accelerated Decline of Physical Function in Older Women With High Interleukin‐6 Serum Levels , 2002, Journal of the American Geriatrics Society.

[7]  S. Katz,et al.  STUDIES OF ILLNESS IN THE AGED. THE INDEX OF ADL: A STANDARDIZED MEASURE OF BIOLOGICAL AND PSYCHOSOCIAL FUNCTION. , 1963, JAMA.

[8]  Sylvain Trepanier,et al.  Detection of Older People at Increased Risk of Adverse Health Outcomes After an Emergency Visit: The ISAR Screening Tool , 1999, Journal of the American Geriatrics Society.

[9]  L. Ferrucci,et al.  Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women. , 2003, The Journal of clinical endocrinology and metabolism.

[10]  L. Ferrucci,et al.  Peripheral Blood Markers of Inflammation Predict Mortality and Functional Decline in High‐Functioning Community‐Dwelling Older Persons , 2002, Journal of the American Geriatrics Society.

[11]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[12]  Joel Tsevat,et al.  Predicting Functional Status Outcomes in Hospitalized Patients Aged 80 Years and Older , 2000, Journal of the American Geriatrics Society.

[13]  B. Pedersen,et al.  Elderly humans show prolonged in vivo inflammatory activity during pneumococcal infections. , 1999, The Journal of infectious diseases.

[14]  F. Formiga,et al.  Serum Insulin-Like Growth Factor Levels Do Not Predict Functional Recovery after Hospitalization in Nonagenarian Patients , 2003, Hormone Research in Paediatrics.

[15]  L. Rodríguez-Mañas,et al.  Effectiveness of acute geriatric units on functional decline, living at home, and case fatality among older patients admitted to hospital for acute medical disorders: meta-analysis , 2009, BMJ : British Medical Journal.

[16]  Philippe Meert,et al.  Early evaluation of the risk of functional decline following hospitalization of older patients: development of a predictive tool. , 2006, European journal of public health.

[17]  J. Hanley,et al.  A method of comparing the areas under receiver operating characteristic curves derived from the same cases. , 1983, Radiology.

[18]  Luigi Ferrucci,et al.  Serum IL‐6 Level and the Development of Disability in Older Persons , 1999, Journal of the American Geriatrics Society.

[19]  M. Lawton,et al.  Assessment of Older People: Self-Maintaining and Instrumental Activities of Daily Living , 1969 .

[20]  G. Brier VERIFICATION OF FORECASTS EXPRESSED IN TERMS OF PROBABILITY , 1950 .

[21]  L. Rubenstein,et al.  Predictors of Immediate and 6‐Month Outcomes in Hospitalized Elderly Patients , 1988, Journal of the American Geriatrics Society.

[22]  K. Grimmer-Somers,et al.  Screening tools to identify hospitalised elderly patients at risk of functional decline: a systematic review , 2008, International journal of clinical practice.

[23]  C. Grunfeld,et al.  Insulin‐like Growth Factor 1 and Functional Status in Healthy Older Men , 1995, Journal of the American Geriatrics Society.

[24]  Deepak L. Bhatt,et al.  Incremental Prognostic Value of Elevated Baseline C-Reactive Protein Among Established Markers of Risk in Percutaneous Coronary Intervention , 2001, Circulation.

[25]  I. Bautmans,et al.  Circulating acute phase mediators and skeletal muscle performance in hospitalized geriatric patients. , 2005, The journals of gerontology. Series A, Biological sciences and medical sciences.

[26]  L. Ferrucci,et al.  Three‐Year Change in Inflammatory Markers in Elderly People and Mortality: The Invecchiare in Chianti Study , 2007, Journal of the American Geriatrics Society.

[27]  G. Frisoni,et al.  CHANGE IN FUNCTIONAL STATUS DURING HOSPITALIZATION IN OLDER ADULTS: A GERIATRIC CONCEPT OF FRAILTY , 2000, Journal of the American Geriatrics Society.

[28]  J. Ketelslegers,et al.  Regulation of Insulin-Like Growth Factor-I by Nutrition , 2004 .

[29]  S. Studenski,et al.  Research Agenda for Frailty in Older Adults: Toward a Better Understanding of Physiology and Etiology: Summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults , 2006, Journal of the American Geriatrics Society.

[30]  R. Beyth,et al.  The Relationship Between Clinical Assessments of Nutritional Status and Adverse Outcomes in Older Hospitalized Medical Patients , 1999, Journal of the American Geriatrics Society.

[31]  T M Morgan,et al.  Functional outcomes of acute medical illness and hospitalization in older persons. , 1996, Archives of internal medicine.