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FRAILTY: KEYSTONE IN THE ARCH BETWEEN INTERNAL MEDICINE AND GERIATRICS --- MOVING BEYOND “YOU KNOW IT WHEN YOU SEE IT”

FRAILTY: KEYSTONE IN THE ARCH BETWEEN INTERNAL MEDICINE AND GERIATRICS --- MOVING BEYOND “YOU KNOW IT WHEN YOU SEE IT”. William R. Hazzard MD January 2008.

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FRAILTY: KEYSTONE IN THE ARCH BETWEEN INTERNAL MEDICINE AND GERIATRICS --- MOVING BEYOND “YOU KNOW IT WHEN YOU SEE IT”

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  1. FRAILTY: KEYSTONE IN THE ARCH BETWEEN INTERNAL MEDICINE AND GERIATRICS ---MOVING BEYOND “YOU KNOW IT WHEN YOU SEE IT” William R. Hazzard MD January 2008

  2. Dr. William Hazzard is the Director of Geriatrics and Extended Care for the VA Puget Sound Health Care System. He is also Professor of Medicine at the University of Washington. He has no significant financial interest and/or relationship with the manufacturer(s) of any product(s) or provider(s) of any of the services or products that may be addressed in this educational seminar.

  3. The Story of Life: a Postcard from 19th Century Germany *Courtesy of Elizabeth Barrett-Connor

  4. Icons of Gerontology and Geriatrics

  5. The Gerontological Holy Grail:Determination of “Physiological Age”

  6. “How old would you be if you didn’t know how old you were?” Satchel Paige

  7. Approaches to Assessmentof Frailty in our Patient • List his diagnoses (co-morbidities)? • List his geriatric syndromes? • Begin with his functional assessment and work backward? • Does he meet the criteria for the diagnosis of FRAILTY? Why/why not? • For FAILURE to Thrive? Why/why not? • Does the way he is classified make an important difference in his management? In his outcome?

  8. FRAILTY: The new-old syndromeA Working Definition • “A biologic syndrome of decreased reserve and resistance to stressors, resulting from cumulative declines across multiple physiologic systems and causing vulnerability to adverse outcomes” --- Fried et al, J. Geront, 2001, 56A, M146-M156

  9. FRAILTY: Toward a scientific definition and diagnosis THE CARDIOVASCULAR HEALTH STUDY (CHS) Fried, et al, Frailty in Older Adults: Evidence for a Phenotype 2001; J. Geront. 56A, M146-156

  10. Cardiovascular Health Study(CHS) • Population-based, prospective, community-based observational epidemiological study • Subjects 65 yrs: Recruited from HCFA Medicare eligibility lists • 1989-90: n = 5201 from 4 Communities • + 1992-3 cohort enriched in African-Americans • Total n = 5317, 15% African-American • Excluded: • Institutionalized • Mentally impaired (MMSE<19) • Active cancer treatment

  11. CHS • Baseline Evaluations • Self-assessed/self-reported health, diagnoses, health habits • Minnesota Leisure Time Activities • Difficulty with daily life tasks: mobility, upper extremity function, ADL’s , and IADL’s • Falls in the past 6 months • Depression assessment (CES-D) • CVD: history, symptoms, ECG, ankle-arm Bp ratio; carotid US • Weight; Blood pressure; • Glucose, albumin, creatinine, fibrinogen • Fasting Lipids (LDL calculated) • Cognitive function: MMSE, digit-symbol substitution • Walking Speed (15 ft) • Maximum grip strength

  12. CHS –follow-up • Annual examinations: • Repeat of Baseline Evaluations • Incident disease review • Hospitalizations • Falls • Disability • Mortality: semi-annual contacts (100% complete through 8yrs) • Frailty assessments (per definitions - see below) • Baseline Evaluation • 3 yr. (cohort 1) • 4 yr. (cohort 2) • 7 yr. (cohort 1)

  13. CHS: Prospective DefinitionPhenotype of Frailty syndrome • “Shrinking”: unintentional weight loss (>10 lb past year) • Weakness (Grip strength: lowest 20%) • Poor endurance: exhaustion (self-report) • Slowness (walking 15 ft: slowest 20%) • Low activity (Kcal/wk: lowest 20%) FRAILTY: 3 or more criteria met PRE-FRAILTY: 1-2 criteria met

  14. FRAILTY IN THE CHS • Baseline frailty in 6.3%: • Age 65-70: 3.2% • Increased progressively with age: 25.9% aged 85-89 • 2-fold higher in women than men at all ages <90 • 2-fold higher in African-Americans at each age • Increased (co-variable-adjusted) 3-year risk of: • Falls (29%) • Worsening mobility (29%) • Worsening ADL disability (98%) • 1st Hospitalization (125%) • Death (124%)

  15. FRAILTY AND SURVIVAL IN CHS

  16. PRE-FRAILTY • Increased risk of conversion to Frailty at 3-4 years: • Unadjusted: 4.51x • Co-variate-adjusted: 2.63x

  17. FRAILTY/ DISABILITY/ CO-MORBIDITY • What are the differences? • What are the similarities? • What are the overlapping domains? • What are the health care implications?

  18. FRAILTY VS. COMORBIDITIES: Definitions 2005 • “Comorbidity: the aggregation of clinically manifest diseases present in an individual” • “Frailty: the aggregate of subclinical losses of reserve across multiple physiologic systems” Fried, et al, Untangling the concepts of disability, frailty, and comorbidity …, J. Geront.2004, 59:255-263

  19. Co-morbidity: Clinically Manifest Disease • Present in 77% of CHS participants defined as having 2 or more of: • MI • Angina • CHF • Claudication • Arthritis • Cancer • Diabetes • Hypertension • COPD

  20. FRAILTY/ CO-MORBIDITIES/DISABILITY

  21. CVD Co-Morbidity and Frailty • Of the comorbidities frailty correlated most closely with CVD, both reported and subclinical • Most closely associated with CHF (OR 7.5) • Subclinically with • >75% carotid stenosis (adjusted OR 3.4) • A/A index <0.8 (OR 3.17) • Major ECG abnormalities (OR 1.58) • ECG LVH (OR 1.16) • Brain infarct-like lesions on MRI (OR 1.71) Newman et al, J. Geront. 2001;56A: M158-M166

  22. Frailty, Co-morbidities, and Disability in the CHS • Overlapping but far from congruent: but the overlap between frailty and disability was stronger as the number of functional impairments increased • Similarly, the overlap between frailty and co-morbidities correlated with the number of co-morbidities • In general, multiple co-variate analysis attributed ca. half of frailty to associated baseline co-morbidities

  23. THE PATHOGENESIS OF FRAILTY: A theoretical construct with a gathering base in evidence Fried and Walston, Frailty and Failure to Thrive, in Hazzard et al. (eds.), Principles of Geriatric Medicine and Gerontology, 5th edition, 2003

  24. FRAILTY:THE CATALOGUE Fried and Walston, Frailty and Failure to Thrive, in Principles of Geriatric Medicine and Gerontology, 2003

  25. What Does Aging Have to do with Frailty?

  26. Aging & Aerobic Capacity Performance Declines with Age even in the Fittest

  27. WHEN AGE-RELATED DECLINE BECOMES FRAILTY --- THE THRESHOLD CONSTRUCT

  28. DECLINE + TRIGGER EVENTS + IMPAIRED RECOVERY

  29. The 2 Main Pathways to Frailty: Diseases and Basal Dysregulation • General dysregulation • immune • metabolic • neural FRAILTY Disease-specific declines

  30. FRAILTY: “PRIMARY” VS. “SECONDARY”

  31. FRAILTY: The pathogenic triad

  32. FRAILTY: THE BIG PICTURE 2007

  33. Can The Downward Spiral of Frailty Be Prevented?TARGET THE TRIGGERS (one geriatrician’s favorite mnemonic) • INFECTIONS • INFARCTIONS • INFRACTIONS

  34. The Research AgendaPotential Interventions to Halt orReverse the Catabolic Cascade Exercise Pharmacological agents? Anabolic hormones? Estrogens? Androgens? GH/IGF? Orexigens? Anti-inflammatory agents? Other disease-modifying agents? Combinations of the above?

  35. A Consensus Hypothesis: Inflammation is a Central Culprit and a Final Common Pathway Inflammation is at the center as well as on all of the arms of the complex web of the frailty syndrome --- it often begins well before any clinical evidence of disease and both permits and perpetuates the process, frequently proceeding in fits and starts, in an ultimately terminal downhill spiral

  36. Inflammation: What are the Markers? Which are Mediators? • IL-1beta, TNFalpha (“cachectin”), other pro-inflammatory cytokines and mediators • IL-6 as final common mediator/marker (?) of the above (and modulated by hormones, such as testosterone and estrogen) • Soluble cytokine receptors • Hepatic acute phase markers • CRP -----SAA • Fibrinogen ---- Others

  37. Frailty Vs. Failure to Thrive • “Frailty and failure to thrive represent a continuum of a clinical syndrome, with failure to thrive being the most extreme manifestation associated with a low rate of recovery and that presages death” --- Fried and Walston, Principles of Geriatric Medicine and Gerontology,2003

  38. When Does Frailty Become Failure to Thrive? • “When the elderly patient … is no longer responsive to medical and non-medical interventions” ………. • Hallmark: unexplained severe, progressive weight loss (esp. >15%) • Multiple “geriatric” syndromes: dementia, depression, delirium, drug reactions, major chronic diseases • Anorexia, pain, malnutrition, falls, limited ability to undertake rehabilitation and follow medical recommendations • Hypoalbuminemia/hypocholesterolemia/low creatinine (markers of sarcopenia and low protein stores)

  39. HOW DOES THE PHYSICIAN IDENTIFY WHEN THE BRIDGE BETWEEN FRAILTY AND FAILURE TO THRIVE HAS BEEN IRREVERSIBLY CROSSED????

  40. THE BRIDGE BETWEEN FRAILTY & FAILURE TO THRIVE (& PALLIATIVE CARE?) • Recognition of the patient who has failure to thrive and is no longer responsive to curative/restorative care (hardest to accept in patients without cancer) • Collaboration with other specialists and especially the patient and supporters in assuring an optimal continuum in the transition to comfort care • Palliative care as a core competency in medicine:e.g., • Pain management • Nutrition management • Psychological and spiritual care • Advance directives • Family/caregiver support • Bereavement care

  41. ARE “STATINS”* THE PANACEA FOR FRAILTY? *HMG CoA reductase inhibitors? (When will we put them in the water?)

  42. Metabolic Path to the Pleiotropic Effects of Statins

  43. Statins and Inflammation • Statins reduce CHD in patients at all LDL levels (and, per British Heart Protection Study, by equivalent [%] extent) • Statins may exert special CHD reduction in patients with activated immune systems (and elevated hsCRP levels - per Ridker) • Statins may have anti-inflammatory effects via general effect on isoprenoids (“pleiotropism”) • Hence statins may reduce FRAILTY via anti-inflammatory action

  44. A Case of Frailty • 84 year-old male veteran recently moved to your area; brought by his daughter with whom he lives • CC: weight loss of 15 lb over 6 months; lack of physical activity and vitality • Other complaints: housebound, little interaction with family, withdrawn, sleepless, falls, incontinent, immobile, needs help with meals, little interest in food or self care • PH: CVA 1 year ago; 80 pack-years; remote alcoholism; CHF; Type 2 diabetes X 18 years • Other problems:hypertension, atrial fibrillation, osteoarthritis, GERD, depression • Meds: glyburide, thiazide, beta blocker, ACE inhibitor, omeprazole, ASA, naproxen, OTC multivitamins, melatonin, donazepil, trazodone • Disabilities: dressing, bathing, continence, mobility, several IADLs

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