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

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 GrailDetermination of
Physiological Age
6
How old would you be if you didnt know how old
you were?

• Satchel Paige

7
(No Transcript)
8
(No Transcript)
9
(No Transcript)
10
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?

11
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

12
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

13
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 (MMSElt19)
• Active cancer treatment

14
CHS

• Baseline Evaluations
• Self-assessed/self-reported health, diagnoses,
  health habits
• Minnesota Leisure Time Activities
• Difficulty with daily life tasks mobility, upper
  extremity function, ADLs , and IADLs
• 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

15
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)

16
CHS Prospective DefinitionPhenotype of
Frailty syndrome

• Shrinking unintentional weight loss (gt10 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

17
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 lt90
• 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)

18
FRAILTY AND SURVIVAL IN CHS
19
PRE-FRAILTY

• Increased risk of conversion to Frailty at 3-4
  years
• Unadjusted 4.51x
• Co-variate-adjusted 2.63x

20
FRAILTY/ DISABILITY/ CO-MORBIDITY

• What are the differences?
• What are the similarities?
• What are the overlapping domains?
• What are the health care implications?

21
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, 59255-263

22
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

23
FRAILTY/ CO-MORBIDITIES/DISABILITY
24
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
• gt75 carotid stenosis (adjusted OR 3.4)
• A/A index lt0.8 (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. 200156A
  M158-M166

25
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

26
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

27
FRAILTYTHE CATALOGUE
Fried and Walston, Frailty and Failure to Thrive,
in Principles of Geriatric Medicine and
Gerontology, 2003
28
What Does Aging Have to do with Frailty?
29
Aging Aerobic Capacity Performance Declines
with Age even in the Fittest
30
WHEN AGE-RELATED DECLINE BECOMES FRAILTY --- THE
THRESHOLD CONSTRUCT
31
DECLINE TRIGGER EVENTS IMPAIRED RECOVERY
32
The 2 Main Pathways to Frailty Diseases and
Basal Dysregulation

• General dysregulation
• immune
• metabolic
• neural

FRAILTY
Disease-specific declines
33
FRAILTY PRIMARY VS. SECONDARY
34
FRAILTY The pathogenic triad
35
FRAILTY THE BIG PICTURE 2007
36
Can The Downward Spiral of Frailty Be
Prevented?TARGET THE TRIGGERS (one
geriatricians favorite mnemonic)

• INFECTIONS
• INFARCTIONS
• INFRACTIONS

37
The Research AgendaPotential Interventions to
Halt or Reverse the Catabolic Cascade

• Exercise
• Pharmacological agents?
• Anabolic hormones?
• Estrogens?
• Androgens?
• GH/IGF?
• Orexigens?
• Anti-inflammatory agents?
• Other disease-modifying agents?
• Combinations of the above?

38
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

39
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

40
(No Transcript)
41
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

42
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. gt15)
• 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)

43
HOW DOES THE PHYSICIAN IDENTIFY WHEN THE BRIDGE
BETWEEN FRAILTY AND FAILURE TO THRIVE HAS BEEN
IRREVERSIBLY CROSSED????
44
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
  medicinee.g.,
• Pain management
• Nutrition management
• Psychological and spiritual care
• Advance directives
• Family/caregiver support
• Bereavement care

45
(No Transcript)
46
(No Transcript)
47
ARE STATINS THE PANACEA FOR FRAILTY?

• HMG CoA reductase inhibitors?
• (When will we put them in the water?)

48
Metabolic Path to the Pleiotropic Effects of
Statins
49
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

50
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 problemshypertension, 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

51
Examination findings
52
Laboratory Values

• Hct 33 hgb 10.2
• Albumin 3.2
• Glucose (random) 160 HgbA1c 7.2
• Folate/B 12 normal
• TSH 2.8
• Creatinine 2.2 BUN 35
• CRP 5.5
• Fasting lipids Cholesterol 142 HDL 32 LDL 58
  TG 260
• Microalbuminuria

• CXR cardiomegaly central congestion and
  cephalization
• EKG AFLVH, non-specific T wave changes

53
HAVE YOU SEEN THIS PATIENT IN YOUR CLINIC? ON
YOUR HOSPITAL SERVICE? ON YOUR TRANSITIONAL
CARE SERVICE? ON YOUR HOME CARE SERVICE?ON YOUR
LONG TERM CARE SERVICE? ON THE PALLIATIVE CARE
SERVICE?IN HOSPICE?