Measuring FrailtyA comparison of the frailty phenotype and frailty

index for the prediction of all-cause mortality

James NazrooAlan Marshall, Kris Mekli and Neil Pendleton

neil.pendleton@manchester.ac.uk

Background

Specific definitions and models of frailty are contested

Broad agreement that frailty is a non-specific state reflecting age-related declines in multiple systems, which lead to adverse outcomes (mortality, hospitalisation)

Two common approaches to characterise frailty:

Frailty index (Rockwood and colleagues) Frailty phenotype (Fried and colleagues)

Compare the two approaches and, in particular, their success in predicting all cause mortality

And how well do they perform compared with other markers of risk?

The English Longitudinal Study of Ageing(www.ifs.org.uk/elsa)

A panel study of people aged 50 and older, recently finished our sixth wave of data collection, with additional wave 0 data available

Sample at wave 1 (2002) was approximately 11,400 people born before 1st March 1952 who were in the private household sector. Drawn from Health Survey for England (wave 0).

Face to face interview every two years since 2002, with a biomedical assessment carried out by a nurse every four years.

Those incapable of doing the interview have a proxy interview.

End of life interviews are carried out with the partners or carers of people who died after wave 1.

Detailed content on: demographics, health, performance, biomarkers, wellbeing, economics, housing, employment, social relationships, social civic and cultural participation, life history.

Sister study to HRS, SHARE, KLOSA, CHARLS, etc.

Frailty Index (FI)

Based on accumulation of ‘deficits’ (from 30 items) Activities of Daily Living Cognitive function Chronic diseases CVD Depression/mental health Poor eyesight/hearing Falls, fractures and joint replacements

0-1 scale for each component

Calculate the proportion of deficits held (so 0-1 scale)

Can be divided into three categories Robust (0-0.12) Pre-frail (0.13-0.21) Frail (>0.21)

Frailty Phenotype (FP): Fried et al. 2001

Aim: to establish a standardized definition of frailty

5 items: Sarcopenia: unintentional weight loss, > 8% bodyweight Exhaustion: had both ‘everything they did was an effort’ and

‘could not get going much of the time’, during the past week Low physical activity: no work and no other physical activities Slowness: timed walk in the slowest 20% of population Weakness: grip strength in the weakest 20% of population

Outcome Robust phenotype: positive for 0 item Pre-frail phenotype: positive for 1-2 items Frail phenotype: positive for 3-5 items

Analysis

Those aged sixty or older (walking speed)

Cumulative distribution of Frailty Index score for each Frailty Phenotype category (‘robust’, ‘pre-frail’ and ‘frail’)

Kaplan-Meier survival plots

Cox proportional hazard models

Test association between Frailty Index and Frailty Phenotype (at wave 2) and all cause mortality

Unadjusted model and then adjusted for demographics and then key risk factors (education, wealth, bmi, smoking)

Compare goodness of fit of models, and compare fit with models using self-assessed health and wealth

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0 .2 .4 .6Frailty index (0 to 1)

0.21 used as a cut-off for dichotomous frailty variable

30% frail in wave 1

Frailty index: distribution (wave 1)

Descriptives

Number (%) All Survived Died pi

FPRobust 2,416 (55) 2,308 (57) 108 (32)Pre-frail 1,657 (38) 1,496 (37) 161 (48)Frail 324 (7) 259 (7) 65 (19)SexMale 1968 (45) 1801 (44) 167 (50)Female 2429 (55) 2262 (56) 167 (50)SmokingNever smoked 1613 (37) 1508 (37) 105 (31)Past smoker 2262 (51) 2086 (51) 176 (53)Current smoker 522 (11) 469 (12) 53 (16)Variable All Survived Died PMean (s.d)Age (years) 71 (8) 70 (7) 77 (8) <0.0000FI 0.18 (0.1) 0.18 (0.9) 0.24 (0.1) <0.0000BMI 27.2 (5.9) 27.3 (5.8) 25.5 (6.9) <0.0000

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P value compares the survived and died groups (t-test and chi squared test)

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Frailty index Frailty index

Obs Spearmans rho Prob > |t| Males 1,968 0.51 <0.0000 Females 2,429 0.59 <0.0000

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Frailty Index cumulative distribution by Frailty Phenotype

Kaplan-Meier survival estimates - Males0

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Kaplan-Meier survival estimates

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Robust Pre-frailFrail

Kaplan-Meier survival estimates

Blue = Robust group. Red = Pre-frail group. Green = Frail group

Frailty Index Frailty Phenotype

Kaplan-Meier survival estimates - females

Blue = Robust group. Red = Pre-frail group. Green = Frail group

Frailty Index Frailty Phenotype

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Kaplan-Meier survival estimates

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Robust Pre-frailFrail

Kaplan-Meier survival estimates

Cox survival model - results

Model 1 controls for age and sex.

Model 2 controls for age, sex, education, wealth, smoking, couple

Unadjusted Model 1 Model 2

FI 1.67 (1.53-1.84) 1.47 (1.32-1.63) 1.43 (1.23-1.54)Harrells C 0.69 0.78 0.79

FPRobust Reference Reference ReferencePre-frail 2.33 (1.81-3.00) 1.54 (1.19-2.01) 1.47 (1.13-1.91)Frail 7.00 (5.11-9.60) 3.01 (2.12-4.27) 2.78 (1.96-3.96)Harrells C 0.66 0.77 0.78

FI (categorical)Robust Reference Reference ReferencePre-frail 2.94 (1.93-4.47) 2.20 (1.44-3.37) 2.16 (1.41-3.30)Frail 6.14 (4.12-9.16) 3.95 (2.61-5.99) 3.72 (2.46-5.64)Harrells C 0.67 0.78 0.78

Cox survival model: Health and wealth

Unadjusted Model 1 Model 2

SAGHExcellent Reference Reference ReferenceVery good 1.4 (0.83-2.39) 1.29 (0.76-2.19) 1.27 (0.76-2.19)Good 2.11 (1.28-3.49) 1.77 (1.08-2.94) 1.78 (1.08-2.94)Fair 3.84 (2.33-6.35) 3.10 (1.87-5.12) 3.10 (1.87-5.12)Poor 6.07 (3.46-10.64) 5.43 (3.09-9.55) 5.43 (3.09-9.55)

Harrells C 0.65 0.79 0.79

Wealth1. Poorest Reference Reference Reference2 0.64 (0.47-0.89) 0.84 (0.61-1.15) 0.89 (0.65-1.24)3 0.47 (0.33-0.65) 0.59 (0.42-0.83) 0.66 (0.47-0.94)4 0.47 (0.34-0.65) 0.59 (0.41-0.82) 0.67 (0.47-0.97)5. Richest 0.28 (0.19-0.41) 0.42 (0.28-0.62) 0.51 (0.33-0.78)

Harrells C 0.61 0.76 0.77

Model 1 controls for age and sex.

Model 2 controls for age, sex, education, (wealth), smoking, couple

Conclusions

Prediction of mortality over an eight year period for older people (aged 60+) living in the community:

Comparable results for Frailty Index and Frailty Phenotype

Comparable results for self-assessed health and wealth

Choice of measure might reflect the particular setting

Frailty Phenotype advantageous in clinical setting: detailed longitudinal ‘diagnostic’ measure

Frailty index useful in community environment: checklist approach