ESPEN Congress Leipzig 2013

Prognostic impact of body composition

Phase angle: the best predictor for outcome?

K. Norman (DE)

Phase angle – the best

predictor of outcome?

Kristina Norman, PhD CHARITÉ Universitätsmedizin Berlin

Research Group on Geriatrics

Background

Bioelectrical Impedance Analysis

“Clinical use of BIA in subjects at extremes of BMI ranges or with abnormal

hydration cannot be recommended for routine assessment of patients until further

validation has proven for BIA algorithm to be accurate in such conditions.” ESPEN GUIDELINES Bioelectrical impedance analysis part I: review of principles and methods Clinical

Nutrition (2004) 23

Requirements for algorithms with tetrapolar BIA:

– BMI range 16 - 34 kg/m²

– undisturbed hydration

Increasing use of raw impedance parameters in

clinical research and practise

I m p e d a n c e (Z)

= Z2 = R2 + Xc2

R e s i s t a n c e

(R)

= pure opposition of a

biological conductor to

alternating electric

current

R e a c t a n c e

(Xc)

= capacitive effect

produced by the

tissue interfaces and

cell membranes

Reactance 180

Resistance π x

P h a s e A n g l e

(α)

Phase angle as indicator of nutritional and

functional parameters

5

Norman et al Nutrition 2007; 23

Norman et al. Am J Clin Nutr 2010;92

Toso et al. Nutrition 2000;16

Age:

65

BMI:

25

Age:

67

BMI:

25

Age:

64

BMI:

25

6

- Cancer (pancreatic, lung, colorectal, breast, mixed)

- HIV/AIDS

- Liver disease

- Neurologic disease (ALS)

- Rheumatic disease (systemic sclerosis)

- Kidney disease (haemodialysis and peritoneal dialysis)

- Cardiac disease

- Geriatrics

- Surgery (cardiac and gastrointestinal)

Norman et al Clin Nutr. 2012;31 [Review article]

Low phase angle values:

highly predictive of outcome (eg disease progression)

and mortality

7

Impact of phase angle on mortality in HIV

Schwenk et al. Am J Clin Nutr 2000;72

n= 257 (234 on HAART)

39.7 y old; 85% male

1.5 y prospective study

Impact of phase angle on mortality in colon

cancer

8

n=52 Patients with colon cancer stage IV

[57% male]

3 y retrospective review

5.57° (median) as the cutoff

> 5.57°

< 5.57°

Gupta et al Am J Clin Nutr 2004;80

Impact of phase angle on mortality in congestive

heart disease

9

n= 41 patients with CHD

Prospective study on 5 y

mortality

AUC

Phase angle 0.86

indexed EAT 0.82

ICW 0.83

MM 0.82

LV-EF 0.68

FFM 0.66

5.5° for PA

sensitivity 75%

specificity 65%

Dösch et al. Obesity 2010;10

EAT epicardial adipose tissue; ICW intracellular water; MM muscle mass; LV-EF left ventricular ejection fraction; FFM fat free mass

22 g/m² for EAT

sensitivity 88%

specificity 67%

Cut off values for

clinical use?

10

Norman et al Clin Nutr. 2012;31 [Review article]

In disease:

Determinants and influencing factors:

Weight loss

Bosy-Westphal et al. JPEN 2006;30

Barbosa- Silva et al. Am J Clin Nutr 2005;82

Stobäus et al. Br J Nutr 2012;107

Johansen et al. Am J Clin Nutr 2003;77

Age

Sex

BMI

Inflammation

Phase angle

In health:

Interpretation in clinical practice:

? ? Phase angle

5.0°

23 yrs

22.6 kg/m2

71 yrs

26.3 kg/m2

…….……. Age.…….…….

…….…….BMI.…….…….

Interpretation of phase angle in clinical practise

13

Sex, age and BMI - stratified reference values

Standardization of raw values

Bosy-Westphal et al. JPEN 2006;30

Barbosa- Silva et al. Am J Clin Nutr 2005;82

Z-score

standardized phase angle = (observed phase angle - mean* phase angle)

SD* of the phase angle

*mean and SD are from sex-, age-, and BMI-stratified reference values.

14

Sex, age and BMI - stratified reference values

Clinical case:

Phase angle: 5.0°

• male

• 71 yrs old

• BMI 26.3 kg/m2

above the 10th

reference percentile

4.45

Bosy-Westphal et al. JPEN 2006; 30

Clinical case:

Phase angle: 5.0°

• female

• 23 yrs old

• BMI 22.6 kg/m2

below the 5th and 10th

reference percentile

5.19

Bosy-Westphal et al. JPEN 2006; 30

5th reference percentile of phase angle in cancer:

Prognostic impact on 6-mo mortality

n= 399 (m/f (208/191)

Age 63.0 ± 11.8 y

Malnourished (SGA B+C) 58.1%

GI tract tumour: 38%

Advanced disease stage: 60.8 (%)

Norman et al. Am J Clin Nutr 2010;92

(n=191)

(n=208)

OR: 4.0; [95% CI: 2.4, 6.8] P< 0.001

Phase angle: Functional parameters and

quality of life in elderly cancer patients

18

Significant impact of phase

(General Linear Model, selected excerpt of

the models):

433 patients < 60 y

mean age 70

EORTC function scales and symptoms

Phase angle

< 5th reference percentile

> 5th reference percentile

ESPEN 2013 Poster PP-136-SUN

19

Standardization of raw values

Z-score

standardized phase angle = (observed phase angle - mean* phase angle)

SD* of the phase angle

*mean and SD are from sex-, age-, and BMI-stratified reference values.

Absolute vs. standardized phase angle

20

Norman et al. Am J Clin Nutr 2010;92

[°]

Phase angle – absolute values

Standardized phase angle in cancer: Prognostic

impact on 6-mo mortality

Norman et al. Am J Clin Nutr 2010;92

1 = 399. Age, sex, standardized phase angle, Subjective Global Assessment (SGA), BMI, handgrip strength, tumor type, disease severity, and type of treatment were introduced into the generalized linear model regression model.

(weight loss)

Standardized phase angle in cancer: Prognostic

impact on 6-mo mortality

22

AUC

Standardized phase angle 0.734

Subjective Global Assessment 0.697

UICC 0.622

Norman et al. Am J Clin Nutr 2010;92

Standardized phase angle in chemotherapy:

prognostic impact on 3 y mortality

23

195 patients before 1.

chemotherapy cycle

3 y prospective study

Cut off for standardized

phase angle -1.65 SD

Paiva et al. Support Care Cancer 2011; 19

RR 2.35 CI: 1.41–3.90; p=0.001

Multivariate Cox regression analysis

Phase angle is a good predictor of clinical outcome,

particularly for short term mortality

Phase angle is influenced by sex and age, hydration and

nutritional status as well as disease severity

Interpretation in clinical use is facilitated by reference values

24

C o n c l u s i o n s