ESPEN Congress Leipzig 2013 Prognostic impact of body composition Phase angle: the best predictor for outcome? K. Norman (DE)
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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
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