research towards active & healthy ageing investigating co ... · wp 16-char/gabo:mi: training...
TRANSCRIPT
1
Investigating Co-MorbiditiesAggravating Heart Failure
Stefan D Anker, MD PhD
Applied Cachexia ResearchCharité University Medicine BerlinDepartment of Cardiology (CVK)BerlinGermany
ResearchTowards Active &Healthy Ageing
ResearchTowards Active &Healthy Ageing
Modern medicine can impact life expectancy
Lenfant C.NEJM 2003.
2
Prevalence of D.m. in Heart Failure trials
0
5
10
15
20
25
30
35
40
CIBIS
-II
VHeFT-II
DIAM
OND-HF
ATLAS
VHeFT-I
CONSENSUS-I
RALES
ELITE-II
COMET
MERIT
-HF
Val-HeF
T
COPERNICUS
SOLVD-TDIG
MACH-I
OVERTURE
BEST
PRAISE-I
Prevalence %
3
7
6
5
4
3
2
1
HR forall-cause mortality
*
<22 22-25 25-30 30-35 ≥≥≥≥35
PROactive population: Type 2 DMplus macrovascular disease
Intervention: Pioglitazone vs placebon=5238 (2605 vs 2633)
BMI (kg/m2)
Placebo groupAll patients
HR 95%CI P
Weight gain (1%) 0.98 0.95-1.02 0.27
Weight loss (1%) 1.14 1.11-1.16 <0.0001
Doehner et al., IJC 2011(supported by SICA-HF)
*
PROactive: BMI vs all-cause mortality in DMT2
4
Cardiac Cachexia & Survival
n=171
0
0 6 12 18
20
40
60
80
100
50%cachectic: n=28 (16.4%)
83%
RR 3.73 95% CI 1.93-7.23p=0.0003
Cardiac Cachexia
Prognostic value
independently of:
• Peak VO2
• LVEF
• NYHA class
• Na
• Age
Months Anker et al., Lancet 1997
Survival (%)
15 yrs of HF epidemiology research
5
6
The FP7 SICA call
3 Mill EUR for EU partnersCo-operation with Russian partners (addit. 2 Mill EUR)
General Overview of the Project
• Collaborative Project
• Start date: 1st October 2009
• Duration: 48 months (+6 months extension)
• 11 Partners (7 European & 4 Russian partners)
• 16 Work packages
7
Partners Involved in SICA-HF
Charité Berlin, Germany
Military Hospital,Wroclaw, Poland
University of Hull, UK
University of Rostock, Germany
Medizinische Hochschule Hannover, Germany
V.A. Almazov Federal Center for Heart,
Blood & Endocrinology
St. Petersburg, Russia
Russian CardiologyResearch and
Production Complex,Moscow, Russia
IRCCS SanRaffaele
Rome, Italy
GABO:mi,Germany
Institute of Cardiology,Tomsk Research
Centre, Tomsk, Russia
M.V.LomonosovMoscow State
University, MoscowRussia
SICA-HF: Main Objectives
– Characterise the prevalence, incidence, persistence, and phenotype of obesity, cachexia, and T2DM in patients with HF
– Describe patterns of exercise capacity and cardiorespiratory reflex control
– Analyse body composition and its changes over time in patients with heart failure and type 2 diabetes, obesity, or cachexia
– Investigate the incidence and prevalence of sleep disordered breathing and its impact on the clinical severity in patients with HF
– Establish the impact of impaired vascular reactivity on impairedskeletal muscle metabolic and functional capacity including its underlying mechanisms
– Describe the interplay and metabolic signaling pathways between adipose tissue, skeletal muscle, the bone marrow and the heart in patients with HF and type 2 diabetes, obesity, and cachexia
8
Patient Recruitment – Inclusion Criteria
• >1600 patients with CHF and
– Obesity and/or
– Cachexia and/or
– Type 2 diabetes mellitus
• >300 patients with diabetes mellitus without HF
• >150 healthy control subjects
• HF patient inclusion criteria: diagnosis of
systolic or diastolic HF with NT-BNP>400,
LVEF<45% or hospitalisation for HF in last 12 mo
Follow-up
Baseline
4 mon
ths
12 m
onth
s
24 m
onths
Clinical examinationResting ECGHR, BP, weight, heightBody composition (DEXA/BIA)EchoExercise test, 6-MWTPlethysmography (blood flow)BloodsQoL
Subgroup AssessmentsivGTT (insulin sensitivity)Muscle/fat tissue biopsyBone marrow biopsySleep studiesEPC isolationReflex control
Central Blood Blood & DNA Bank
9
Overview and Interaction of the Work Packages
WP 03-HULL:
Recruitment and
characterisation
WP 10-CHAR:
Blood and DNA bank, biomarker
research
WP 11-MSU:
Blood and DNA bank, biomarker research, gene
identification
WP 07-CHAR: Metabolic and vascular studies &
biopsies (patients)
WP 05-CHAR:Body composition and test
standardisation
WP 16-CHAR/GABO:mi: Training & dissemination
WP 01-GABO:mi: Project Management
WP 06-ROS:Sleep Studies
WP 08-ROME:
Cellular research (human muscle)
WP 09-MHH:Cellular research
(human fat)
EU
RUSSIA
WP 02-CHAR: Statistical support
WP 13-AC:
Cellular mechanisms and therapy
WP 12-CT:Molecular
pathways, cell cultures
WP 14-CRC:
Vascular research, ex vivo
WP 15-AC: Academic coordination (Russia)
WP 04-WROC:QoL, exercise testing & reflex
research
WP08 – Cellular Research on Human Muscle
• Ultrastructural analysis of SMT samples by immuno-histochemistry and microscopy
• Investigate cross-talk between muscle, adipose tissue and the immune system (“ex vivo“)
• Investigate cellular functions potentially affected in CHF or by comorbidities (in vitro)
Muscle Biopsiesfrom Quadriceps Muscle
10
WP09 – Cellular Research in Human Fat Tissue
1. Assess circulating adipokine levels and mRNA in adipose tissue samples in ≈125 subjects
-- clarify adipose tissue dysfunction vs adipokine production
2. Analyse dysfunctional lipid mobilization and lipolytic stimuli
3. Provide training & SOPs and build a uniform & high-quality biobank
Subcutaneous biopsy Adipose tissue Cellular studies
SICA-HF – First Results
11
Pathophysiology of tissue wasting
Protect muscle for a happy & independent life
"PB Sitting" (Berlin, 2006)Artist: Stephan WeberJCSM – issue 1 (2010)
"Sitzende Alte" (1965)Artist: Prof. Bernd GöbelJCSM – issue 2 (2012)
Standing Women(1955)Artist: Alberto GiacomettiJCSM – issue 4 (2011)
12
Targets to treat muscle wasting & cachexia
Problems & solutions in Japan & EU are similar
• Prevention & treatment of cachexia
• Prevention & treatment of muscle wasting of the elderly (i.e. sarcopenia)
• Enhance independent living in good QoL
• Treat co-morbidities of the elderly (particularly HF and DMT2)
• Promote longevity ResearchTowards Active &Healthy Ageing
ResearchTowards Active &Healthy Ageing