old and new markers for microinflammation: which are relevant?
TRANSCRIPT
![Page 1: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/1.jpg)
Phenotyping hypertensive patients Phenotyping hypertensive patients with blood and urine - with blood and urine -
inflammation, oxidative stress, fibrosis, angiogenesisinflammation, oxidative stress, fibrosis, angiogenesis
Jan Menne, Hermann Haller Department of Nephrology, Medical School Hannover
![Page 2: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/2.jpg)
The first problem: The first problem: how translate risk factors into vascular disase ?how translate risk factors into vascular disase ?
Risk factors Clinical diseaseClinical disease
years and decadesyears and decades
Organ damage Organ damage „subclinical“„subclinical“
glucoseglucoselipidslipids
smokingsmokinghypertensionhypertension
![Page 3: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/3.jpg)
Mechanisms of cardiovascular morbidity and mortalityMechanisms of cardiovascular morbidity and mortality
Progressive deterioration of organ function
years and decades
Sympatheticactivity
RAAS
Hypertension
DiabetesSmoking
Cholesterol
Risk factors
Clinical diseaseClinical disease
![Page 4: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/4.jpg)
Mechanisms of cardiovascular morbidity and mortalityMechanisms of cardiovascular morbidity and mortality
Progressive deterioration of organ function
years and decades
Sympatheticactivity
RAAS
Hypertension
DiabetesSmoking
Cholesterol
Risk factors
Clinical diseaseClinical disease
Oxidative stress
![Page 5: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/5.jpg)
Mechanisms of cardiovascular morbidity and mortalityMechanisms of cardiovascular morbidity and mortality
Progressive deterioration of organ function
years and decades
Sympatheticactivity
RAAS
Hypertension
DiabetesSmoking
Cholesterol
Risk factors
Clinical diseaseClinical disease
Oxidative stress
EC dysfunction
![Page 6: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/6.jpg)
Mechanisms of cardiovascular morbidity and mortalityMechanisms of cardiovascular morbidity and mortality
Progressive deterioration of organ function
years and decades
Sympatheticactivity
RAAS
Hypertension
DiabetesSmoking
Cholesterol
Risk factors
Clinical diseaseClinical disease
Oxidative stress
EC dysfunction
Microinflammation
![Page 7: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/7.jpg)
Mechanisms of cardiovascular morbidity and mortalityMechanisms of cardiovascular morbidity and mortality
Progressive deterioration of organ function
years and decades
Sympatheticactivity
RAAS
Hypertension
DiabetesSmoking
Cholesterol
Risk factors
Clinical diseaseClinical disease
Oxidative stress
EC dysfunction
Microinflammation
Hypertrophy/Fibrosis
![Page 8: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/8.jpg)
Risk Factors for Future Cardiovascular Events
Relative Risk of Future Cardiovascular Events0
Ridker PM et al. N Engl J Med 2000;342:836-843.
Lipoprotein(a)
Homocysteine
IL-6
TC
LDL-C
sICAM-1
SAA
Apo B
TC:HDL-C
hs-CRP
hs-CRP + TC:HDL-C1.0 2.0 4.0 6.0
![Page 9: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/9.jpg)
PREVEND Study (n = 8,592)
Blood pressure, hsCRP and microalbuminuria
Stuveling EM et al. Hypertension 2004; 43: 791
![Page 10: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/10.jpg)
phenotyping - we are looking for patterns phenotyping - we are looking for patterns
hypertensionhypertension
OxidativeOxidativestressstress
Micro-Micro-inflammationinflammation
Hypertrophy Hypertrophy fibrosisfibrosisEC function/EC function/
AngiogensisAngiogensis
![Page 11: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/11.jpg)
Ingenious Hypercare phenotyping platformsIngenious Hypercare phenotyping platforms
Oxidative stressOxidative stress
Micro-Micro-inflammationinflammation
Hypertrophy Hypertrophy FibrosisFibrosis
EC function/EC function/AngiogenesisAngiogenesis
![Page 12: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/12.jpg)
Structure of the phenotyping program
patient information
Clinical assessment
clinical data
data processing and management
vascular function
blood samples
ELISAMS
UltrasoundNMRFMDSphygmocor
urine analysis
proteomics
storage
![Page 13: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/13.jpg)
Ingenious Hypercare phenotyping platformsIngenious Hypercare phenotyping platforms
Oxidative stressOxidative stress
Micro-Micro-inflammationinflammation
Hypertrophy Hypertrophy FibrosisFibrosis
EC function/EC function/AngiogenesisAngiogenesis
![Page 14: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/14.jpg)
Ingenious Hypercare phenotyping platformsIngenious Hypercare phenotyping platforms
Oxidative Oxidative stressstress
ADMAADMAAOPPAOPPOx-LDLOx-LDL
GlutathionperoxidaseGlutathionperoxidaseCarbonylated proteinsCarbonylated proteinsMPOMPOMalondialdehydMalondialdehyds-RAGEs-RAGE
Others others others ?Others others others ?
![Page 15: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/15.jpg)
Zoccali et al. Lancet 358:2113-7, 2001
Fatal and non fatal Fatal and non fatal cardiovascular eventscardiovascular events
1.01.0
.9.9
.8.8
.7.7
.6.6
.5.5
46.746.740.040.033.333.326.726.720.020.013.313.36.76.700
TimeTime(months)(months)
All cause mortalityAll cause mortality
46.746.740.040.033.333.326.726.720.020.013.313.36.76.700
1.01.0
.9.9
.8.8
.7.7
.6.6
.5.5
TimeTime(months)(months)
Cumulative Cumulative survivalsurvival
<50<50thth percentile percentile
5050thth –75th percentile –75th percentile
>75th percentile>75th percentile
<50<50thth percentile percentile
5050thth –75th percentile –75th percentile
>75th percentile>75th percentile
* * Fully adjusted for traditional and non Fully adjusted for traditional and non traditional risk factorstraditional risk factors
* * Fully adjusted for traditional and non Fully adjusted for traditional and non traditional risk factorstraditional risk factors
ADMA and cardiovascular mortality
![Page 16: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/16.jpg)
Ingenious Hypercare phenotyping platformsIngenious Hypercare phenotyping platforms
Micro-Micro-inflammationinflammation
C-reactive proteinC-reactive proteinSerum amyloid ASerum amyloid AFibrinogenFibrinogenIL-6IL-6IL-6 STIL-6 STIL-12IL-12TNF-aTNF-aMCP-1MCP-1s-ICAMs-ICAMCD 40CD 40s-VCAMs-VCAM
gluPAI ?gluPAI ?Others others others ?Others others others ?
LeukocytesLeukocytesAlbuminAlbumin
![Page 17: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/17.jpg)
Ingenious Hypercare phenotyping platformsIngenious Hypercare phenotyping platforms
EC function/EC function/AngiogenesisAngiogenesis vWFvWF
circulating damaged ECcirculating damaged ECMicroparticlesMicroparticlesEPCsEPCs
VEGFVEGFs-flt-1s-flt-1angiopoietin-1, -2angiopoietin-1, -2
uPA/s-uPA-R ?uPA/s-uPA-R ?
![Page 18: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/18.jpg)
Endothelial cell
Basement membrane
Tie2 controls endothelial activation
Ang-1Ang-1
Ang-2Ang-2(Weibel-Palade-(Weibel-Palade-
bodies)bodies)
Disassembley of
adherence junctions
E-selectin, ICAM-1, VCAM-1
Survival
Tie2Tie2RezeptorRezeptor
Stimulation (e.g. Immune complex)
Maintenance
![Page 19: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/19.jpg)
(A) CKD Patienten (HD, PD, und NTx zusammen, n=117) (B) HD Patienten (n=61) (C) PD Patienten (n=24) und (D) NTx Patienten (n=32)
Coronary angiography
Doppler ultrasound
PAOD [Fontaine]
CHD (1 VD)
CHD (2 VD)
CHD (3 VD)
Stadium I
Stadium IIa
Stadium IIb
Stadium III
Stadium IV
mild
moderate
severe
+1
+2
+3
+2
+3
+4
+5
+1
+3
+1
+2
min points 00
max points 1111
Circulating Ang-2 correlates with atherosclerotic burden
Kümpers P, David S, Hellpap J, Horn R, Leitolf H, Haller H, Kielstein JT.Angiopoietin 2 and Cardiovascular Disease in Dialysis and Kidney Transplantation.Am J Kidney Dis. 2009 Mar 4. [Epub ahead of print]
![Page 20: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/20.jpg)
Circulating Ang-2 levels are higher in hypertensive patients
Kümpers P, David S, Hellpap J, Horn R, Leitolf H, Haller H, Kielstein JT.Angiopoietin 2 and Cardiovascular Disease in Dialysis and Kidney Transplantation.Am J Kidney Dis. 2009 Mar 4. [Epub ahead of print]
![Page 21: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/21.jpg)
Ingenious Hypercare phenotyping platformsIngenious Hypercare phenotyping platforms
TGF-bTGF-bOsteopontinOsteopontinCTGFCTGFMMPMMPAdiponectinAdiponectinFGFsFGFs
gluPAI ?gluPAI ?Others others others ?Others others others ?
Hypertrophy Hypertrophy FibrosisFibrosis
![Page 22: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/22.jpg)
Effects of treatment is important to knowEffects of treatment is important to know
30
40
Baseline 6 weeks 12 weeks
p < 0.05
p < 0.001
A
plas
ma
OP
N (
ng
/ml)
Angiopoetin -2 Osteopontin
![Page 23: Old and new markers for microinflammation: which are relevant?](https://reader038.vdocument.in/reader038/viewer/2022103115/5576eb69d8b42ab22b8b4a76/html5/thumbnails/23.jpg)
no phenotyping without well characterized no phenotyping without well characterized patients and families !patients and families !
hypertensionhypertension
OxidativeOxidativestressstress
Micro-Micro-inflammationinflammation
Hypertrophy Hypertrophy fibrosisfibrosisEC function/EC function/
AngiogensisAngiogensis