Phenotyping hypertensive patients  with blood and urine -  inflammation, oxidative stress, fibrosis, angiogenesis Jan Menn...
The first problem:  how translate risk factors into vascular disase ? Risk factors glucose lipids smoking hypertension Cli...
Mechanisms of cardiovascular morbidity and mortality Progressive  deterioration  of organ function years and decades Sympa...
Mechanisms of cardiovascular morbidity and mortality Progressive  deterioration  of organ function years and decades Sympa...
Mechanisms of cardiovascular morbidity and mortality Progressive  deterioration  of organ function years and decades Sympa...
Mechanisms of cardiovascular morbidity and mortality Progressive  deterioration  of organ function years and decades Sympa...
Mechanisms of cardiovascular morbidity and mortality Progressive  deterioration  of organ function years and decades Sympa...
Risk Factors for Future Cardiovascular Events Relative Risk of Future Cardiovascular Events 0 Ridker PM et al.  N Engl J M...
PREVEND Study (n = 8,592) Blood pressure,   hsCRP and microalbuminuria Stuveling EM et al.  Hypertension  2004; 43: 791
phenotyping - we are looking for patterns  hypertension Micro- inflammation Hypertrophy  fibrosis Oxidative stress EC func...
Ingenious Hypercare phenotyping platforms Oxidative stress Micro- inflammation Hypertrophy  Fibrosis EC function/ Angiogen...
Structure of the phenotyping program  patient information Clinical assessment clinical data data processing and management...
Ingenious Hypercare phenotyping platforms Oxidative stress Micro- inflammation Hypertrophy  Fibrosis EC function/ Angiogen...
Ingenious Hypercare phenotyping platforms Oxidative  stress ADMA AOPP Ox-LDL Glutathionperoxidase Carbonylated proteins MP...
Zoccali et al.  Lancet  358:2113-7, 2001 <50 th   percentile 50 th  –75th percentile >75th percentile <50 th   percentile ...
Ingenious Hypercare phenotyping platforms Micro- inflammation C-reactive protein Serum amyloid A Fibrinogen IL-6 IL-6 ST I...
Ingenious Hypercare phenotyping platforms EC function/ Angiogenesis vWF circulating damaged EC Microparticles EPCs VEGF s-...
Endothelial cell Basement membrane Tie2 controls endothelial activation Ang-2 (Weibel-Palade- bodies) E-selectin, ICAM-1, ...
(A)  CKD Patienten (HD, PD, und NTx zusammen, n=117)  (B)  HD Patienten (n=61)  (C)  PD Patienten (n=24) und  (D)  NTx Pat...
Circulating Ang-2 levels are higher in hypertensive patients Kümpers P, David S, Hellpap J, Horn R, Leitolf H, Haller H, K...
Ingenious Hypercare phenotyping platforms TGF-b Osteopontin CTGF MMP Adiponectin FGFs gluPAI ? Others others others ? Hype...
Effects of treatment is important to know Angiopoetin -2  Osteopontin
no phenotyping without well characterized patients and families ! hypertension Micro- inflammation Hypertrophy  fibrosis O...
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Old and new markers for microinflammation: which are relevant?

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  • Slide 21. Risk factors for future cardiovascular events: WHS How well does the CRP test compare with other novel and emerging risk factors for vascular disease? This issue was directly addressed in the Women&apos;s Health Study, in this direct comparison of ten putative risk factors for vascular disease. In each case, the point estimate is based on being in the top versus bottom quartile for that particular analyte, and the horizontal bars represent the 95% confidence intervals for that effect. Starting from the top, we see that lipoprotein(a) screening was not a statistically significant predictor of risk, and below that, homocysteine screening, while statistically significant, was only of modest predictive value. This plot also indicates that the predictive value for LDL cholesterol, while highly statistically significant, sits approximately midway in terms of our overall risk prediction models. Interestingly, plasma levels of soluble intercellular adhesion molecule 1 (ICAM-1), a molecular marker associated with the adhesion and transmigration of leukocytes across the endothelial wall, as well as serum amyloid A (SAA), a nonspecific marker of inflammation, were in fact better markers of risk than was the LDL cholesterol or the total cholesterol level. Also of note from a clinical perspective, the best lipid marker was the total cholesterol:HDL cholesterol ratio. This finding is highly consistent with many prior epidemiologic studies and in fact is why many preventive practices prefer to use the ratio rather than any single lipid marker. However, the critical observation in this study was that plasma levels of hs-CRP on their own were actually the single strongest predictor for future vascular events, and those data are shown in the second line from the bottom. On its own, hs-CRP screening was associated with a 4.4-fold increase in risk for future vascular events among these otherwise healthy, middle-aged women. But again, the important issue is to consider combining the inflammatory screening with the lipid screening, and that is shown in the bottom line of data on the slide, suggesting that the combination of CRP level with total cholesterol: HDL cholesterol ratio provides the best overall risk estimate. Reference: Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836-843. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=10733371&amp;dopt=Abstract Keywords: C-reactive protein, ICAM-1, serum amyloid A, TC:HDL-C ratio, Women&apos;s Health Study Slide type: graph
  • Old and new markers for microinflammation: which are relevant?

    1. 1. Phenotyping hypertensive patients with blood and urine - inflammation, oxidative stress, fibrosis, angiogenesis Jan Menne, Hermann Haller Department of Nephrology, Medical School Hannover [email_address]
    2. 2. The first problem: how translate risk factors into vascular disase ? Risk factors glucose lipids smoking hypertension Clinical disease years and decades Organ damage „subclinical“
    3. 3. Mechanisms of cardiovascular morbidity and mortality Progressive deterioration of organ function years and decades Sympathetic activity RAAS Hypertension Diabetes Smoking Cholesterol Risk factors Clinical disease
    4. 4. Mechanisms of cardiovascular morbidity and mortality Progressive deterioration of organ function years and decades Sympathetic activity RAAS Hypertension Diabetes Smoking Cholesterol Risk factors Clinical disease Oxidative stress
    5. 5. Mechanisms of cardiovascular morbidity and mortality Progressive deterioration of organ function years and decades Sympathetic activity RAAS Hypertension Diabetes Smoking Cholesterol Risk factors Clinical disease Oxidative stress EC dysfunction
    6. 6. Mechanisms of cardiovascular morbidity and mortality Progressive deterioration of organ function years and decades Sympathetic activity RAAS Hypertension Diabetes Smoking Cholesterol Risk factors Clinical disease Oxidative stress EC dysfunction Microinflammation
    7. 7. Mechanisms of cardiovascular morbidity and mortality Progressive deterioration of organ function years and decades Sympathetic activity RAAS Hypertension Diabetes Smoking Cholesterol Risk factors Clinical disease Oxidative stress EC dysfunction Microinflammation Hypertrophy/Fibrosis
    8. 8. Risk Factors for Future Cardiovascular Events Relative Risk of Future Cardiovascular Events 0 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-C 1.0 2.0 4.0 6.0
    9. 9. PREVEND Study (n = 8,592) Blood pressure, hsCRP and microalbuminuria Stuveling EM et al. Hypertension 2004; 43: 791
    10. 10. phenotyping - we are looking for patterns hypertension Micro- inflammation Hypertrophy fibrosis Oxidative stress EC function/ Angiogensis
    11. 11. Ingenious Hypercare phenotyping platforms Oxidative stress Micro- inflammation Hypertrophy Fibrosis EC function/ Angiogenesis
    12. 12. Structure of the phenotyping program patient information Clinical assessment clinical data data processing and management vascular function blood samples ELISA MS Ultrasound NMR FMD Sphygmocor urine analysis proteomics storage
    13. 13. Ingenious Hypercare phenotyping platforms Oxidative stress Micro- inflammation Hypertrophy Fibrosis EC function/ Angiogenesis
    14. 14. Ingenious Hypercare phenotyping platforms Oxidative stress ADMA AOPP Ox-LDL Glutathionperoxidase Carbonylated proteins MPO Malondialdehyd s-RAGE Others others others ?
    15. 15. Zoccali et al. Lancet 358:2113-7, 2001 <50 th percentile 50 th –75th percentile >75th percentile <50 th percentile 50 th –75th percentile >75th percentile * Fully adjusted for traditional and non traditional risk factors * Fully adjusted for traditional and non traditional risk factors ADMA and cardiovascular mortality Fatal and non fatal cardiovascular events 1.0 .9 .8 .7 .6 .5 46.7 40.0 33.3 26.7 20.0 13.3 6.7 0 Time (months) All cause mortality 46.7 40.0 33.3 26.7 20.0 13.3 6.7 0 1.0 .9 .8 .7 .6 .5 Time (months) Cumulative survival
    16. 16. Ingenious Hypercare phenotyping platforms Micro- inflammation C-reactive protein Serum amyloid A Fibrinogen IL-6 IL-6 ST IL-12 TNF-a MCP-1 s-ICAM CD 40 s-VCAM gluPAI ? Others others others ? Leukocytes Albumin
    17. 17. Ingenious Hypercare phenotyping platforms EC function/ Angiogenesis vWF circulating damaged EC Microparticles EPCs VEGF s-flt-1 angiopoietin-1, -2 uPA/s-uPA-R ?
    18. 18. Endothelial cell Basement membrane Tie2 controls endothelial activation Ang-2 (Weibel-Palade- bodies) E-selectin, ICAM-1, VCAM-1 Stimulation (e.g. Immune complex) Ang-1 Disassembley of adherence junctions Survival Tie2 Rezeptor Maintenance
    19. 19. (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 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] min points 0 max points 11
    20. 20. 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]
    21. 21. Ingenious Hypercare phenotyping platforms TGF-b Osteopontin CTGF MMP Adiponectin FGFs gluPAI ? Others others others ? Hypertrophy Fibrosis
    22. 22. Effects of treatment is important to know Angiopoetin -2 Osteopontin
    23. 23. no phenotyping without well characterized patients and families ! hypertension Micro- inflammation Hypertrophy fibrosis Oxidative stress EC function/ Angiogensis
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