炎症和chd的流行病学hscrp的证据ppt课件

Epidemiology of Inflammatory Markers and CHD: Evidence for High-Sensitivity C-Reactive Protein Paul M. Ridker, MD, MPH Beyond Cholesterol: Predicting Cardiovascular Risk In the 21st Century Cardiovascular RiskCardiovascular Risk LipidsLipids HTNHTN DiabetesDiabetes BehavioralBehavioral HemostaticHemostatic ThromboticThrombotic InflammatoryInflammatoryGeneticGenetic Total Cholesterol Distribution: CHD vs Non-CHD Population Castelli WP. Atherosclerosis. 1996;124(suppl):S1-S9. 1996 Reprinted with permission from Elsevier Science. 35% of CHD 35% of CHD Occurs in People Occurs in People with TC0.211 P 0.211 P =0.02P =0.02 P P Trend 0.73 P P Trend 0.73 No hypertension No hyperlipidemia No current smoking No diabetes No family history hs-CRP and Coronary Heart Disease in Initially Healthy Men: MONICAAugsburg Cohort Koenig W et al. Circulation 1999;99:237-242. 1 4.5 hs-CRP as a Risk Factor for Future CVD 1.02.03.04.05.06.0 Relative Risk (upper vs lower quartile) CHD Death MI Stroke CHD PVD CVD CHD CHD CHD CHD 0 MRFIT (Kuller 1996) PHS (Ridker 1997) PHS (Ridker 1997) CHS/RHPP (Tracy 1997) PHS (Ridker 1998) WHS (Ridker 1998, 2000) MONICA (Koenig 1999) Helsinki (Roivainen 2000) Caerphilly(Mendall 2000) Britain (Danesh 2000) hs-CRP Adds to the Predictive Value of Total Cholesterol in Determining Risk of First MI Ridker PM et al. Circulation 1998;97:2007-2011. 1998 Lippincott Williams 97:2007-2011. 1998 Lippincott Williams 342:836-843. Relative Risks for First MI for Baseline sICAM-1 260 ng/dL Ridker PM et al. Lancet 1998;351:88-92. 1998 Reprinted with permission from Elsevier Science. Years of Study Follow-up 01 3 2 1 0 122448 Relative Risk Predictivity of Interleukin-6 on CV Risk in Women Ridker PM et al. N Engl J Med 2000;342:836-843. 2000 Massachusetts Medical Society. All rights reserved. 4 3 2 1 0 High Medium Low High Medium Low InterleukinInterleukin-6-6 Total cholesterolTotal cholesterol Plasma Concentration of TNF- and Risk of Recurrent Coronary Events Ridker PM et al. Circulation 2000;101:2149-2153. 2000 Lippincott Williams 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 1.02.04.06.0 Predictive Value of CRP and Other Inflammatory Markers: LDL 130 mg/dL Ridker PM et al. N Engl J Med 2000;342:836-843. 4 3 2 1 1 Relative Risk of Future Coronary Events Quartile of Inflammatory Marker hs-CRP 234 SAA IL-6 sICAM-1 Potential Mechanisms Linking CRP to Atherothrombosis nConfounding by cigarette consumption nInnocent bystander - Acute phase response nCytokine surrogate - IL-6, TNF-, IL-1 nDirect effects of CRP - Innate immunity - Complement activation - CAM induction nPrior infection - Chlamydia, H pylori, CMV nMarker for subclinical atherosclerosis - EBCT / IMT / ABI nMarker for insulin resistance/ obesity nMarker for endothelial dysfunction nMarker for dysmetabolic syndrome nMarker for plaque vulnerability Evaluating Novel Risk Factors for CAD nConsistency of prospective data nStrength of association nIndependence of association nImprove predictive value nStandardized measure nLow variability nHigh reproducibility nBiologic plausibility nLow cost nModifiable CRP vs hs-CRP nCRP is an acute-phase protein produced by the liver in response to cytokine production (IL-6, IL-1, tumor necrosis factor) during tissue injury, inflammation, or infection. n n Standard CRPStandard CRP tests determine levels which are increased up to 1,000-fold in response to infection or tissue destruction, but cannot adequately assess the normal range n n High-sensitivity CRPHigh-sensitivity CRP (hs-CRP) assays (i.e. Dade Behring) detect levels of CRP within the normal range, levels proven to predict future cardiovascular events. hs-CRP: Automated Commercial Latex- Enhanced Assay (Dade) vs Validated in- House ELISA 5 4 3 2 1 0 -1 -2 -3 Dade hs-CRP (Latex, Inmg/L) hs-CRP (ELISA, Inmg/L) (In-house) -3-2-1012354 Rifai N et al. Clin Chem 1999;45:2136-2141. r = 0.93 P 0.001 Age-Adjusted Correlation Coefficients for hs-CRP Levels and Lipid Parameters over a 5-Year Follow-up Period ParameterrP hs-CRP0.600.001 Total Cholesterol0.370.001 LDL-C0.320.001 HDL-C0.740.001 Triglycerides0.490.001 Ridker PM et al. Circulation 1999;100:230-235. Population Distribution of hs-CRP in Apparently Healthy American Men and Women QuintileRange (mg/dL)Risk Estimate 10.010.069Low 20.070.11Mild 30.120.19Moderate 40.200.38High 50.391.50Highest Ridker PM et al. Circulation. In press. Biomarkers for Venous and Arterial Thrombosis ParameterVenousArterial Fibrinogen+ Factor VII+ vWF: ag+ tPA: ag+ PAI-1: ag+ Platelet function+ Lp(a)+ hs-CRP / SAA / IL-6 / TNF+ Biomarkers for Venous and Arterial Thrombosis (contd) ParameterVenousArterial Factor V Leiden+ Prothrombin mutation+ Prothrombin+ Factor VIII+ Anti-thrombin III+ Protein C+ Protein S+ Homocysteine+ D-dimer+ Assessment of the Clinical Utility of Novel Markers of Cardiovascular Risk MarkerMarker Assay Assay Conditions Conditions