炎症和CHD的流行病学：hs-CRP的证据PPT课件.ppt

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 Risk Lipids HTN Diabetes Behavioral HemostaticThrombotic Inflammatory Genetic 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 Occurs in People with TC0.211 P 0.211 P =0.02 P =0.02 P Trend 0.73 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: MONICA–Augsburg Cohort Koenig W et al. Circulation 1999;99:237-242. 1 4.5 hs-CRP as a Risk Factor for Future CVD 1.0 2.0 3.0 4.0 5.0 6.0 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 0–1 3 2 1 0 1–2 2–4 4–8 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 Interleukin-6 Total 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 1.0 2.0 4.0 6.0 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 2 3 4 SAA IL-6 sICAM-1 Potential Mechanisms Linking CRP to Atherothrombosis n Confounding by cigarette consumption n Innocent bystander - Acute phase response n Cytokine surrogate - IL-6, TNF-, IL-1 n Direct effects of CRP - Innate immunity - Complement activation - CAM induction n Prior infection - Chlamydia, H pylori, CMV n Marker for subclinical atherosclerosis - EBCT / IMT / ABI n Marker for insulin resistance/ obesity n Marker for endothelial dysfunction n Marker for dysmetabolic syndrome n Marker for plaque vulnerability Evaluating Novel Risk Factors for CAD n Consistency of prospective data n Strength of association n Independence of association n Improve predictive value n Standardized measure n Low variability n High reproducibility n Biologic plausibility n Low cost n Modifiable CRP vs hs-CRP n CRP 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 Standard 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 High-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, In[mg/L]) hs-CRP (ELISA, In[mg/L]) (In-house) -3 -2 -1 0 1 2 3 54 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 Parameter r P hs-CRP 0.60 0.001 Total Cholesterol 0.37 0.001 LDL-C 0.32 0.001 HDL-C 0.74 0.001 Triglycerides 0.49 0.001 Ridker PM et al. Circulation 1999;100:230-235. Population Distribution of hs-CRP in Apparently Healthy American Men and Women Quintile Range (mg/dL) Risk Estimate 1 0.01–0.069 Low 2 0.07–0.11 Mild 3 0.12–0.19 Moderate 4 0.20–0.38 High 5 0.39–1.50 Highest Ridker PM et al. Circulation. In press. Biomarkers for Venous and Arterial Thrombosis Parameter Venous Arterial 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 (cont’d) Parameter Venous Arterial Factor V Leiden +++ – Prothrombin mutation ++ – Prothrombin + – Factor VIII ++ – Anti-thrombin III ++ – Protein C + – Protein S + – Homocysteine ++ ++ D-dimer ++ ++