1 / 20

Inflammation = Thrombosis

wing-richards
Download Presentation

Inflammation = Thrombosis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. AHA / CDC Scientific StatementMarkers of Inflammation and Cardiovascular Disease: Applications to Clinical and Public Health PracticeCirculation January 28, 2003“Measurement of hs-CRP is an independent marker of riskand may be used at the discretion of the physician as partof global coronary risk assessment in adults without known cardiovascular disease. Weight of evidence favors use, particularly among those judged at intermediate risk byglobal risk assessment”.

  2. Inflammation = Thrombosis Tissue factor E-selectin ICAM-1 VCAM-1 Thrombin L-selectin GPIb/X MAC-1 Tissue factor GP IIb/IIIa CD40 ligand CD40 P-selectin

  3. The Role of Platelets in Inflammation and Plaque Stability Activated platelets Inflammatory modulators CD40L Platelet-derived growth factor Platelet factor 4 RANTES Thrombospondin Transforming growth factor- Nitric Oxide Plaque rupture & thrombosis Libby P. Circulation 2001:103:1718-1720

  4. Relative Risk of Cardiovascular Events Estimated by Several Biochemical Markers Relative Risk of Future CV Events Lipoprotein(a) Homocysteine Total cholesterol LDL-cholesterol Apolipoprotein B TC:HDL-C ratio hs-CRP hs-CRP + TC:HDL-C ratio 0 1.0 2.0 4.0 6.0 adapted from Ridker PM, et al. N Engl J Med 2000;342:836-843

  5. Clinical Application of hs-CRP for Cardiovascular Risk Prediction >100 mg/L 3 mg/L 10 mg/L 1 mg/L Low Risk Moderate Risk Acute-Phase Response: Ignore Value, Repeat Test in 3 Weeks High Risk AHA/CDC Statement. Circulation 2003; 107:499–511

  6. CRP Adds Prognostic Information at All Levels of LDL-C and at All Levels of the Framingham Risk Score <1.0 1.0-3.0 >3.0 1.0-3.0 >3.0 <1.0 3 25 C-Reactive Protein (mg/L) C-Reactive Protein (mg/L) 20 2 15 Relative risk Multivariable relative risk 10 1 5 0 0 0-1 2-4 5-9 10-20 <130 130-160 >160 Framingham estimate of 10-year risk (%) LDL cholesterol (mg/dL) Ridker et al. N Engl J Med 2002;347:1557

  7. CRP Adds to the ATP-III Definition of the Metabolic Syndrome (N = 3097 with ATP-III Metabolic Syndrome) 1.00 0.99 0.98 CRP < 1 mg/L CVD Event-Free Survival Probability 0.97 CRP 1-3 mg/L 0.96 CRP > 3 mg/L 0.95 Years of Follow-Up 0 2 4 6 8 Ridker et al, Circulation 2003;107:391-397

  8. C-Reactive Protein Levels Predict All-Cause Death After Ischemic Stroke *Kaplan-Meier survival curves based on mortality from all causes adapted from Muir K. Stroke 2000;30:981-985

  9. Elevated CRP Predicts Risk of Cardiovascular Events After First Stroke Villa Pini Stroke Data Bank Study CRP Level 70 > 33 mg/L n=473 60 50 p <0.001 log rank test 40 p <0.001 chi-square for trend MI, Stroke, or Vascular Death (%) 5 - 33 mg/L 30 20 < 5 mg/L 10 0 0 2 4 6 8 10 12 14 16 18 20 22 24 Months Napoli M, et al. Stroke 2002: 33:1763-1771

  10. Novel Risk Factors as Predictors of Peripheral Arterial Disease Lipoprotein(a) Homocysteine VCAM-1 Fibrinogen LDL-C ICAM-1 hs-CRP TC:HDL-C CRP + TC: HDL-C 0 1.0 2.0 4.0 6.0 Relative Risk of Incident Peripheral Arterial Disease (Adjusted for age, smoking, DM, HTN, family history, exercise level, and BMI) Ridker et al. JAMA 2001;285:2481-2485

  11. CRP Level Predicts Prevalence of Multiple Coronary Plaques in Patients with Unstable Angina Patients by CRP Tertile (mg/L) Patients with Multiple Plaques >2(p < 0.001) Patients (%) n=71 n=78 n=79 Zairis MN, et al. Atherosclerosis 2002;164:355-359

  12. 0.5 control 0.4 ADP, 30 uM 0.3 p<0.05 vs ADP- stimulated controls CD40L Expression (Mn X) 0.2 0.1 0 control ASA* clopidogrel† ASA* + clopidogrel† Clopidogrel Reduces ADP-Induced Expression of Platelet-Derived CD40L * ASA 100 uM in vitro † clopidogrel 75 mg/d for 7 days Hermann A, et al. Platelets 2001:12;74-82

  13. Clopidogrel Therapy Reduces the Risk Associated With Elevated Baseline CRP Status Death or MI by Day 30 in Patients Undergoing PCI With Stenting No thienopyridinepretreatment 24% n=74 25 Thienopyridinepretreatment 20 13% n=295 15 10.2% n=136 Percent 10% n=565 10 58% RRR p = 0.002 5 0 Total population0-<1.1 mg/dL Highest quartile>1.1 mg/dL Chew DP, et al. Am J Cardiol 2001;88:672-674

  14. Clopidogrel Pretreatment Reduces CRP levels in Patients Undergoing PCI No Clopidogrel Pretreatment n=533 CRP levels measured 24 hours post-PCI Clopidogrel Pretreatment n=282 0.43 mg/dL 0.38 mg/dL 0.39 mg/dL p = 0.026 p = 0.89 CRP Level (mg/dL) 0.15 mg/dL Baseline CRP Pre-PCI CRP Level Post-PCI Vivekananthan DP, Bhatt DL, et al. ACC Scientific Sessions. Chicago 2003.

  15. Assays of Inflammatory Markers for Potential Clinical Use WHO Standard Analyte Stability Availability Precision s-CAMs Unstable(unless frozen) Limited No CV < 15% Cytokines Unstable(unless frozen) Few IL-6 CV < 15% Acute-Phase Reactants Fibrinogen Unstable(unless frozen) Many Yes CV < 8% SAA Stable One Yes CV < 9% hsCRP Stable Many Yes CV < 10% WBC Stable Many Yes CV < 3% AHA/CDC Statement. Circulation 2003; 107:499–511

  16. AHA/CDC Recommendations for Clinical and Public Health Practice Class I: Should be performed Class II: Conflicting evidence/opinion a: Weight in favor of usefulness/efficacy b: Usefulness/efficacy less well established Class III: Should not be performed Laboratory Tests • Of current inflammatory markers identified, hs-CRP has the analyte & assay characteristics most conducive to use in practice(Class IIa, Level of Evidence B). • Other inflammatory markers should not be measured for determination CV risk in addition to hs-CRP (Class III, Level of Evidence C) AHA/CDC Statement. Circulation 2003; 107:499–511

  17. AHA/CDC Recommendations for Clinical and Public Health Practice Clinical Practice • Measurement of hs-CRP is an independent marker of risk and, in those judged at intermediate risk by global risk assessment (10%-20% CHD/yr) may help direct further evaluation & therapy in primary prevention of CHD (Class IIa, Level of Evidence B) • Measurement of hs-CRP may be used at discretion of the physician as part of global risk assessment in adults without known CVD(Class IIb, Level of Evidence C) • The benefits of such therapy based on these strategies remain uncertain AHA/CDC Statement. Circulation 2003; 107:499–511

  18. AHA/CDC Recommendations for Clinical and Public Health Practice Clinical Practice / Population Science • Benefit of strategy of evaluation and therapy guided byhs-CRP remains uncertain • hs-CRP levels may be useful in motivating patients to improve lifestyle behaviors (Class IIb, Level of Evidence C) • The entire adult population should not be screened for hs-CRP for purposes of cardiovascular risk assessment (Class III, Level of Evidence C) • ADDITIONAL CLINICAL EVIDENCE REGARDING THE POTENTIAL BENEFITS & HARM, AS WELL AS COST-EFFECTIVENESS OF SUCH SCREENING, IS NEEDED AHA/CDC Statement. Circulation 2003; 107:499–511

  19. AHA/CDC Recommendations for Clinical and Public Health Practice Clinical Practice • In patients with documented CAD or ACS, hs-CRP may be useful as an independent marker of prognosis (death, MI, restenosis after PCI) (Class IIa, Evidence C) • Application of secondary prevention measures (Class III, Level of Evidence A) or management guidelines for ACS should not be dependent on hs-CRP levels (Class III, Level of Evidence C) AHA/CDC Statement. Circulation 2003; 107:499–511

  20. AHA/CDC Recommendations for Clinical and Public Health Practice Laboratory Testing • Should ordinarily be done 2x (averaging results) 2 weeks apart (fasting/non-fasting), in metabolically stable patients. If hs-CRP >10 mg/L repeat & assess for sources of infection or inflammation (Class IIa, Evidence B) • hs-CRP results should be expressed as mg/L only (Class I, Level of Evidence A) • hs-CRP (using standardized assays), categorize as: • Average LevelRelative Risk Category< 1 mg/L Low 1.0 – 3.0 mg/L Average > 3.0 mg/L High AHA/CDC Statement. Circulation 2003; 107:499–511

More Related