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  1. 1. Editorial Slides VP Watch –June 5, 2002 - Volume 2, Issue 22 Markers for Vulnerable Patients
  2. 2.  Atherosclerotic cardiovascular disease, which results in more than 6.3 million deaths annually, is the leading cause of mortality worldwide.  The major underlying cause of acute coronary syndromes and sudden cardiac death is vulnerable plaque, which is often associated with hypercoagulability and/or preexisting myocardial damage.
  3. 3. Underlying pathology of acute coronary syndrome (unstable angina, acute MI) and sudden cardiac death
  4. 4. • Culprit Plaque, a Retrospective Terminology • Vulnerable Plaque, a Prospective Terminology Vulnerable Plaque = Future Culprit Plaque
  5. 5. Different Types of Vulnerable Plaques Major Underlying Cause of Acute Coronary Events Normal Rupture-prone Fissured Eroded Critical Stenosis Hemorrhage
  6. 6. • Vulnerable Patient = Vulnerable Plaque + Vulnerable Blood + Vulnerable Myocardium Vulnerable Patient
  7. 7.  A vulnerable patient is a person with vulnerable plaque, and/or vulnerable blood, and/or vulnerable myocardium who has a high likelihood of developing a sudden cardiac event (acute coronary syndrome and sudden cardiac death). Vulnerable Patient
  8. 8. The risk of a vulnerable patient is affected by vulnerable plaque and/or vulnerable blood and/or vulnerable myocardium. Vulnerable Patient
  9. 9.  Markers of vulnerable plaque: • Active Inflammation • Very Thin Cap and Large Lipid Core • Endothelial Denudation with Superficial Platelet Aggregation • Fissure / Wounded Plaque  Markers of vulnerable blood: • Increased Platelet Aggregation • Increased Coagulation Factors • Decreased Anti-Coagulation Factors • Other Thrombogenic Factors • Transient Hypercoagulemia by External Factors
  10. 10.  Markers of vulnerable myocardium:  T-Wave Alternans  Non-Esterified Fatty Acid  It may be more appropriate to measure the total risk of vulnerability in a patient rather than searching for a single vulnerable plaque.
  11. 11.  As reported in VP Watch of this week, Albert, Ridker, and colleagues in Physician’s Health Study showed that baseline CRP level was significantly associated with the risk of sudden cardiac death (SCD) over the ensuing 17 years of follow-up.
  12. 12.  They found that increase in risk associated with CRP levels was primarily seen among men in the highest quartile, who were at a 2.78-fold increased risk of SCD compared with men in the lowest quartile .  In contrast to the positive relationship observed for CRP, neither homocysteine nor lipid levels were significantly associated with risk of SCD.
  13. 13. Conclusion  Unlike other risk factors, high-sensitivity CRP is a strong independent predictor of sudden cardiac death in healthy men.  Therefore CRP may serve as a valuable measure for risk stratification of vulnerable patients.
  14. 14. Questions: • Is CRP an independent predictor of sudden cardiac death in women as well? • Is this predictive value of CRP independent from its association with atherosclerosis and atherosclerosis- derived myocardial injury?
  15. 15. Questions: • Is association of CRP and sudden cardiac death confounded by MI? • Can CRP directly play a role in development of arrhythmia?
  16. 16. 1) Christine M. Albert, Jing Ma, Nader Rifai, Meir J. Stampfer, and Paul M. Ridker; Prospective Study of C-Reactive Protein, Homocysteine, and Plasma Lipid Levels as Predictors of Sudden Cardiac Death. Circulation 2002 105: 2595 - 2599 2) Yusuf S, Reddy S, Ounpuu S, Anand S. Global Burden of Cardiovascular Diseases: Part I: General Considerations, the Epidemiologic Transition, Risk Factors, and Impact of Urbanization. Circulation. 2001;104:2746-2753. 3) Kolodgie FD, Burke AP, Farb A, Gold HK, Yuan J, Narula J, Finn AV, Virmani R. The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr Opin Cardiol. 2001;16:285-92. 4) Farb A, Burke AP, Tang AL, Liang TY, Mannan P, Smialek J, Virmani R. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation. 1996;93:1354-63. 5) Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons From Sudden Coronary Death : A Comprehensive Morphological Classification Scheme for Atherosclerotic Lesions. Arterioscler Thromb Vasc Biol. 2000;20:1262-1275. 6) Davies MJ, Thomas AC. Plaque fissuring--the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J. 1985;53:363-73. 7) Naghavi M, Madjid M, Khan MR, Mohammadi RM, Willerson JT, Casscells SW. New developments in the detection of vulnerable plaque. Curr Atheroscler Rep. 2001;3:125-35. 8) Albert CM, Ruskin JN. Risk stratifiers for sudden cardiac death (SCD) in the community: primary Prevention of SCD. Cardiovasc Res. 2001; 50: 186–196 References