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Esv2n47

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Esv2n47

  1. 1. What Do You Do With A Patient Who Has High CRP and Low LDL? Editorial Slides VP Watch – November 27, 2002 - Volume 2, Issue 47
  2. 2.  More than 200 risk factors have been suggested for atherosclerotic cardiovascular disease.  However, only hypercholesterolemia, hypertension, diabetes, and smoking, are traditionally considered as modifiable major risk factors for CAD.
  3. 3.  During the last decade, atherosclerosis has found a new face as an inflammatory disease, with a its metabolic aspect (e.g. hypercholesterolemia) as a background component.  A composite marker that reflects the combined metabolic and inflammatory aspects of atherosclerosis, and their interactions, is now wanted more than ever.
  4. 4.  Cholesterol screening was the first screening tests used for CAD risk assessment and still is the major routine clinical test.  LDL cholesterol is the focus of current national guidelines for the determination of the risk of atherosclerotic cardiovascular disease. 11
  5. 5.  Results of Framingham study showed that more than 35% of CAD events occur in people with total cholesterol of less than 200 mg/dl. 10  Based on this result, most of the cases of acute MI occur in people with less than average cholesterol levels which is around 200-240mg/dl in the USA.
  6. 6.  Ridker et al showed that CRP predicts adverse cardiovascular events in asymptomatic healthy populations. 4,5,14,15  They also showed that CRP can predict future incidence of diabetes in apparently healthy people. 4,5,14,15
  7. 7.  As reported in VP Watch of this week, Ridker and his colleagues showed that CRP is a stronger predictor of future cardiovascular events than LDL cholesterol. 12  They measured CRP and LDL at base line in (all of) 27,939 apparently healthy American women, who were then followed for a mean of eight years for the occurrence of myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. 12
  8. 8.  Seventy seven percent of all events (MI, ischemic stroke, coronary revascularization, or death from cardiovascular causes) occurred among women with (normal) LDL below 160 mg/dl, and 46% occurred among those with LDL levels below (current treatment target) 130 mg/dl. 12  CRP and LDL levels were minimally correlated, which shows that each biologic marker was detecting a different group of people at risk. 12 Results
  9. 9. 0 0.5 1 1.5 2 2.5 3 3.5 4 1 2 3 4 5 LDL CRP Quintile RelativeRisk All Cardiovascular Events Age-Adjusted Relative Risk of Future Cardiovascular Events, According to Base- Line CRP and LDL Cholesterol Levels. Adopted from: Ridker et al. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002 Nov 14;347(20):1557-65.
  10. 10.  Increasing levels of CRP were associated with increased risk of cardiovascular events at all levels of estimated 10-year risk based on the Framingham risk score. 12  Increasing CRP were associated with increased risk of cardiovascular events at LDL cholesterol levels below 130, 130-160, and above 160 mg/dl. 12 Results
  11. 11. Advantages of measuring CRP: 13  stable over long periods  has no diurnal variation  can be measured inexpensively with available high-sensitivity assays  Not directly related to lipid metabolism  More importantly, CRP predicts incidence of diabetics and insulin resistance syndrome as it does cardiovascular events, which means it can be considered as a cumulative risk marker of metabolic as well as inflammatory aspects of atherosclerosis.
  12. 12. Conclusion:  CRP is a stronger predictor of future cardiovascular events than LDL.  CRP and LDL are minimally correlated. The combined evaluation of both CRP and LDL is superior as a method of risk detection to measurement of either biologic marker alone.
  13. 13.  CRP now has the final verdict to be considered as a major risk factor/marker for prediction of adverse cardiovascular events. Conclusion:
  14. 14. Questions:  What do you do with a patient who has high CRP and low LDL (<160mg/dl)? • What are the other useful combinations of risk markers (factors), like CRP and LDL in this study, for risk assessment?
  15. 15. Questions:  Do you agree that CRP, LDL, and Coronary Calcium Score jointly can provide a more powerful predictive value for risk assessment?
  16. 16. Questions:  What is the difference in value of CRP in primary versus secondary prevention?  And which one of the following should be used for patient follow up and monitoring their response to treatment? CRP, LDL, Calcium Score, or all?
  17. 17. 1) Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med 1999;340:115-126 2) Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995;91:2844-2850. 3) MB Pepys, GM Hirschfield:C-reactive protein and atherothrombosis. Ital Heart J 2001, 2: 196-199 4) Wilson PWF, D’Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998; 97: 1837–1847. 5) Pekkanen J, Linn S, Heiss G, Suchindran CM, Leon A, Rifkind BM, Tyroler HA; Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease. N Engl J Med. 1990 Jun 14;322(24):1700-7. 6) Speidl et al. High-sensitivity C-reactive protein in the prediction of coronary events in patients with premature coronary artery disease. Am Heart J. 2002 Sep;144(3):449-55. 7) Anderson JL, Carlquist JF, Muhlestein JB, Horne BD, Elmer SP; Evaluation of C-reactive protein, an inflammatory marker, and infectious serology as risk factors for coronary artery disease and myocardial infarction.J Am Coll Cardiol. 1998 Jul;32(1):35-41. 8) Ridker PM, Glynn RJ, Hennekens CH. C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation. 1998; 97: 2007–2011. 9) Koenig W, Sund M, Frohlich M, et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation. 1999; 99: 237–242 10) Castelli WP. Lipids, risk factors and ischaemic heart disease. Atherosclerosis 1996;124(Suppl):S1-9. 11) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97. 12) Ridker et al. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002 Nov 14;347(20):1557-65. 13) Ockene IS, Matthews CE, Rifai N, Ridker PM, Reed G, Stanek E. Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults. Clin Chem 2001;47:444-50 14) Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto AM Jr Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001 Jun 28;344(26):1959-65. 15) 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 Mar 23;342(12):836-43. References

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