1 / 64

Emerging Cardiac Risk Factors

Emerging Cardiac Risk Factors. Jon W. Wahrenberger, MD FACC. DHMC Cardiology Update Symposium 2003 December 1, 2003. Traditional Risk Factors. Tobacco Exposure Hypertension Diabetes Mellitus Lipid Disorders Family History. Audience Response Question 1.

craig
Download Presentation

Emerging Cardiac Risk Factors

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. Emerging Cardiac Risk Factors Jon W. Wahrenberger, MD FACC DHMC Cardiology Update Symposium 2003 December 1, 2003

  2. Traditional Risk Factors • Tobacco Exposure • Hypertension • Diabetes Mellitus • Lipid Disorders • Family History

  3. Audience Response Question 1 Question: Traditional risk factors are present in what percentage of patients with coronary heart disease: A. Less than 50% B. Greater than 50% C. Conflicting data

  4. Total Cholesterol Distribution: CHD vs Non-CHD Population Framingham Heart Study—26-Year Follow-up No CHD 35% of CHD Occurs in People with TC<200 mg/dL CHD 150 300 250 200 Total Cholesterol (mg/dL) Castelli WP. Atherosclerosis. 1996;124(suppl):S1-S9.

  5. Prevalence of Risk Factors in Patients with Coronary Heart Disease Khot, et al. JAMA 2003;290:898-904

  6. Prevalence of Risk Factors in CHD 4 3 0 2 1

  7. Emerging Cardiac Risk Factors The Four Big Ones • C-Reactive Protein • Lipoprotein (a) • Fibrinogen • Homocysteine

  8. Atherosclerosis Current Understanding

  9. Vessel Lumen Monocyte Endothelium Cytokines Growth Factors Metalloproteinases Cell ProliferationMatrix Degradation Intima Macrophage Foam Cell Atherosclerosis and Inflammation Ross R. N Engl J Med 1999;340:115-126.

  10. Vessel Lumen Monocyte LDL AdhesionMolecules Endothelium MCP-1 LDL Intima Modified LDL Cytokines Growth FactorsMetalloproteinases Cell ProliferationMatrix Degradation Macrophage Foam Cell Atherosclerosis and Inflammation Ross R. N Engl J Med 1999;340:115-126.

  11. Fibrous cap Lumen Lipid Core Shoulder Intima Internal Elastic laminæ Media External Anatomy of the Mature Plaque

  12. Matrix Metabolism and Integrity of the Plaque’s Fibrous Cap Synthesis Breakdown Collagen-degrading Proteinases Fibrouscap IFN- – CD-40L + + IL-1TNF-MCP-1M-CSF + + + + Lipid core Tissue Factor Procoagulant Libby P. Circulation 1995;91:2844-2850.

  13. Plaque Rupture with Thrombosis From A Slide Atlas Atherosclerosis Progression and Regression, Parthenon Publishing, 1999

  14. Emerging Cardiac Risk Factors The Four Big Ones • C-Reactive Protein • Lipoprotein (a) • Fibrinogen • Homocysteine

  15. Characteristics of an Ideal Screening Test • Presence of reliable assay • Independence from other risk factors • Presence of populations norms to allow interpretation of test • Clear statistical association of test and clinical endpoint • Ability to improve prediction beyond traditional risk factors • Ability to generalize results to other groups • Acceptable cost for assay Circulation 2003;107:499-511

  16. C-reactive Protein • Circulating acute phase reactant • Many-fold increase with injury & infection • Synthesized in liver, induced primarily by interleukin-6 (IL-6) • Stable levels in circulation, not affected by meals, no circadian levels • Level – within normal range – predicts CVD risk

  17. Hs-CRP predicts first events

  18. hs-CRP and Risk of Future MI in Apparently Healthy Men P Trend <0.001 P < 0.001 P < 0.001 P = 0.03 Relative Risk of MI 1<0.055 20.056–0.114 30.115–0.210 4>0.211 Quartile of hs-CRP (range, mg/dL) Ridker PM et al. N Engl J Med 1997;336:973-979.

  19. hs-CRP and Risk of Future MI: Analysis Stratified by Smoking Status All Patients Nonsmokers Relative Risk of Future MI 1 2 3 4 Quartile of CRP Ridker PM et al. N Engl J Med 1997;336:973-979.

  20. CRP and Risk: Overview of 18 Studies Ridker PM. Circulation 2003;107:363-9

  21. C-Reactive Protein and CHD Danesh, et al. BMJ. 2000;321:199-204

  22. CRP and Cardiovascular Risk CRP will Predict: • MI • Stroke • Peripheral arterial disease • Sudden cardiac death • Recurrent ischemia and death in: • Unstable Angina • Myocardial Infarction • Percutaneous intervention

  23. hs-CRP and Risk of T2DM P value for trend = 0.001 Pradhan, et al. JAMA 2001;286:327-34

  24. hs-CRP and Risk of Metabolic Syndrome • ATP III Definition of the Metabolic Syndrome • Three of the following five characteristics: • Midline obesity • Elevated TG • Low HDL • Hypertension • Glucose Intolerance P value for trend < 0.0001 Ridker, et al. Circulation 2003;107:391-7

  25. CRP, Metabolic Syndrome and CV Events Ridker, et al. Circulation 2003;107:391-7

  26. Elevated CRP Levels in Obesity: NHANES 1988-1994 Percent with CRP 0.22 mg/dL Normal Overweight Obese Visser M et al. JAMA 1999;282:2131-2135.

  27. Does CRP provide predictive information beyond existing global predictors?

  28. CRP and Framingham Risk Score Ridker PM. Circulation 2003;107:363-9

  29. CRP and LDL Cholesterol Ridker PM. Circulation 2003;107:363-9

  30. Lipoprotein(a) Homocysteine Total Cholesterol Fibrinogen tPA Antigen TC:HDL-C hs-CRP hs-CRP + TC/HDL-C 1.0 2.0 4.0 6.0 0 Relative Risks of Future MI among Apparently Healthy Middle-Aged Men: Physician’s Health Study Relative Risk for Future MI Ridker PM. Ann Intern Med 1999;130:933-937.

  31. Rotterdam Study: Prospective trial of 7093 apparently healthy men and women, age > 55, in which 157 with myocardial infarction were compared with 500 selected controls were compared in nested case control analysis based on baseline CRP levels. • CRP compared with Framingham Risk Score (FRS): • Receiver operating characteristic curve was not improved when hs-CRP was added FRS: • AUC FRS: 0.745 • AUC FRS + CRP = 0.748 P Trend = 0.50 CRP and Risk of MI: Rotterdam Study van der Meer, et al Arch Intern Med 2003;164:1323-8

  32. Can intervention lower CRP levels? Statins? Yes Weight loss ?? Smoking cessation?? Physical activity?? No studies to date have shown CRP lowering in itself is associated with reduced event rates!

  33. * * * Effect of Statin Therapy on hs-CRP Levels at 6 Weeks 6 5 4 3 2 1 0 *p<0.025 vs. Baseline hs-CRP (mg/L) Baseline Prava(40 mg/d) Simva(20 mg/d) Atorva(10 mg/d) Jialal I et al. Circulation 2001;103:1933-1935. 2001 Lippincott Williams & Wilkins.

  34. Routine screening with c-reactive protein?

  35. CRP Limitations • Most studies limited to North American and European population -- limited ability to extrapolate to Native American, African and South Asian • Not good indicator of extent of disease burden • Most studies have not adjusted for body-mass-index • Strength of association lessoned in some studies when adjusting for other risk factors

  36. AHA/CDC Consensus Panel Hs-CRP Recommendations Class I: None Class IIa: • In primary prevention, CRP measurement may be useful in those at intermediate risk (10-20% 10-year CHD risk), to help direct further evaluation and treatment. • In patients with stable CAD or ACS, CRP may be useful as an independent marker of recurrent events, including death, MI and restenosis following PCI. Circulation 2003;107:499-511

  37. AHA/CDC Consensus Panel Hs-CRP Recommendations Class IIa: • Measurement should be done twice (two weeks apart) and results averaged. • If level > 10 mg/L, test should be repeated and patient examined for sources of infection or inflammation • Classify risk as follows: Low < 1 mg/L Average 1.0 – 3.0 mg/L High: > 3.0 mg/L Circulation 2003;107:499-511

  38. AHA/CDC Consensus Panel Hs-CRP Recommendations • Screening of the population as a whole is NOT recommended • Application of secondary prevention measures should not depend upon hs-CRP results • Application of management guidelines for acute coronary syndromes should not be dependent upon hs-CRP level • Serial CRP levels should not be used to monitor effects of treatment Circulation 2003;107:499-511

  39. Emerging Cardiac Risk Factors The Four Big Ones • C-Reactive Protein • Lipoprotein (a) • Fibrinogen • Homocysteine

  40. Lipoprotein (a) • LDL-like particle consisting of apolipoprotein moiety attached to apoB-100 • Levels under genetic control and don’t vary with diet or exercise • Acute phase reactant, doubling in concentration after IL-6 stimulation • Structural similarities to plasminogen

  41. Lipoprotein (a) Danesh, et al. Circulation 2000;102:1082-5

  42. Lipoprotein (a) • Lp(a) levels not affected by usual lipid lowering drugs; lowered only by high-dose niacin • No prospective trials showing reduction of cardiac endpoints with Lp(a) lowering • Not recommended for general screening

  43. Emerging Cardiac Risk Factors The Four Big Ones • C-Reactive Protein • Lipoprotein (a) • Fibrinogen • Homocysteine

  44. Fibrinogen • Circulating glycoprotein involved in final steps of coagulation • Other actions: • Regulation of cell adhesion, chemotaxis and proliferation • Vasoconstriction at sites of vascular injury • Stimulation of platelet aggregation • Influence on blood viscosity

  45. Fibrinogen • Acute phase reactant, increasing up to 4-fold after infectious or inflammatory stimuli • Levels also increased by: • Cigarette smoking • Diabetes • Hypertension • Obesity • Sedentary lifestyle • Levels lowered with fibrates and niacin; no effect from statins or aspirin

  46. Emerging Cardiac Risk Factors The Four Big Ones • C-Reactive Protein • Lipoprotein (a) • Fibrinogen • Homocysteine

  47. Causes of elevated Homocysteine • Homozygous homocysteinurias • MTHFR mutations • Others: • Renal failure • Hypothyroidism • Drugs interfering with folate metabolism (niacin)

More Related