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Atherosclerosis, pumpsandpipesmdhc

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    • 1. Pumps & Pipes 1 Christie M. Ballantyne, M.D. Center for Cardiovascular Disease Prevention Methodist DeBakey Heart Center Baylor College of Medicine Houston, Texas Atherosclerosis
    • 2. Key Clinical Issues
      • What causes the development of atherosclerosis?
      • Why do some atherosclerotic plaques develop a thrombus leading to vessel occlusion and clinical symptoms (MI, stroke)
      • How do we identify early atherosclerosis which does not limit flow and does not cause symptoms?
      • How do we stop or reverse atherosclerosis?
      • How do we monitor whether therapy is successful?
    • 3. How do you know if you are at risk for a heart attack?
    • 4. Case
      • A 58-year-old former CEO, recently retired, concerned about his risk for heart disease because of a family history of heart disease. He exercises on a regular basis; diet and weight have fluctuated over the years with his stress and workload. His only medical problem is high blood pressure, which is controlled with medication.
    • 5.  
    • 6.  
    • 7. Case
      • Physical examination: Blood pressure 142/80 Height 6'2", Weight 210 lb
      • Labs: Total cholesterol 233
      • Triglycerides 100
      • HDL cholesterol 36
      • LDL cholesterol 177
      • What is his risk for coronary heart disease?
    • 8. Major Risk Factors That Modify LDL-C Goals
      • Cigarette smoking
      • Hypertension:  140/90 mm Hg or on antihypertensive medication
      • Low HDL-C: <40 mg/dL *
      • Family Hx of premature CHD: male first-degree relative <55 years, female first-degree relative <65 years
      • Age: men  45 years, women  55 years
      • *High HDL-C (  60 mg/dL) is a negative risk factor and decreases by 1 the total number of risk factors
      Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
    • 9. Assessing CHD Risk in Men Note: Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian population in Massachusetts, USA. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA . 2001;285:2486-2497. Step 2: Total Cholesterol Point Total 10-Year Risk Point Total 10-Year Risk <0 <1% 11 8% 0 1% 12 10% 1 1% 13 12% 2 1% 14 16% 3 1% 15 20% 4 1% 16 25% 5 2%  17  30% 6 2% 7 3% 8 4% 9 5% 10 6% Step 7: CHD Risk ATP III Framingham Risk Scoring TC Points at Points at Points at Points at Points at (mg/dL) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 <160 0 0 0 0 0 160-199 4 3 2 1 0 200-239 7 5 3 1 0 240-279 9 6 4 2 1  280 11 8 5 3 1 Step 1: Age Years Points 20-34 -9 35-39 -4 40-44 0 45-49 3 50-54 6 55-59 8 60-64 10 65-69 11 70-74 12 75-79 13 HDL-C (mg/dL) Points  60 -1 50-59 0 40-49 1 <40 2 Step 3: HDL-Cholesterol Systolic BP Points Points (mm Hg) if Untreated if Treated <120 0 0 120-129 0 1 130-139 1 2 140-159 1 2  160 2 3 Step 4: Systolic Blood Pressure Step 5: Smoking Status Points at Points at Points at Points at Points at Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 Nonsmoker 0 0 0 0 0 Smoker 8 5 3 1 1 Age Total cholesterol HDL-cholesterol Systolic blood pressure Smoking status Point total Step 6: Adding Up the Points
    • 10. What is his Framingham Risk Score?
      • Age
      • Total cholesterol
      • HDL cholesterol
      • Systolic blood pressure
      • Smoking
      • Total:
      • 8
      • 3
      • 2
      • 2
      • 0
      • 15
      Points Risk of CHD event (MI or death): 20%
    • 11.
      • High risk for CHD event: >20% over 10 years
      • Intermediate risk: 10 – 20%
      • Low risk: <10%
    • 12. Current Approaches to &quot;Risk Assessment&quot; (Predicting Heart Attack and Stroke)
      • Count risk factors
      • Equations to quantitate absolute 10-year risk or lifetime risk
    • 13. What causes a heart attack?
    • 14. Endothelial Dysfunction in Atherosclerosis Ross R. N Engl J Med 1999; 340:115–126.
    • 15. Fatty-Streak Formation in Atherosclerosis Ross R. N Engl J Med 1999; 340:115–126.
    • 16. Formation of an Advanced, Complicated Lesion in Atherosclerosis Ross R. N Engl J Med 1999; 340:115–126.
    • 17. Unstable Fibrous Plaques in Atherosclerosis Ross R. N Engl J Med 1999; 340:115–126.
    • 18. Are there other tests to identify better who might have a heart attack or stroke?
    • 19. New Tests for Risk Assessment
      • Blood tests related to inflammation
        • High-sensitivity C-reactive protein (CRP)
        • Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 )
    • 20. LDL LUMEN MEDIA INTIMA The Role of Lp-PLA 2 in CVD Lp-PLA2
    • 21. Adhesion Molecules LUMEN MEDIA INTIMA Lp-PLA2 The Role of Lp-PLA 2 in CVD Oxidized LDL Cytokines Lyso-PC + OxFA LDL
    • 22. LUMEN MEDIA INTIMA Lyso-PC + OxFA Lp-PLA2 Adhesion Molecules Cytokines Plaque Formation Foam Cell Monocytes Macrophage The Role of Lp-PLA 2 in CVD Oxidized LDL LDL
    • 23. Association of Lp-PLA 2 and CRP with Incident Ischemic Stroke 5.52 CRP, mg/L Lp-PLA 2 ,  g/L Ischemic Stroke Hazard Ratio 95% CI 3.13 –41.41, p<0.001 (>3) (1 –3 ) (<1) (  422) (310 –422 ) (<310) 6.02 2.85 4.27 4.36 Ballantyne CM et al. Arch Intern Med 2005;165:2479-2484.
    • 24.
      • Ankle-brachial index (ABI)
      • B-mode ultrasound of carotids (intima-media thickness)
      • Electron beam computed tomography (EBCT)
      • Exercise and nuclear stress tests
      Noninvasive Assessments for Subclinical Atherosclerosis
    • 25.
      • ARIC study – 16,000 individuals with 20 years of follow up
      • 1.2 million SNPs per individual by end of year
      • Multiple imaging and blood tests on each individual (100s to 1000s of data points per patient
      • How to analyze and “mine” the data?
      Biomarkers, Genes, Imaging and Prediction of MI and Stroke
    • 26. ABCs of Prevention
      • Aspirin, ACE inhibitor
      • Blood pressure, beta-blocker
      • Cholesterol
      • Diet
      • Exercise
    • 27. Intensity of lipid-modifying therapy is dependent upon the absolute risk for CHD events
    • 28. Assessment of Therapeutic Efficacy
      • Prostate Cancer
      • Symptoms: urine flow
      • Blood tests: PSA
      • Imaging: ultrasound, MRI, CT
      • Invasive: biopsy
      • CAD
      • Symptoms: blood flow
      • &quot;Stress&quot; tests: to assess blood flow
      • Invasive: cath
    • 29. Barriers to New Drug Development
      • Lack of blood tests (biomarkers) to quantitate atherosclerosis
      • No imaging tests to track progression/ regression in routine clinical practice