Atherosclerosis, pumpsandpipesmdhc

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  • Atherosclerosis, pumpsandpipesmdhc

    1. 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. 2. Key Clinical Issues <ul><li>What causes the development of atherosclerosis? </li></ul><ul><li>Why do some atherosclerotic plaques develop a thrombus leading to vessel occlusion and clinical symptoms (MI, stroke) </li></ul><ul><li>How do we identify early atherosclerosis which does not limit flow and does not cause symptoms? </li></ul><ul><li>How do we stop or reverse atherosclerosis? </li></ul><ul><li>How do we monitor whether therapy is successful? </li></ul>
    3. 3. How do you know if you are at risk for a heart attack?
    4. 4. Case <ul><li>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. </li></ul>
    5. 7. Case <ul><li>Physical examination: Blood pressure 142/80 Height 6'2&quot;, Weight 210 lb </li></ul><ul><li>Labs: Total cholesterol 233 </li></ul><ul><li>Triglycerides 100 </li></ul><ul><li>HDL cholesterol 36 </li></ul><ul><li>LDL cholesterol 177 </li></ul><ul><li>What is his risk for coronary heart disease? </li></ul>
    6. 8. Major Risk Factors That Modify LDL-C Goals <ul><li>Cigarette smoking </li></ul><ul><li>Hypertension:  140/90 mm Hg or on antihypertensive medication </li></ul><ul><li>Low HDL-C: <40 mg/dL * </li></ul><ul><li>Family Hx of premature CHD: male first-degree relative <55 years, female first-degree relative <65 years </li></ul><ul><li>Age: men  45 years, women  55 years </li></ul><ul><li>*High HDL-C (  60 mg/dL) is a negative risk factor and decreases by 1 the total number of risk factors </li></ul>Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
    7. 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
    8. 10. What is his Framingham Risk Score? <ul><li>Age </li></ul><ul><li>Total cholesterol </li></ul><ul><li>HDL cholesterol </li></ul><ul><li>Systolic blood pressure </li></ul><ul><li>Smoking </li></ul><ul><li>Total: </li></ul><ul><li>8 </li></ul><ul><li>3 </li></ul><ul><li>2 </li></ul><ul><li>2 </li></ul><ul><li>0 </li></ul><ul><li>15 </li></ul>Points Risk of CHD event (MI or death): 20%
    9. 11. <ul><li>High risk for CHD event: >20% over 10 years </li></ul><ul><li>Intermediate risk: 10 – 20% </li></ul><ul><li>Low risk: <10% </li></ul>
    10. 12. Current Approaches to &quot;Risk Assessment&quot; (Predicting Heart Attack and Stroke) <ul><li>Count risk factors </li></ul><ul><li>Equations to quantitate absolute 10-year risk or lifetime risk </li></ul>
    11. 13. What causes a heart attack?
    12. 14. Endothelial Dysfunction in Atherosclerosis Ross R. N Engl J Med 1999; 340:115–126.
    13. 15. Fatty-Streak Formation in Atherosclerosis Ross R. N Engl J Med 1999; 340:115–126.
    14. 16. Formation of an Advanced, Complicated Lesion in Atherosclerosis Ross R. N Engl J Med 1999; 340:115–126.
    15. 17. Unstable Fibrous Plaques in Atherosclerosis Ross R. N Engl J Med 1999; 340:115–126.
    16. 18. Are there other tests to identify better who might have a heart attack or stroke?
    17. 19. New Tests for Risk Assessment <ul><li>Blood tests related to inflammation </li></ul><ul><ul><li>High-sensitivity C-reactive protein (CRP) </li></ul></ul><ul><ul><li>Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) </li></ul></ul>
    18. 20. LDL LUMEN MEDIA INTIMA The Role of Lp-PLA 2 in CVD Lp-PLA2
    19. 21. Adhesion Molecules LUMEN MEDIA INTIMA Lp-PLA2 The Role of Lp-PLA 2 in CVD Oxidized LDL Cytokines Lyso-PC + OxFA LDL
    20. 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
    21. 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.
    22. 24. <ul><li>Ankle-brachial index (ABI) </li></ul><ul><li>B-mode ultrasound of carotids (intima-media thickness) </li></ul><ul><li>Electron beam computed tomography (EBCT) </li></ul><ul><li>Exercise and nuclear stress tests </li></ul>Noninvasive Assessments for Subclinical Atherosclerosis
    23. 25. <ul><li>ARIC study – 16,000 individuals with 20 years of follow up </li></ul><ul><li>1.2 million SNPs per individual by end of year </li></ul><ul><li>Multiple imaging and blood tests on each individual (100s to 1000s of data points per patient </li></ul><ul><li>How to analyze and “mine” the data? </li></ul>Biomarkers, Genes, Imaging and Prediction of MI and Stroke
    24. 26. ABCs of Prevention <ul><li>Aspirin, ACE inhibitor </li></ul><ul><li>Blood pressure, beta-blocker </li></ul><ul><li>Cholesterol </li></ul><ul><li>Diet </li></ul><ul><li>Exercise </li></ul>
    25. 27. Intensity of lipid-modifying therapy is dependent upon the absolute risk for CHD events
    26. 28. Assessment of Therapeutic Efficacy <ul><li>Prostate Cancer </li></ul><ul><li>Symptoms: urine flow </li></ul><ul><li>Blood tests: PSA </li></ul><ul><li>Imaging: ultrasound, MRI, CT </li></ul><ul><li>Invasive: biopsy </li></ul><ul><li>CAD </li></ul><ul><li>Symptoms: blood flow </li></ul><ul><li>&quot;Stress&quot; tests: to assess blood flow </li></ul><ul><li>Invasive: cath </li></ul>
    27. 29. Barriers to New Drug Development <ul><li>Lack of blood tests (biomarkers) to quantitate atherosclerosis </li></ul><ul><li>No imaging tests to track progression/ regression in routine clinical practice </li></ul>

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