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Markers for coronary artery disease and their treatment

Markers for coronary artery disease and their treatment. Robert Baldor, MD FAAFP Professor, Family Medicine &Community Health University of Massachusetts Medical School. At the end of this session, you will:. Appreciate the importance of new and established risk factors for CVD

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Markers for coronary artery disease and their treatment

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  1. Markers for coronary artery disease and their treatment Robert Baldor, MD FAAFP Professor, Family Medicine &Community Health University of Massachusetts Medical School

  2. At the end of this session, you will: • Appreciate the importance of new and established risk factors for CVD • Consider the best means for evaluating and addressing treatment and prevention of these risk factors

  3. Traditional Risk Factors (JNC/7) • Age (>55 men; >65 women) • FH premature CVD (men < 55; women < 65) • Tobacco Abuse • Physical Inactivity • Obesity (BMI > 30 kg/m2 • Diabetes • Microalbuninuria (GFR < 60ml/min) • Hypertension • Dyslipidemia

  4. Therapeutic Life Changes • Diet of 5 servings of fruits and vegetables daily • Weight management • Increased physical activity to at least 120 minutes/week

  5. Foods to lower BP High Potassium • Banana/Oranges • Cantaloupe/Honeydew • Raisins/dates/apricots • Avocado/artichoke • Squash/beans/chickpeas • Potato/broccoli • Tomato sauce High Magnesium • Nuts/seeds • Halibut • Whole grains/bran • Beans/lentils • Soybeans • Spinach/dark green vegetables

  6. Traditional Risk Factors (JNC/7) • Age (>55 men; >65 women) • FH premature CVD (men < 55; women < 65) • Diabetes • Tobacco Abuse • Physical Inactivity • Obesity (BMI > 30 kg/m2 • Hypertension

  7. Hypertension targeted ... < 140/90 mmHg targeted treatment goal < 130/80 for diabetes and chronic kidney disease

  8. Traditional Risk Factors (JNC/7) • Age (>55 men; >65 women) • FH premature CVD (men < 55; women < 65) • Diabetes • Microalbuninuria (GFR < 60ml/min) • Tobacco Abuse • Physical Inactivity • Obesity (BMI > 30 kg/m2 • Hypertension • Dyslipidemia

  9. LDL-C: Primary Target of Therapy • Cigarette smoking • Hypertension • Low HDL cholesterol (<40 mg/dL) • Family history of premature CHD • male 1st degree relative <55 years • female 1st degree relative <65 years • Age (men 45 years; women 55 years)

  10. LDL-C: Primary Target of Therapy

  11. http://hp2010.nhlbihin.net/ATPIII/calculator.asp?usertype=profhttp://hp2010.nhlbihin.net/ATPIII/calculator.asp?usertype=prof

  12. LDL-C: Primary Target of Therapy 9% Risk

  13. LDL-C: Primary Target of Therapy > 100 mg/dL ! Equivalents = DM, PAD, AAA, symptomatic carotid AD

  14. Very high-risk patients…. • A recent heart attack or • Cardiovascular disease with either: • Diabetes • A severe or poorly controlled risk factors (such as continued smoking) • Metabolic syndrome

  15. LDL-C: Primary Target of Therapy > 100 mg/dL

  16. Treat metabolic syndrome • Intensify physical activity & weight loss • Treat hypertension • ASA daily • Treat elevated triglycerides or low HDL

  17. DM really CVD equivalent? • Recent systematic review • 45,000 pts followed over 13.4 yrs • DM alone is a weak predictor • DM but no prior MI had a 43% ↓ risk of CHD event vs. pts w/prior MI but no DM • Diabet Med. 2009;26:142-148

  18. Other factors? • 50% of MI’s & strokes occur in individuals with LDL levels below recommended levels

  19. Emerging factors? • Factors must be easily measured • Modifying treatments available • Is there evidence that the factors causes CVD (risk mediator) or is it noted because CVD is present (risk marker)?

  20. Emerging Risk Factors • Lipoprotein (a) • Homocysteine • Prothrombotic factors • Proinflammatory factors • Subclinical atherosclerosis • Impaired fasting glucose

  21. 1. Lipoprotein(a) • LDL like compound • Similar to plasminogen, with thrombotic properties • 40% cholesterol

  22. Lp(a) levels • Desirable < 20 mg/dL • Borderline 20-30 • High risk 31-50 • V. high risk > 50

  23. Associated with ↑Lp(a) • Inflammation • Genetic predisposition • Metabolic syndrome

  24. Lowering Lp(a) ? • High-dose extended-release niacin 3gm/d • above recommended max dose • Estrogens (HRT) - but HRT associated increased CVD risk!

  25. 2. Homocysteine • Metabolism By-product • requires folic acid, B12 and pyridoxine(B6) • No known biologic function • Increases CVD risk

  26. Associated with ↑ Homocysteine • Renal failure • Hypothyroidism • Folate/B6/B12 deficiency • Methotrexate • Genetic predisposition • MTHFR mutation • Bile acid sequestrants

  27. Associated with ↓ Homocysteine • Folate/B6/B12 supplements • Genetic predisposition

  28. Marker? • Meta-analysis OF 8 RCTs • 24,210 pts with > 1 yr follow-up • MI and stroke were primary outcomes • No CVD benefit from lowering homocysteine with B vitamins • Cochrane Database Syst Rev 2009;4:CD006612

  29. 3.Prothrombotic factor (fibrinogen) • An acute phase reactant • Levels > 350 mg/dl considered elevated • The conversion of fibrinogen to fibrin is the final step in the clotting cascade • No treatment has been shown to lower levels enough to reduce risk

  30. Associated with ↑ Fibrinogen • Inflammation • Smoking • Increased age • Obesity • Diabetes • Menopause • Oral contraceptives/estrogens

  31. Associated with ↓ Fibrinogen • Fibrates (not clinically significant) • Niacin (not clinically significant) • Smoking cessation • Exercise • Alcohol (in moderation)

  32. 4. Proinflammatory factors (hsCRP) • high-sensitivity C-reactive protein • An acute phase reactant • Elevated with inflammation • Associated with an increased risk of CAD, independent of other factors, except LDL

  33. hs-CRP • Low risk < 1 mg/L • Mod risk (1-3) • High risk (>3 mg/L) • Need a least 2 measurements • If > 10mg/dL – repeat in 2 weeks to ensure that reading is not due to acute inflammatory reaction

  34. Associated with ↑hsCRP • HTN • Obesity • Tobacco use • Metabolic syndrome • Diabetes mellitus • Low HDL/High TG • Oral estrogen/progesterone • Chronic infections (gastritis, gingivitis) • Chronic inflammation (rheumatoid arthritis)

  35. Associated with ↓hsCRP • Moderate alcohol consumption • Increased activity/exercise • Weight loss

  36. Reducing hs-CRP • Statins • Ezetimibide (Zetia) • Fibrates • Niacin • Colesevelam (Welchol) • Thiazolidinediones • ASA

  37. Risk mediator or a risk marker? • evidence that changes in CRP level lead to primary prevention of CHD events is inconclusive…. • Ann Intern Med 2009;151:496-507.

  38. 5. Sub-clinical atherosclerosis • Coronary Artery Calcium (CAC) score • ideal CAC score is zero • Coronary CT (EBCT) to quantify coronary artery calcification • The amount of calcium detected correlates with the presence of atherosclerotic plaque

  39. CAC value? • CAC score of 0 does not exclude risk • Sensitivity of 80%-92% • Specificity of 40%-51% • Unclear value - studies have shown variability in repeated measures of CAC over time

  40. ? Apolipoprotein B (apo B) • The major atherogenic apolipoprotein • apo B predicts severity of CHD events • High correlation with non-HDL cholesterol • ATP III cites this as the basis for non-HDL cholesterol as a secondary treatment target

  41. Non-HDL Cholesterol ? • Non-HDL-C = VLDL + LDL (Total C – HDL C) • VLDL- C: atherogenic remnant lipoproteins • Secondary target when triglycerides 200 mg/dL • Goal: LDL goal + 30 mg/dL

  42. Triglycerides ? • Normal <150 mg/dL • Borderline high 150–199 mg/dL • High 200–499 mg/dL • Very high 500 mg/dL

  43. High Triglycerides • Obesity • Physical inactivity • Tobacco abuse • Excess alcohol intake • High carbohydrate diet (>60% of energy intake) • DM, CRF, Nephrotic syndrome

  44. Non-HDL C: Secondary Target • Achieve LDL goal before treating non-HDL • Therapeutic approaches to elevated non-HDL • Intensify therapeutic lifestyle changes • Intensify LDL-lowering drug therapy • Nicotinic acid or fibrate therapy to lower VLDL

  45. Elevated Triglycerides (>500 mg/dL) • Goal of therapy: prevent acute pancreatitis • Dietary consultation • Fibrate or nicotinic acid • Fish oil supplements • 1 gm omega 3 fatty acids daily

  46. Low HDL Cholesterol (<40 mg/dL) • High triglycerides • Overweight and obesity • Physical inactivity • Type 2 diabetes • Tobacco abuse • High carbohydrate intake (>60% energy)

  47. Low HDL Cholesterol • Achieve LDL goal • Weight reduction & ↑ physical activity • Consider nicotinic acid or fibrates for high risk patients

  48. Statin side effects • Check LFTs at onset and 12 weeks after starting or after any dose increase • Check annually or if symptoms • No evidence for harm from mildly elevated ALT/AST (< 3x normal) • 0.69 cases of hepatitis/million statin prescriptions

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