Dyslipidemia and Coronary Artery Disease Risk Assessment and Prevention

Transcription

1 Dyslipidemia and Coronary Artery Disease Risk Assessment and Prevention June 12, 2011 Raul J Seballos, MD, FACP Vice Chair, Preventive Medicine seballr@ccf.org

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3 Question #1 55 yo man with a history of CAD is seeing you for advice. He is tolerating Simva 40 mg po qd. He is asymptomatic. He exercises regularly and is following the therapeutic lifestyle change diet. Lipid profile: Total 200; TG 150; HDL 41; LDL 125. Thyroid function and liver function are normal. What is the most appropriate therapy for this patient? 1. Increase Simva to 80 mg qd 2. Add ezetimibe or bile acid sequestrant 3. No further lipid lowering therapy 4. Add gemfibrozil 150 mg BID

4 Question #2 59 yo male, has HTN (142/94 mm Hg) and BMI of He smokes and does not exercise. He is asymptomatic. EKG is normal. Fasting lipid profile: Total 284; HDL 34; LDL 190; TG 300 mg/dl Framingham risk is > 30% for coronary artery disease within the next 10 years. The next step is to: 1. Begin TLC diet, exercise program, and f/u in 6 mths 2. Begin statin with goal LDL of less than 130 mg/dl 3. Begin statin with goal LDL of less than 100 mg/dl 4. Begin bile acid sequestrant

5 Question #3 60 yo male with CAD, on Atorvastatin 40 mg po qd. Lipids: Total 202; HDL 41; LDL 98; TG 315, non-hdl (total-hdl) is 161; VLDL 63 The next step in treatment should focus to which target goal: 1. Total < 200 mg/dl 2. TG < 200 mg/dl 3. HDL > 45 mg/dl 4. Non-HDL < hscrp < 0.5 mg/l

6 Dyslipidemia/CVD Scope of the problem Who and when to screen Global Risk Assessment Treatment - Non-pharmacologic - Pharmacologic - Treatment goals Complications of treatment and other options

7 Classification Dyslipidemias were traditionally classified by patterns of elevation in lipids and lipoproteins (Fredrickson phenotypes). A more practical system categorizes dyslipidemias as - Primary or Secondary, and - Characterizes them by increases in cholesterol only (pure or isolated hypercholesterolemia), increases in TGs only (pure or isolated hypertriglyceridemia), or increases in both cholesterol and TGs (mixed or combined hyperlipidemias).

8 Secondary causes Increased LDL - Hypothyroidism - Dysglobulinemias - Nephrotic syndrome - Obstructive liver disease - Progestins - Steroids - Anorexia nervosa - Acute intermittent porphyria Increased triglycerides - Obesity - Diabetes - Hypothyroidism - Sedentary lifestyle - Alcohol - Renal insufficiency - Estrogens - Beta blockers - Thiazides - Steroids - Dysglobulinemia - SLE

9 Secondary causes Decreased HDL - Hypertriglyceridemia - Obesity - Diabetes - Cigarette smoking - Sedentary lifestyle - Beta blockers - Progestin - Anabolic steroids

11 Scope of the problem Cardiovascular disease (CVD) - Underlying cause of 36.3% of all deaths (1 of every 2.8 deaths) in US - 770,000 had first MI or unstable angina (2008) Avg age of first MI (M:66 / F: 70) - 175,000 had silent or unrecognized MI

12 Scope of the problem Cardiovascular disease (CVD) - Total cost of CVD and stroke: $448.5 B (2007) - 40% of US pop will have some form of CVD by 2030 (AHA) 27 million HTN ($200 B in direct cost by 2030) 8 million CAD 4 million stroke 3 million CHF - Direct medical cost by 2030 will triple ($273 B to $818 B) Circulation, 1/2011

13 Scope of the problem Acute coronary syndromes - Culprit lesions that cause ACS Only 15% have luminal diameter stenosis >70% immediately before rupture and thrombosis that precipitate the acute arterial occlusion - Not surprising then that revascularization of 1 or more high-grade lesions do not lower risks of MI or death for a patient with stable CHD

15 Who and when to screen Adult Treatment Panel III (ATP III, 2007) Guidelines - All adults starting at age 20 - Fasting lipid panel Q 5 yrs (low risk) - LDL = Total HDL TG/5 - Direct LDL if TG > measurements 1 week apart if considering treatment

16 Who and when to screen USPSTF (6/2008) - All: Screen M > 35, W > 45; Q 5 yrs - Increased risk: Screen M: 20-35, W: Increased risk DM FMHx (M < 50, F < 60) Smoking Obesity (BMI > 30) Previous personal h/o CHD or non-coronary atherosclerosis (eg AAA, PAD, CAS)

17 Who and when to screen ACC/AHA 2009 Performance measures for Primary Prevention of CVD - JACC 2009;54: Screen all adults at age 18 - Global risk score Q 5 yrs starting at age 35 (M) and age 45 (W)

19 Global Risk Assessment Numerous assessments of absolute risk for CHD in the next 10 yrs available Framingham Risk Score (1998) assessed and validated in broadest range of population and most years of follow up

20 Framingham risk score Atrial fibrillation Congestive heart failure Coronary heart disease (2-yr risk and 10-yr risk) General cardiovascular disease Hard coronary heart disease (MI or coronary death) Intermittent claudication Recurring coronary heart disease Stroke Stroke after fibrillation Stroke or death after atrial fibrillation

21 Framingham risk score Total score depends on - Sex and Age - Total or LDL cholesterol - HDL cholesterol - Blood pressure (SBP and DBP) - Diabetes yes or no - Smoking status yes or no

22 Framingham risk score Classification of 10-year risk for CV event - High risk: > 20% (considered a CHD equivalent) - Moderate: 10-20% - Low: < 10% Assessment of risk should guide treatment strategies

23 Framingham Risk Score (Men) 1 Age Points SBP Points < > HDL C Points > < 40 2 Total C Age Age Age Age Age < > Smoker No Smoker Yes Total Pts 10 yr risk Total Pts 10 yr risk < 0 < >17 > Hard Coronary Heart Disease (MI or Coronary Death

24 President Obama (2/28/10) Age: 48 BP: 105/62 Total: 209 HDL: 62 LDL: 138 FBS: 87 Smoker: YES!

25 Obama s Framingham Risk Score Age Points SBP Points < > HDL Points > < 40 2 Total C Age Age Age Age Age < > Smoker No Smoker Yes Total Pts 10 yr risk Total Pts 10 yr risk < 0 < >17 >30 8 4

26 Obama s Framingham Risk Score Age Points SBP Points < > HDL Points > < 40 2 Total C Age Age Age Age Age < > Smoker No Smoker Yes Total Pts 10 yr risk Total Pts 10 yr risk < 0 < >17 >30 8 4

28 Overview of treatment NCEP ATP III Guidelines are used to guide therapy Target LDL depends on presence of heart disease (secondary prevention) or risk factors for heart disease (primary prevention) Statins are the first choice medication to lower LDL cholesterol to reduce coronary heart disease event rate High risk patients have 2 or more risk factors

29 Risk factors Age/Sex: M > 45, F > 55 FMHx: 1 st deg M < 55, 1 st deg F < 65 Active smoking Hypertension HDL < 40 HDL > 60 (positive risk factor)

30 CAD Equivalents Diabetes mellitus Aortic aneurysm PVD (claudication, ABI < 0.9) Symptomatic carotid artery disease (TIA, stroke) FRS 10-yr risk > 20%

31 Overview of treatment LDL Goals Clinical risk assessment Initiate TLC Initiate drug therapy Goal of therapy Low risk: < 1 risk factor Moderate risk: > 2 risk factors 10-yr risk <10% > 160 mg/dl > 190 mg/dl < 160 mg/dl > 130 mg/dl > 160 mg/dl < 130 mg/dl Moderate high risk: > 2 risk factors 10-yr risk 10-20% High risk: CHD risk equivalent; 10-yr risk > 20% > 130 mg/dl > 130 mg/dl (or ) > 100 mg/dl > 100 mg/dl (or > 70) < 130 mg/dl < 100 mg/dl (optional) < 100 mg/dl < 70 mg/dl (optional)

32 Treatment considerations In patients with very high TG (>200): Secondary target is non-hdl (Total HDL ) Non-HDL goal is 30 mg/dl higher than the goal LDL So

33 Overview of treatment: non-hdl goals Clinical risk assessment Goal LDL Goal non-hdl (Total HDL) Low risk: < 1 risk factor Moderate risk: > 2 risk factors 10-yr risk <10% < 160 mg/dl < 190 mg/dl < 130 mg/dl < 160 mg/dl Moderate high risk: > 2 risk factors 10-yr risk 10-20% High risk: CHD risk equivalent; 10-yr risk > 20% < 130 mg/dl < 100 mg/dl (optional) < 100 mg/dl < 70 mg/dl (optional) < 160 mg/dl < 130 mg/dl

34 Therapeutic Lifestyle Changes (TLC) Avoid all forms of tobacco Attain and maintain healthy weight - BMI < 30 - Waist circum < 40 M, < 35 F - Waist-to-height ratio (goal is waist circumference is < half of height) Exercise aerobically 30 min most days of the week Consume < 1-2 alcohol drinks/day Diet

35 Diet therapy Total fat: 25-30% calories Protein: Approx 15% of total calories Carbs: 50-60% of total calories Fiber: gm/day Cholesterol < 200 mg/d Saturated fat: < 7% of total calories Reduce saturated and transfats - Replace with polyunsaturated fat (up to 10% of total calories) and monounsaturated fat (up to 20% of total calories)

36 Diet therapy Increase soluble fiber (3 oz/d) - oats, barley, psyllium, okra, eggplant Increase soy protein (1.5 oz/day) - Tofu and soy foods Increase consumption of tree nuts (1.5 oz/d) - Almonds, walnuts, pecans Increase plant stanols and sterols (1 oz/d) - Promise Activ or Benecol Increase Omega-3 FA (EPA+DHA 1000 mg/d) - 6 oz salmon or tuna 2d/wk

37 Drug therapy 1 st line treatment (statins) 2 nd line treatment - Ezetimibe - Omega-3-Acid Ethyl Esters - Niacin - Fibrates - Bile acid sequestrants

38 Range of effects on lipids

39 Drug therapy Statins (HMG-CoA reductase inhibitors) - 1st line treatment and drug of choice for treating dyslipidemia and improving the prognosis of patients with CVD - Lowers LDL 18-55% - Reduce the number of LDL particles - Raise HDL by 4-9% - Lowers TG by 7-30%

40 Overview of treatment The lower the LDL at end of trial, the lower CHD event rate.

41 All cause mortality reduction of 12% Major cerebrovascular event reduction of 19% Major coronary event reduction of 30% Statin use not associated with increased risk of cancer. Brugts, J J et al. BMJ 2009;338:b2376

42 Statin dose comparison

43 Lipid changes with standard doses Statin Dose LDL decr HDL incr TG decr (mg/d) (%) (%) (%) Rosuvastatin Atorvastatin Simvastatin Pravastatin Lovastatin Fluvastatin

44 Drug therapy Ezetimibe - Selectively inhibits intestinal absorption of cholesterol and related phytosterols - Weak monotherapy for patients intolerant to statins - Can be added to statin therapy to further lower LDL - Further event rate reduction with combo therapy? - Side effects: bloating, constipation

45 Drug therapy Omega-3-Acid Ethyl Esters Omega-3-Acid Ethyl Esters (Lovaza) - Adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe ( 500 mg/dl) hypertriglyceridemia - Inhibits hepatic TG synthesis and augment chylomicron TG clearance - Dose 1 gm cap: 4 caps QD or 2 caps BID - Can be used in combo with statin - Other potential benefits of omega-3 Lowers sudden cardiac death and all-cause mortality Mildly lower BP Decrease risk of inflammation and thrombosis

47 Drug therapy Niacin (Nicotinic acid) - Best combo with statin for hyperlipidemia with low HDL - Reduces FFA flux to liver - Decr TG up to 50% - Decr LDL up to 25% - Decr recurrent nonfatal MI vs placebo - Flushing most common side effect ASA or NSAID with snack 30 min before taking Slow up titration (500 mg every 4 weeks) Extended release - High doses my worsen DM2 control

49 Drug therapy Fibrates - Best monotherapy for high TG - Decr VLDL synthesis and induces lipoprotein lipase - Can be used in combo with statins with persistent high TG (incr risk for myositis & myalgias) - Does not reduce LDL significantly - Fenofibrate (Tricor) has less impact than Gemfibrozil (Lopid) on drug-drug interactions - Side effects: GI (nausea), gallstones, skin rash

50 Hypertriglyceridemia Levels (mg/dl) - Normal: < Borderline high: High: Very high: > 500 TLC can decr TG by 50% Weight loss of 5-10% can decrease TG by 20% Low carb diet can decr TG by 10-20% AHA (Circulation, 4/18/2011)

51 Drug therapy Bile acid sequestrants - Interrupts bile acid reabs requiring bile acid synthesis from cholesterol - Meds Cholestyramine (Questran: 1-2 scoops BID) Colestipol (Cholestid: 2 scoops BID-TID) Colesevalam (WelChol 625 mg, 3 po BID) - Drug of choice for children and women with child bearing potential - Can be used in combo with statins to synergistically induce LDL receptors

52 Selection of drugs for lipid therapy Type 1 st choice 2 nd choice 3 rd choice High LDL only Statin Bile acid sequestrants Ezetimibe Niacin High LDL Low HDL Statin Niacin High LDL Low HDL High TG Statins Niacin Fibrates Omega-3 High TG +/- Low HDL Fibrates Niacin Omega-3 Statins Low HDL only Niacin Fibrates

53 Drug therapy monitoring Follow-up fasting lipid profile 6 weeks after initiation Order LFTs before starting statin therapy, 12 weeks after initiation, with any dose increase, and periodically for long-term maintenance therapy. Mild elevations of ALT or AST (<3 times the upper limit of normal) following statin therapy do not appear to lead to significant liver toxicity over time.

54 Statin intolerant patient Rechallenge with another statin: fluvastatin (Lescol) and pravastatin Alternating day statin (rosuvastatin, atorvastatin) Use different lipid agent (ezetimibe, niacin, bile acid sequestrants, fibrate) CoQ mg daily Vitamin D IU daily

55 Are women different? Women present with cardiac events 10 yrs later than men Women who have MIs - 20% have no risk factors - 50% have normal cholesterol levels Framingham Risk Score may underestimate risk in women Reynolds Risk Score tailored to women - Age, SBP, smoking, Total-C, HDL-C - hscrp, + FMHx

56 Other preventive measures Blood pressure - Goal is low as possible - Goal for most is < 140/90 mm Hg - Goal is < 130/85 mm Hg with CKD, DM, and HF - See JNC 7 Guidelines (JAMA 2003; 289:2560) - JNC 8 (Fall 2011)

57 Other preventive measures Aspirin - Decr risk of MI in Men - Decr risk of stroke in Women - Incr risk of bleeding in both mg adequate to inhibit platelet aggregation esp for high risk group - See USPSTF statement on ASA (Annals Int Med 2009;150:396)

58 Aspirin (USPSTF, 2009) Use in MEN ages when potential benefit due to a reduction in MI outweighs risk Use in WOMEN ages when potential benefit due to a reduction in ischemic stroke outweighs risk Use in age > 80 insufficient evidence

59 Other preventive measures Diabetes mellitus - Consider as a risk factor rather than CHD equivalent (ACC/AHA 2009 Performance measures for Primary Prevention of CVD. JACC 2009;54:1364) - Goal A1c < 7% for DM2 - Goal LDL < 100 mg/dl - BP < 130/85 mm Hg

60 Other labs tests to consider Direct LDL: if fasting TG > 400 hscrp: for intermediate risk Apo A-1: in patients with low HDL (<40) with low Total (< 200) Apo B: normal LDL and high TG (>150) Chylomicron: if fasting TG > 1000 Lp(a): Premature + FMHx

61 Emerging hyperlipidemia therapy New statin: Pitavastatin (Livalo) Combinations: Atorva + Ezetimibe Rosuv + Fenofibrate New bile acid seq colestilan MTP inhibitor lomitapide Niacin+DP1 inhibitor Nicotinic Acid/Laropiprant CETP inhibitor anacetrapib, dalcetrapib

62 Future directions NCEP ATP IV (due late 2011) AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High TG and Impact on Global Health Outcomes) - Extended release Niacin + Simva vs Simva alone HPS2-THRIVE (Treatment of HDL to Reduce the Incidence of Vascular Events) - Assess effects of raising HDL with extended release niacin + laropiprant vs placebo

63 Conclusions Atherosclerosis is a lifelong process Intervention reduces the risk of cardiovascular disease Primary prevention involves identification and modification of risk factors Statins are the first choice medication to lower LDL cholesterol Ezetimibe, omega-3-acid ethyl esters, niacin, fibrates, bile acid sequestrants maybe appropriate adjunctive therapies

64 Recent FDA Warnings on Simva Because if increased risk of myopathy, the FDA recommends limiting the use of simvastatin at the 80 mg dose Physicians advised to - Not start patients on the 80 mg dose - Continue pts on 80 mg dose if they have tolerated this dose for 12 or more months - Use other treatments if pts LDLtarget are not met at the 40 mg dose

65 Recent FDA Warnings on Simva Drugs contraindicated for use with simva b/c they can increase the dose: itraconazole, ketoconazole, posacanozole, e mycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine and danazol Drugs that should not be used with simva doses - Higher then 10 mg: amiodarone, verapamil, and diltiazem - Higher than 20 mg: amlodipine and ranazoline

66 Conclusions Use global estimation risk scores to identify patients at high risk and candidates for primary prevention Begin lipid testing at age 20 Begin with therapeutic lifestyle changes and add medication if needed to achieve LDL cholesterol goals Clinical judgment is important in treating patients at intermediate risk

69 Question #2 59 yo male, has HTN (142/94 mm Hg) and BMI of He smokes and does not exercise. He is asymptomatic. EKG is normal. Fasting lipid profile: Total 284; HDL 34; LDL 190; TG 300 mg/dl Framingham risk is > 30% for coronary artery disease within the next 10 years. The next step is to: 1. Begin TLC diet, exercise program, and f/u in 6 mths 2. Begin statin with goal LDL of less than 130 mg/dl 3. Begin statin with goal LDL of less than 100 mg/dl 4. Begin bile acid sequestrant.

70 Question #2 59 yo male, has HTN (142/94 mm Hg) and BMI of He smokes and does not exercise. He is asymptomatic. EKG is normal. Fasting lipid profile: Total 284; HDL 34; LDL 190; TG 300 mg/dl Framingham risk is > 30% for coronary artery disease within the next 10 years. The next step is to: 1. Begin TLC diet, exercise program, and f/u in 6 mths 2. Begin statin with goal LDL of less than 130 mg/dl 3. Begin statin with goal LDL of less than 100 mg/dl 4. Begin bile acid sequestrant.

71 Question #3 60 yo male with CAD, on atorvastatin 40 mg po qd. Lipids: Total 202; HDL 41; LDL 98; TG 315, non-hdl (total-hdl) is 161; VLDL 63 The next step in treatment should focus to which target goal: 1. Total < 200 mg/dl 2. TG < 200 mg/dl 3. HDL > 45 mg/dl 4. Non-HDL < hscrp < 0.5 mg/l

72 Question #3 60 yo male with CAD, on atorvastatin 40 mg po qd. Lipids: Total 202; HDL 41; LDL 98; TG 315, non-hdl (total-hdl) is 161; VLDL 63 The next step in treatment should focus to which target goal: 1. Total < 200 mg/dl 2. TG < 200 mg/dl 3. HDL > 45 mg/dl 4. Non-HDL < hscrp < 0.5 mg/l

73 Thank you and good luck on your boards!