Introduction and Rationale

1. 2009 Guidelines for the Diagnosis and Treatment of Dyslipidemia and Prevention of Cardiovascular Disease

2. 2009 Dyslipidemia Guidelines Introduction and Rationale

3. Burden of Disease: Cardiovascular Disease in Canada *Causes of death are coded to the 10th revision of the World Health Organization's International Statistical Classification of Diseases and Related Health Problems (ICD-10).

4. A Look at Canada… In the last decade • 40% ↓ in mortality from CVD • Improvements in control of CVD risk factors and medical management of patients with CVD • New clinical data available → may enhance prevention and management of CVD • Despite these improvements, CVD remains a major societal burden Need for harmonization of CVD prevention practices across Canada CVD=Cardiovascular disease

5. Use of the 2009 CCS Dyslipidemia Guidelines • 2011 Survey of Canadian Health Care Professionals asked if they were aware of the 2009 CCS Dyslipidemia Guidelines

6. Use of the 2009 CCS Dyslipidemia Guidelines • 2011 Survey of Canadian Health Care Professionals asked if they usethe 2009 CCS Dyslipdemia Guidelines in their practice

8. 2009 Dyslipidemia Guidelines The Screening Process

9. William D. Dyslipidemia Screening • Male; bank manager; 38 years of age • Height: 180 cm (5’ 11”) • Weight: 98.5 kg (217 lbs) • BMI: 30.3 kg/m2 • Waist circumference: 97cm • Fasting glucose: 5.8 mmol/L • Blood pressure: 132/95 mmHg (not on any medication) • Smokes ½ pack of cigarettes per day • Father suffered fatal MI at age 59 • Mother has type 2 diabetes Would you screen William’s plasma lipid profile?

10. Target Patients • Men ≥40 years • Women ≥50 years or postmenopausal • Children with family history of hypercholesterolemia or chylomicronemia

11. Target Patients Cont’d… • Adults of any age with: • Hypertension • Diabetes • Current cigarette smoking • Overweight (BMI 27-30kg/m2) or obesity (BMI >30kg/m2) • Family history of premature CAD(<60 years in first-degree relatives) • Inflammatory diseases* (systemic lupus erythematosis, rheumatoid arthritis, psoriasis) • Evidence of atherosclerosis • Chronic renal disease (eGFR <60 mL/min/1.73m2) • HIV infection treated with highly active antiretroviral therapy • Clinical manifestations of hyperlipidemia (xanthomas, xanthelasmas,premature arcus cornealis) • Erectile dysfunction • Smoking * Data on inflammatory bowel diseases are lacking. BMI=body mass index; CAD=coronary artery disease; eGFR=estimated glomerular filtration rate

12. The Metabolic Syndrome (MetS) • The MetS is an association of several metabolic abnormalities including: • Visceral adipose tissue mass (i.e. toxic waist) • Dyslipidemia (elevated triglycerides and low HDL-C) • Elevated blood pressure • Elevated serum glucose Individuals with the metabolic syndrome are more likely to be at higher long-term cardiovascular risk than estimated by the Framingham Risk Score (FRS) alone. HDL-C=high-density lipoprotein cholesterol

13. International Diabetes Federation Classification of the Metabolic Syndrome HDL-C=high-density lipoprotein cholesterol

14. 2009 Dyslipidemia Guidelines Cardiovascular Risk Assessment

15. William D. CV Risk Assessment • William’s lipid profile: • HDL-C: 1.0 mmol/L • LDL-C: 3.8 mmol/L • Total cholesterol: 5.3 mmol/L • Triglycerides: 2.2 mmol/L • TC/HDL-C: 5.3 • FRS: 18.8% How would you categorize William’s CV Risk?

16. Risk Assessment Risk assessment options • Framingham Risk Score [FRS] • Commonly preferred → measures CVD (validated in Canada*) • May underestimate risk in some patients • Reynolds Risk Score [RRS] • Measures CVD → optional risk engine (includes family history and hsCRP) Cardiovascular (CV) risk assessment remains imperfect Total Cardiovascular Disease (CVD) Risk assessment recommended hsCRP=high-sensitivity C-reactive protein; CVD=cardiovascular disease *Validated with Cardiovascular Life Expectancy Model

17. Special Considerations CVD=Cardiovascular disease; hs-CRP=High-sensitivity C-reactive protein; LDL-C=Low density lipoprotein cholesterol

18. Screening for High-Sensitivity C-reactive Protein (hsCRP) • Baseline criteria • Men ≥50 years and women ≥60 years • Moderate risk for CVD (by FRS) • LDL-C is <3.5mmol/L • Free of acute illness • Baseline value • Lower of two hs-CRP values, taken at two weeks apart Not required for all patients FRS=Framingham risk score; LDL-C=low density lipoprotein cholesterol; hsCRP=high-sensitivity C-reactive protein; CVD=cardiovascular disease

19. Testing for Atherosclerosis Noninvasive assessment of atherosclerosis • Ankle-brachial index • Exercise stress test • Carotid B mode ultrasonography • Coronary calcium score • Cardiac computed tomography (Electron beam computed tomography [EBCT]); Multi-detector computed tomography coronary angiography (MDCT-CA) Atherosclerosis places the patient at HIGH RISK

20. Short-term versus Long-term Risk • FRS estimates 10-year risk • Family history increases risk: • 1.7-fold in women • 2-fold in men • Elevated hs-CRP may also modulate risk • Risk levels change over time Reassess CVD risk every 3 years FRS=Framingham risk score, hsCRP=high-sensitivity C-reactive protein; CVD=Cardiovascular disease

21. High Risk Level Target Demographic • Diabetic adults >45 (men), >50 (women) • Documented evidence of atherosclerosis Risk Score • FRS or RRS ≥ 20% Overview of Treatment Recommendations • Provide intensive lifestyle modification advice • Pharmacological lowering of LDL-C FRS= Framingham risk score; RRS=Reynolds Risk Score; LDL-C=low-density lipoprotein cholesterol

22. Moderate Risk Level Target Demographic • Middle-aged Canadians Risk Score • FRS 10-19% • Family history and high hsCRP modulate risk → RRS may be useful Overview of Treatment Recommendations • Provide lifestyle modification advice • May require pharmacological lowering of LDL-C FRS= Framingham risk score; RRS=Reynolds Risk Score; hsCRP= high-sensitivity C-reactive protein; LDL-C=low-density lipoprotein cholesterol

23. Low Risk Level Risk Score • FRS <10% • Careful family history may add risk factors → RRS may re-classify low-risk patients Overview of Treatment Recommendations • Use clinical judgment and proper timing for initiation of pharmacological lipid-lowering therapy FRS=Framinham risk score; RRS= Reynolds risk score

24. 2009 Dyslipidemia Guidelines Recommended Approach to Treatment

25. William D. Approach to Treatment • According to the guidelines William's CV risk is moderate • Would you treat William for dyslipidemia? • If yes, how? • Health behaviour/lifestyle? • Pharmacotherapy? • What are your treatment targets for William?

26. Targets of Therapy * Atherosclerosis in any vascular bed, including carotid arteries. apoB=apolipoprotein B level; CAD=coronary artery disease; FRS=Framingham risk score; HDL-C=high-density lipoprotein cholesterol; hs-CRP=high-sensitivity C-reactive protein; PVD=peripheral vascular disease; RRS=Reynolds Risk Score; TC=total cholesterol

27. Secondary Targets of Therapy (once LDL-C is at goal) TC=Total cholesterol; HDL-C=High-density lipoprotein cholesterol ; LDL-C=low-density lipoprotein cholesterol ; apoAI/B=apolipoprotein AI/B;evel; hsCRP= high-sensitivity C-reactive protein

28. Residual Risk • Clinical data suggests patients achieving secondary targets have better outcomes • Therapeutic options may include: • Fibrates → lower triglycerides, • Niacin → increase HDL-C, • Increase statins and/or, • Add cholesterol absorption inhibitors (i.e. ezetimibe*) to further lower LDL-C, apo B and hsCRP • Must be clinically tested with CV outcome data HDL-C=High-density lipoprotein cholesterol ; LDL-C=low-density lipoprotein cholesterol ; apoB=apolipoprotein B; hsCRP= high-sensitivity C-reactive protein; CV=Cardiovascular *No outcome data available

29. Health Behaviour and Lifestyle Changes BMI=Body mass index

30. What Works… Smoking Cessation • Address the issue clearly • Provide counseling, repetition • Offer medical options • Review aids and programs • Be supportive and non-judgmental (respect patient’s choice) • Consider what motivates patient (family, reasons, concerns) Alcohol Intake • Men: 2 drinks per day, not more than 14/week • Women : 1 drink a day, not more than 9 drinks/week • Should not be saved up to be had all at once! Lifestyle intervention is cornerstone therapy

31. What Works… • Weight Management • Provide realistic dietary options • Encourage physical activity • Establish multi-disciplinary team • Consider behavior modification(i.e. motivational enhancement) • Assess readiness and barriers to change • Physical Activity • Recommend 30-60 min of moderate activity every day of the week → slow start, gradual increase in frequency, duration, consistency • Consider exercise prescriptions Lifestyle intervention is cornerstone therapy

32. Lipid-Lowering Pharmacotherapy Rationale • Meta-analysis of statin trials show: 1.0 mmol/L decrease in LDL-C → 20% to 25% RR reduction Intensive LDL-C lowering therapy is associated with decreased CV risk Clinicians must exercise expert judgment and caution when implementing lipid-lowering therapy CV=cardiovascular; LDL-C=low-density lipoprotein cholesterol

33. Overview of Lipid-Lowering Medications • Statins: • Lower LDL-C • Bile Acid and/or Cholesterol absorption inhibitors: • May lower LDL-C • Fibrates: • May lower triglycerides, prevent pancreatitis in patients with extreme hypertriglyceridemia (>10 mmol/L) • Niacin: • May raise HDL-C, lower LDL-C LDL-C=low-density lipoprotein cholesterol, HDL-C=High-density lipoprotein cholesterol

34. Recommendations for Treatment LDL-C • Most patients will achieve target LDL-C levels on statinmonotherapy • Ezetimibe, cholestyramine or colestipol, niacin may be required in a minority of cases • In high-risk individuals, treatment should be started immediately HDL-C • Low HDL-C may pose no risk, depending on genetic type • Medications may not increase HDL-C to a clinically significant extent • Health behaviour interventions increase HDL-C LDL-C=low-density lipoprotein cholesterol ; HDL-C=high-density lipoprotein cholesterol

35. Recommendations for Treatment Triglycerides • No specific target level for high-risk • Lower triglyceride levels are associated with decreased CVD risk • Health behaviour interventions are first-line • Fibrates may prevent pancreatitis in patients with extreme hypertriglyceridemia (>10 mmol/L) Combination Therapy • Statin with niacin - For combined dyslipidemia and low HDL-C • Statin with a fibrate - Close patient follow-up required • Statin with omega-3 fatty acids - May lower triglycerides and help achieve TC/HDL-C ratio target in patients with moderate hypertriglyceridemia CVD=cardiocascular disease; HDL-C=high-density lipoprotein cholesterol; TC=total cholesterol

36. Safety and Monitoring ALT=alanine aminotransferase; ASA=acetylsalicylic acid (aspirin)

37. Referral and Advanced Testing Referral may be warranted in the following cases: • Drug intolerance or lack of response to therapy • Complex diagnostic cases • Lack of laboratory resources • Unexplained atherosclerosis • Extremes of lipoprotein disorders • Genetic testing required

38. William D. Treatment Outcomes Patient has moderate 10-year risk for CVD Patient was started on a statin therapy, and provided with lifestyle recommendationsincluding smoking cessation After one month of treatment, his lipids were within target and he had stopped smoking

39. Framingham Risk Score