1. Which one of the following patients does not need to be screened for hyperlipidemia:

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1 Questions:

2 1. Which one of the following patients does not need to be screened for hyperlipidemia: a) Diabetes mellitus b) Hypertension c) Family history of premature coronary disease (first degree relatives: male < 60, female < 70) a) Chronic Kidney Disease

3 2. 75-year-old gentleman wants to know what his lipid profile is and you measure it. He is hypertensive with diabetes, and has a LDL cholesterol of 4.0mmol/L. What would you do with this information? a) Treat the diabetes in the hypertension b) Start a statin c) Go with dietary management first

4 3. Benefits of lowering lipids in the elderly Clinical Trials: Limited clinical trial information but subgroup analysis of trials suggest similar benefit from lipid lowering therapy as younger patients 4S included ten 21 patients > 65 years of age, and with similar reduction there was all cause mortality decrease by 34%, decrease coronary events by 34% CARE included 1283 patients aged 65 to 75. For every 1000 treated 225 hospitalizations and 207 events would be prevented Heart protection study showed criteria at entry of 40 to 80 years, and was similar in patients above and below 65 Pulled data from 19,768 patients showed relative risk of cardiac events comparable for patients > 55, 55 to 64 and 65 to 75

5 3. Benefits of lowering lipids in the elderly Clinical Trials: Subgroup analysis from two primary prevention trials AFCAPS/TexCAPS and ASCOT-LLA similar affects on clinical end points in younger and older PROSPER 5804 men and women aged 70 to 82 reduce risk of coronary death MI and fatal or non-fatal stroke Clinical benefits seen as early as six months to 2 years No significant differences in side affects versus the young Decision in an elderly individual needs to be individualized based on chronological and physiologic age One study of 500 patients aged 81 and QA Infarction, showed only 5% were treated with lipid lowering drugs

6 4. Is there data showing the benefits of treatment for women with hyperlipidemia? Yes No Uncertain

7 5. Management of hyperlipidemia in Women Cardiovascular disease is the leading cause of death in women Coronary disease mortality is higher in women compare to men Total cholesterol to HDL-C ratio is the most predictive of cardiovascular events Data from prospective primary prevention studies are lacking but current practices to treat high-risk women in the same fashion as men.

8 5. Management of hyperlipidemia in Women Meta-analysis of clinical studies, including women, showed that lipid altering medications has similar affects in women and men on lipid profile and reduction CHD. Secondary Intervention trials showed compared to men, women have increased regression of coronary lesions and similar improvement in survival, e.g., 4S, CARE, REVERSAL Diabetes is an important predictor of CHD risk, and women with Type 2 diabetes without infarction were the same risk for MI, and mortality is non-diabetic patients with prior MI

9 6. Genetic risk in treating hyperlipidemia Subheading: When considering the Framingham, risk or positive family history of premature coronary disease should: a) not change the 10 year risk b) triple the 10 year risk c) double the 10 year risk d) quadruple the 10 year risk

10 7. In an assessing risk of coronary artery disease I utilize hscrp in all patients: a) yes b) no c) I would have no idea what to do with the information

11 8. Homocysteine patients with atherosclerotic disease should be treated aggressively with vitamin therapy to decrease homocysteine: a) yes, the evidence is clear b) no, the evidence is clear c) I will until more information is available

12 9. Which of the following groups may not require aggressive therapy to decrease LDL below to: a) patients with known coronary atherosclerosis b) patients with known cerebrovascular disease c) patients with chronic renal failure d) all diabetics

13 10. Is there a difference between statins: a) yes, there is clear added benefit beyond lipid lowering for some but not all statins b) I don t believe there is a difference, and targets are the most important

14 Canadian Cardiovascular Society Position Statement: Guidelines for the Diagnosis and Treatment of Dyslipidemia and Prevention of Cardiovascular Disease Canadian Journal of Cardiology 2006; Ruth McPherson MD, PhD, Jiri Frohlich MD, George Fodor MD, & Jacques Genest MD Primary Review Panel Steven Grover MD, Norman Campbell MD, Rafik Habib MD, Stewart Harris MD, Heather Arthur Secondary Review Panel Peter Bogaty MD, Dominic Ng MD PhD, André Carpentier MD, Robert A. Hegele MD, Ehud Ur, John Mancini MD, Glen J. Pearson PhD, Milan Gupta MD

15 2006 Lipid Guidelines collaboration with the Canadian Cardiovascular Society establishment of primary and secondary review panels adherence to the AGREE principles for guideline formulation all recommendations evidence based and graded harmonization with CDA & CHEP lipid guidelines.

16 Primary Prevention Lifetime risk of CAD is 1 in 2 for men and 1 in 3 for women Lloyd-Jones DM. Lancet 1999 Short-term vs long-term risk

17 CAD risk factors Conventional CAD risk factors are present in 80 to 90% of patients who develop CAD. Amongst the best predictors of long-term risk is the TC/HDL-C ratio. 40 y old Framingham man TC/HDL-C ratio of > year cumulative CAD risk of 20.1% TC/HDL-C ratio < year cumulative CAD risk of 5.4%

18 Screening-1 Physicians should screen every 1 to 3 years, with a full lipid profile (after a 9-12 h fast) and other investigations as indicated, all men 40 years or older and all women who are post-menopausal and/or 50 years or older. Children should be investigated with a fasting lipid profile screened if there is a family history of a monogenic lipid disorder, such as familial hypercholesterolemia or chylomicronemia.

19 Screening - 2 Adult patients with the following additional risk factors should be screened at any age: Diabetes mellitus Current or recent (within last year) cigarette smoking Hypertension Abdominal obesity (WC > 102 cm/88 cm; lower in E Asians) Family history of premature CAD (esp 1 o relatives: M<55 y; F< 65y) Manifestations of hyperlipidemia (e.g. xanthelasma, xanthoma, arcus) Exertional chest discomfort, dyspnea, erectile dysfunction Chronic kidney disease, SLE Evidence of possible atherosclerosis e.g. arterial bruit

20 Cardiovascular Disease Risk Evaluation Framingham risk equations Ten-year hard end-points (death/mi) Age Cholesterol (Age adj.) Smoking (Age adj.) HDL-C Blood Pressure (treated or not) Calculate score, risk stratify

21 FRS: 10-Year Risk Points 10-year Risk How accurate is Risk prediction in This group? Low Risk } } Medium Risk High Risk >17 >30

22 Beyond Framingham Genetic risk hscrp HbA1c Lp(a) Apo B Exercise capacity Noninvasive assessment of atherosclerosis

23 Genetic Risk Khot & Topol, JAMA ,458 patients in 14 RCTs 15% women & 20% men with events had no risk factors Greenland & Wilson, JAMA ,000 subjects followed yr 10% of those with fatal CAD events who were 40-59y at baseline had no CAD risk factors Lloyd-Jones, O Donnell et al JAMA 2004 Parental history of early CAD 2X increase in CAD risk after correction for all conventional risk factors Framingham 10 year risk should be doubled in patients with a positive family history

24 FRS: 10-Year Risk Points 10-year Risk Multiply calculated 10 year risk by 2 if family history of premature CAD Low Risk } } Medium Risk High Risk >17 >30

25 hscrp Adds Prognostic Information at all Levels of LDL-C C and at all Levels of the Framingham Risk Score < >3.0 < >3.0 Relative risk C-Reactive Protein (mg/l) Multivariable relative risk 1 C-Reactive Protein (mg/l) Real 3 10 year risk for patients in the intermediate risk category varies by 2- fold 2dependent on plasma hscrp < >160 Framingham estimate of 10-year risk (%) LDL cholesterol (mg/dl) N Engl J Med. 2002;347:1557.

26 hscrp hscrp measurement may be useful in the further definition of CAD risk for patients in the intermediate risk category (FRS of 10-19%). (Class IIb; Level C)

27 HOPE-2 Lonn E et al NEJM 2006

28 Homocysteine Treatment with vitamin supplements to lower homocysteine concentrations is not currently recommended. (Class III; Level A)

29 Measurements of Glycemia Fasting plasma glucose (FPG) should be measured every 1 to 3 years in adults over the age of 50 years and in younger adults with abdominal obesity and/or a family history of type 2 diabetes. Measurement of HbA 1c is not recommended unless FPG is elevated. Moderate elevations in HbA 1c may indicate increased CAD risk. (Class IIa; Level C)

30 HbA 1c Strongly Predicts CVD Events in the Absence of Known Diabetes < 5% 5-5.4% % 6-6.4% % > 7.0% known men women diabetes European Prospective Investigation into Cancer in Norfolk; 4662 M/5570 F; y 7 yr follow-up (806 CVD events, 506 deaths) Ann Intern Med 2004;141:413-20

31 Noninvasive Assessment of CVD Risk The following noninvasive investigations may be useful for patients in the intermediate risk category to detect subclinical atherosclerosis and/or further define future CVD risk: Ankle Brachial Index (ABI) (Class IIa, Level B) Carotid ultrasound (Class IIa, Level B) Graded exercise testing (GXT) (Class IIa, Level B)

32 10 yr Risk of CAD for Subjects in any Risk Category may be Modified on Basis of GXT % Framingham 10 yr normal GXT abnormal GXT risk of coronary event Greenland P NEJM 2003;349: after Gibbons LW Am J Cardiol 2003;86:53-3

33 New Targets in Secondary Prevention Data from RCTs TNT IDEAL REVERSAL/ASTEROID (surrogate endpoint)

34 LDL-Cholesterol Reduction & CVD Events With CVD event (%) S-Pl TNT Entry Lipid-Pl 4S-Rx HPS Placebo GREACE-Pl Lipid-Rx CARE-Pl CARE-Rx ALLHAT-Pl TNT-10 ALLHAT-Rx HPS-Rx GREACE-Rx TNT LDL-cholesterol [mmol/l]

35 High Risk High risk is defined as patients with diagnosis of atherosclerotic vascular disease or a calculated > 20% ten year risk of CHD death or non fatal MI Most people with type 1 or type 2 diabetes should be considered at high risk for vascular disease (Class 1; Level A) However, some people with diabetes may not be, such as younger patients with shorter duration of disease and without complications of diabetes and without other risk factors (Class 2b; Level C) Primary target: LDL-C < 2.0 mmol/l (Class 1; Level A) Secondary target: TC/HDL-C < 4.0 (Class 2 a; Level C) Optimally lower LDL-C by at least 50%.

36 Risk Categories & Target Levels Risk Level Treat to: LDL-C TC/HDL-C Ratio High >20% <2.0 & <4.0 Treat If: LDL-C TC/HDL-C Ratio Moderate 10-19% >3.5 or >5.0 Low <10% >5.0 or >6.0 May initiate treatment at lower or higher levels if family history or other investigations indicate elevated or reduced risk Optimal plasma apo B concentrations are < 1.2 g/l in low risk patients, <1.05 g/l in intermediate risk and < 0.85 g/l in high risk patients.

37 Drug Treatment A. Achieve LDL-C target. 1) Start with statin (Class 1a; Level A) 2) Adjust dose (Class 1a; Level A) or add second agent (ezetimibe or resin) as necessary to achieve goals (Class 2a, Level C) B. Adjust therapy to achieve TC/HDL-C target 1) Intensify lifestyle therapy 2) Increase statin dose 3) Add second agent (e.g. niacin) (Class 2a, Level B)

38 Adequacy of Treatment The reduction in CAD and stroke events and overall cost-effectiveness of therapy is proportional to the decrease in LDL-cholesterol and increase in HDLcholesterol. After 5 to 10 years of treatment, a reduction in LDL-C of 1.8 mmol/l (~40%) could reduce CAD events by approximately 60% Thus, for those individuals who are candidates for statin therapy, treatment to lower LDL-C by at least 40% is generally appropriate.