Objectives

1. LIPIDSANDHEART DISEASEGLENN H. LYTLE, MDMEDICAL DIRECTOROKLAHOMA FOUNDATION FOR MEDICAL QUALITY

2. Objectives At the end of this presentation, attendees will: • Understand the role of lipids in both health and disease • Understand an evidence-based approach for lipid screening • Understand how controlling lipid levels may decrease the risk of heart disease

3. Lipids My first thoughts about what to present : • The importance of lipid levels in heart disease • The need for screening and subsequent treatment for abnormal lipid levels • The impact this can have on society My first thoughts about how to do the presentation : • Difficult at best • How do you make this at all interesting?

4. Lipids The word boring doescome to mind

5. Lipids I still remember some advice I once read: “The secret to a good presentation is to have a good beginning and a good ending, and to have the two as close together as possible.” George Burns So, this presentation will be short and hopefully to the point

6. Lipids I was a General Surgeon for 30+ years and now I am a Medical Director, not a Cardiologist so I am discussing this topic as I understand it

7. Lipids When I taught in Medical School, my favorite Dean would refer to me by saying: “Never in doubt, but occasionally wrong.”

8. Lipids • Heart disease is the number one killer of women and men in the United States. • Each year, more than a million haveheart attacks, and • A half million die • Abnormal lipid levels are a major risk factor for heart disease. • The more abnormal the lipid levels are, the greater the risk for heart disease

9. Lipids • Lipids include Cholesterol, Triglycerides, and Lipoproteins • Cholesterol is essential for the normal function of animal cells • It is a fundamental element of their cell membranes • It is a precursor of various critical substances such as adrenal and gonadal steroid hormones.

10. Lipids • Cholesterol and triglycerides are insoluble in water • They are transported in the plasma by lipoproteins • Lipoproteins are separated by density • They include low-density lipoproteins (LDL), and high-density lipoproteins (HDL). • Both LDL and HDL particles are variable and have more than just the function of carrying cholesterol. .

11. Lipids Schematic View of Lipoproteins

12. Lipids • The levels of lipids have a bell-shaped distribution in the general population • The definition of either a high or a low value of these substances is an arbitrary decision.

13. Lipids Total Cholesterol was identified in 1961 with the original Framingham study to be a risk factor for heart disease.

14. Lipids Elevated levels of low-density lipoproteins (LDL) are proven to be strongly related to a greater incidence of heart disease.

15. Lipids Elevated levels of plasma triglycerides are associated with increased risk of atherosclerotic heart disease.

16. Lipids • Elevated levels of HDL-C may be associated with decreased risk of atherosclerotic heart disease. • HDL-C has been known as the “good” cholesterol since higher levels are supposedly associated with a lower risk of heart disease but HDL-C may be a marker not the cause patients’ genetically predisposed to having high HDL-C do not have a lower risk of heart disease • The value of raising HDL-C is not conclusively proven

17. Lipids Simplistic View of HDL and LDL

18. Lipids • Biomarkers, such as apolipoprotein B (apoB) and apolipoprotein A (apoA), have been looked at with the aim of ‘fine tuning’ the risk predictions for heart disease • So far, measuring some of these other biomarkers has not been very helpful “it is probably not worth measuring them routinely for screening purposes”1 1. Dr. Emanuele Di Angelantonio quoted 6/19/2012 at: http://www.theheart.org/article/1417589/print.do

19. Lipids Role of other lipid biomarkers in screening Or as Einstein once stated: “Not everything that can be counted counts, And not everything that counts can be counted.”

20. Lipids • Less Simplistic View • Other particles attached to the lipoproteins may or may not play a role in atherosclerosis • This may explain why just knowing the LDL-C or the HDL-C may not be enough • The research is confusing and at times contradictory • This topic seems to be where much research • is focused today.

21. Lipids • Role of Non-HDL-C • Total Cholesterol – HDL-C = Non-HDL-C • Target goal for Non-HDL-C = Goal for LDL-C + 30 mg/dL • This can be measured on non-fasting samples • According to some, Non-HDL-C may be superior to LDL-C in predicting cardiac risk. • From Webinar: Residual CVD risk virtual education series, 5/22/2012 and 6/7/2012 at:http://www.cardiocarelive.com/

22. Lipids How do Lipids cause Heart Disease? • Elevated lipids build up in the walls of arteries – called atherosclerosis. • Arteries become narrowed - blood and oxygen delivery to the heart muscle is decreased. • If blockage results in not enough blood and oxygen reaching the heart muscle, one may suffer chest pain • If the blood and oxygen is cut off, the result is ischemia and may lead to heart damage - a heart attack. From: http://www.webmd.com/heart-disease/guide/heart-disease-lower-cholesterol-risk

23. Lipids Atherosclerosis

24. Lipids Screening “Half of cardiac deaths happen in people who have not previously had heart disease, so there is a limit to what can be achieved just with secondary prevention. So primary prevention is obviously needed.” 1 Screening allows us to intervene before a cardiac event This is the potential great benefit of screening 1. From: http://www.theheart.org/article/1401485.do?utm_campaign=newsletter&utm_medium=email&utm_source=20120517_EN_Heartwire

25. Lipids When To Start Screening ? Who To Screen? Lowering LDL-C early in life prevents three times more cardiovascular events than the same decrease of LDL-C later in life, but would be very expensive. So, what are the guidelines and recommendations for screening?

26. Lipids NIH Guidelines for Lipid Management in Children and Teens Released in 2011 • The guidelines recommend universal screening for all children (regardless of risk factors) between the ages of 9 and 11 years, and at least once between the ages of 17 and 21 years. • Routine screening is not recommended for children aged 0-2 years, and screening for 2-8 years and 12-16 years are based on family history. • When screening reveals abnormal lipid levels, two follow-up lipid panels should be completed within 3 months, at least 2 weeks apart. Mainstay of therapy in children is lifestyle and diet management. Guidelines at: Http://www.nhlbi.nih.gov/guidelines/cvd_ped/index.htm

27. Lipids Recent “push-back” on these screening guidelines for children – guidelines too aggressive may have been influenced by panel members' financial ties to drugmakers. The panel contended in rebuttal that payments covered costs of evaluating drugs did not influence their recommendations. • http://news.yahoo.com/docs-odds-over-kids-cholesterol-test-guidance-041316737.html

28. Lipids U.S. Preventive Services Task Force • Cardiovascular disease accounts for 50% all deaths in our country. • Good evidence that high levels of total cholesterol and LDL-C, are risk factors for coronary heart disease • Highest risk in those that have a combination of factors • Low levels of HDL-C may contribute to the risk. • The U.S. Preventive Services Task Force concluded the benefit of screening and treating lipid disorders outweighs any potential harm 1. in all men>35 years 2. women>45 years with risk factors for coronary artery heart disease From: : U.S. Preventive Services Task Force Guideline Summary NGC-6542 at http://www.uspreventiveservicestaskforce.org/uspstf08/lipid/lipidrs.htm

29. Lipids Final U.S.P.ST.F. recommendations: • Recommends screening all men aged 20 to 35 years for lipid disorders if they are at increased risk for coronary heart disease • Strongly recommends screening all men aged 35 and older for lipid disorders. • Recommends screening women aged 20 to 45 years for lipid disorders if they are at increased risk for coronary heart disease • Strongly recommends screening women aged 45 and older for lipid disorders if they are at increased risk for coronary heart disease • Optimal screening interval – recommends 5 years – this becomes less important after age 65 years. From: U.S. Preventive Services Task Force Guideline Summary NGC-6542 at http://www.uspreventiveservicestaskforce.org/uspstf08/lipid/lipidrs.htm

30. Lipids Total Cholesterol Below 200 mg/dL Desirable 200-239 mg/dL Borderline High 240 mg/dL and above High From: http://www.mayoclinic.com/health/cholesterol-levels/CL00001

31. Lipids LDL Cholesterol Below 100 mg/dL Optimal 100-129 mg/dL Near Ideal 130-159 mg/dL Borderline High 160-189 mg/dL High 190 mg/dL and above Very High From: http://www.mayoclinic.com/health/cholesterol-levels/CL00001

32. Lipids HDL Cholesterol Below 40 mg/dL for men Low – higher risk Below 50 mg/dL for women for heart disease 60 mg/dL and greater High – lower risk for heart disease From: http://www.mayoclinic.com/health/cholesterol-levels/CL00001

33. Lipids Non-HDL Cholesterol Below 130 mg/dL Ideal 131-159 mg/dl Near Ideal 160-189 mg/dL Borderline High 190 mg/dL and above High From: http://www.mayoclinic.com/health/cholesterol-levels/CL00001

34. Lipids Triglycerides Below 150 mg/dL Normal 150-199 mg/dL Borderline High 200-499 mg/dL High 500 mg/dL and above Very High From: http://www.mayoclinic.com/health/cholesterol-levels/CL00001

35. Lipids Interventions Non-Pharmacological Therapeutic Lifestyle Changes • diet • physical activity • weight management

36. Lipids Therapeutic Lifestyle Changes • Children – emphasis on saturated fat-restricted and cholesterol-restricted diets; encourage physical activity • Adults – diet low in saturated fat and cholesterol may lower LDL-C by 10-20% - especially if coupled with weight management and exercise • Weight loss also helps to lower Triglycerides • Exercise helps mostly by weight loss

37. Lipids Therapeutic Lifestyle Changes This naturally leads us to what is commonly referred to as: The Cardiologist’s Diet If it tastes good, Spit it out !

38. Lipids Therapeutic Lifestyle Changes • If overweight - reduce caloric intake for weight loss. • Follow diet and exercise program over time to determine effect. • Recommend diet low in saturated and trans fats • Recommend diet high in soluble fiber •Recommend Omega-3 fatty acids in patients with dyslipidemia or

39. Lipids Therapeutic Lifestyle Changes Smoking cessation Smoking associated with changes in the lipoprotein distribution that promote atherogenesis. Nicotine stimulates sympathetic nervous system activity resulting in elevation of plasma free fatty acids and very low density lipoproteins, and also reduces HDL-C). From: Health Care Guideline: Institute for Clinical Systems Improvement. Twelfth Edition October 2011. Found at: http://www.icsi.org/lipid_management_3/lipid_management_in_adults_4.html

40. Lipids Pharmacological When to intervene: Elevated LDL-C (goal <100) Elevated non-HDL-C (such as patients with high triglycerides but at target for LDL-C) Diabetic Dyslipidemia Very high triglycerides ? Low HDL-C – unclear of value of intervening

41. Lipids Pharmacological Basic Principles Effective diet implemented first. Decision to begin drug therapy based on evidence-based outcome data, possible side effects, and cost No evidence to support drug therapy in those at low risk for CHD. Lipid lowering has not decreased mortality, but has shown a 30% reduction in CHD events. From: Health Care Guideline: Institute for Clinical Systems Improvement. Twelfth Edition October 2011. Found at: http://www.icsi.org/lipid_management_3/lipid_management_in_adults_4.html

42. Lipids Pharmacological Basic Principles If elevated LDL-C a statin is the drug of choice . If elevated triglyceride a statin or a fibrate may be drug of choice. Currently, no medicine should be prescribed to just raise HDL-C.

43. Lipids Pharmacological Statins Inhibits HMG-CoAreductase (rate limiting step synthesis) Decreases LDL-C 18% - 55%, Triglycerides by 7% - 30%. Adverse Effects Statins are well tolerated No conclusive evidence of significant liver damage Serum creatine kinase need not be determined routinely. The incidence of myopathy is about 0.5% and dose-related.

44. Lipids Pharmacological Statins (continued) Debate - Statins may have less benefit in women - it is proven that statins in women prevent cardiovascular events but no proven benefit on all cause mortality for women 1 Statins over-time increase incidence of diabetes Role in memory loss is less conclusive Benefits outweigh risks even in patients at low cardiac risk. 2 1.Are statins less effective in women. 6/25/2012. Found at: http://www.theheart.org/article/1419505/print.do 2. Zoler ML. Meta-Analysis: Statins prevent first major vascular events. Family Practice News; Vol. 42, #11, p. 2. June 15, 2012

45. Lipids Pharmacological Statins (continued) Some research using a ‘polypill’ • Proposed to be given to all over the age of 50 • Four-in-one cocktail of medications, including anti-hypertensives and a statin • In a small study, the ‘polypill’ decreased blood pressure by 12 percent and lowered LDL-C by 39 percent. • Need larger trials to evaluate potential for risk and harm. 1 • http://theweek.com/article/index/230811/polypill-the-magic-pill-that-could-add-11-years-to-your-life

46. Lipids Pharmacological Resins (Cholestyramine Colestipol) Resins absorb bile acids and enhance excretion of bile acids resulting in increased metabolism of cholesterol into bile acids. Total cholesterol and LDL cholesterol decrease by 15%-30%. Adverse Effects Constipation, flatulence, nausea, and epigastric pain Deficiency of fat-soluble vitamins and folic acid Interactions: Digoxin, Thyroxine, Warfarin, Thiazides

47. Lipids Pharmacological Fibrates (Gemfibrozil Bezafibrate and Fenofibrate) Fibrates act through the nuclear peroxisome proliferator-activated receptor (PPAR) system that regulates lipid metabolism. Triglycerides decreased by 20% to 70%. If high, LDL cholesterol is also decreased. Adverse Effects : Abdominal and bowel irritation, myalgia, increase in creatine kinase and transaminase levels, and gallstones. Contraindicated if renal or hepatic dysfunction.

48. Lipids Pharmacological Niacin (nicotinic acid) B-complex vitamin, lowers LDL-C by 5-25% and triglycerides by 20-50%. Often added to a statin regimen. Adverse Effects Flushing, pruritus, gastrointestinal distress, blurred vision, and exacerbations of peptic ulcer disease. May cause hepatic toxicity.

49. Lipids Pharmacological Ezetimibe Inhibits cholesterol absorption in the small intestine by half - no affect on triglyceride absorption - effect is additive to statins - decreases LDL cholesterol by 18%. Adverse Effects Few side effects 4% low back pain

50. Lipids Revised from: http://www.empr.com/dyslipidemia-treatments/article/123682/