1. Sponsored by National Lipid Association Comprehensive Cardiometabolic Risk-Reduction Program Phase 2 2009

2. Mixed Dyslipidemia in the Patient With Cardiometabolic Risk Case Study

3. Overview 57-year-old white female presents for new patient examination – History of hypertension and borderline high cholesterol – Family history of heart disease (mother, age 57-years) and diabetes – Does not smoke and is not on hormone-replacement therapy Current medications: none On examination – Blood pressure: 139/84 mm Hg, BMI: 29.6, height: 65 inches, weight: 178 lbs, waist: 37 inches – No peripheral bruits, normal heart exam, and normal peripheral pulses BMI=body mass index

4. Laboratory Results TC: 219 mg/dL TG: 330 mg/dL HDL-C: 44 mg/dL LDL-C: 109 mg/dL Non–HDL-C: 175 mg/dL FPG: 108 mg/dL TSH: within normal limits ALT: 68 U/L AST: 46 U/L Case Study TC=total cholesterol, TG=triglycerides, HDL-C=high-density lipoprotein cholesterol, LDL-C=low-density lipoprotein cholesterol, FPG=fasting plasma glucose, TSH=thryoid-stimulating hormone, ALT=alanine aminotranferase, AST=aspartate aminotransferase

5. A.Low B.Intermediate C.High What is her Framingham risk for future coronary heart disease events in the next 10 years? ARS Question

6. Points Age: 57-years8 TC4 Nonsmoker0 HDL-C1 SBP2 Total points15 10-year risk=3% Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. Case Study Framingham Risk Score TC=total cholesterol, HDL-C=high-density lipoprotein cholesterol, SBP=systolic blood pressure

7. Patient Characteristics Meeting Metabolic Syndrome Criteria Waist: 37 inches TG: 330 mg/dL HDL-C: 44 mg/dL Blood pressure: 139/84 mm Hg Glucose: 108 mg/dL Case Study TG=triglycerides, HDL-C=high-density lipoprotein cholesterol

8. A.≤5% B.10% C.20% D.30% E.≥50% What is her risk for developing diabetes in the next 10 years? ARS Question

9. Prediction of Diabetes in ARIC: 9-Year Follow-Up Schmidt MI, et al. Diabetes Care. 2005;28:2013-2018. Decile of Estimated Risk Percent of Total Incident Cases of Diabetes Per Decile Percent of People in Each Decile Who Developed Diabetes 605040302010060504030201001102345678911023456789 Clinical information (waist, height, hypertension, blood pressure, family history, ethnicity, age) Fasting glucose Clinical information plus fasting glucose Clinical information, fasting glucose, high-density lipoprotein cholesterol, triglycerides

10. In your opinion, which of the following is the most useful motivator to get this patient to embark on a weight-reduction program? A. Reduce blood pressure B. Improve lipids C. Prevent diabetes D. Prevent heart attack ARS Question

11. 0 10 20 30 40 Cumulative Incidence of Diabetes (%) Years 01234 Placebo Lifestyle Metformin Weight loss Decrease in risk* 0.1 kg 2.1 kg31% 5.6 kg58% P<0.001 for each comparison *Decrease in risk of developing diabetes compared to placebo group Knowler WC, et al. N Engl J Med. 2002;346:393-403. Diabetes Prevention Program: Modest Weight-Loss Reduces the Incidence of New-Onset Diabetes in an At-Risk Population

12. Diabetes Prevention Program: Greater Weight- Loss Further Reduces the Incidence of New- Onset Diabetes *In the lifestyle intervention group over an average 3.2 years of follow-up Hamman RF, et al. Diabetes Care. 2006;29:2102-2107. -15-10505 20 15 10 5 0 Incidence Rate per 100 Person-Years Change in Weight from Baseline (kg) =Overall risk at the mean weight-loss*

13. Weight loss of 9–18 lbs (5–10%) would markedly reduce the risk of diabetes in a patient with these characteristics Clinical Pearl

14. Case Study What is her lipid phenotype? What would be the impact of losing 15 lbs with lifestyle modification?

15. Look AHEAD (Action for Health in Diabetes): Lipid Results Change from Baseline (%) Look AHEAD Research Group. Diabetes Care. 2007;30:1374-1383. * * * *P<0.001 -20 -15 -10 -5 0 5 10 LDL-CTGHDL-C Weight Loss Lifestyle Control

16. Which additional laboratory test would be helpful for cardiovascular risk assessment? A.hs-CRP B.Lp(a) C.Lp-PLA 2 D.apo B E.Lipoprotein particle size/number ARS Question hs-CRP=high-sensitivity C-reactive protein, Lp(a)=lipoprotein a, Lp-PLA 2 =lipoprotein-associated phospholipase A 2, apo B=apolipoprotein B

17. *Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. † Chobanian AV, et al. JAMA. 2003;289:2560-2572. ‡ American Diabetes Association. Diabetes Care. 2004;27:S36-S46. First-line therapy=weight reduction with lifestyle modification Treatment of “Metabolic Syndrome” or “Cardiometabolic Risk” According to guidelines from – Adult Treatment Panel III (ATP III)* – The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) † – American Diabetes Association (ADA) ‡

18. Dietary Approaches to Cardiometabolic Health MetabolicTarget Diets or Dietary Components LDL-CDiet portfolio: fats, fiber, stanols High TG, low HDL Weight loss, low glycemic index (GI) Blood pressureWeight loss, DASH diet Diabetes, prediabetes Weight loss, ↓ refined carbohydrates, ↑ fiber Metabolic syndrome Weight loss, Mediterranean, DASH diet, low GI, therapeutic lifestyle change (TLC) Regardless of what dietary approach is taken, all patients will benefit cardiometabolically by increasing their physical activity level

19. Comparison of Popular Diets Dansinger, et al. JAMA. 2005;293:43-53. Attrition and Mean Changes in Weight and LDL-C at 12 Months -3.3 -12.6 -2.1 -7.1 -3.2 -11.8 -3.0 -9.3 -12 -10 -8 -6 -4 -2 0 Weight, kg LDL-Cholesterol, mg/dL Mean Change Attrition (%) Atkins ® 48 Zone Diet ® 35 Weight 35 Watchers ® Ornish Program50 -14 Intent-to-Treat Population

20. Adherence and Weight Loss Are Paramount “Short-term metabolic studies support that metabolic risk factors are affected by carbohydrate restriction, but longer- term effectiveness trials suggest the degree of dietary adherence and associated weight losses, rather than diet type, are the key predictors of metabolic cardiac risk factor reduction.” Dansinger ML. Curr Diabetes Reports. 2006;6(1):55-63. Comparison of Popular Diets

21. The most effective diet is the one that the patient has the best chance of following Clinical Pearl

22. Additional Laboratory Tests hs-CRP: 6.5 mg/L (high risk: >3 mg/L) Lp-PLA 2 : 180 ng/mL (high risk: >200 ng/mL) Lp(a): 130 nmol/L (ULN: 75 mmol/L) apo B: 122 mg/dL Case Study hs-CRP=high-sensitivity C-reactive protein, Lp-PLA 2 =lipoprotein-associated phospholipase A 2, Lp(a)=lipoprotein a, apo B=apolipoprotein B

23. Reynolds Risk Score* 10-year risk of having a heart attack, stroke, or other heart disease event Case Study 6% *Includes high-sensitivity C-reactive protein and family history

24. What are her ADA/ACC lipid goals? A. LDL-C <100 mg/dL B.Non–HDL-C <130 mg/dL C.TG <150 mg/dL D.HDL-C >50 mg/dL E.All of the above F.A and C ARS Question LDL-C=low-density lipoprotein cholesterol, HDL-C=high-density lipoprotein cholesterol, TG=triglycerides

25. ADA=American Diabetes Association, ACC=American College of Cardiology, CVD=cardiovascular disease, CAD=coronary artery disease ADA/ACC Consensus Conference Report: Suggested Treatment Goals in Patients With Cardiometabolic Risk and Lipoprotein Abnormalities Risk Category Goals, mg/dL LDL-CNon–HDL-C apo B Highest-risk patients, including those with Known CVD or Diabetes +  1 other major CVD risk-factor* <70<100<80 High-risk patients, including those with No diabetes or known clinical CVD, but  2 other major CVD risk factors or Diabetes, but no other major CVD risk- factors* <100<130<90 *Other major risk factors (beyond dyslipoproteinemia) include smoking, Brunzell JD, et al. J Am Coll Cardiol. 2008;51:1512-1524. hypertension, and family history of premature CAD

26. Intervention The doctor explains that she has metabolic syndrome and high levels of – Non–HDL-C – apo B – hs-CRP – Lp(a) She was told – She has high-risk for diabetes and intermediate- risk for heart disease – With improvements in lifestyle and weight loss she could probably avoid both Case Study HDL-C=high-density lipoprotein cholesterol, apo B=apolipoprotein B, hs-CRP=high-sensitivity C-reactive protein, Lp(a)=lipoprotein a

27. “Retirement Plan” for Your Health A small investment in lifestyle on a daily basis will result in a large return in health dividends Clinical Pearl

28. Questions to Ask Before Prescribing Diet and Lifestyle Modification Are they ready/able to change their lifestyle? – If no, do not prescribe; focus on increasing awareness of their risk  This patient: “tried to lose weight in the past but nothing worked.” Closer questioning reveals patient used magazine or fad diets Is cost an issue? – Low cost options include Weight Watchers and the Cardiometabolic Support Network  This patient: Yes Do they eat for emotional reasons? – If yes, Overeaters Anonymous ® or working with therapist or registered dietitian will be more effective  This patient: Often, especially in the last year Do they prefer working in groups or individually? – Group: Weight Watchers. Individually: registered dietitian  This patient: Not sure

29. Do they have access to a track or a gym? – Need for a safe, accessible, and affordable place to be active  This patient: There’s a mall where she can walk Do they have Internet capability and do they feel comfortable on the Internet? – Internet weight-loss support programs like Livestrong TM.com, chat rooms, Weight Watchers ® online, CMSNonline, eDiets ®  This patient: Limited – not comfortable on the Internet Do they have time to plan and prepare food? – If yes, any option is viable. If no, meal replacements, Jenny Craig ®, use of lean frozen entrees  This patient: Yes, she is organized and likes to cook for her family Questions to Ask Before Prescribing Diet and Lifestyle Modification (cont.)

30. Patients may lack confidence if they’ve been unsuccessful at weight loss in the past, even if they’ve only followed fad diets that had little chance of working Reassure them that the prescribed changes will be a medically sound, comprehensive approach to managing their health Clinical Pearl

31. Intervention Goals were set for weight loss of 10 lbs (6%* body weight) with a program of diet and exercise – She was referred to a commercial weight-loss program – Advised to walk 30-minutes daily – Prescribed a statin *Per Diabetes Prevention Program Case Study

32. What are the benefits of starting statin therapy in a person of her age, with metabolic syndrome, elevated hs-CRP, and LDL-c less than 130 mg/dL? A.Decreases the rate of myocardial infarction B.Decreases the rate of stroke C.Decreases the rate of hospitalization for unstable angina D.All of the above ARS Question hs-CRP=high-sensitivity C-reactive protein, LDL-C=low-density lipoprotein cholesterol

33. Placebo 251/8901 Rosuvastatin 142/8901 Hazard Ratio (HR) 0.56, 95% Confidence Interval (CI) 0.46-0.69 P<0.00001 -44% 01234 0.00 0.02 0.04 0.06 0.08 Cumulative Incidence Follow-Up (years) Ridker PM,et al. N Engl J Med. 2008;359:2195-2207. MI=myocardial infarction, UA=unstable angina, CV=cardiovascular Although a little younger than the JUPITER population, this patient would most likely see similar benefits JUPITER: Primary Endpoint (MI, Stroke, UA/Revascularization, CV Death)

34. Intervention Follow-Up Patient calls the office – After 3 weeks, the patient leaves a commercial weight-program She felt uncomfortable working in a group setting – She called her insurance company, they will cover 4 visits with a registered dietitian Case Study

35. Update on Reimbursement for Medical Nutrition Therapy (MNT) With Registered Dietitian Most insurances cover MNT for diabetes and renal disease Medicare bill HR-6331 expands use of MNT by a registered dietitian to Medicare beneficiaries with risk factors for developing diabetes – January 1, 2009: bill being reviewed by CMS Medicare can cover preventive services that are USPSTF grade-A or grade-B recommendations American Dietetic Association is preparing an evidence- based report of the effectiveness/cost-effectiveness of MNT for dyslipidemia and hypertension with hopes of future coverage USPSTF=United States Preventive Service Task Force, CMS=Centers for Medicare & Medicaid Services

36. Initial Meeting With Dietitian Diet – Eats 3 meals, 2 snacks/day (~2100 calories/day) – Snacks on salty, crunchy foods (pretzels, crackers, chips) “during periods of stress” – ~30% of calories come from snacks and calorie-containing beverages – Wants to change diet, but not sure she has the “willpower” Activity – Began walking after MD told her to walk 30 minutes, 5 days/week – Currently walking 20 minutes, 3 days/week Psychosocially – Experiences stress often – Has supportive husband Case Study

37. Lifestyle Plan of Action To build patient’s self-efficacy,* dietitian will focus on small, consistent changes Goals should be set by both dietitian and patient 1.Diet 500/day caloric reduction from usual intake Focus on reducing snack foods; replace with crunchy, lower-calorie snacks and water 2.Emotional eating Over next 2-weeks, complete food-records with hunger scales to increase awareness of hunger, satiety, and reasons for eating 3.Physical activity Gradually increase walking to 30 minutes, 6 days/week Case Study *Self-efficacy is the belief that one can make and sustain lifestyle changes

38. 6–Week Interim Laboratory Data TC: 133 mg/dL TG: 185 mg/dL HDL-C: 41 mg/dL LDL-C: 55 mg/dL Non–HDL-C: 92 mg/dL ALT: 46 U/L AST: 37 U/L Glucose: 104 mg/dL Case Study TC=total cholesterol, TG=triglycerides, HDL-C=high-density lipoprotein cholesterol, LDL-C=low-density lipoprotein cholesterol, ALT=alanine aminotranferase, AST=aspartate aminotransferase

39. 3 Months: MD Follow-Up Visit The patient continues statin therapy – Lost 9 pounds and feels much better – Has decreased her snack-food intake, which has decreased her fat intake; now consumes more fruits/vegetables and water Feels more confident about maintaining these changes – Has realized and addressed some negative eating patterns – Walks 30 minutes, 5 days/week and usually 1x/weekend Physical examination – Blood pressure: 128/82 mm Hg, pulse: 72 bpm – Height: 65 inches, weight: 169 lbs – Waist: 34 inches, body mass index: 28.1 Case Study

40. 3 Months: MD Follow-Up Visit (cont.) Action plan – Encourage patient to continue statin and advise her that  HDL-C is related to caloric restriction/weight loss – Instruct her to increase her exercise Aim for 30-minutes/day on weekdays, more on weekends; goal of ≥180 minutes/week – Encourage her to continue dietitian visits Case Study HDL-C=high-density lipoprotein cholesterol

41. 6 Months: MD Follow-Up Visit The patient is continuing her statin therapy She seems a little embarrassed that she lost only 3 lbs in the last 3 months, but overall she feels well – She has lost 3 inches from her waist – She is consistently eating a lower-fat diet with greater intake of fiber, fruits, and vegetables – She walks 30 minutes, 5 days/week and for 1 hour, 1 day/weekend Physical examination – Blood pressure: 128/82 mm Hg, pulse: 72 bpm – Height: 65 inches, weight: 166 lbs – Waist: 34 inches, body mass index: 27.6 Case Study

42. 6-Month Laboratory Data TC: 135 mg/dL TG: 170 mg/dL HDL-C: 46 mg/dL LDL-C: 55 mg/dL Non–HDL-C: 89 mg/dL ALT: 43 mg/dL AST: 36 mg/dL Glucose: 101 mg/dL Case Study TC=total cholesterol, TG=triglycerides, HDL-C=high-density lipoprotein cholesterol, LDL-C=low-density lipoprotein cholesterol, ALT=alanine aminotranferase, AST=aspartate aminotransferase

43. 6 Months: MD Follow-Up Visit The patient is praised for her sustained weight loss and the improvements in lipids, glucose, and weight, as well as for her exercise and diet Action plan – Continue statin – Maintain or increase exercise Key to maintaining weight loss and metabolic benefits – Discuss use of meal replacements for weight maintenance, self monitoring – Encourage her to follow-up with dietitian as needed – Schedule follow-up appointment in 3 months Case Study

44. Redefine success – Patient’s image of success may be unrealistic and wanting to please MD – Weight loss and stabilization (12 lbs, 3 inches off waist), improved diet quality, and increased physical activity are successes that need reinforcement Tools to use if patients believe they are slipping – Monitor weight regularly – Complete diet records – Use meal replacements for 1 meal/day – Get support (friends, family, commercial or medical programs) Case Study

45. The Framingham score may underestimate risk in women, especially those with the metabolic syndrome The risk levels for CHD and diabetes may be very different in a patient with the metabolic syndrome – Avoidance of diabetes is a strong motivator for patients to lose weight Patients without diabetes or CVD, but with ≥2 major CV risk-factors need to be treated to goal – LDL-C: <100 mg/dL, non–HDL-C: <130 mg/dL, apo B: <90 mg/dL 5%–10% weight-loss can greatly improve a patient’s lipid profile and markedly reduce the risk of diabetes in a patient with IFG Key Learnings: Medical CHD=coronary heart disease, CVD=cardiovascular disease, LDL-C=low-density lipoprotein cholesterol, HDL-C=high-density lipoprotein cholesterol, apo B=, IFG=impaired fasting glucose CHD=coronary heart disease, CVD=cardiovascular disease, LDL-C=low-density lipoprotein cholesterol, HDL-C=high-density lipoprotein cholesterol, apo B=apolipoprotein B, IFG=impaired fasting glucose

46. Before prescribing general lifestyle advice, ask the patient questions to help you tailor the initial approach The most successful diet is the one to which the patient can adhere Lifestyle self-efficacy—the belief that one can make and sustain lifestyle changes—is often undermined by repeated failures in “dieting,” even though some of those attempts were not reliable approaches to weight loss Small, simple, consistent changes over time make the biggest difference Key Learnings: Behavioral