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©2012 MFMER | slide-0 Lipid Management: Role of Foods, Lifestyle, & Drugs for Management Steve Kopecky MD Preventive Cardiology Mayo Clinic Rochester MN.

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Presentation on theme: "©2012 MFMER | slide-0 Lipid Management: Role of Foods, Lifestyle, & Drugs for Management Steve Kopecky MD Preventive Cardiology Mayo Clinic Rochester MN."— Presentation transcript:

1 ©2012 MFMER | slide-0 Lipid Management: Role of Foods, Lifestyle, & Drugs for Management Steve Kopecky MD Preventive Cardiology Mayo Clinic Rochester MN

2 ©2012 MFMER | slide-1 Disclosure : Conflict of Interest Stephen L Kopecky Research Grants: NIH/NHLBI, Mayo Clinic, Genzyme, Sanofi, Genetech, Regeneron Consultant: Amer Soc for Prev Card- President (2012-2014) Acad of Clin Research Professionals: Chair, Global Certification Exam Committee Applied Clinical Intelligence: DSMB Chair Prime Therapeutics – Formulary Committee

3 ©2012 MFMER | slide-2 Learning Objectives 1.Appreciate the different lipid biomarkers and their role in assessing risk from hyperlipidemia 2. Understand lifestyle issues involved with hyperlipidemia 3. Learn the beneficial effects and side effects of drug therapy for hyperlipidemia

4 ©2012 MFMER | slide-3 Secondary CV Prevention: US 2011 Frieden and Berwick N Engl J Med 2011; 365:e27 September 29, 2011 In patients with Hyperlipidemia: 1/3 have adequate treatment Million Hearts Campaign

5 ©2012 MFMER | slide-4 35 Seven Countries Study: Relationship of Serum Cholesterol to Mortality Adapted from Verschuren WM et al. J Am Med Assoc 1995;274(2):131–136 Serum total cholesterol (mmol/L) 30 25 20 15 10 5 0 Death rate from CHD/1000 men 2.603.253.904.505.155.806.457.107.758.409.05 Northern Europe United States Southern Europe, inland Southern Europe, Mediterranean Japan Serbia

6 ©2012 MFMER | slide-5 What Diet Components Decrease Risk for MI ? Iqbal et al INTERHEART Study:Dietary patterns and risk of MI AHA Epi Conf Orlando 2007 Western Diet: Fried foods, salty snacks, and meat Association w/ MI Increases Oriental Diet: Tofu, pickled foods, soy and other sauces Prudent Diet: Dairy, fruits, vegetables, nuts Neutral Decreases INTERHEART Study: 55 countries All inhabited continents of the world

7 ©2012 MFMER | slide-6 CAD Associated with Daily Replacement (1 serving) of Protein Source Bernstein Circulation. 2010;122:876-883 Replacing 1 serving per day of red meat with 1 serving per day of fish was associated with a 24% (95% CI, 6% to 39%) lower risk High Fat Dairy for Fish Nurses Health Study 27 Year Follow-up RRs and 95% CIs Fish for Red Meat Nuts for Red Meat Beans for Red Meat 0.4 0.6 0.8 1 1.2 1.4 1.6 Hazard Ratio Poultry for Red Meat Less Heart Disease More Heart Disease

8 ©2012 MFMER | slide-7 Low Carbohydrate Diets : Mortality Effect ? Fung Low Carbohydrate Diets and All-Cause and Cause-Specific Mortality Ann Int Med 2010;153:289-298 All Cause Mortality (HR) Any Low Carb Diet 1.12 ( 95% CI 1.01-1.24) Health Professionals Follow Up Study n=51,529 : 20 Yr follow-up Animal Low Carb Vegetable Low Carb p<0.001 p=0.051 p=0.029 Low Carb Diet : Hi Animal – Increased Total/CV Mortality Hi Vegetable – Decreased Total/CV Mortality

9 ©2012 MFMER | slide-8 Block cholesterol Ezetimibe absorption Reduce hepatic Statin cholesterol synthesis Increase bile Cholestyramine acid losses Reducing Heart Disease Risk: Lowering Cholesterol Plant Sterols/Stanols 1.6 / 3.4 gm/day Oat b-glucan Viscous Fiber Psyllium Nuts Almonds 42 g Annals Int Med 2005;142:793-795 Drug Effect Source of plant sterols monounsaturated fats, vegetable protein Diet Soy 0.8 Oz

10 ©2012 MFMER | slide-9 Portfolio Diet : Per 1000 kcal of Diet Lower LDL ~15% over 6 months Plant sterols- 0.94 g in margarine; Viscous fibers- 9.8 g from oats, barley, and psyllium; Soy protein-22.5 g as soy milk, tofu, and soy meat ; Nuts - 22.5 g (including tree nuts and peanuts) ¾ of an ounce Consumption of peas, beans, and lentils encouraged. 1.Jenkins et al. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum Lipids and C-reactive protein. JAMA. 2003;290(4):502–510 2.Jenkins et al JAMA.2011;306(8):831-839. doi: 10.1001/jama.2011.1202

11 ©2012 MFMER | slide-10 Supplements to Reduce LDL: Reduce Intestinal Cholesterol Absorption Product How much to take Plant stanols 800 - 4,000 mg/day divided and taken with meals (2 to 3 tsps Benecol Light Spreads or 2 to 4 Smart Chews) Plant sterols 800 mg to 6 gms/day, divided and taken with meals (= 2 tsps Promise activ Spread or -2 servings of SuperShots) Plant stanol, 900 mg (usually found in 450 mg caplets) sterol supplements two times per day with a meal (sitostanol, such as Benecol Light Spreads, Smart Chews) (Promise activ Spreads, SuperShots) (CholestOff and Centrum Cardio)

12 ©2012 MFMER | slide-11 Product How much to take Oat bran Up to 150 g of whole oat products per day (about equal to eating 1½ cups of cooked oatmeal) Supplements to Reduce LDL: Reduce Cholesterol Production in Liver (oatmeal,oat bran products; look for oat bran or whole oats as ingredient on label) Do not use Red Yeast Rice – Contains lovastatin Not regulated adequately Dosage variable Instead-Use generic (low cost) statin

13 ©2012 MFMER | slide-12 Product How much to take Blonde psyllium 5 g seed husk twice per day, or 1 serving of product such as Metamucil Supplements to Reduce LDL : Increase Loss of Cholesterol via Bile Acid into Intestine (seed husks and products such as Metamucil)

14 ©2012 MFMER | slide-13 Lipid Management Drugs and their Effects on Lipids/Lipoprotein NCEP/ATP III 2001 % Fish Oil : EPA and DHA = 4-6 gms/day

15 ©2012 MFMER | slide-14 95% UL Risk ratio RR (95% CIPI 2 (%) Statins (n=35)0.87 (0.81-0.94)0.0530 0-54 Fibrates (n=17)1.00 (0.91-1.11)0.0133 0-63 Resins (n=8)0.84 (0.66-1.08)0.86 0 0-68 Niacin (n=2)0.96 (0.86-1.08)0.81 0 n-3 FA (n=14)0.77 (0.63-0.94)0.015314-75 Diet (n=18)0.97 (0.91-1.04)0.1923 0-56 95% UL Risk ratio RR (95% CIPI 2 (%) Statins (n=35)0.87 (0.81-0.94)0.0530 0-54 Fibrates (n=17)1.00 (0.91-1.11)0.0133 0-63 Resins (n=8)0.84 (0.66-1.08)0.86 0 0-68 Niacin (n=2)0.96 (0.86-1.08)0.81 0 n-3 FA (n=14)0.77 (0.63-0.94)0.015314-75 Diet (n=18)0.97 (0.91-1.04)0.1923 0-56 Favors Tx Favors ctrl Effect of Different Anti-lipidemic Agents and Diets on Overall Mortality Effect of Different Antilipidemic Agents and Diets on Mortality: A Systematic Review Studer et al Arch Intern Med. 2005;165:725-730. AIM-HIGH : Niacin no benefit once LDL reduction acheived

16 ©2012 MFMER | slide-15 Oscai et al AJC 1972; 30:775-780 Normalization of Serum Triglycerides by Exercise 7 Men – Sedentary then 4 days of exercise, 3 to 4 miles in approximately 40 minutes. Ask about : White –bread, rice, pasta Soft drinks Juices Sports drinks Alcohol

17 ©2012 MFMER | slide-16 Statins : LDL Reduction From Starting to Max Dose Illingworth Medical Clinics of North America- Volume 84, Issue 1(January 2000);23-42 Fluva Prava Lova Simva Atorva Rosuva 20-80 20-40 20-80 20-80 10-805-40 Dose Increase : 4x 2x 4x4x 8x 8x

18 ©2012 MFMER | slide-17 Are Statins of Benefit in Primary Prevention ? Efficacy and safety of more intensive lowering of LDL cholesterol : meta-analysis of 170 000 participants in 26 randomised trials Lancet 2010; 376: 1670–81 RR= Rate ratios CHD=coronary heart disease Effects on major vascular events at 1 Yr per 1·0 mmol/L reduction in LDL C 99% CI 95% CI Statin/More Better Controls/Less Better LDL cholesterol : 1.0 mmol/L reduction = 38 mg/dl reduction

19 ©2012 MFMER | slide-18 Statins for Primary Prevention of CV Disease Study ACAPS 1994 Adult Japanese MEGA AFCAPS/TexCAPS 1998 ASPEN 2006 CARDS 2004 KAPS 1995 PREVEND IT 2004 WOSCOPS 1997 Total (95% CI) Statins for the primary prevention of cardiovascular disease (Review) 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Favors Statin Control.2.5 1 2 5 Total Statin Placebo n 14,058 14,103 Risk Ratio 0.84 [0.73,0.96] Total Mortality Does not include JUPITER, which also showed decrease in Total Mortality

20 ©2012 MFMER | slide-19 Arch Intern Med. 2010;170(12):1024-1031 Statins and All-Cause Mortality in High-Risk Primary Prevention: Benefit by Baseline Age Age explained ~70% of variation in events between groups 11 Trials p<.001 Would you send this patient to the cath lab if they had a STEMI tomorrow ?

21 ©2012 MFMER | slide-20 Proposed Definitions for Statin-Related Myopathy Clinical EntityACC/AHA 1 NLA 2 FDA 3 MyopathyGeneral term- any disease of muscles Sx of myalgia & CK > 10x ULN CK > 10x ULN MyalgiaMuscle ache/weakness w/o Hi CK NA MyositisMuscle Sx w/ Hi CKNA RhabdomyolysisMuscle Sx w/ CK > 10x ULN & Hi Creat (Us w brown urine) CK > 10,000IU/L or CK> 10x ULN & Hi Creat or IV Hydration CK> 50x ULN & organ damage 1.Joy Ann Intern Med 2009;150:858-868 2.ACC/AHA/NHLBI clinical advisory on the use and safety of statins. J Am Coll Cardiol. 2002;40:567-72. 3.NLA Am J Cardiol. 2006;97:89C-94C 4.Sewright Statin myopathy: incidence, risk factors, and pathophysiology. Curr Atheroscler Rep. 2007;9:389-96

22 ©2012 MFMER | slide-21 Statin Intolerance: Definition Unable to take statin to get to goal due to symptoms of intolerance Most common symptom : muscle aches, weakness, cramps

23 ©2012 MFMER | slide-22 Statins: Side Effects in Clinical Trials – METEOR (Rosuva 40) Placebo 12.1 7.1 10.3 2.8 2.1 2.8 1.1 0.7 3.6 1.1 46% Age 57 Yrs; n=984 MM=Muscle; Ext=Extremity Crouse et al METEOR Trial JAMA. 2007;297(12)1344-1353 Event (%) Rosuva Placebo Musculoskeletal Side Effect or Withdrew Consent 75% 72% Arthralgia10.1 Back Pain8.4 MM Spasms3.7 Tendinitis3.3 Ext Pain2.9 Shoulder Pain2.0 Neck Pain1.6 Arthritis1.6 Stiffness1.1 MM Weak0.7 Total48% Event (%) Rosuva Myalgia12.7 Exclusion Criteria: Statin Intolerance

24 ©2012 MFMER | slide-23 Run-in (10 weeks), if side-effects to treatment - then do not randomize Heart Protection Study Collaborative Group European Heart Journal (1999) 20, 725–741 At 25 months - no difference in myalgias. 81% still on simvastatin or placebo Heart Protection Study Simvastatin 40 mg vs Placebo n=20,536 patients randomized 32,145 pre-randomization run-in phase 63,603 attended study screening clinics 32% of original patient pool randomized How was the study performed ?

25 Any region 1.33 (1.06-1.67) 0.96 (0.81-1.15) Neck/upper back 0.88 (0.53-1.45) 0.81 (0.61-1.08) Upper extremities 0.82 (0.49-1.35) 0.84 (0.62-1.15) Lower back 1.47 (1.02-2.13) 1.05 (0.81-1.37) Lower extremities 1.59 (1.12-2.22) 0.96 (0.76-1.22) *Adjusted :age, sex, race, smoking, self-reported health, CHD, DM, cancer, Sys BP, BMI, TC,ABI Buettner et al American Journal of Medicine (2012) 125, 176-182 Statin use was associated with a higher prevalence of musculoskeletal pain in the lower extremities, among individuals without arthritis Body Region W/O Arthritis (n=5170) W/ Arthritis (n=3058) Prevalence of Statin Use on Self Reported Musculoskeletal Pain: NHANES

26 Risk Factors for Statin Intolerance: Patient-related Patient Advanced age (>80) Female sex Low BMI Multisystem disease (particularly liver, kidney, or both) Hypothyroidism (untreated) Excess Alcohol Grapefruit or Cranberry juice consumption (_1 qt/d) Vigorous activity Major surgery or trauma Intercurrent infections History of myopathy on another lipid-lowering therapy History of creatine kinase elevation Unexplained cramps Family history of myopathy on lipid-lowering therapy Family history of myopathy (polymorphisms of P450 isoenzymes or drug transporters, inherited defects of muscle metabolism, traits that affect oxidative metabolism of fatty acids)

27 Risk Factors for Statin Intolerance: Treatment-Related High-dose statin therapy Interactions with concomitant drugs (esp P450 Pathway) Amiodarone Antifungals ( Azoles) Cyclosporine Fibrates Macrolide antibiotics Nefazodone Nicotinic acids Protease inhibitors Thiazolidinediones Verapamil Warfarin

28 Differential Diagnosis of Myopathy or Creatine Kinase Elevations Not Due to Lipid-Lowering Therapy Muscle symptoms Physical exertion (deconditioned) Viral illness Vitamin D deficiency Hypo- or hyperthyroidism Cushing syndrome or adrenal insuffic Hypoparathyroidism Fibromyalgia Polymyalgia rheumatica Polymyositis Systemic lupus erythematosus Tendon or joint disorder Trauma Seizures or severe chills Peripheral arterial disease Medications Glucocorticoids Antipsychotics Antiretroviral drugs Illicit drugs (cocaine or amphetamines) Creatine kinase elevations Physical exertion Hypothyroidism Metabolic or inflammatory myopathies Alcoholism Neuropathy or radiculopathy Ethnicity (black Americans may have elevated baseline creatine kinase levels) Idiopathic hyperCKemia Seizure or severe chills Trauma Medications Illicit drugs (cocaine or amphetamines) Antipsychotics For patients who present with cramping in their calves or thighs. Refers to elevated creatine kinase level without another cause identified

29 Routine monitoring of liver enzymes in the blood is no longer needed FDA Advisory : Statins Feb 28, 2012 People being treated with statins may have an increased risk of raised blood sugar levels and the development of Type 2 diabetes Some medications interact with lovastatin and can increase the risk of muscle damage. Cognitive impairment ( memory loss, forgetfulness and confusion) has been reported by some statin users

30 Shepardson et al Arch Neurol. 2011 Nov;68(11):1385-92. Cholesterol level and statin use in Alzheimer disease Blood-Brain Barrier Permeability of Major Statins NamePermeability LovastatinYes PravastatinNo FluvastatinNo SimvastatinYes AtorvastatinDisputed CerivastatinDisputed RosuvastatinNo

31 Statin Use and Risk of DM in Postmenopausal Women in the Women's Health Initiative Culver et al Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women in the Women's Health Initiative Arch Intern Med. 2012;172(2):144-152.

32 Are Statins Associated with Dementia ? Statin Ever User Statin Never User Beydoun et al J Epidemiol Community Health 2011;65:949-957 doi:10.1136/jech.2009.100826 Ageing Research report Statins and serum cholesterol's associations with incident dementia and mild cognitive impairment Dementia-free survival probability

33 ©2012 MFMER | slide-32 Take Home Messages: Integrating lifestyle and diet changes with medical Rx key to lipid management Dietary changes and exercise are best initial steps to treating hypertriglyceridemia Statins and fish oil are the only medical Rx shown to consistently lower CV mortality For primary prevention, elderly patients derive most benefit from statin therapy. Statin intolerance is more common than previously thought and must be addressed

34 Thank you for your attention !


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