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Lifestyle Modifications for Cardiovascular Prevention: The Mediterranean Diet, Fish, Oils and other Supplements: should we recommend them? Outline • What are the benefits of the • • Mediterranean diet? Should we advise our patients to take fish oil supplements? What are the risks and benefits of complementary/alternative medications? “Father of the low carb diet” Herbivorous animals do not grow fat easily, at least until age has reduced them to a state of inactivity; but they fatten very quickly as soon as they begin to be fed on potatoes, grain, or any kind of flour. ... The second of the chief causes of obesity is the floury and starchy substances which man makes the prime ingredients of his daily nourishment. As we have said already, all animals that live on farinaceous food grow fat willy-nilly; and man is no exception to the universal law. Brillat-Savarin, Jean-Anthelme (1825). The Physiology of Taste. Penguin Books. Mediterranean Diet Paradox • People living in Mediterranean • countries tend to consume relatively high amounts of fat, they have far lower rates of cardiovascular disease than in countries like the United States, where similar levels of fat consumption are found. A parallel phenomenon is known as the “French Paradox” Mediterranean Diet • Modern nutritional recommendation • inspired by the traditional dietary patterns of coastal regions of Spain, southern Italy, Crete, and coastal Greece in the 1960s The most commonly version of the Mediterranean diet was presented by Dr Walter Willett of Harvard University's School of Public Health in the mid-1990s USDA Center for Nutrition Policy and Promotion 2005 Mediterranean Diet • • • • • • • • Abundant plant foods (legumes), fresh fruit as the typical daily dessert Olive oil is the principal source of fat Dairy products (principally cheese and yogurt) Fish and poultry consumed in low to moderate amounts Zero to four eggs consumed weekly Red meat consumed in low amounts Wine consumed in low to moderate amounts Total fat: 25 - 30%, < 8% Saturated fats Mediterranean Diet: Possible Mechanisms for Beneficial Effects • • • • Low in saturated fat, high in monounsaturated fat and dietary fiber Olive oil : very high levels of monounsaturated fats (oleic acid) Epidemiological studies suggests that a higher proportion of monounsaturated fats in the diet is linked to a reduction in coronary heart disease risk Clinical data shows that antioxidants in olive oil provide additional heart health benefits: • LDL cholesterol reduction • anti-inflammatory • anti-hypertensive effects Covas, M.I., 2007;Pharmacol. Res. 55 (3): 175–86 359:229-241 July 17, 2008 Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet • Iris Shai, R.D., Ph.D., Dan Schwarzfuchs, M.D., Yaakov Henkin, M.D., Danit R. Shahar, R.D., Ph.D., Shula Witkow, R.D., M.P.H., Ilana Greenberg, R.D., M.P.H., Rachel Golan, R.D., M.P.H., Drora Fraser, Ph.D., Arkady Bolotin, Ph.D., Hilel Vardi, M.Sc., Osnat TangiRozental, B.A., Rachel Zuk-Ramot, R.N., Benjamin Sarusi, M.Sc., Dov Brickner, M.D., Ziva Schwartz, M.D., Einat Sheiner, M.D., Rachel Marko, M.Sc., Esther Katorza, M.Sc., Joachim Thiery, M.D., Georg Martin Fiedler, M.D., Matthias Blüher, M.D., Michael Stumvoll, M.D., Meir J. Stampfer, M.D., Dr.P.H., for the Dietary Intervention Randomized Controlled Trial (DIRECT) Group NEJM Study • Examined the effects of three diets: • • low-carb • low-fat • Mediterranean Involved 322 participants x 2 years Effect of Diet Type on Weight Change: 2 Years Results • Low-carb and Mediterranean promoted • • greatest weight loss, 12 lbs and 10 lbs, respectively. Low-fat diet resulted in a loss of 7 lbs Caveats: • 86% of the study participants were men • low-carb and Mediterranean diets produced similar amounts of weight loss in the overall study results and in the men In women, the Mediterranean diet produced 3.8 kg (8.4 lbs) more weight loss on average than the low-carb diet Effect of Diet Type on Lipids Evidence Statement: • “LDL-C should continue to be the • primary target of cholesterol lowering therapy” Multiple lines of evidence: - Genetic - Epidemiologic - Experimental animals and Lab investigations - Controlled clinical trials – strong causal relationship between LDL and CHD Lowering LDL-C: Dietary Portfolio • Objective: • To determine whether a diet containing all recommended food components (AHA/NCEP Panel III) leads to cholesterol reduction comparable with that of a statin Dietary Portfolio: • 1.0 g plant sterols/1000 kcal • 9.8 g viscous fibers/1000 kcal • 21.4 g soy protein/1000 kcal • 14 g whole almonds/1000 kcal Jenkins et al. JAMA . 2003;290:502-510 Lowering LDL-C: The Portfolio Diet as Good as Lovastatin 20 mg daily LDL-C LDL-C/ HDL Ratio C-Reactive Protein o Control Portfolio Statin Jenkins et al. JAMA . 2003;290:502-510 Effects of Diet on CV Complications After 1st MI: The Lyon Diet-Heart Study • Aim: To assess whether a Mediterranean • Diet diet would reduce recurrence rate after a first MI Design: • Prospective – s/p first MI • Randomized 605 men and women to control or diet • Follow up: 46 months De Lorgeril et al. Lancet 1994, Circulation 1999 Mediterranean Style Diet in the Lyon Heart Study • Increase whole grains – bread • Increase root and green vegetables • Increase fish • Fruit daily • Less red meat – more poultry • Pragmatic approach: most pts would not • replace butter for olive oil - replace with margarine - high in linoleic and α-linolenic fatty acids Use canola or olive oil for food preparation De Lorgeril et al. Lancet 1994, Circulation 1999 Effect of Mediterranean Lyon Diet % Without Event Cumulative survival without non-fatal MI or major secondary end points De Lorgeril et al. Lancet 1994, Circulation 1999 Lyon Diet Study • Al cause mortality was reduced by 70% • Study was so successful that the ethics committee decided to stop the study prematurely so that the results could be made available to the public immediately De Lorgeril et al. Lancet 1994, Circulation 1999 All Cause Mortality Based on 2 point increase in Adherence to Med Diet Sofi, F. et al. BMJ 2008;337:a1344 Sofi F, et al. Adherence to Mediterranean diet and health status BMJ 2008; 337: a1344. Copyright ©2008 BMJ Publishing Group Ltd. CV mortality associated with 2 point increase in adherence for Mediterranean diet Sofi, F. et al. BMJ 2008;337:a1344 Copyright ©2008 BMJ Publishing Group Ltd. Meta-analysis • Strict adherence to a Mediterranean diet reduced • Risk of dying from cancer – 9% • Risk of dying from CV disease – 6% • Risk of developing Parkinson’s and Alzheimer’s – 13 % Sofi F, et al. Adherence to Mediterranean diet and health status BMJ 2008; 337: a1344. Mediterranean Diet: Beneficial Health Effects • A study published in Archives of General Psychiatry shows that people who followed the Mediterranean diet, an eating regimen that is rich in fruits, vegetables, whole grains, fish, and nuts, were less likely to develop depression Sanchez et al. Arch Gen Psychiatry 2009 Summary: Mediterranean Diet • CV Benefits: • Overall lower CV risk • Decreased mortality post-MI • Actions: • Promotes weight loss • Lowers LDL cholesterol and triglycerides • Raises HDL • Anti-inflammatory effects • Lowers Blood pressure AHA 2006 Diet and Lifestyle Recommendations • • • • • Balance calorie intake and physical activity Consume diet rich in vegetables and fruits. Choose whole-grain, high-fiber foods. Consume fish, especially oily fish, at least twice a week. Limit your intake of saturated fat to <7% of energy, trans fat to <1% of energy, and cholesterol to <300 mg per day by • choosing lean meats and vegetable alternatives • selecting fat-free (skim), 1%-fat, and low-fat dairy products; and • minimizing intake of partially hydrogenated fats. Circulation. 2006;114:82-96s AHA 2006 Diet and Lifestyle Recommendations • Minimize your intake of beverages and foods with added sugars. • Choose and prepare foods with little or no salt. • If you consume alcohol, do so in moderation. • When you eat food that is prepared outside of the home, follow the AHA Diet and Lifestyle Recommendations Circulation. 2006;114:82-96 Rationale for Lifestyle Changes • Atherosclerosis linked to obesity early in life • PDAY study • Lifestyle changes prevent progression of borderline risk factors • Diabetes Prevention Program • Finnish Diabetes Prevention Trial • In patients with CHD, lifestyle changes can improve outcomes • STARS Trial, Lyon Trial Fish Oil and Heart Disease: Long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) • • • • • From UptoDate Absorbed from GI tract Transported to liver as TG w/in chylomicrons Released into circulation as lipoprotein particles (LDL, HDL, phospholipids Incorporated into cell membranes in heart and brain EPA may be converted to PGE3 which affects inflammation and thrombosis Intake of Fish or Fish Oil and Relative Risk of CHD Death • Study of Prospective Cohort Studies and • • Randomized Clinical Trials Modest consumption of fish ( 250-500 mg/d of EPA and DHA) lowers relative risk for CVD by 25% or more Higher intakes do not substantially further lower CHD mortality. Mozaffarian D, Rimm EB. JAMA. 2006 Intake of Fish and Fish Oil and RR of CHD Death Mozaffarian D, Rimm EB.JAMA. 2006 296:1885 Potential Dose Responses and Time Course of Clinical Events in Response to Fish Oil Intake Mozaffarian D, Rimm EB. JAMA. 2006 296:1885 Fish Oil: Where do we stand? • PRO: • • • • • Modest reduction in progression of atherosclerosis May reduce risk of Nonfatal MI/ACS at high doses Reduces incidence of sudden death Mild reduction in total mortality Reduced incidence of Atrial fibrillation • CON: • No effect on • • • restenosis post-PCI No effect on recurrent VT in patients with ICD’s No effect on stroke No effect on HF Fish Oil: Beneficial Effects • Lowers triglycerides by 25 - 30%: • Dose: 3 - 4 g/d • Reduced HR and BP ( SVR) • Age > 45 • Dose: 3 - 4 g/d for 8 wks • Increased HR variability • Improved diastolic LV function without • effect on systolic function Antiarrythmic effects not well understood Fish Oil: No Effects • • • Glucose metabolism • No change in HgA1C levels Inflammation • No appreciable effect on CRP levels in controlled studies No consistent effect on platelet aggregation, fibrinogen levels or Factors VII and VII Fish Oil: Side effects • GI disturbances, especially nausea, dose • • • dependent (20% at 4 g/d) Fishy taste with eructation Bleeding - no increased risk at up to 4 g/d Contaminants • Mercury - most preparations have no to • • minimal mercury PCB’s Dioxan Practical Fish Oil Facts: • Active Forms: • Eicosapentaenoic acid (EPA) • Docosahexaenoic acid (DHA) • Preparations: • Prescription: Lovaza and Omacor • Should contain both EPA and DHA • Use the ones made from small fish (less mercury) or algae • Dosing: • Target dose = 250 - 500 mg/d of EPA and DHA • Approximately 1g fish oil supplement/day Who should take Fish Oils? • Patients with known CHD • 1 - 2 servings of oily fish/week recommended • (Class I) If unable or unwilling, daily fish oil supplement is reasonable (Class II) • Patients without known CHD • 1 - 2 servings of oily fish/week recommended • (Class II) If unable or unwilling, daily fish oil supplement is reasonable (Class II) From UptoDate How much fish is necessary? From UptoDate Complementary and Alternative Medicines • > 15 million people consume CAM • $34 billion dollars in US alone out of • • pocket Majority are Herbal products, considered “food” and not regulated as drugs Use not consistently disclosed to MD Data from Tindle HA, Davis RB, Phillips RS, Eisenberg DM. Trends in use of complementary and alternative medicine by US adults: 1997– 2002. Altern Ther Health Med 2005;11:42–9. QuickTime™ and a decompressor are needed to see this picture. 75 yo man presents with new onset of atrial fibrillation • Anticoagulation and amiodarone are • • recommended Medications: none PE: • BP 155/96, HR 100 irreg, irreg • Lungs clear • No JVD, cor - holosystolic murmur at apex • No edema • EKG: atrial fibrillation rate 90-120, LVH 75 yo man presents with new onset of atrial fibrillation On closer questioning he is taking the following supplements: Ginseng Ginkgo biloba St. John’s Wort Saw Palmetto Vitamin D Folate Vitamin E Fish oil He is reluctant to start anticoagulation and metoprolol 25 mg bid is prescribed • What are potential interactions • • between his CAM and warfarin? Could they be contributing to his hypertension and atrial fibrillation? Are there other potentially harmful effects? Increased bleeding risk with Warfarin Herb Use Alfalfa Arthritis, hyperlipidemia, DM Angelica (dong quai) Appetite loss, dyspepsia Bilberry Circulatory disorder, DM Fenugreek Hyplipidemia Garlic High cholesterol, HTN Gingko Poor circulation, cognitive disorder Ginger High cholesterol, indigestion Kelp Cancer, obesity Khelia Muscle spasms Decreased effectiveness of Warfarin Herb Use Ginseng Aging, stress Green tea Cognition, weight loss, diuretic Other important considerations: Herb Use Potential adverse effect Hawthorn CHF, hypertension Digoxin toxicity Licorice Ulcer, cirrhosis, cough Digoxin toxicity Storphanthus CHF Digoxin toxicity Lily of the valley CHF Digoxin toxicity, inc betablocker effect St. John’s wort Depression Decreased digoxin concentration Night-blooming cereus CHF Increases effects of ACE, beta-blocker, digoxin Effects on Blood Pressure • Increase • Capsicum • Ginseng • Licorice • Ma-huang (ephedra) • Yohimbine • Decrease • Irish moss • Kelp • Yohimbine Arrhythmic considerations: • Hypkalemia • Aloe vera • Gossypol • Licorice • Hyperkalemia • Oleander • QT prolongation • • • • • • • • • • • • • • Aloe vera Bitter orange Echinacea Ginkgo biloba Ginseng Guarana Hawthorn Horny goat weed Licorice Lily of the valley Night-blooming cereus Oleander Rhodiola St. John’s wort Contamination relatively common • Heavy metals • Pharmaceuticals • Colchicine in ginkgo • Dietary supplements containing drugs for erectile dysfunction, lovastatin and sibutramine Vitamins in Prevention of CV Disease • Folate • Lowers homocysteine levels, which are • • • associated with CV disease Randomized trials show no benefit May lower risk of HTN (Retrospective study from NHS in women) Supplementation not recommended • Vitamin D • Increasing recognition of vitamin D deficiency • Low levels associated with increased total and • CV mortality Recommendation: • 600 IU daily for Fx prevention • 800 IU daily if previous Fx Vitamins in Prevention of CV Disease • Anti-oxidant vitamins • Vitamin A, E and C • No benefit on cardiovascular disease • Vitamin E may increase risk of HF • Vitamin B12 • Deficiency common in elderly • Supplement of 2.4 mcg/day reasonable • No known toxity at these doses Finnish Alpha Tocopherol Beta Carotene Cancer Prevention Study • • • 1862 male smokers with prior Hx MI Randomly assigned to alpha tocopherol (50 mg per day), beta carotene (20 mg per day), both, or placebo Endpoint: first major cardiac event Rapola, JM, Virtamo, J, Ripatti, S, et al Lancet 1997; 349:1715 Most of evidence does not favor use of antioxidants • HOPE (HOPE-TOO showed slight increase • • • • • in HF in Vit E treated group Heart Prevention study Women’s Antioxidant Cardiovascular Study WAVE GISSI CHAOS - reduced rate of MI not CV mortality Patient reluctant to follow my advice and has started selenium and magnesium; he refers me to this web site Two years later . . . • Remains in atrial fibrillation • BP 140’s - 160’s • Suffered minor stroke but still refuses warfarin Complementary and Alternative Medications: • Routinely inquire about their use and • • • doses as well as preparations Discuss potential adverse effects Inform patients about drug-herb interactions Additional clinical trials needed and better regulation of the industry is warranted.