1. Lifestyle Modifications for Cardiovascular Prevention: The Mediterranean Diet, Fish, Oils and other Supplements: should we recommend them?

2. Outline What are the benefits of the Mediterranean diet? What are the benefits of the Mediterranean diet? Should we advise our patients to take fish oil supplements? Should we advise our patients to take fish oil supplements? What are the risks and benefits of complementary/alternative medications? What are the risks and benefits of complementary/alternative medications?

3. 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. Brillat-Savarin, Jean-Anthelme Penguin BooksBrillat-Savarin, Jean-Anthelme Penguin Books

4. 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. 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 A parallel phenomenon is known as the French Paradox

5. 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 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 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

6. USDA Center for Nutrition Policy and Promotion 2005

7. Mediterranean Diet Abundant plant foods (legumes), fresh fruit as the typical daily dessert Abundant plant foods (legumes), fresh fruit as the typical daily dessert Olive oil is the principal source of fat Olive oil is the principal source of fat Dairy products (principally cheese and yogurt) Dairy products (principally cheese and yogurt) Fish and poultry consumed in low to moderate amounts Fish and poultry consumed in low to moderate amounts Zero to four eggs consumed weekly Zero to four eggs consumed weekly Red meat consumed in low amounts Red meat consumed in low amounts Wine consumed in low to moderate amounts Wine consumed in low to moderate amounts Total fat: 25 - 30%, < 8% Saturated fats Total fat: 25 - 30%, < 8% Saturated fats

8. Mediterranean Diet: Possible Mechanisms for Beneficial Effects Low in saturated fat, high in monounsaturated fat and dietary fiber Low in saturated fat, high in monounsaturated fat and dietary fiber Olive oil : very high levels of monounsaturated fats (oleic acid) 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 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: Clinical data shows that antioxidants in olive oil provide additional heart health benefits: LDL cholesterol reduction LDL cholesterol reduction anti-inflammatory anti-inflammatory anti-hypertensive effects anti-hypertensive effects Covas, M.I., 2007;Pharmacol. Res. 55 (3): 175–86

9. 359:229-241 July 17, 2008 July 17, 2008July 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 Tangi- Rozental, 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 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 Tangi- Rozental, 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

10. NEJM Study Examined the effects of three diets: Examined the effects of three diets: low-carb low-carb low-fat low-fat Mediterranean Mediterranean Involved 322 participants x 2 years Involved 322 participants x 2 years

11. Effect of Diet Type on Weight Change: 2 Years

12. Results Low-carb and Mediterranean promoted greatest weight loss, 12 lbs and 10 lbs, respectively. Low-carb and Mediterranean promoted greatest weight loss, 12 lbs and 10 lbs, respectively. Low-fat diet resulted in a loss of 7 lbs Low-fat diet resulted in a loss of 7 lbs Caveats: 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 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 In women, the Mediterranean diet produced 3.8 kg (8.4 lbs) more weight loss on average than the low-carb diet

13. Effect of Diet Type on Lipids

14. Evidence Statement: LDL-C should continue to be the primary target of cholesterol lowering therapy LDL-C should continue to be the primary target of cholesterol lowering therapy Multiple lines of evidence: Multiple lines of evidence: - Genetic - Epidemiologic - Experimental animals and Lab investigations - Controlled clinical trials – strong causal relationship between LDL and CHD

15. 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 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: Dietary Portfolio: 1.0 g plant sterols/1000 kcal 1.0 g plant sterols/1000 kcal 9.8 g viscous fibers/1000 kcal 9.8 g viscous fibers/1000 kcal 21.4 g soy protein/1000 kcal 21.4 g soy protein/1000 kcal 14 g whole almonds/1000 kcal 14 g whole almonds/1000 kcal Jenkins et al. JAMA. 2003;290:502-510

16. Lowering LDL-C: The Portfolio Diet as Good as Lovastatin 20 mg daily o Control Portfolio Statin LDL-C LDL-C/ HDL Ratio C-Reactive Protein Jenkins et al. JAMA. 2003;290:502-510

17. Effects of Diet on CV Complications After 1 st MI: The Lyon Diet-Heart Study Aim: To assess whether a Mediterranean Diet diet would reduce recurrence rate after a first MI Aim: To assess whether a Mediterranean Diet diet would reduce recurrence rate after a first MI Design: Design: Prospective – s/p first MI Prospective – s/p first MI Randomized 605 men and women to control or diet Randomized 605 men and women to control or diet Follow up: 46 months Follow up: 46 months De Lorgeril et al. Lancet 1994, Circulation 1999

18. Mediterranean Style Diet in the Lyon Heart Study Increase whole grains – bread Increase whole grains – bread Increase root and green vegetables Increase root and green vegetables Increase fish Increase fish Fruit daily Fruit daily Less red meat – more poultry 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 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 Use canola or olive oil for food preparation De Lorgeril et al. Lancet 1994, Circulation 1999

19. Effect of Mediterranean Lyon Diet Cumulative survival without non-fatal MI or major secondary end points % Without Event De Lorgeril et al. Lancet 1994, Circulation 1999

20. Lyon Diet Study Al cause mortality was reduced by 70% 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 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

21. Copyright ©2008 BMJ Publishing Group Ltd. Sofi, F. et al. BMJ 2008;337:a1344 All Cause Mortality Based on 2 point increase in Adherence to Med Diet Sofi F, et al. Adherence to Mediterranean diet and health status BMJ 2008; 337: a1344.

22. Copyright ©2008 BMJ Publishing Group Ltd. Sofi, F. et al. BMJ 2008;337:a1344 CV mortality associated with 2 point increase in adherence for Mediterranean diet

23. Meta-analysis Strict adherence to a Mediterranean diet reduced Strict adherence to a Mediterranean diet reduced Risk of dying from cancer – 9% Risk of dying from cancer – 9% Risk of dying from CV disease – 6% Risk of dying from CV disease – 6% Risk of developing Parkinsons and Alzheimers – 13 % Risk of developing Parkinsons and Alzheimers – 13 % Sofi F, et al. Adherence to Mediterranean diet and health status BMJ 2008; 337: a1344.

24. 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 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

25. Summary: Mediterranean Diet CV Benefits: CV Benefits: Overall lower CV risk Overall lower CV risk Decreased mortality post-MI Decreased mortality post-MI Actions: Actions: Promotes weight loss Promotes weight loss Lowers LDL cholesterol and triglycerides Lowers LDL cholesterol and triglycerides Raises HDL Raises HDL Anti-inflammatory effects Anti-inflammatory effects Lowers Blood pressure Lowers Blood pressure

26. AHA 2006 Diet and Lifestyle Recommendations Balance calorie intake and physical activity Balance calorie intake and physical activity Consume diet rich in vegetables and fruits. Consume diet rich in vegetables and fruits. Choose whole-grain, high-fiber foods. Choose whole-grain, high-fiber foods. Consume fish, especially oily fish, at least twice a week. 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 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 choosing lean meats and vegetable alternatives selecting fat-free (skim), 1%-fat, and low-fat dairy products; and selecting fat-free (skim), 1%-fat, and low-fat dairy products; and minimizing intake of partially hydrogenated fats. minimizing intake of partially hydrogenated fats. Circulation. 2006;114:82-96s

27. AHA 2006 Diet and Lifestyle Recommendations Minimize your intake of beverages and foods with added sugars. Minimize your intake of beverages and foods with added sugars. Choose and prepare foods with little or no salt. Choose and prepare foods with little or no salt. If you consume alcohol, do so in moderation. 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 When you eat food that is prepared outside of the home, follow the AHA Diet and Lifestyle Recommendations Circulation. 2006;114:82-96

28. Rationale for Lifestyle Changes Atherosclerosis linked to obesity early in life Atherosclerosis linked to obesity early in life PDAY study PDAY study Lifestyle changes prevent progression of borderline risk factors Lifestyle changes prevent progression of borderline risk factors Diabetes Prevention Program Diabetes Prevention Program Finnish Diabetes Prevention Trial Finnish Diabetes Prevention Trial In patients with CHD, lifestyle changes can improve outcomes In patients with CHD, lifestyle changes can improve outcomes STARS Trial, Lyon Trial STARS Trial, Lyon Trial

29. Fish Oil and Heart Disease: Long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) Absorbed from GI tract Absorbed from GI tract Transported to liver as TG w/in chylomicrons Transported to liver as TG w/in chylomicrons Released into circulation as lipoprotein particles (LDL, HDL, phospholipids Released into circulation as lipoprotein particles (LDL, HDL, phospholipids Incorporated into cell membranes in heart and brain Incorporated into cell membranes in heart and brain EPA may be converted to PGE3 which affects inflammation and thrombosis EPA may be converted to PGE3 which affects inflammation and thrombosis From UptoDate

30. Intake of Fish or Fish Oil and Relative Risk of CHD Death Study of Prospective Cohort Studies and Randomized Clinical Trials 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 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. Higher intakes do not substantially further lower CHD mortality. Mozaffarian D, Rimm EB. JAMA. 2006

31. Intake of Fish and Fish Oil and RR of CHD Death Mozaffarian D, Rimm EB.JAMA. 2006 296:1885

32. Potential Dose Responses and Time Course of Clinical Events in Response to Fish Oil Intake Mozaffarian D, Rimm EB. JAMA. 2006 296:1885

33. Fish Oil: Where do we stand? PRO: PRO: Modest reduction in progression of atherosclerosis Modest reduction in progression of atherosclerosis May reduce risk of Non- fatal MI/ACS at high doses May reduce risk of Non- fatal MI/ACS at high doses Reduces incidence of sudden death Reduces incidence of sudden death Mild reduction in total mortality Mild reduction in total mortality Reduced incidence of Atrial fibrillation Reduced incidence of Atrial fibrillation CON: CON: No effect on restenosis post-PCI No effect on restenosis post-PCI No effect on recurrent VT in patients with ICDs No effect on recurrent VT in patients with ICDs No effect on stroke No effect on stroke No effect on HF No effect on HF

34. Fish Oil: Beneficial Effects Lowers triglycerides by 25 - 30%: Lowers triglycerides by 25 - 30%: Dose: 3 - 4 g/d Dose: 3 - 4 g/d Reduced HR and BP ( SVR) Reduced HR and BP ( SVR) Age > 45 Age > 45 Dose: 3 - 4 g/d for 8 wks Dose: 3 - 4 g/d for 8 wks Increased HR variability Increased HR variability Improved diastolic LV function without effect on systolic function Improved diastolic LV function without effect on systolic function Antiarrythmic effects not well understood Antiarrythmic effects not well understood

35. Fish Oil: No Effects Glucose metabolism Glucose metabolism No change in HgA1C levels No change in HgA1C levels Inflammation Inflammation No appreciable effect on CRP levels in controlled studies No appreciable effect on CRP levels in controlled studies No consistent effect on platelet aggregation, fibrinogen levels or Factors VII and VII No consistent effect on platelet aggregation, fibrinogen levels or Factors VII and VII

36. Fish Oil: Side effects GI disturbances, especially nausea, dose dependent (20% at 4 g/d) GI disturbances, especially nausea, dose dependent (20% at 4 g/d) Fishy taste with eructation Fishy taste with eructation Bleeding - no increased risk at up to 4 g/d Bleeding - no increased risk at up to 4 g/d Contaminants Contaminants Mercury - most preparations have no to minimal mercury Mercury - most preparations have no to minimal mercury PCBs PCBs Dioxan Dioxan

37. Practical Fish Oil Facts: Active Forms: Active Forms: Eicosapentaenoic acid (EPA) Eicosapentaenoic acid (EPA) Docosahexaenoic acid (DHA) Docosahexaenoic acid (DHA) Preparations: Preparations: Prescription: Lovaza and Omacor Prescription: Lovaza and Omacor Should contain both EPA and DHA Should contain both EPA and DHA Use the ones made from small fish (less mercury) or algae Use the ones made from small fish (less mercury) or algae Dosing: Dosing: Target dose = 250 - 500 mg/d of EPA and DHA Target dose = 250 - 500 mg/d of EPA and DHA Approximately 1g fish oil supplement/day Approximately 1g fish oil supplement/day

38. Who should take Fish Oils? Patients with known CHD Patients with known CHD 1 - 2 servings of oily fish/week recommended (Class I) 1 - 2 servings of oily fish/week recommended (Class I) If unable or unwilling, daily fish oil supplement is reasonable (Class II) If unable or unwilling, daily fish oil supplement is reasonable (Class II) Patients without known CHD Patients without known CHD 1 - 2 servings of oily fish/week recommended (Class II) 1 - 2 servings of oily fish/week recommended (Class II) If unable or unwilling, daily fish oil supplement is reasonable (Class II) If unable or unwilling, daily fish oil supplement is reasonable (Class II) From UptoDate

39. How much fish is necessary? From UptoDate

40. Complementary and Alternative Medicines > 15 million people consume CAM > 15 million people consume CAM $34 billion dollars in US alone out of pocket $34 billion dollars in US alone out of pocket Majority are Herbal products, considered food and not regulated as drugs Majority are Herbal products, considered food and not regulated as drugs Use not consistently disclosed to MD Use not consistently disclosed to MD

41. 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.

42. 75 yo man presents with new onset of atrial fibrillation Anticoagulation and amiodarone are recommended Anticoagulation and amiodarone are recommended Medications: none Medications: none PE: PE: BP 155/96, HR 100 irreg, irreg BP 155/96, HR 100 irreg, irreg Lungs clear Lungs clear No JVD, cor - holosystolic murmur at apex No JVD, cor - holosystolic murmur at apex No edema No edema EKG: atrial fibrillation rate 90-120, LVH EKG: atrial fibrillation rate 90-120, LVH

43. 75 yo man presents with new onset of atrial fibrillation On closer questioning he is taking the following supplements: Ginseng Ginkgo biloba St. Johns Wort Saw Palmetto Vitamin D Folate Vitamin E Fish oil

44. He is reluctant to start anticoagulation and metoprolol 25 mg bid is prescribed What are potential interactions between his CAM and warfarin? What are potential interactions between his CAM and warfarin? Could they be contributing to his hypertension and atrial fibrillation? Could they be contributing to his hypertension and atrial fibrillation? Are there other potentially harmful effects? Are there other potentially harmful effects?

45. Increased bleeding risk with Warfarin HerbUse Alfalfa Arthritis, hyperlipidemia, DM Angelica (dong quai) Appetite loss, dyspepsia Bilberry Circulatory disorder, DM FenugreekHyplipidemia Garlic High cholesterol, HTN Gingko Poor circulation, cognitive disorder Ginger High cholesterol, indigestion Kelp Cancer, obesity Khelia Muscle spasms

46. Decreased effectiveness of Warfarin HerbUse Ginseng Aging, stress Green tea Cognition, weight loss, diuretic

47. Other important considerations: HerbUse Potential adverse effect Hawthorn CHF, hypertension Digoxin toxicity Licorice Ulcer, cirrhosis, cough Digoxin toxicity StorphanthusCHF Lily of the valley CHF Digoxin toxicity, inc beta- blocker effect St. Johns wort Depression Decreased digoxin concentration Night-blooming cereus CHF Increases effects of ACE, beta-blocker, digoxin

48. Effects on Blood Pressure Increase Increase Capsicum Capsicum Ginseng Ginseng Licorice Licorice Ma-huang (ephedra) Ma-huang (ephedra) Yohimbine Yohimbine Decrease Decrease Irish moss Irish moss Kelp Kelp Yohimbine Yohimbine

49. Arrhythmic considerations: Hypkalemia Hypkalemia Aloe vera Aloe vera Gossypol Gossypol Licorice Licorice Hyperkalemia Hyperkalemia Oleander Oleander QT prolongation QT prolongation Aloe vera Aloe vera Bitter orange Bitter orange Echinacea Echinacea Ginkgo biloba Ginkgo biloba Ginseng Ginseng Guarana Guarana Hawthorn Hawthorn Horny goat weed Horny goat weed Licorice Licorice Lily of the valley Lily of the valley Night-blooming cereus Night-blooming cereus Oleander Oleander Rhodiola Rhodiola St. Johns wort St. Johns wort

50. Contamination relatively common Heavy metals Heavy metals Pharmaceuticals Pharmaceuticals Colchicine in ginkgo Colchicine in ginkgo Dietary supplements containing drugs for erectile dysfunction, lovastatin and sibutramine Dietary supplements containing drugs for erectile dysfunction, lovastatin and sibutramine

51. Vitamins in Prevention of CV Disease Folate Folate Lowers homocysteine levels, which are associated with CV disease Lowers homocysteine levels, which are associated with CV disease Randomized trials show no benefit Randomized trials show no benefit May lower risk of HTN (Retrospective study from NHS in women) May lower risk of HTN (Retrospective study from NHS in women) Supplementation not recommended Supplementation not recommended Vitamin D Vitamin D Increasing recognition of vitamin D deficiency Increasing recognition of vitamin D deficiency Low levels associated with increased total and CV mortality Low levels associated with increased total and CV mortality Recommendation: Recommendation: 600 IU daily for Fx prevention 600 IU daily for Fx prevention 800 IU daily if previous Fx 800 IU daily if previous Fx

52. Vitamins in Prevention of CV Disease Anti-oxidant vitamins Anti-oxidant vitamins Vitamin A, E and C Vitamin A, E and C No benefit on cardiovascular disease No benefit on cardiovascular disease Vitamin E may increase risk of HF Vitamin E may increase risk of HF Vitamin B12 Vitamin B12 Deficiency common in elderly Deficiency common in elderly Supplement of 2.4 mcg/day reasonable Supplement of 2.4 mcg/day reasonable No known toxity at these doses No known toxity at these doses

53. Rapola, JM, Virtamo, J, Ripatti, S, et al Lancet 1997; 349:1715 Finnish Alpha Tocopherol Beta Carotene Cancer Prevention Study 1862 male smokers with prior Hx MI 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 Randomly assigned to alpha tocopherol (50 mg per day), beta carotene (20 mg per day), both, or placebo Endpoint: first major cardiac event Endpoint: first major cardiac event

54. Most of evidence does not favor use of antioxidants HOPE (HOPE-TOO showed slight increase in HF in Vit E treated group HOPE (HOPE-TOO showed slight increase in HF in Vit E treated group Heart Prevention study Heart Prevention study Womens Antioxidant Cardiovascular Study Womens Antioxidant Cardiovascular Study WAVE WAVE GISSI GISSI CHAOS - reduced rate of MI not CV mortality CHAOS - reduced rate of MI not CV mortality

55. Patient reluctant to follow my advice and has started selenium and magnesium; he refers me to this web site

56. Two years later... Remains in atrial fibrillation Remains in atrial fibrillation BP 140s - 160s BP 140s - 160s Suffered minor stroke but still refuses warfarin Suffered minor stroke but still refuses warfarin

57. Complementary and Alternative Medications: Routinely inquire about their use and doses as well as preparations Routinely inquire about their use and doses as well as preparations Discuss potential adverse effects Discuss potential adverse effects Inform patients about drug-herb interactions Inform patients about drug-herb interactions Additional clinical trials needed and better regulation of the industry is warranted. Additional clinical trials needed and better regulation of the industry is warranted.