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American Society of Hypertension, Inc. (ASH) Disclosure of Relationships Over the past 12 months Nothing to disclose regarding information pertaining to this presentation Matthew J Sorrentino MD

Hypertension Highlights 2011: Complimentary and Alternative Therapies in Hypertension: Focus on Nutrition American Society of Hypertension 26 th Annual Scientific Meeting May 21, 2011 Matthew Sorrentino MD University of Chicago Section of Cardiology

American Society of Hypertension, Inc. (ASH) Objectives Review the rationale for reducing sodium intake to improve blood pressure control Evaluate diet information regarding fruits, vegetables and whole grains and their impact on blood pressure Discuss the use of marine fish oils in the diet as a cardiovascular protective

Lifestyle Modifications for BP Control Modification Weight reduction DASH eating plan Restrict sodium intake Physical activity Moderate alcohol Recommendation Maintain normal body weight (BMI=18.5-25) Diet rich in fruits, vegetables, low fat dairy and reduced in fat <2.4 grams of sodium per day (100 mmole sodium) Regular aerobic exercise for at least 30 minutes most days of the week <2 drinks/day for men and <1 drink/day for women Approximate SBP Reduction Range 5-20 mmhg/10 kg weight lost 8-14 mmhg 2-8 mmhg 4-10 mmhg 2-4 mmhg BMI=Body mass index, SBP=Systolic blood pressure JNC 7 Chobanian AV et al. JAMA 2003;289:2560

The INTERSALT Study 52 centers, averages for urinary Na+ excretion (reflects dietary Na+ intake) and blood pressure rise with age Intersalt Cooperative Research Group Br Med J 1988;297:319

Salt and Blood Pressure Population studies Rise in BP correlated with Na + intake Low Na + intake (<50 mmol/d) little or no hypertension Animal Models Na + load leads to hypertension Clinical Studies Salt sensitive pts increase vascular resistance and BP with Na + load Increased Na + in vascular tissue and blood cells Na + restriction (60-90mmol/d) lowers BP Diuretics lower BP with initial natiuresis From Kaplan, Etiologies and treatment of systemic arterial hypertension, Willerson et al. (ed) Treatment of Heart Disease,1994 (Gower Medical Publishing), p.7.39

Salt and Hypertension Meta-analysis 100 mmol/d Na + change Older Htn Trials n=17 Younger Htn Trials n=11 Normotensive Trials n=14 SBP 6.3 (4.11 to 8.44) 2.4 (0.35 to 4.38) -0.2 (-1.48 to 1.01) DBP 2.2 (0.58 to 3.87) -0.1 (-1.61 to 1.37) 0.6 (-0.88 to 2.07) N=56 trials, 3.7/0.9 mmhg in all Htn trials (2400 mg = 104 mmol of Na + ) Midgley et al. JAMA 1996;275:1590-1597

Dietary Approach to Stop Hypertension (DASH) 459 adults Control Diet Low in Fruits, Vegetables, and Dairy Products Fat Content Typical of Average US Diet Diet Rich in Fruit, Vegetables and Fiber Combination Diet Rich in Fruits, Vegetables, & Low-Fat Dairy Products Reduced Saturated and Total Fat All on Control Diet for 3 weeks Randomized to One Diet for 8 weeks Na + intake and body weight maintained constant (Na + about 3000 mg/day) Appel LJ, Moore TJ, Obarzenek E, et al. A Clinical Trial of the Effects of Dietary Patterns on Blood Pressure. N Engl J Med 1997;336:1117-24.

DASH Results Combination Diet: -5.5/-3.0 mmhg Fruit/Vegetable Diet: -2.8/1.1 mmhg Appel LJ et al. N Engl J Med 1997;336:1122.

DASH-Sodium Design n=412 Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on Blood Pressure of Reduced Dietary Sodium and the Dietary Approaches to Stop Hypertension (DASH) Diet. N Engl J Med 2001;344:3-10.

DASH- Sodium Results High Na + 150 mmol/d (3.3 g/d) Intermed. Na + 100 mmol/d (2.5 g/day) Low Na + 50 mmol/d (1.5 g/day) Sacks FM et al. N Engl J Med 2001;344:6.

Total mortality by Sodium intervention Trials of Hypertension Prevention (TOHP) 10-15 yrs f/u Dietary Na+ reduction (44 & 33 mmole) TOHP1 18 mo TOHP2 36-48 mo Cook, BMJ 2007;334:885

Urinary Sodium Excretion and Outcomes European Project on Genes in Hypertension Investigators 3681 participants 24-hour urinary sodium excretion CVD deaths decreased across increasing tertiles of Sodium excretion SBP aligned with change in sodium excretion but did not translate into higher risk of hypertension or CVD complications Lower sodium excretion associated with higher CVD mortality Stolarz-Skrzypek et al., JAMA 2011;305:1777

Urinary Sodium Excretion and Outcomes Stolarz-Skrzypek et al., JAMA 2011;305:1777

Salt Intake Recommendations Not Enough Evidence to Support Dietary Sodium Reduction In All Individuals? DASH - 30 day intervention only Normotensive patients on Healthy Diet Current Recommendations DASH Diet Sodium Intake of 1.5 g/day Institute of Medicine Committee 1.5 g/day adequate to assure nutrient adequacy US Dietary guidelines 2005 < 2.3 g for general population, 1.5 g/day for htn, blacks, middle & older age adults 2010 Dietary Guidelines Committee 1.5 g/day, recently recommended by AHA (March, 2011)

Fruits and Vegetables

Diet Evidence: Benefits of Fruits and Vegetables Nurses Health Study and Health Professional s Follow-up Study 126,399 persons followed for 8-14 years to assess the relationship between fruit and vegetable intake and adverse CV outcomes* 1.2 Relative Risk for Coronary Heart Disease 1.0 0.8 0.6 0.4 0.2 0 <3.0 3.0-3.9 4.0-4.9 5.0-5.9 6.0-7.9 >8.0 Fruit and Vegetable Intake, servings/d Increased fruit and vegetable intake reduces CV risk * Includes nonfatal MI and fatal coronary heart disease CV = Cardiovascular, MI = Myocardial infarction Joshipura KJ et al. Ann Intern Med 2001;134:1106-14

Oxford Fruit and Vegetable Study Group 6 month, randomized, controlled trial Brief negotiation method to encourage an increase in consumption of fruit and vegetables to at least 5 daily portions 690 individuals Results SBP difference: 4.0 mmhg (2.0-6.0, p<.0001) DBP difference: 1.5 mmhg (0.2-2.7, p=.02) Reduction of DBP by 2 mmhg = 17% decrease in incidence of Htn, 6% decrease in CHD, 15% decrease CVA/TIA John et al., Lancet 2002:359:1969

Celery and Blood Pressure Can lower BP 12-14% Smooth muscle relaxation Reduce catecholamines Diuretic effect High potassium content 3-n-butylphthalide (3nB) Gives celery its taste and aroma Active component that lowers BP Dose 4 stalks daily No clinical trials

Whole Grains Whole grains or foods made from them contain all the essential parts and naturally-occurring nutrients of the entire grain seed (bran, germ and endosperm). If the grain has been processed (e.g. cracked, crushed, rolled, extruded, and/or cooked), the food product should deliver approximately the same balance of nutrients that are found in the original grain seed.

Diet Evidence Benefits of Whole Grain and Fiber 336,244 persons followed for 6-10 years to assess the relationship between dietary fiber intake and adverse CV outcomes Relative Risk of CHD Death 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0 RR=0.73, P<0.001 <12 12-<15 15-<18 18-<21 21-<24 24-<27 >27 Total Dietary Fiber Intake, Energy-Adjusted g/d Increased dietary fiber intake reduces CV risk CV = Cardiovascular, CHD = Coronary heart disease Pereira MA et al. Arch Int Med 2004;164:370-76

BP Response To Fiber -1.13 mmhg SBP -1.26 mmhg DBP Streppel et al. Arch Intern Med 2005; 165:150

BP effects of Whole Grains Step 1 diet Whole Grain Diets Whole wheat/brown rice Half/Half SBP, mmhg -2.2-1.4 to -6.7 DBP, mmhg -2.0-2.9 to -3.7 Healthy men and women, BP <140/90 Step 1 AHA diet for 2 weeks Whole grains replaced refined carbohydrates: - barley, whole wheat-brown rice diet (5 weeks) - half barley/half whole wheat-brown rice (5 weeks) Behall et al. J Am Diet Assoc 2006;106:1445

Relative Risks of Hypertension: Whole and Refined Grain Intake Prospective study 28,926 female US health professionals, semi-quantitative Food-frequency questionnaires; 8722 incident cases of hypertension 10 y f/u Lower risk of hypertension began with whole grain consumption of 1-2 and 2-4 servings/d (43-58% of total grains as whole grains) Wang, L. et al. Am J Clin Nutr 2007;86:472-479

Whole Grains and BP 3 daily portions of whole-grain foods: Refined diet Wheat Wheat + Oats N=233 healthy middle-aged volunteers Normotensive Results: Systolic BP reduced by 6 mmhg Tighe et al. Am J Clin Nutr 2010;92:733

Whole Grain Conclusions Multiple nutritional components of whole grains: dietary fiber, folate, potassium, magnesium Protective effects of whole grains on development of hypertension: Reductions in abdominal obesity Increases in peripheral insulin sensitivity Improve vascular endothelial function Benefits digestion and absorption of foods Refined grains low in beneficial nutrients (removal of bran and germ during refining)

Meat Intake and Hypertension Wang et al. J Hyperten 2008;26:215

Fish and Fish Oils

Omega-3 Fatty Acids Eicosapentaenoic Acid (C20:5n-3) EPA Docosahexaenoic Acid (C22:6n-3) DHA Major Source is Fatty Fish Salmon, Mackerel, Herring, Trout α-linolenic acid (C18:3n-3) ALA Major food sources are vegetable oils such as canola, flaxseed and soybean oil Flaxseed, English walnuts, Mustard Oil Kris-Etherton PM et al. Circulation 2002;106:2727-57. Singh RB et al. Cardiovas Drugs Ther 1997;11:485-91.

Schema of Potential Dose Responses and Time Courses for Altering Clinical Events of Physiologic Effects of Fish or Fish Oil Intake Mozaffarian, D. et al. JAMA 2006;296:1885-1899.

GISSI-Prevenzione Trial 11,324 patients (mean follow-up of 42 months) Secondary Prevention Randomized, Controlled Trial 4 groups ω-3 fatty acids (1 g of EPA/DHA per day) 300 mg of Vitamin E Both or placebo CVD deaths reduced from 6% to 5% Total Mortality decreased from 10% to 8% No difference for non-fatal MI No effect of Vitamin E GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty facids and vitamin E after mycocardial infarction: results of the GISSI-Prevenzione Trial. Lancet 1999;354:447-55.

GISSI-Prevenzione Survival Curves Marchioli R et al. Circulation 2002;105:1897-1903.

Fish oils and Blood Pressure Meta-analysis of 36 randomized trials Reduction in BP 2.1/1.6 mmhg Geleijnse et al. J Hypertens 2002;20:1493.

Fish Oils and Blood Pressure BP response in 36 randomized trials of fish oil and BP by mean age and presence of hypertension in the study populations. BP effect tended to be larger in: -Older populations -Hypertensive populations Geleijnse et al. J Hypertens 2002;20:1493.

Garlic and Blood Pressure When garlic is cut or crushed the enzyme allinase interacts with the cysteine compound alliin to produce allicin Allicin is likely an active compound Allicin gives garlic its typical aroma and taste Breaks down in few hours or with cooking Garlic powder (Kwai) coated and contain freeze-dried fresh garlic Once ingested, surface coating is digested, alliin is converted to allicin Mild cholesterol lowering effect Anti-thrombotic effect Sorrentino, Alt Med Alert 1998;1:97

Garlic and Blood Pressure Silagy, Neil. J Hypertens 1994;12:463 Kwai dried garlic powder, 415 subjects

Mediterranean Diet Abundance of Plant Food Fruits, Vegetables, Nuts, Beans, Legumes Whole-Grain Cereal, Bread, Potatoes Olive Oil as Principle Fat Source Fish, Poultry, Dairy Products Low-Moderate Amounts Low Consumption of Red Meat Eggs consumed 0-4 times weekly Moderate Alcohol Consumption (Wine with Meals) Hu FB. N Engl J Med 2003;348:2595-96. Kris-Etherton PM et al. Circulation 2002;106:2727-57.

Mediterranean Diet and Risk of CHD and Stroke A. RR of CVD (combined CHD and Stroke by quintiles of amed B. RR of fatal CVD (combined CHD and stroke mortality) by quintiles of amed N=74,886 women 38-63 yrs in Nurses Health Study amed score = adapted from the Mediterranean diet scale Components include: -Vegetables -Fruits -Nuts -Whole grains -Legumes -Fish -Ratio of monounsat to saturated fat -Red/processed meats -Alcohol Fung, T. T. et al. Circulation 2009;119:1093-1100 Higher score = closer to Med diet

American Society of Hypertension, Inc. (ASH) Disclosure of Relationships Over the past 12 months Nothing to disclose regarding information pertaining to this presentation Matthew J Sorrentino MD