Berries and Cardiovascular Health

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Berries and Cardiovascular Health Britt Burton-Freeman, PhD Institute for Food Safety and Health Illinois Institute of Technology bburton@iit.edu Berry Health Benefits Symposium Westlake Village CA, 2011

Speakers Marva Sweeny Univ Prince Edward Island A hyperberry for hypertension Indika Edirisinghe Illinois Institute of Technology Effect of fruit antioxidant on endothelial function Arpita Basu Oklahoma State University Berries and Metabolic Syndrome Charles Coulliard Laval University, Canada Evidence Supporting the cardiometabolic effects of cranberries

OUTLINE Cardiovascular Disease what is it? Statistics Risk factors Traditional Emerging Managing risk through diet and lifestyle Research

Cardiovascular disease What is it? Class of diseases that include the heart and blood vessels Coronary Heart Disease Atherosclerosis Stroke Peripheral artery disease Heart Failure Hypertension Congenital Heart Defects

Death from Cardiovascular Disease still the #1 killer among men and women in the U.S. Accounts for 34.2% of all deaths (>800,000 d/yr) 2400 Americans die from CVD each day 1 person every 37 seconds Heart Disease and Stroke Stats, Circulation 2009

Costs of Cardiovascular Disease, 2010 >$316 Billion CDC: http://www.cdc.gov/chronicdisease/resources/publications/aag/dhdsp.htm#aag

CVD/CAD is no longer considered just a cholesterol accumulation disease Lipid panel Family history Medical history Lifestyle history

Contributors and markers of disease: Inflammation, oxidative stress, Platelet- and Endothelial dysfunction Atherosclerosis / Thrombosis Heart attack, Stroke Libby P, Ridker PM, Maseri A. Circulation. 2002;105:1135 1143.

Libby, Copyright P. 2005 et American al. Circulation Heart Association 2005;111:3481-3488 Atheromas contain multiple cell types that critically influence atherogenesis Vascular cells --Endothelium --Smooth muscle cells Inflammatory cells --Macrophages --T lymphocytes --Mast cells

Traditional Risk Factors for Cardiovascular Disease Smoking High blood pressure Dyslipidemia Overweight, Obesity Diabetes Inactivity Diet Stress Age Gender Family history/ genetics Race Modifiable Endothelial Dysfunction

Selected Emerging Risk Factors and Biomarkers Lipids Lp(a) apoa/apob Particle size/density Oxidation Ox-LDL MPO Glutathione Inflammation CRP IL-6 TNF Lp-PLA 2 CD40L CSF SAA IL-18 Adhesion mols Hemostasis/Thrombosis Homocysteine TAFI D-dimer tpa/pai-1 Fibrinogen Genetic Asp299Gly polymorphism in TLR4 gene MCP-1 2578G allele CX3CR1 chemokine receptor polymorphism V249I 16Gly variant of β 2 -adrenergic receptor 260T/T CD14 allele 117 Thr/Thr variant of CSF LIGHT CSF = colony-stimulating factor MPO = myeloperoxidase TAFI = thrombin activatable fibrinolysis inhibitor Adapted from Stampfer MJ et al. Circulation. 2004;109(suppl):IV3-IV5.

Risk Factors for Cardiovascular Disease Directly Influenced by Diet Smoking High blood pressure High Cholesterol -Total cholesterol, LDL High Triglycerides Overweight and Obesity Diabetes (Type II) Insulin resistance Oxidative stress Blood properties Dietary factors Food choice, preparation, portion, etc. Inactivity Stress

Berry Polyphenols Stoclet et al 2004

Blood Lipids / lipoprotein metabolism influenced by diet Fat type, Berries?

Selected Emerging Risk Factors and Biomarkers Lipids Lp(a) apoa/apob Particle size/density Oxidation Ox-LDL MPO Glutathione Inflammation CRP IL-6 TNF Lp-PLA 2 CD40L CSF SAA IL-18 Adhesion mols Hemostasis/Thrombosis Homocysteine TAFI D-dimer tpa/pai-1 Fibrinogen Genetic Asp299Gly polymorphism in TLR4 gene MCP-1 2578G allele CX3CR1 chemokine receptor polymorphism V249I 16Gly variant of β 2 -adrenergic receptor 260T/T CD14 allele 117 Thr/Thr variant of CSF LIGHT CSF = colony-stimulating factor MPO = myeloperoxidase TAFI = thrombin activatable fibrinolysis inhibitor Adapted from Stampfer MJ et al. Circulation. 2004;109(suppl):IV3-IV5.

Strawberry Intake and Elevations in Lipids and C-Reactive Protein Sesso HD et al. J Am Coll Nutr 2006;26:303-310

Strawberry reduces inflammatory response to a meal in overweight (OW) men and women 4 3.5 3 2.5 2 1.5 1 0.5 0 * * IL-6 pg/ml IL-6 hscrp mg/l Placebo + 40% fat Meal Strawberry + 40% fat Meal Edirisinghe et al. BJN 2011

Selected Emerging Risk Factors and Biomarkers Lipids Lp(a) apoa/apob Particle size/density Oxidation Ox-LDL MPO Glutathione Inflammation CRP IL-6 TNF Lp-PLA 2 CD40L CSF SAA IL-18 Adhesion mols Hemostasis/Thrombosis Homocysteine TAFI D-dimer tpa/pai-1 Fibrinogen Genetic Asp299Gly polymorphism in TLR4 gene MCP-1 2578G allele CX3CR1 chemokine receptor polymorphism V249I 16Gly variant of β 2 -adrenergic receptor 260T/T CD14 allele 117 Thr/Thr variant of CSF LIGHT CSF = colony-stimulating factor MPO = myeloperoxidase TAFI = thrombin activatable fibrinolysis inhibitor Adapted from Stampfer MJ et al. Circulation. 2004;109(suppl):IV3-IV5.

Modified / Oxidized LDL LDL Readily Enter the Artery Wall Where They May Be Modified LDL Vessel Lumen Oxidation of Lipids and Apo B Aggregation LDL Endothelium Hydrolysis of Phosphatidylcholine to Lysophosphatidylcholine Other Chemical Modifications Modified LDL (oxidized LDL) Pro-Inflammatory Intima Steinberg D, et al. N Engl J Med. 1989;320:915-924. Slide Source: Lipids Online

Strawberry prevents meal-induced increase in oxidized LDL in OW men and women Bagel Cream cheese Whole milk cantaloupe Whole milk Bagel n cream cheese Egg with margarine Canteloupe 735 Calories 40% fat Breakfast + Placebo beverage Breakfast + Strawberry beverage Oxidized LDL 15 10 U/L 5 0-5 -10 0 60 120 180 240 300 360 Oxidation PMBL SMBL Protection Burton-Freeman et al. JACN 2010 Treatment, p<0.0008 Time, p=ns

Selected Emerging Risk Factors and Biomarkers Lipids Lp(a) apoa/apob Particle size/density Oxidation Ox-LDL MPO Glutathione Inflammation CRP IL-6 TNF Lp-PLA 2 CD40L CSF SAA IL-18 Adhesion mols Hemostasis/Thrombosis Homocysteine TAFI D-dimer tpa/pai-1 Fibrinogen Genetic Asp299Gly polymorphism in TLR4 gene MCP-1 2578G allele CX3CR1 chemokine receptor polymorphism V249I 16Gly variant of β 2 -adrenergic receptor 260T/T CD14 allele 117 Thr/Thr variant of CSF LIGHT CSF = colony-stimulating factor MPO = myeloperoxidase TAFI = thrombin activatable fibrinolysis inhibitor Adapted from Stampfer MJ et al. Circulation. 2004;109(suppl):IV3-IV5.

6-weeks on strawberry supplemented diet protects against meal-induced increases in PAI-1. 9 7 5 3 1 PAI-1 0 180 360 time (min) Placebo Strawberry Ellis et al. 2011 J Athero Thrombosis

Berry Intake and CVD Summary Complex disease Multiple targets for promoting health Berries appear to have role in reducing CVD risk Several unanswered questions, but promising opportunity Future research warranted