2/10/2014. The Vascular Biology of Eating. Robert A. Vogel, MD Clinical Professor of Medicine University of Colorado Denver

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1 //4 The Vascular Biology of Eating Robert A. Vogel, MD Clinical Professor of Medicine University of Colorado Denver Disclosure: Consultant Pritikin Longevity Center Histological and Vascular Biological Pathways to Atherosclerosis Poor diet hypercholesterolemia LDL deposition & oxidation Macrophage uptake foamcells SMC proliferation & matrix prod. Plaque rupture/erosion (inflamm.) Thrombosis SFA, Hyperglycemia oxygen-frs NO inactivation (superoxide prod.) DDAH mediated ADMA prod. NO Endothelial dysfunction NF-ƙB mediated inflammation Vogel RA, 995 Example of a Decrease in Brachial Artery Flow-Mediated Vasodilation After a High Fat Meal 3.6 mm 4. mm Fasting Baseline Post-Occlusion 3 Hours After High Fat Meal 3.6 mm 3.7 mm

2 //4 Vogel RA et al, Am J Cardiol997;79:35 Effect of High and Low-Fat Meals on FMD in Normal Subjects Van OostromA et al, Circulation ;6:II-563 % Change in FMD and Inflammatory Parameters after a High-Fat Meal 5 * P <.5 5 Egg McMuffin, Sausage McMuffin, Hash Browns -5 - Triglycerides FMD Leukocytes IL-8 DoiH et al, Atherosclerosis 998;37:34 Effect of Human Postprandial Remnant-Like Particles on Rabbit Endothelium-Dependent and Endothelium-Independent Relaxation Ferreira AC et al, Circulation 4;:3599 Effect of a High-Fat Fast Food Meal on Circulating Endothelial Cell Microparticlesin Healthy Subjects (Measured by flow cytometrycd3+, CD4-, <.5 μm) Log EMP Log TG Change in EMP.8. R= P= P=..85 P= Baseline hr 3 hr Baseline hr 3 hr 5 Change in TG (3 hrs) high fat meal low fat meal

3 //4 Effect of High Glucose on Superoxide Production from Endothelial Cells 8 * O - Production (nmol/well/hr) 6 4 Control (5 mm) High Glucose ( mm) Cosentino et al., Circulation, 997 Yang Q et al, JAMA Intern Med /3/4 CVD Mortality vs. Dietary Added Sugar in,733 Healthy Subjects in NHANES III 3.5 U.S. Mean = 5% (8 ozregular soda).5.5 <% Cal from Added Sugar -5% Cal from Added Sugar >5% Cal from Added Sugar CerielloA et al, Circulation 5;:58 Effect of High Sugar and High Fat Meals on FMD &CRP before & after Atorvastatin + Irbesartan in Subjects with DM- Baseline Hr PP 4 Hr PP High Sugar High-Fat High Sugar & Fat FMD CRP FMD CRP FMD CRP FMD CRP Atorvastatin 4mg + Irbesartan 3mg 3

4 //4 DeCaterinaR, Libby P, J Lipid Res 998;39:6 Effect of MUFA, PUFA, and Omega-3 Fatty Acids on Inhibition of Inflammation (6 DB s) (4 DB s) ( DB s) ( DB) 3 ACC/AHA Dietary Guidelines to Lower LDL Cholesterol and Blood Pressure Appropriate calories High in vegetables, fruits, and whole grains Only low-fat dairy products Fish, legumes, and poultry for protein Vegetable oils and nuts for fat Less sugar-sweetened beverages and red meats <5-6% of calories from saturated fat Reduction in trans-fat <4 mg Na + (<5 is better), if not possible > mg Increase in Levels of Obesity in Last 5 Years Sturm, R., J. Ringel, and T. Andreyeva, "Increasing Obesity Rates and Disability Trends, "Health Affairs, Vol. 3, No., March/April 4, pp. 7. 4

5 //4 MadalaMC et al, J Am CollCardiol8;5:979 BMI vs. Age of First NSTEMI in the CRUSADE Registry (N=,847) lbs.5 yrs earlier NSTEMI Age st NSTEMI For every lbsover ideal weight at, the chance of dying before 9 increases by 8% BMI (kg/m ) Weindruch R et al, N Engl J Med 997;337:986 Median Survival of Genetically Obese Female Mice begun on Calorie Restriction at Month 45 Survival (months) ~5 kcal/wk Ad Libitum 85 kcal/wk 5 kcal/wk 4 kcal/wk PerticoneF et al. Diabetes ;5:59, Al SuwaidiJ, et al. ClinCard 8/ Effect of Obesity on Endothelial Function BMI (kg/m ) WHR 5

6 //4 Dandona P et al. J ClinEndicrinolMetab;86:355 Effect f Dietary Restriction ( kcal) on Neutrophil Reactive Oxygen Species Production in Obese Subjects Baseline 4 Weeks TchernofA et al, Circulation ;5:564 Effect of 5 kg Weight Loss (BMI 35 3kg/m ) on Lipids and CRP in Obese Postmenopausal Women * Baseline Wt loss * P<. LDL-C HDL-C TG CRP (mmol/l) (mmol/l) (mmol/l) (ug/ml) * * Popular Diet Study: Lipids 3 Atkins So Be Ornish Prot 6 Carb Fat SFA * Atkins South Beach Ornish ** * - ** - TC LDL-C TG HDL-C Miller M, et al, J Am Diet Assoc9;9:7 *P <.5 **P<. vs. other diets 6

7 //4 Miller M, et al Effect of Popular Diets on Fasting Flow-Mediated Dilation in 8 Healthy Subjects at Month Ornish Diet FMD(%) 9 8 South Beach Diet Baseline Diet R = -.97 Atkins Diet 7 3 Dietary Saturated Fat (%) Burr ML, et al. Lancet 989;334:757 DART Trial: Three Dietary Interventions in 33 Men with Prior MI over Years.4. Death CHD HR *P<.5 Fish: + servings/wk Fat: <3% cal Fiber: >8 g/d (.4 vs..6 g/wkn-3) de Longerilet al, Am J ClinNutr995;6:36S, JACC 996;8:3 Lyon Diet Heart Study 5 year RCT trial in 65 CHD subjects more whole grains more fruits, beans, and vegetables more fish less meat skim milk products canola oil margarine % Change % -% -% -3% -4% -5% -6% -7% -8% Chol CVE Death Late Cancer 7

8 //4 EstruchR, et al, NEJM 3;368:69, Sala-Vila et al, ESC 9/3 PREDIMED STUDY: Randomized Mediterranean Diets in 7447 Subjects with High CV Risk over 5 Yrs: Primary Outcome (MI, Stroke, CVD Death) 6% 5% 4% 3% % % % Carotid Plaque (mm 3 ) Low-fat:.37 EVOO:.44 Nuts: -.3* Low-fat (37%) Med diet Years TrichopoulouA et al, BMJ 9;338:b337 Greek EPIC Study: Contribution of Dietary Components to Reduction in All-cause Mortality (4%) in,655 Subjects over 9 Yrs High vegetable / legume % % 6% Moderate alcohol Low meat 7% 4% High monunsat-tosaturated fat High fruit / nut Vogel RA, et al. JACC ;36:455 Postprandial Effect of Components* of the Mediterranean Diet on Brachial Artery FMD FMD P=.8 Olive Oil Olive Oil, Vinegar, & Salad Preprandial Canola Oil Postprandial Salmon * 5 g fat 8

9 //4 BhupathirajuSN et al, Am J ClinNutr3:DOI:.3945/ajn Quantity and Variety in Fruits and Vegetables vs. CHD Risk in the NHS (n=7,4 women) and HP F/U (n=4,35 men) Studies HR < >8 Servings / day Quantity, but not variety was associated with reduced risk Dickinson KM et al, Am J ClinNutr9;89:485 Cook NR et al, BMJ 7 5 vs. 5 mmol Na + Diets in 9 TOHP: 5% Na+ in 3,6 Subjects Overweight Subjects Weeks for 5 Years mmol 5 mmol % -5% -% Baseline BP 6/ % -% 95-5% 9-3% SBP (mmhg) FMD (%) SBP CVE Death Mukamal KJ et al, Circulation 5;:3839 Steady vs. Binge Drinking vs. Recurrent MI in 935 Post-MI Subjects.4. Relative Risk for MI Steady Binge Abstainers Light Drinkers Heavy drinkers 9

10 //4 ImhofA et al, EurHeart J ;:497 Effect of Alcohol Consumption on C-Reactive Protein in 8 German Men and Women 8-88 Years Old C-Reactive Protein (mg/l).5.5 Alcohol Consumption g/d - g/d -4 g/d 4-6 g/d 6-8 g/d >8 g/d CorrettiM et al, J Am CollCardiol;39:8A Effect of Fast Food Meal with/without 8 Oz Black or Green Tea on Brachial Artery FMD % -5% -% -5% -% -5% -3% Fast Food Fast Food + Black Tea P <.5 Fast Food + Green Tea Histological and Vascular Biological Pathways to Atherosclerosis Poor diet hypercholesterolemia LDL deposition & oxidation Macrophage uptake foamcells SMC proliferation & matrix prod. Plaque rupture/erosion (inflamm.) Thrombosis SFA, Hyperglycemia oxygen-frs NO inactivation (superoxide prod.) DDAH mediated ADMA prod. NO Endothelial dysfunction NF-ƙB mediated inflammation