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Presentation Outline
Chapter 1: The Impact of Dietary Guidelines and Dietary Nutrients on Dyslipidemia AHA and NCEP ATP III Diet and Lifestyle Recommendations Dietary Di t Ch Cholesterol l t l Fats and Fatty Acids Dietary Nutrients Clinical Trials Dietary Interventions Chapter 2: The Management of Dyslipidemia through Diet, Exercise and Weight Loss Hypertriglyceridemia Exercise Guidelines Weight Management Behavior Modification
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Background
Data from INTERHEART, MRFIT, the Nurses Health Study, etc. suggest that 80% of cardiovascular events can be attributed to potentially y modifiable or preventable risk factors1-3 According to the AHA, in 2009 ~45% of adults had TC 200 mg/dL and 33% had LDL-C 130 mg/dL Meta-regression g analysis y showed that the relationship p between LDL-C lowering and the reduction in risk of CHD and stroke over 5 years of treatment was independent of the type of treatment used4 5 studies lowered LDL-C by diet, 3 by resins, 1 via ileal bypass, and 10 by statins
INTERHEART = A St Study d Of Ri Risk kF Factors t F For Fi First tM Myocardial di l I Infarction f ti I In 52 Countries C t i And A d Over 27,000 Subjects, MRFIT = Multiple Risk Factor Intervention Trial, AHA = American Heart Association, TC = Total Cholesterol, LDL-C = low-density lipoprotein cholesterol, CHD = coronary heart disease
1. Yusuf S, 1 S et al. al Lancet. Lancet 2004;364:937-952. 2004;364:937 952 2. Stamler J, et al. JAMA. 2000;284:311-318. 3. Hu FB, et al. N Eng J Med. 1997;337:1491-1499. 4. Robinson JG, et al. J Am Coll Cardiol. 2005;46:1855-1862.
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NCEP ATP = National Cholesterol Education Program Adult Treatment Panel JNC C = Joint National Committee C NHLBI = National Heart, Lung, and Blood Institute
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Cholesterol Absorption p
Most of cholesterol absorbed in upper part of small intestine at the brush border Diet: Approximately 200-300 mg/day 17 Mixed micelle C D Dietary fat 3A B Monoglycerides HO 5 Fatty F tt acids id 6 Phospholipids (biliary lecithin) Cholesterol Bile acid reabsorption: 600 mg/day Total: Approximately 800 mg/day reabsorbed intestinal cholesterol to hepatic cholesterol
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Cholesterol Synthesisa
1200
1192
P < 0.05
40
20
0
Obese (n = 10) Lean (n = 10)
aDetermined
by sterol balance technique and calculated as fecal steroids of cholesterol origin dietary Mietinnen TA, Gylling H. Atherosclerosis. 2000;153:241-248.
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cholesterol
Western Pattern Higher intake of Red meat Processed meat Refined grains Sweets S t and d desserts French fries High-fat dairy products RR for highest quintile: 1.64
Hu FB, et al. Am J Clin Nutr. 2000;72:912-921.
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AHA 2006 Diet and Lifestyle Recommendations for CVD Risk Reduction
Consume an overall healthy diet rich in fruits, vegetables, whole grain, high-fiber foods and include fish at least 2x/week Aim for:
A healthy body weight Recommended levels of LDL-C, HDL-C, and TG A normal blood pressure A normal blood glucose level
AHA 2006 Diet and Lifestyle y Recommendations for CVD Risk Reduction
Limit saturated fat to <7%, trans fats to <1%, and cholesterol h l t lt to <300 300 mg/day*. /d * D Do thi this b by: Choosing lean meats + vegetable alternatives Selecting fat-free fat free (skim), 1% fat, and low-fat low fat dairy products Minimizing intake of partially hydrogenated fats Minimize Mi i i i intake t k of fb beverages and df foods d with ith added dd d sugars Choose and prepare foods with little or no salt If alcohol is consumed, do so in moderation When eating food prepared outside of the home, follow the AHA Diet and Lifestyle Recommendations
*NCEP ATP III recommends <200 mg/day of cholesterol
Lichtenstein AH, et al. Circulation. 2006;114:82-96.
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* Lower trans fatty acids ** Emphasize complex sources TLC = Therapeutic Lifestyle Changes
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NCEP ATP III Recommends Avoiding High and Low Fat Intakes
Avoid very high fat intake Can lead to excess calories obesity Difficult Diffi lt t to meet t SFA goal l Concerns about some cancers Avoid very low fat intake Poor compliance p low HDL-C and high TG
Factors that Affect Diet Diet-Related Related LDL-C LDL C Response Beyond Genetic Influences
A higher initial serum cholesterol level is associated with a greater response1 An elevated CRP level decreases the diet response2 Maximum M i adherence dh t to di diet t greater t LDL-C LDL C l lowering i 3 Excess body weight cholesterol synthesis LDL-C4
1. Yu 1 Yu-Poth Poth S, S et al. al Am J Clin Nutr. 1999;69:632 1999;69:632-646 646. 2. Erlinger TP, et al. Circulation. 2003;108:150-154. 3. National Cholesterol Education Program Expert Panel on Detection. Circulation. 2002;106:3143-3421. 4. Denke MA , et al. Arch Intern Med. 1994;154:401-410.
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4 Studies Show Atherogenic Role for Elevated Dietary Ch l t l Independent Cholesterol I d d t of f Serum S Cholesterol Ch l t l Ch Change Irish Brothers Study Honolulu Heart Study Western Electric Study (Chicago) Zutphen Netherlands Study
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Food and Nutrition Board, Institute of Medicine, National Academies. 2002. Dietary reference intakes: energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. Washington, DC: National Academy Press.
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US Department of Health and Human Services and US Department of Agriculture. Dietary Guidelines for Americans, 2005. 6th ed. Washington, DC: Government Printing Press; 2005.
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*Effect is neutral as it is converted to monounsaturated fat in the body It neither ith raises i nor l lowers cholesterol h l t ll levels l
http://www.cfsan.fda.gov/~dms/qatrans2.html#s1q2
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50
Mensink and Katan (1992) Hegsted et al. (1993) Clarke et al. (1997) Mean
40
30
20
10
0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
TFA
TFA
Facts About TFA More densely yp packed than the cis mono fatty y acids ~ 2-3 % of energy intake is TFA If TFA Are A Consumed C d in i High Hi h A Amounts t LDL-C HDL HDL-C C Major Sources of Dietary TFA Baked goods (cookies, donuts, biscuits, pies) Snack foods (crackers, chips) Stick margarine margarine, shortening (fries (fries, fried foods)
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Effects on LDL-C and HDL-C when Replacing Carbohydrates with Fatty Acids
LDL
mm mol/L chang ge per 1% e energy LDL cholesterol (m mmol/L)
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Summary of Epidemiological Studies Regarding the Frequency of Nut Intake and RR of CHD
MUFAs in Humans
National dietary guidelines increasingly recommend MUFAs* (e.g., NCEP ATP III, AHA, United States Department of Agriculture, American Dietetic Association, Dietitians of Canada, FAO/WHO) Consumption of MUFA Promotes healthy lipid profiles Mediates blood pressure Improves I insulin i li sensitivity iti it Regulates glucose levels * Enhancing MUFA intakes up to 25% of energy
Gillingham LG, et al. Lipids. 2011;46:209-228. American Heart Assoc. Circulation. 2010;121:e46-e215. US Dept of Agriculture 2010 http://www.cnpp.usda.gov/dietaryguidelines.htm Kris-Etherton PM, et al. J Am Diet Assoc. 2007;107:1599-1611. FAO/WHO 2010 http://www.fao.org/ag/agn/nutrition/docs
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Relationship between Intake of Fish or Fish Oil and Relative Risk of CHD Death (in Prospective Studies and Randomized Clinical Trials)
Modest consumption of fish (1 to 2 servings per week; higher in EPA & DHA) reduces risk of coronary death by 36% Mozaffarian D, Rimm EB. JAMA. 2006;296:1885-1899.
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Risk of Total Mortality Due to Intake of Fish or Fish Oil in Randomized Clinical Trials
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Plant Sterols
Occur naturally Are structurally similar to cholesterol ~150-400 mg/d provided by typical western diet Higher intakes (1-3 (1 3 g/d) are needed to atherogenic lipoproteins >40 (also called phytosterols) identified Most common: sitosterol, campesterol & stigmasterol
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Plant Stanols
Similar to sterols but have no double bonds i.e., i th they are saturated t t d sterols t l Less abundant in foods than sterols Most common stanols found naturally y are sitostanol and campestanol
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Plant Sterols/Stanols
Are absorbed to a lesser degree than cholesterol1,2
50-60% cholesterol is absorbed in the intestinal lumen mainly y by y the action of Niemann-Pick C1-Like 1 0.5-15% of plant sterols/stanols are absorbed
Mechanisms of action
Because of structural similarity to cholesterol, may compete with cholesterol for incorporation into micelles and for transport across the brush border (therefore reducing cholesterol absorption) Accumulation of plant sterols or stanols in the enterocyte may upregulate production of ABC G5 and G8 proteins, which transport sterols out of the enterocyte into the intestinal lumen3 ABC = adenosine triphosphate binding cassette
1. Katan MB, et al. Mayo Clinic Proc. 2003;78:965-978. 2. Demonty I, et al. J Nutr. 2009;139:271-284. 3. Jones PJH. J Clin Lipidol. 2008; 2:S4-S10.
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Plant Sterols/Stanols
Efficacy ~2 g/d of plant sterols/stanols is equivalent to ~3.3 g/d of sterol or stanol esters and associated with mean 12 LDL C of LDL-C f 13.1 13 1 mg/dL /dL1,2 Can lower LDL-C by 10-15% TG and HDL-C are generally unchanged LDL-C lowering may be greater in older adults No fat malabsoprtion3,4 Plant sterols/stanols are equally efficacious
1 Katan MB, 1. MB et al. al Mayo Clinic Proc. 2003;78:965 2003;78:965-978 978. 2. Demonty I, et al. J Nutr. 2009;139:271-284. 3. Miettinen TA, Gylling H. Curr Opin Lipidol. 1999;10:9-14. 4. Gylling H, et al. J Lipid Res. 1999;40:593-600.
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Plant Sterols/Stanols
Tips for Patient Education
At 2 g/d (recommended by NCEP), neither the food form nor the background diet impact response Some evidence that once-daily dosing is less effective than more frequent dosing Recommend consumption with meals Some patients may prefer to use them in cooking or melt on vegetables g rather than use as a spread p
Negative Aspects
Expense Preference P f some do d not t lik like margarine; i other th products d t available (orange juice, smoothies) Decrease in carotenoids in some studies Adjust by increasing fruits and vegetables in diet
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Dashed curve is created for sterol studies; ; Solid curve is created for stanol studies
Data adapted from Katan MB, et al. Mayo Clin Proc. 2003;78:965-978.
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1.
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Effect of a Dietary y Portfolio of Cholesterol Lowering Foods vs. Lovastatin on p and CRP Serum Lipids
Design: Randomized controlled trial Who: 46 healthy y hyperlipidemic yp p adults 25 men 21 postmenopausal women Methods: Compared control diet, control diet plus lovastatin 20 mg/day, and dietary portfolio
Mechanism
Increase bile acid losses Reduce hepatic cholesterol synthesis, increase LDL receptor messenger RNA Reduce cholesterol absorption b ti Shown to lower LDL-C
-15 -20 -25 -30 -35 35 -40 LDL-C LDL-C: HDL-C Ratio
c c c b c a
CRP
aP
Soy y Protein
Effect on CAD: Evidence de ce for o a co consistent, s ste t, s significant g ca t e effect ect o of soy protein on CHD was not found by ATP III FDA health claim for soy protein: Diets low in saturated fat and cholesterol that include 25 g of soy protein per day may reduce the risk of heart disease
Meta-analysis: Effective at higher LDL-C levels only1 LDL-C lowering depends on the amount of soy consumed d
Effects of Plant Stanols (2 g/d) and Si Simvastatin t ti (10 mg/d) /d) i in S Subjects bj t with ith Metabolic Syndrome
Control 20.0 Stanol Simvastatin Stanol+Simvastatin
11.7
10.3
% Chan nge
0.0
-1.7
-10.0
-11.6
-5.9 -10.0
-15.9
21.0 21 0
Non-HDL-C
HDL-C
TG
Plat J, et al. J Nutr. 2009;139:1143-1149.
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Prospective Cohort Studies of CVD Show the Benefits of High Fiber Carbohydrates
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Chapter 2 The Management of Dyslipidemia through Diet, Exercise and Weight Loss
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F ll Follow up Vi Visit it @ 6 mo
May labs: TC 182, TG 74, HDL 40, LDL 127, Apo B 101, Lp(a) 27 Weight 166 (lost 11 pounds) Exercise: TM + Bike 4x/week EBCT = Electron Beam Computed Tomography CMP = Comprehensive Metabolic Panel TSH = Thyroid Stimulating Hormone WNL = Within Normal Limits
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CHO = Carbohydrate
epidemiological studies Resveratrol in red wine may CV benefits via LDL oxidation, nitric acid, or by changes in thrombogenicity, ischemia, or vascular tone1 Observational data Al h l intake Alcohol i t k may b be causally ll related l t dt to l lower risk i k of f CHD through changes in lipids (HDL-C, Apo AI, TG) and hemostatic factors2
1. Opie LH, et al. Eur Heart J. 2007;28:1683-1693. 2. Rimm EB, et al. BMJ. 1999;319:1523-1528.
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OMNI
Macronutrient Goals, % kcal
CARB Carbohydrate Protein Fat Monounsaturated Polyunsaturated Saturated
* 58*
PROT UNSAT 48 25 27 13 8 6 48 15 37 21 10 6
15 27 13 8 6
*Similar to DASH diet, except that the carbohydrate content of DASH was 55% kcal and its protein content 18% kcal. OMNI = Optimal Macronutrient Intake Heart DASH = Dietary Approaches to Stop Hypertension
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0 -10
CARB*
PROT
UNSAT
mg/dL
-20 -30
-19 -24
* -28
CARB
PROT
UNSAT
mg/dL
-29 29
-33
* -56
HDL-C Response to Exercise Training in the HERITAGE G Family Study S (20 ( Weeks) )
C Change From Ba aseline (% %)
1. Significantly different from the normolipidemic men; 2. Significantly different from men with isolated low HDL-C; 3. 3 Significantly different from men with isolated high TGs
HERITAGE = Health, Risk Factors, Exercise Training and Genetics Family Study
Couillard C, et al. Arterioscler Thromb Vasc Biol. 2001;21:1226-1232.
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