1 School of Nursing Talk 4-21-11 Nutrition, Hyperlipidemia, Thrombosis and Atherosclerosis. What Are...

1School of Nursing Talk

4-21-11

Nutrition, Hyperlipidemia, Thrombosis and Atherosclerosis. What Are The Nutrition Choices?

Lewis H. Kuller, M.D., Dr.P.H.Distinguished University Professor of Public Health

Department of EpidemiologyUniversity of Pittsburgh

April 21, 201110:30-11:30am

School of Nursing


4-21-11

Dietary Approaches Associated with Low Risk of CHD

1. Vegetarian - very low fat, saturated fat.2. High polyunsaturated fat (vegetable sources)

Linoleic acid – Israel (omega-6)α-linolenic acid – France (omega-3)

3. High in polyunsaturated fat, fish sourcesJapan (omega-3)

4. French diet may be fourth, not Mediterranean diet.5. Mediterranean diet, olive oil, fruits, vegetables, low

beef, red wine.


4-21-11

Twenty-five-Year Coronary Heart Disease (CHD) Mortality Rates per Baseline Cholesterol Quartile, Adjusted for Age, Cigarette Smoking, and Systolic Blood Pressure

Verschuren WM Monique; et al. Serum total cholesterol and long-term coronary heart disease mortality in different cultures: Twenty-five-Year Follow-up of the Seven Countries Study. JAMA, July 12, 1995, 274 (2):131-136.


4-21-11

Relative Risks (95% Confidence Intervals) per 0.50-mmol/L [20-mg/dL] Cholesterol Increase, Before and After Correction for Regression Dilution, Adjusted for Age,

Smoking, and Systolic Blood Pressure

Cohort Unadjusted for Regression Dilution

Adjusted for Regression Dilution

Northern Europe 1.12 (1.08-1.15) 1.18

United States 1.15 (1.10-1.19) 1.21

Southern Europe, Inland 1.10 (1.04-1.16) 1.14

Southern Europe, Mediterranean 1.12 (1.04-1.22) 1.18

Serbia 1.11 (0.97-1.28) 1.14

Japan 0.96 (0.77-1.18) Not available

Overall 1.12 (1.09-1.16) 1.17*

Verschuren WM Monique; et al. Serum total cholesterol and long-term coronary heart disease mortality in different cultures: Twenty-five-Year Follow-up of the Seven Countries Study. JAMA, July 12, 1995, 274 (2):131-136.

*Based on the average regression dilution factor of 1.4


4-21-11

8.49

126.37

0

20

40

60

80

100

120

140

0 DM,Htn, Tob

+ Tob + Htn + Htn,Tob

+DM,Htn, Tob

CH

D In

cid

en

ce

pe

r 1

0,0

00

PY

18.5-24.5 25-29.9 30-34.9 35-39.9 40+

14.9-folddifference

Marked increase in CHD risk

McTigue K, Chang Y, Valoski A, Eaton CB, Garcia L, Lewis CE, Liu S, Johnson K, Robinson J, Rosal M, Kuller L. Adding Weight Status to Cardiovascular Risk Factor Presence Can Help Delineate Coronary Heart Disease Risk in 50-59 Year Old White & Black Women. AHA Talk:2008.


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Multivariable* model for incident CHD risk BMI ≥ 40

Entire Cohort No Diabetes Type 2 DiabetesHR(95%CI) HR(95%CI) HR(95%CI)

N (cases/total) 117/677 68/467 49/210Diabetes 1.60 (1.17, 2.39)Age 1.04 (1.01, 1.07) 1.06 (1.01,1.10) 1.02 (0.95,1.09)Current smoking 2.83 (1.18, 6.79) 2.65 (0.99,7.11) 4.32 (1.03, 18.21)Total LDL-P 4.95 (2.56, 9.58) 3.03 (1.41,6.51) 14.90 (3.01, 73.73)Total HDL-P 0.15 (0.05, 0.45) 0.14 (0.03,0.57) 0.63 (0.08, 5.08)

*Model includes ethnicity, BMI, waist circumference, hypertension, lipid-lowering medications, Recreational Phys. Activity, adiponectin, leptin, ghrelin.


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©2005 PPS®

Trends in Total Cholesterol* for US Adults, 1960-1962 to 1999-2002

1960-1962 1971-1974 1976-1980 1988-1994 1999-2002200

210

220

230

240

250

260

270 Men (aged 60-74)Women (aged 50-59)Women (aged 60-74)

†

†

†

*Mean values. †P<0.001 for difference between NHANES III (1988-1994) and NHANES 1999-2002.

Carroll MD et al. JAMA. 2005;294:1773-1781.

TC (m

g/dL

)


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Macronutrient Intake (percent kcals) by Sex in Adults Aged 20 and Over, 1999-2008

NOTE: Kcals are kilocalories.SOURCE: CDC/NCHS, National Health and Nutrition Examination Survey.

Wright JD, Wang C-Y. Trends in intake of energy and macronutrients in adults from 1999-2000 through 2007-2009. NCHS Data Brief, No. 49, November 2010.


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Lower Saturated Fat

– Very successful in reducing the amount of saturated fat in the diet, 16-17% or more to 10-11% or less.

– Major source of saturated fat now are meat products, baked goods and cheese

– Unsuccessful to further reduce saturated fat 6-7% except by reducing beef consumption and possibly further modification of cheeses – Vegetarian Diets?

– Decrease in blood cholesterol level in the US population may be slowing. Obesity epidemic, lack of nutrition effects, mixed messages.

– Vegetarian diets associated with lower BMI– Reduction of animal food – beef – may be key.– Reduce quantity, frequency and type of foods eaten between meals:

no grazing.


4-21-11

Diet Effects on Lipids and Apolipoproteins

AAD Step 1 (9%) Low-Sat (6%)

TC 202.1 ± 2.8*† 191.0 ± 2.7‡ 183.4 ± 2.7

LDLC 131.4 ± 2.7*† 122.2 ± 2.6‡ 116.9 ± 2.6

HDLC 52.2 ± 1.1*† 48.5 ± 1.1‡ 46.2 ± 1.0

TG 85.1 ± 3.4* 92.4 ± 3.7 93.0 ± 3.7

TC indicates total cholesterol; LDLC, LDL cholesterol; HDLC, HDL cholesterol; and TG, triglyceride. These values are mean ±SEM, for the overall group of 103 subjects. They have been adjusted only for slight period effects observed. The TG values are antilogs of In(TG) data. The Lp (a) values are square-root data. All values are mg/dL.*P<.01 AAD vs Step 1, based on adjusted values from the linear regression model descries in “Methods”.†P<.01 AAD vs Low-Sat, based on adjusted values from the linear regression model described in “Methods”.‡P<.01 Step 1 vs Low-Sat, based on adjusted values from the linear regression model described in “Methods”.

Ginsberg HN, Kris-Etherton P, Dennis B, et al. Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: The Delta Study, Protocol 1. Arterioscler Thomb Vasc Biol 1998;18:441-449.


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Major Contributors of Saturated Fat in the US Diet: Data from the NHANES II Survey, 1976-1980

Rank Description % of total saturated fat

Cumulative % of saturated fat

1 Hamburgers, cheeseburgers, meat loaf 9.31 9.31

2 Whole milk, whole milk beverages 9.11 18.42

3 Cheeses, excluding cottage cheese 7.28 25.70

4 Beef steaks, roasts 7.28 32.98

5 Hot dogs, ham, lunch meats 7.04 40.02

6 Doughnuts, cookies, cake 4.84 44.86

7 Eggs 4.52 49.38

Block G, Dresser CM, Hartman AM, Carroll MD. Nutrient sources in the American diet: quantitative data from the NHANES II survey. American Journal of Epidemiology 1958;122(1):27-40.


4-21-11

The Level of LDL-C in Different Species and Populations

Animals Neonates Hunter-gatherers US Adults0

40

80

120

70

35

Mean LDL-C in USAAge LDL-C m/dl

20-29 111

30-39 121

40-49 126

50-59 133

60-69 130

Forrester JS. Redefining normal low-density lipoprotein cholesterol: a strategy to unseat coronary disease as the nation’s leading killer. J Am Coll Cardiol 2010;56:630-6.


4-21-11

Age-Specific Risks of Fatal Coronary Heart Disease in Non-Vegetarians Compared to Vegetarians, 1960-1980

Age-group (years) Relative risk for nonvegetarians compared to vegetarians

Men Women

45-54 4.02 (1.6-9.9) 0.93 (0.4-2.4)

55-64 1.79 (1.2-2.6) 1.40 (0.8-2.4)

65-74 1.68 (1.3-2.2) 1.40 (1.1-1.8)

75-84 1.28 (1.1-1.6) 1.38 (1.2-1.6)

RR (95% CI); adapted from Snowdon, et al., Preventive Medicine 1984;13:490-500. Reprinted with permission.

Luepker RV. Feasibility of Risk Factor Reduction in the Elderly. Coronary Heart Disease in the Elderly. NK Wenger, CD Furberg and E Pitt (eds.). 1986, Elsevier Science Publishing Co., Inc. p. 145.


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• When the diet contains substantial amounts of hydrogenated fats, the effect of the trans isomers they contain must be considered. The trans acids tend to elevate the serum cholesterol level as compared with equal amounts of the natural cis isomers in the diet, and a still greater effect on the serum triglycerides is observed (Anderson, et al., 1961).

• The chain length of the saturated fatty acids also has an effect but this has little importance in natural diets (Grande et al., 1961). Saturated fatty acids with 10 or fewer carbons in the chain have little or no effect while the most powerful cholesterol-raising effect is observed with the 12-carbon lauric acid.

Keys, A. (1957). The role of the diet in human atherosclerosis and its complications.


4-21-11

Changes in Weight and Cardiovascular Risk Factors with Plant-Based Diets

Reference/year Duration Weight change, kg (%) LDL, % change

Gardner et al./2005 4 weeks NC -9.3

Barnard et al./2005 14 weeks -5.8 (6.5) ND

Barnard et al./2006 22 weeks -6.5 (6.3) -21.2

Pischke et al./2006 1 year -5.0 (6.1) -14.7

Daubenmier et al./2006 12 weeks -4.8 (5.4) -15.4

Ornish et al./2005 1 year -4.5 (5.6) -22.9

Jenkins et al./2006 1 year -0.7 (1.0) -13.6

Chen et al./2006 2 weeks -4.3 (4.7) -25.3

Roberts et al./2006 3 weeks -3.2 (3.0) -25.6

Dewell A, Ornish D. Plant-based dietary patterns in the control of obesity and cardiovascular risk. Current Cardiovascular Risk Reports 2007;1:9-15.


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Polyunsaturated Fat in US Diets

1. Very popular in the 1950s-1960sa. High polyunsaturated fat, 12-18% more in National Diet- Heart Study.b. Cleveland Clinic, Helen Brown, Irving Page.

Fad – linseed oil mania: Liquid oils on ALL foods!!2. Problem – concern that very high polyunsaturated fat diet

not “natural”. No population at level of polyunsaturated fat.3. Risk of oxidative effects and increased risk of cancer and

other diseases and calories result in increased weightThus, compromise was to lower total polyunsaturated fat 10%


4-21-11

• A suitable diet for serum cholesterol reduction is our standard, which contained 38% (range 34.7-40.5) of calories as total fat, 11% (10.6-12.6) saturated fatty acids, 17% (15.2-18.1) polyunsaturated fatty acids, and 200 mg (180-238) of cholesterol.

• The critical limit of fat composition for significant reduction in serum cholesterol depends upon the amount of total fat in the diet. When 36% to 42% of calories come from fat, saturated fatty acids must be less than 14% and the polyunsaturated fatty acids more than 15%. If 30% of calories are derived from fat, the maximum allowable amount of saturated fatty acids is 10% and the minimum polyunsaturates is 13%. At both levels of total fat, dietary cholesterol must be less than 450 mg/day.

Brown HB, Farrand M, Page IH. Design of practical fat-controlled diets: foods, fat composition, and serum cholesterol content. Journal of The American Medical Association 1966;196:205-213.

1966


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Critical Limits of Dietary Fat Composition for Serum Cholesterol Reduction - 1966

Component Diet with 36-40% Fat Calories

Diet with 25-30% Fat Calories

Saturated fatty acids Less than 14% calories Less than 11% calories

Polyunsaturated fatty acids More than 14% calories More than 13% calories

Cholesterol Less than 350 mg. Less than 300 mg.

Brown HB, Farrand ME. Pitfalls in constructing a fat-controlled diet. Journal of the American Dietetic Association 1966;49(4):303-308.


4-21-11

1960’s• Summarizing, then, the fats and oils industry

responded to the urging of the health professions for a higher ratio of polyunsaturated to saturated fats in the diet by modifying their products, so that:

Shortening P/S ratios doubled,(from 0.5/1 to 1/1).

Margarine P/S ratios tripled,(from 1/1 to 3/1).

Salad oil P/S ratios quadrupled,(from 0.75/1 to 3/1).

Hastert, R. C. (1983). Hydrogenation-A tool, Not an Epithet. In E.G. Perkins, W. J. Visek (Eds.), Dietary Fats and Health (pp. 53-69). Champaign, Illinois. American Oil Chemists’ Society.


4-21-11

Mean (±S.E.) Serum Cholesterol Change after 4 and 11 Days on Diet with 450 cal of Rice Being Replaced with 50 g of Fat: “B” = Butter; “AM” = Animal Fat (mostly

whale oil) Margarine; “VM” = All-Vegetable-Oil Hydrogenated Fat 41%

Group N

∆ Total Cholesterol

mg/100 ml

4 Days 11 Days

B 7 +0.43 ± 6.58 +17.57 ± 5.23

AM 6 +2.17 ± 3.65 +19.00 ± 7.98

VM 5 +8.80 ± 5.09 +14.20 ± 6.92

AM + VM 11 +5.18 ± 3.62 +16.82 ± 4.82

All 18 +3.30 ± 3.11 +17.11 ± 3.66

Keys A, Kimura N, Kusukawa A, Toshitomi M. Serum cholesterol in Japanese coal miners: a dietary experiment. American Journal of Clinical Nutrition1957;5:245-250.

1957 – Ancel Keys


4-21-11

1960’s• The plan of action described earlier had succeeded. The saturated

fat controversy had been handled in a serious manner. Consumer acceptance of traditional products had been maintained. Hydrogenation had again proven its versatility and worth.

• At the 1974 spring meeting of the AOCS, F.A. Kummerow, a long time member of the Society, presented a paper (13) which indicated that ingestion of trans-isomers resulted in the formation of more-plasma cholesterol than cis-isomers. His evidence was based on feeding tests with swine.

• Enjoyment of eating is one of the few pleasures left to humankind. We certainly have a responsibility to cooperate in keeping it from become another neurotic experience in our hectic world.

Hastert, R. C. (1983). Hydrogenation-A tool, Not an Epithet. In E.G. Perkins, W. J. Visek (Eds.), Dietary Fats and Health (pp. 53-69). Champaign, Illinois. American Oil Chemists’ Society.


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• In terms of diet and control of hyperlipidemia, these types generally respond to a diet moderate in total fat (30 to 35% of total calories), low in saturated fat (less than 10% of calories), low in cholesterol (less than 300 mg/day), moderate in calories to effect and maintain correction of overweight, moderate in polyunsaturated fat (10 to 15% of calories), moderate in carbohydrate (40 to 45% of calories), low in sugar, moderate in alcohol, and high in protein (20 to 25% of calories).

Page IH, Stamler J. Diet and coronary heart disease (I). Modern concepts of cardiovascular disease 1968;37(9):119-124.

1968


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Comparison of results in 10 cholesterol (C) –lowering drug trials with experience of the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT). Reduction in total cholesterol level was associated with a reduction in incidence of coronary heart disease

(CHD) in all trials

(Reprinted with permission from Lipid Research Clinics Program. JAMA 1984; 251:365-74).

Castelli WP. Cardiovascular disease in women. Am J Obstet Gynecol 1988;158:1553-1560.


4-21-11

Forest Plot of Non-Fatal Myocardial Infarction (MI) + CHD Death

The lower box and indicate that n-6 specific PUFA trials increased the risk of non-fatal MI + CHD death by 13% (risk ratio (RR) 1.13; 95% CI 0.84, 1.53; P=0.427). These data do not include the Sydney Diet-Heart Study, an n-6 PUFA RCT that found a 49% increased risk of death from all causes (RR 1.49; 95% CI 0.95, 2.34; P=0.08). The upper box and indicate that mixed n-3/n-6/ PUFA trials reduced the risk of non-fatal MI + CHD death by 22% (RR 0.78; 95% CI 0.65, 0.93; P=0.005). Overall and accompanying indicates that the combination of n-6 specific PUFA and mixed n-3/n-6 PUFA diets reduced the risk of non-fatal MI + CHD death by 15% (RR 0.85; 95% CI 0.73, 0.99; P=0.04). n-3 + n-6, mixed n-3/n-6 PUFA studies; n-6, n-6 specific PUFA studies; overall, all included PUFA trials; Soy Oil, Medical Research Council Soy trial; STARS, St Thomas Atherosclerosis Regression Study; MCS, Minnesota Coronary Survey.

Ramsden CE, Hibbeln JR, Majchrzak SF, Davis JM. n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials. British Journal of Nutrition. 2010;104:1586-1600.


4-21-11

Serum Levels of Fatty Acids in Japanese Men, White Men, and Japanese-American Men in 2002 to 2006

Japanese Men (n = 281)

White Men (n = 306)

Japanese-American Men

(n = 281)p Value

Total fatty acids (mg/dl) 245 237 243 NS

Marine-derived n-3 fatty acids 9.2 3.9 4.8 *†‡

Total n-6 fatty acids 35.1 41.4 41.4 *‡

Linoleic acid 26.8 29.9 30.2 *‡

Trans fatty acids (%) 0.6 1.0 0.9 *†‡

*p<0.01 between the Japanese and white men.†p<0.01 between white and Japanese-American men.‡p<0.01 between the Japanese and Japanese-American men.

Sekikawa A, Curb JD, Ueshima H; et al. Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese-American, and white men: a cross-sectional study. J Am Coll Cardiol 2008;52:417-24.


4-21-11

Extent of Atherosclerosis in Japanese, White, and Japanese-American Men in 2002 to 2006

Japanese Men (n = 281)

White Men (n = 306)

Japanese-American Men (n = 281)

p Value

Coronary artery

CCS (median IQR) 0 1.0 0 *†

Prevalence of CAC (%) 9.3 26.1 31.4 *†

Carotid artery

CCA IMT (μm), mean SD 614 670 720 *†‡

Prevalence of CCA plaque (%) 0 0.7 16.7 *†‡

*p<0.01 between Japanese versus white men.†p<0.01 between Japanese versus Japanese-American men.‡p<0.01 between white and Japanese-American men.

Sekikawa A, Curb JD, Ueshima H; et al. Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese-American, and white men: a cross-sectional study. J Am Coll Cardiol 2008;52:417-24.


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Kaplan-Meier Estimates of Incidence of Coronary Events in JELIS Study:Primary Prevention Group

Saravanan P, Davidson NC, Schmidt EB, Calder PC. Cardiovascular effects of marine omega-3 fatty acids. Lancet 2010;376 (9740):540-50.


4-21-11

Proportional Use of Cooking Fats and Fatty Acid Composition of Average Cooking Fat in Mauritius, 1987-92

Saturated Monounsat-urated

Polyunsat-urated

Saturated Monounsat-urated

Polyunsat-urated

0

10

20

30

40

50

60

37.5 37.3

20.4

14.5

24.1

56.4

1987 1992

Prop

ortio

n of

Use

75 g palm oil/25 g soya bean oil99 g soya bean oil/.6g ghee/

0.4 g polyunsaturated margarine

Average Fat Composition/100 g Cooking Fat

Uusitalo U, Feskens EJM, Tuomilehto J, Dowse G, Haw U, Fareed D, Hemraj F, Gareeboo H, Alberti KGMM, Zimmet P. Fall in total cholesterol concentration over five years in association with changes in fatty acid composition of cooking oil in Mauritius: cross sectional survey. BMJ 1996;313:1044-46.


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Age Standardized Prevalence of Non-Communicable Diseases and Risk Factors in Mauritians, 1987-92

Diabetes Impaired Glucose Tol-

erance

Hypertension Borderline Hypertension

Obesity (BMI >30 kg/m²)

Overweight (BMI 25-30

kg/m²)

Cholesterol ≥6.5 mmol/l

Triglycerides ≥2.0 mmol/l

0

5

10

15

20

25

30

35

12.113.5

15

11

3.4

22.824.5

28.2

13.9 1412.1

8.3

5.3

30.4

5.6

25.4

1987 1992

Disease or Risk Factor

Prev

alen

ce

Dowse GK, Gareeboo H, Alberti KGMM, Zimmet P, Tuomilehto J, Purran A, Fareed D, Chitson P, Collins V R, Hemraj F for the Mauritius Non-communicable Disease Study Group. Changes in population cholesterol concentrations and other cardiovascular risk factor levels after five years of the non-communicable disease intervention programme in Mauritius. BMJ 1995;311:1255-9.


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“However, it is fair to say that a French paradox does appear to exist in that the archetypal slender profile of French people occurs against a backdrop of a diet dominated by high-fat foods (rich sauces, red meat, and cheese) and accompanied by significant intake of wine. To understand this paradox, one must consider not only what a culture eats but also how it eats---in other words, it is important consider the relationship of people with food not simply the food’s nutritional composition. Compared to western societies, the French eat differently in that they consume most of their food at meal times shared with others, they spend a much longer period of time eating their meals, and they rarely snack between meals. The differences between the French and Americans in their relationship with food are illustrated by the results of a sociological study of eating habits of French-speaking subjects (French and some Swiss) and English-speaking subjects (the US and UK). When asked what “eat well” meant for them, Americans immediately mentioned health; in contrast, health came far after pleasure for the French. The study also jokingly referred to the two styles of eating as “the stable” for the US (where individuals eat anytime of day), and “the Zoo” for the French (where individuals eat at set feeding time). As a consequence, the French pattern of eating contributes to the overall consumption of few calories while maximising gustatory enjoyment by engaging all the senses.”

Azaïs-Braesco V, Brighenti F, Paoletti R, et al. Healthy food and healthy choices: A new European profile approach. Atherosclerosis Supplements. 2009;10:1-11.

“The Stable” American or “The Zoo” French


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Compared With Dietary Monounsaturated and Saturated Fat, Polyunsaturated Fat Protects African Green Monkeys From Coronary Artery

Atherosclerosis

• Atherogenic diets enriched in saturated, n-6 polyunsaturated, and monounsaturated fatty acids were fed to African green monkeys for 5 years to define effects on plasma lipoproteins and coronary artery atherosclerosis. The monkeys fed polyunsaturated and monounsaturated fat had similar plasma concentrations of LDL cholesterol, and these values were significantly lower than for LDL in the animals fed saturated fat. Plasma HDL cholesterol concentrations were comparable in animals fed saturated and monounsaturated fat and were significantly higher than in animals fed polyunsaturated fat. Coronary artery atherosclerosis as measured by intimal area was less in the polyunsaturated fat compared with the saturated fat groups, was less in the animals fed polyunsaturated fat compared with the monounsaturated fat-fed animals, but did not differ between the monounsaturated and saturated fat groups.

Rudel LL, Parks JS, Sawyer JK. Compared with dietary monounsaturated and saturated fats, polyunsaturated fat protects African green monkeys from coronary artery atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology 1995;15:2101-2110.


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Mediterranean Dietary Pattern in a Randomized Trial: Prolonged Survival and Possible Reduced Cancer Rate

α-Linolenic Acid

Cancers Total deaths Cardiac death Total deaths + nonfatal cancers

Total deaths + nonfatal cancers + nonfatal MIs

0

0.1

0.2

0.3

0.4

0.5

0.390000000000002

0.44

0.35

0.44

0.380000000000002

Event

Risk

Rati

o

P=.05

P=.03

P=.01

P<.001

(0.15-1.01) (0.21-0.94) (0.15-0.83) (0.24-083) (0.23-0.61)

P=.01

De Lorgeril M, Salen P, Martin J-L, Monjaud I, Boucher P, Mamelle N. Mediterranean dietary pattern in a randomized trial. Prolonged survival and possible reduced cancer rate. Arch Intern Med 1998;158:1181-1187.


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Kaplan-Meier Curves for Primary and Secondary End Points

Kaplan-Meier curves are shown for the cumulative incidence of major cardiovascular events (the primary end point) and fatal coronary heart disease (a secondary end point) among 4837 patients who had had a myocardial infarction and were assigned to receive a study margarine containing supplemental eicosapentaenoic acid (EPA) combined with docosahexaenoic acid (DHA), a margarine containing alpha-linolenic acid (ALA), a margarine containing both EPA-DHA and ALA, or a placebo margarine.

Kromhout D, Giltay EJ, Geleijnse JM, for the Alma Omega Trial Group. n=-3 fatty acids and cardiovascular events after myocardial infarction. N Eng J Med 2010; August 28, 2010.


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Change in LDLc In Women’s Study by Weight Loss – Intervention OnlyWomen Not on HT at Baseline or Lipid Lowering Therapy by 48 Months

LDL-Baseline 128mg% (6 on lipid lowering at 48 months excluded)

20+ 10-19 5-9.5 0-0.5 Gained Total Assessment-25

-20

-15

-10

-5

0

5

10

Intervention Weight Loss in lbs at 48 Months

Perc

ent C

hang

e in

LD

L Ch

oles

tero

l

n=14

n=17

n=71 n=78

n=9

n=14

n=17

Kuller, LH. WOMAN Study. Submitted for publication.


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WOMAN Study – Changes in Risk Factors at 48 Months by Weight Loss – Intervention Group Not on HT at Baseline Or On Lipid Lowering Drugs at 48 Months

Weight Loss N % LDLc HDLc Systolic Blood

Pressure

Glucose Insulin

>20 lbs 9 12 -22 6.3 -1.6 -1.0 -4.0

10 to 19.5 15 21 -10 6.3 -5.6 2.4 -4.0

9.5 to 5.0 17 24 +05 4.8 -6.6 6.9 ---

4.8 to0 14 19 -03 1.2 +3.4 4.7 -1.4

Weight Gain 1 to 39.50 17 24 +03 -3.1 +3.3 10.2 +1.4

Total 72 100 -03 2.6 -1.5 5.5 -1.3

*6 on lipid lowering at 48 months (excluded)


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Adjusted CHD risk for LDL particlesHazard ratios for 1 unit log-LDL particles

Model 1 Model 2 Model 30.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

Small LDL-PTotal LDL-P

Model 1 Model 2 Model 30.0

1.0

2.0

3.0

Model 1: age, race. Model 2: Model 1+ BMI, waist Model 3: Model 2+ diabetes, hypertension, smoking, lipid lowering, adiponectin, leptin, ghrelin recreational physical activity


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Adjusted CHD risk for HDL particlesHazard ratios for 1 unit log-HDL particles

Model 1 Model 2 Model 3 Model 1 Model 2 Model 30.0

0.2

0.4

0.6

0.8

1.0

1.2

Total HDL-P Large HDL-P

Model 1: age, race. Model 2: Model 1+ BMI, waist Model 3: Model 2+ diabetes, hypertension, smoking, lipid lowering, adiponectin, leptin, ghrelin recreational physical activity


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Energy Intake (kcals) by Sex and Race-Ethnicity for Adults Aged 20 and Over, 1999-2008




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Mean Food Energy and Fat/Saturated Fat Intake from USDA Surveys for Selected Sex/Age Groups

Men 19 to 50 Women 19 to 50

% Energy fat % Saturated fat % Energy fat % Saturated fat

HFCS Spring 1965 43.7 41.9

NFCS 1977-78 41.4 40.9

CSFII 1985 41.5 13.3 36.7 13.5

CSFII 1986 36.4 13.3

NFCS 1987-88 37.3 13.4 36.2 13.0

CSFII 1989-91 35.4 12.5 34.4 12.0

CSFII 1994 33.7 11.3 32.5 10.9

CSFII 1995 33.1 11.3 32.8 11.1

Kennedy ET, Bowman SA, Powell R. Dietary-fat intake in the US population. Journal of the American College of Nutrition 1999;18(3):207-212.


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Risk of Death from Coronary Heart Disease over 19 Years in 1900 Men, According to Base-Line Level of Dietary Variables

Dietary Variables Coronary Deaths (percent) Logistic Regression

Low 3D Middle 3D High 3D P

Hegsted et al. Diet score 9.8 10.6 13.6 0.004

Keys et al. Diet score 9.3 11.2 13.4 0.010

Saturated fatty acids (percent cal) 10.9 11.2 11.8 0.144

Polyunsaturated fatty acids (percent cal) 13.5 10.4 10.1 0.010

Dietary cholesterol (mg/1000 kcal) 10.9 9.5 13.6 0.008

Shekelle RB, MacMillan Shryock A, Paul O, Lepper M, Stamler J, Liu S, Raynor WJ. Diet, serum cholesterol, and death from coronary heart disease: the Western Electric Study. The New England Journal of Medicine 1981;304(2):65-70.


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The level of evidence (“EBM”) indicated for each study is based on a grading system that evaluates the scientific rigor of the study design, as developed by the U.S. Preventive Services Rask Force

Agent Lipoprotein effects Lipid effects DoseClinical/

Surrogate Outcomes

EBM Level

Pantethine ↓apoB, ↑apo-A-1↓TC, LDL-C (12%),

TG (18%) ↑HDL-C (9%)

900 mg qd, divided No II-(1-3)

Tocotrienois ↓apoB (~10-14%) ↓TC, TG, LDL-C ~15-20%

200 mg qd purified δ / γ q-evening with meal/12 hrs form tocopherols

Carotid ultrasound I

ECCG n/a “Reduces LDL oxidation” 60 oz green tea/day, or 500 mg EGCG qd-bid No II-3

Myo-inositol n/a ↓TG 20%↑HDL-C 22% 2g myo-inositol bid No I

Mediterranean Diet + medical food (soy, plant

sterols, phyto-chemicals)↓apoB 18%, ↓apoB/apoA-1

22%, ↓LDL-P 16% ↓LDL-C 15% No I

Portfolio Diet ↓apoB 24% ↓apoA-1 7.5% apoB/apoA-1 ratio ↓22%

↓LDL-C 29%, TG 10%, HDL-C 7%

↑sterols, viscous fiber, nuts, soy protein (see text) No I

Combination Sterols, EGCG, δ tocotrienol,

phytolens

↓LPP-LDL-P 20% (esp. small dense LDL

fraction)↓LDL-C 14%, TG 5%

↓HDL-C 11.5%

900 mg pantethine, 800 mg plant sterols, 600 mg green tea extract (50% EGCG), 75

mg δ tocotrienol and 5 mg Phytolens (extract of lentil husks)

No II-3

Level I Properly randomized, controlled trial.Level II-1 Well designed controlled trial but without randomization.Level II-2 Well designed cohort or case-control analytic study.Level II-3 Multiple time series with or without the intervention(e.g., cross-sectional and uncontrolled investigational studies).Level III Meta-analyses; reports from expert committees; descriptive studies and case reports.LPP-LDL-P = Lipoprotein Profile LDL Particle Count (Spectracell Labs)TG = TriglyceridesMetSyn = Metabolic Syndrome

Pokrywka GS. Nonpharmacologic and complementary approaches to lipid management. LipidSpin


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Forest Plot of Total Deaths From All Causes

The lower box and indicate that n-6 specific PUFA diets increased the risk of death from all causes by 16% (risk ratio (RR) 1.16; 95% CI 0.95, 1.42; P=0.15. The upper box and indicate that mixed n-3/n-6 PUFA diets reduced the risk of death from all causes by 8% (RR 0.92, 95% CI 0.80, 1.06; P=0.25). Overall and accompanying indicate that the combination of all n-6 specific PUFA and mixed n-3/n-6 PUFA diets had no effect on the risk of death from all causes (RR 0.99; 95% CI 0.89, 1.11; P=0.91). n-3 + n-6, mixed n-3/n-6 PUFA trials; overall, all included PUFA trials; Soy Oil, Medical Research Council Soy trial; STARS, St Thomas Atherosclerosis Regression Study; MCS, Minnesota Coronary Survey.

Ramsden CE, Hibbeln JR, Majchrzak SF, Davis JM. n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials. British Journal of Nutrition. 2010;104:1586-1600.


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Saturated Fat Intake (percent kcals) by Sex and Race-Ethnicity for Adults Aged 20 and Over, 1999-2008




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Two Examples of Daily Dietary Patterns That Are Consistent With AHA-Recommended Dietary Goals at 2000 Calories

Eating Pattern DASH* TLC† Serving Sizes

Grains 6 to 8 servings per day 7 servings per day 1 slice bread; 1 oz dry cereal; ½ cup cooked rice, pasta, or cereal

Vegetables 4 to 5 servings per day 5 servings per day1 cup raw leafy vegetable, ½ cup

cut-up raw or cooked vegetable, ½ cup vegetable juice

Fruits 4 to 5 servings per day 4 servings per day1 medium fruit; ¼ cup dried fruit; ½ cup fresh, frozen, or canned fruit;

½ cup fruit juiceFat-free or low-fat milk

and milk products 2 to 3 servings per day 2 or 3 servings per day

Lean meats, poultry, and fish <6 oz per day ≤5 oz per day 1 cup milk, 1 cup yogurt, 1 ½ oz

cheese

Nuts, seeds, and legumes 4 to 5 servings per week Counted in vegetable servings.

1/3 cup (1 ½ oz), 1 Tbsp peanut butter, 2 Tbsp or ½ oz seeds, ½ cup

dry beans or peas

Fats and oils 2 to 3 servings per day Amount depends on daily calorie level

1 tsp soft margarine, 1 Tbsp mayonnaise, 2 Tbsp salad dressing,

1 tsp vegetable oil

Sweets and added sugars 5 or fewer servings per week No recommendation

1 Tbsp sugar, 1 Tbsp jelly or jam, ½ cup sorbet and ices, 1 cup

lemonade

*Dietary Approaches to Stop Hypertension.†Therapeutic Lifestyle Changes. Lichtenstein AH; et al. Diet and lifestyle recommendations revision 2006: a scientific

statement from the American Heart Association Nutrition Committee. Circulation. 2006;114:82-96.


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Median Concentrations of Low-Density Cholesterol in US Adolescents 12 to 17 Years of Age,

NHANES 1999 to 2006

Median

Boys (Age, y)

6 …

7 …

8 …

9 …

10 …

11 …

12 87.0

13 92.6

14 83.1

15 78.8

16 87.8

17 85.4

Median

Girls (Age, y)

6 …

7 …

8 …

9 …

10 …

11 …

12 85.2

13 90.1

14 84.3

15 88.7

16 84.8

17 91.4Ford ES, Li C, Zhao G, Mokdad AH. Concentrations of low-density lipoprotein cholesterol and total cholesterol among children and adolescents in the United States. Circulation 2009;119:1108-1115.


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Diet – Atherosclerosis = Heart Disease

I. Three Diseases: Atherosclerosis, Arteriosclerosis, Excess Body Fat, Insulin Resistance

A. AtherosclerosisLarge – medium sized arteries caused by high saturated fat, low polyunsaturated fat, diet and dietary cholesterol. Keys and Hegsted equation (1.35 (25FA – PFA )+ 1.5 chol – mg/1000kcal) and genetic susceptibility leads to elevated ApoB, + LDL particles LDLc. Begins in childhood - incubation period to heart attacks, some strokes, peripheral vascular disease.(1). Conversion of atherosclerosis to clinical CHD - changes in atherosclerotic plaque, rupture, hemorrhage, fissure and/or increased thrombosis or decreased fibrinolysis.At present unknown both how to measure these changes at population level and second, effects of specific nutrients especially polyunsaturated fatty acids, very important in thrombosis and platelet function. Thus, differences in rates of CHD among populations in relation to nutrition can be a function of extent of atherosclerosis or determinants of thrombosis.


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Public Health Implications• The combined evidence from the 10 largest cohort studies, three

international (ecological) studies, and 28 randomised trials shows conclusively that lowering a person’s serum cholesterol concentration results in substantial protection from ischaemic heart disease

• The benefits of serum cholesterol reduction are related to age; a 10% reduction in serum cholesterol concentration produces a reduction in ischaemic heart disease of 50% at age 40, 40% at age 50, 30% at age 60, and 20% at age 70

• The benefit can be realised quickly-the greater part after two years and the full benefit after five years

• Lowering serum cholesterol concentrations in a population is critical in reducing mortality from ischaemic heart disease

• Appropriate action is needed, including wider health education, labeling of foods, and policies on food subsidies that are linked to health priorities

Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994;308:367-73.


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Variability in Response of Squirrel Monkeys to a Cholesterol Containing Diet (10mg/Cal)

Clarkson TB. Genetic studies of atherosclerosis in animals. In: U.S. Department of Health, Education and Welfare, NIH, National Heart and Lung Institute, Division of Heart and Vascular Diseases. Report by the Task Force on Genetic Factors in Atherosclerotic Diseases. DHEW Publication #76-922, 1974, page 134.

1 School of Nursing Talk 4-21-11 Nutrition, Hyperlipidemia, Thrombosis and Atherosclerosis. What Are...

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