Risk factors for cardiovascular disease:             Focus on Dietary Fats       R. Uauy 2014
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Risk factors for cardiovascular disease: Focus on Dietary Fats R. Uauy 2014. * Fats & fatty acids. The Lipid Hypothesis. Dietary fats and fatty acids Health effect of cis vs trans unsaturated fatty acids Quality of Dietary fat has a significant effect on CVDs

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Fats fatty acids

Risk factors for cardiovascular disease: Focus on Dietary Fats R. Uauy 2014

* Fats & fatty acids


The lipid hypothesis

The Lipid Hypothesis

  • Dietary fats and fatty acids

  • Health effect of cis vs trans unsaturated fatty acids

  • Quality of Dietary fat has a significant effect on CVDs

  • Conclusions and Recommendations


Fats fatty acids

Total Fat – Ecological Data

Seven Countries Study


Fats fatty acids

Associations Between the Percent of

Calories Derived from Specific Foods and

CHD Mortality in the 20 Countries Study*

Food Source Correlation Coefficient†

Butter 0.546

All dairy products 0.619

Eggs 0.592

Meats 0.561

Sugar and syrup 0.676

Grains, fruits, and vegetables-0.633

*1973 data, all subjects. From Stamler J: Population studies. In Levy R: Nutrition, Lipids, and CHD.

New York, Raven, 1979.

†All coefficients are significant at the P<0.05 level.


Fats fatty acids

Men Participating in the Ni-Hon-San Study*

Residence

Japan HawaiiCalifornia

Age (years) 57 5452

Weight (kg) 55 6366 +20%

Serum cholesterol (mg/dL)181 218 228 +26%

Dietary fat (% of calories) 15 3338 +253%

Dietary protein (%) 14 1716

Dietary carbohydrate (%) 63 46 44 -30%

Alcohol (%) 9 4 3 -67%

5-yr CHD mortality rate 1.3 2.2 3.7 +285%

(per 1000 persons)

*Data from Kato et al., Am J Epidemiol 97:372, 1973. CHD, coronary heart disease.


Fats fatty acids

Epidemiologic Studies*

  • Populations on diets high in total fat, saturated and trans fats, cholesterol, and sugar have high age-adjusted CHD death rates as well as more obesity, hyperlipidemia, and diabetes

  • The converse is also true

*Results from Seven Countries, 18 countries, 20 countries, 40 countries, and Ni-Hon-San Studies


Fats fatty acids

Total Fat and CHD - Cohort Evidence

28.3%32.6% 35.6% 38.7% 44.0%

77,878 women in the Nurses Health Study, 1980-2002, Oh et al, AJE 2005


Simopoulos ap am j clin nutr 1999 70 560 9s

Simopoulos AP. Am J Clin Nutr. 1999;70:560-9S.

Changes in dietary fat sources during Evolution

Industrial

Agricultural

Hunter-Gatherer


Fats fatty acids

Saturated Fatty Acid

Stearic acid 18:0

melting point 70 o C

Unsaturated Fatty Acid(cis)

Oleic acid c 18:1 n-9

melting point 16 o C

Unsaturated Fatty Acid

(trans)

Elaidic acid t 18:1 n-9

melting point 43 o C


Dietary fatty acids

Dietary fatty acids

There are 3 types of dietary fatty acids

Saturated fatty acids (no double bond)

COOH

CH3

Mono-unsaturated fatty acids (one double bond)

CH3

COOH

Polyunsaturated fatty acids (two or more double bonds)

COOH

CH3


Fats fatty acids

w-

COOH

Stearic acid (C18:0 )

CH3

n-

COOH

COOH

Elaidic acid (C18:1 n-9 trans)

Oleic acid (C18:1 n-9)

Essential Fats

COOH

COOH

a - Linolenic acid (C18:3n-3)

Linoleic Acid (18:2 n-6)

COOH

COOH

Docosahexaenoic acid DHA(C22:6 n-3)

Arachidonic acid AA(C20:4 n-6)


Quality of fats in modern nutrition

Quality of Fats in Modern Nutrition

  • Saturated fats (C12:0, C14:0, C16:0, C18:0)

  • Trans fatty acids (hydrogenated fats)

  • Monounsaturated fatty acids (18:1)

  • Sats/MUFA/PUFA

  • Cholesterol

  • Essential fatty acids w -3 and w -6

  • Long Chain PUFAs (AA, EPA, DHA)

  • Energy Density of diet (fats and carbohydrates)


Fats fatty acids

n - 6 / n - 3 LCPUFA ratio modulates inflammation and thrombosis

Linoleate

Arachidonic

Eicosapentaenoic

Linolenate

n-6 PUFA

n-3 PUFA

Membrane Phospholipids

Arachidonic ac /

Eicosapentaenoic ac

Leukotrienes

Prostacyclins

Thromboxanes

Prostaglandin

Inflammation

Inmune response

Thrombosis

Bronchoconstriction

Vascular reactivity

Bronchoconstriction

Chemotaxis

Citokines

Inflammation


Fats fatty acids

Fatty acids % total

n-3 PUFA

n-6 PUFA

Monounsaturated

Saturated


Fats fatty acids

Diet and Fats Influence Risk of Coronary Heart Disease

  • Effects on Lipoprotein and Cholesterol metabolism receptor systems, gene expression and regulation (LDL, HDL, Lp(a), TG) : TRANS FATS, SATS, PUFAs n-3 and n-6,

  • Prostanoids:(Eicosanoids and Docosanoids) related functions Inflammation/cytokines depend on: PUFAs n-3 & n-6,

  • Blood pressure. SODIUM POTASSIUM & PUFAs n-3 & n-6,

  • Thrombosis and thrombolytic mechanisms PUFAs n-3 & n-6

  • Oxidative stress and re-perfusion injury PUFAs n-3 & n-6

  • Endothelial function & adhesion molecules PUFAs n-3 & n-6

  • Cardiac Rhythm (arrhythmias) PUFAs n-3

  • Insulin Sensitivity PUFAs n-3 & n-6; Trans


Who trs 916 report strength of evidence on nutritional factors and risk of developing cvd

WHO TRS 916 Report : strength of evidence on nutritional factors and risk of developing CVD

Evidence Decreased risk No relationshipIncreased risk

Convincing Regular physical activityVitamin E Myristic and palmitic acids

Linoleic acid 18:2n-6Supplements 14:0 16:0

Fish and fish oils Trans fatty acids

(EPA &DHA) High sodium intake

Vegetables & fruits (including Overweight

berries) High alcohol intake

Potassium

Low to moderate alcohol intake

Probableα-Linolenic acid18:3 n-3 Stearic acidDietary cholesterol

Oleic acid 18:1 n-918:0 Unfiltered boiled coffee

Fibre

Nuts (unsalted)

Plant sterols/stanols

Folate

Possible Flavonoids Fats rich in lauric acid

Soy products Impaired fetal nutrition

Beta-carotene supplement

TRS 916 WHO 2003


Who trs 916 report risk of developing cvd

WHO TRS 916 Report : risk of developing CVD

Evidence Decreased risk No relationshipIncreased risk

Convincing Regular physical activityMyristic and palmitic acids

Linoleic acid 18:2n-6Vitamin E 14:0 16:0

Fish and fish oils (EPA &DHA) Supplements Trans fatty acids

Vegetables & fruits High sodium intake

(berries) Overweight

Potassium

Low to moderate High alcohol intake

alcohol intake

Probable α-Linolenic acid 18:3 n-3 Stearic acid Dietary cholesterol

Oleic acid 18:1 n-918:0Unfiltered boiled coffee

Fibre

Nuts (unsalted)

Plant sterols/stanols

Folate

PossibleFlavonoids Fats rich in lauric acid

Soy productsRestricted fetal growth

Beta-carotene supplement

TRS 916 WHO 2003


Population dietary changes explain much of the reduction in heart disease mortality in finland

Observed and Predicted Declines in Coronary Mortality in Eastern Finland, Men

Population dietary changes explain much of the reduction in heart disease mortality in Finland.

% Decline in mortality

0

-10

-20

Observed

Predicted

Cholesterol

Blood pressure

Smoking

-30

-40

-50

-60

72

76

80

84

88

92

74

78

82

86

90

Vartiainen, Puska et al BMJ 1995


Fats fatty acids

UK White Paper 04 Dept Health


Fats fatty acids

Causal relationship web

Physical

Age

Activity

Diabetes

DIET

Fat & Salt

-

LDL

HDL

CHD

Chol

BMI

Diastolic

BP

Smoking

A B marks a postulated influence from A to B


Fats fatty acids

Saturated or Trans

fatty acids

Diet effects on LDL receptor activity

High saturated

or trans fat diets

Healthy fats


The lipid hypothesis1

The Lipid Hypothesis

  • Dietary fats and fatty acids

  • Health effect of cis vs trans unsaturated fatty acids

  • Quality of Dietary fat has a significant effect on CVDs

  • Conclusions and Recommendations


Fats fatty acids

Associations Between the Percent of

Calories Derived from Specific Foods and

CHD Mortality in the 20 Countries Study*

Food Source Correlation Coefficient†

Butter 0.546

All dairy products 0.619

Eggs 0.592

Meats 0.561

Sugar and syrup 0.676

Grains, fruits, and vegetables-0.633

*1973 data, all subjects. From Stamler J: Population studies. In Levy R: Nutrition, Lipids, and CHD.

New York, Raven, 1979.

†All coefficients are significant at the P<0.05 level.


Fats fatty acids

Total Fat – Ecological Data

Seven Countries Study


Fats fatty acids

Men Participating in the Ni-Hon-San Study*

Residence

Japan HawaiiCalifornia

Age (years) 57 5452

Weight (kg) 55 6366 +20%

Serum cholesterol (mg/dL)181 218 228 +26%

Dietary fat (% of calories) 15 3338 +253%

Dietary protein (%) 14 1716

Dietary carbohydrate (%) 63 46 44 -30%

Alcohol (%) 9 4 3 -67%

5-yr CHD mortality rate 1.3 2.2 3.7 +285%

(per 1000 persons)

*Data from Kato et al., Am J Epidemiol 97:372, 1973. CHD, coronary heart disease.


Fats fatty acids

Epidemiologic Studies*

  • Populations on diets high in total fat, saturated and trans fats, cholesterol, and sugar have high age-adjusted CHD death rates as well as more obesity, hyperlipidemia, and diabetes

  • The converse is also true

*Results from Seven Countries, 18 countries, 20 countries, 40 countries, and Ni-Hon-San Studies


Fats fatty acids

Total Fat and CHD - Cohort Evidence

28.3%32.6% 35.6% 38.7% 44.0%

77,878 women in the Nurses Health Study, 1980-2002, Oh et al, AJE 2005


Reduction in the consumption of trans fatty acids and the risk of chd in the netherlands zutphen

Reduction in the Consumption of Trans Fatty Acids and the Risk of CHD in The Netherlands-Zutphen

TFA 2.4%

 CHD 23%

Oomen CM, et al. Lancet 2001; 357: 746-51


Health benefits of polyunsaturated fatty acids

Health benefits of polyunsaturated fatty acids


Dietary intervention studies

Dietary Intervention Studies

  • Significant benefit in CHD risk reduction and mortality

  • in primary and secondary prevention noted with:

    • Decreasing saturated fat and increasing

    • polyunsaturated fat (Finnish Mental Hospital, LA-VA,

    • and Oslo Diet Heart Studies)

    • Increasing fish or fish oil intake (DART, GISSI)

    • Increasing alpha linolenic acid intake (Lyon Diet

    • Heart Study)

    • Dietary Counseling can work, but it must be intensive and sustained

Circulation 59:1,1979; Acta Med Scand 466:1,1966; Circulation 40:1,1969;

Lancet 2:757,1989, Lancet 343:1454,1994; Lancet 354:447,1999.


Dietary fatty acids and blood cholesterol

SAFA

MUFA

PUFA

Dietary fatty acids and blood cholesterol

TC=1.2(2S'-P)

S'=C12+C14+C16

change in TC (mg/dL)

change in fat intake (en%)

Source: Keys et al. Metabolism, 1965


Effect on lipoproteins of replacing saturated fat with specific fatty acids or carbohydrates

0.02

0.01

0.01

0

0

-0.01

-0.01

changes per en%

-0.02

-0.02

mmol/ L change per % energy

-0.03

-0.03

-0.04

-0.04

-0.05

monounsaturated FAs

polyunsaturated FAs

carbohydrates

trans FAs

Effect on lipoproteins of replacing saturated fat with specific fatty acids or carbohydrates

LDL-chol

HDL-chol

TC/HDL-chol ratio

Source: Mensink et al Am J Clin Nutr 2003


Fats fatty acids

In summary, our results provide evidence that high intake of trans-fat increases the risk of CHD in women, the effects are stronger among younger women.

Our findings also support a benefit of polyunsaturated fat intake, at least up to approximately 7 percent of energy, in preventing CHD, particularly among women who are younger or overweight.

Am J Epidemiol 2005;161:672–679


Fats fatty acids

Nurses’ Health Study: changes in risk of coronary heart disease associated with iso-energetic diet substitutions

Source: Hu et al, JAMA, 2002

Decreased Risk

Increased Risk


Adverse effects of trans fas on blood cholesterol

0.4

Nestel

Mensink

Judd

LDL

Lichtenstein

0.2

Zock

Judd

Change in (mmol/L)

0

HDL

-0.2

0

2

4

6

8

10

12

Adverse effects of trans FAs on blood cholesterol

% of energy as trans fatty acids (C18:1 trans)

Zock et al Am J Clin Nutr, 1995


Fats fatty acids

Changes in serum lipids (mmol/L by replacing 1% E individual fatty ac for carbohydrate based on meta-analysis [EFSA J (2004) 81, 1-49]


Fats fatty acids

Relative risk was after adjusting for dietary fiber intake.

Saturated Fat Intake Quintiles (% of calories)

Alpha Linolenic Fatty Acid Intake Quintiles (% of calories)

1.72

0.41

a 1% increase in calories from linolenic acid (2-3 grams/day).

Ascherio et al BMJ 1996


Fats fatty acids

ORs for Risk of Nonfatal Acute MI by tercile of Linolenic & Trans FA content of Adipose Tissue in Costa Rica

Odds

Ratio

Adipose Tissue

trans fatty acids

Adipose Tissue n-3

alpha-linolenic acids

A Baylin et al Circulation 107:1586-91 2003


Small reduction in blood cholesterol significant reduction in chd

Small reduction in blood cholesterol  significant reduction in CHD

A reduction in total blood cholesterol level by

each percent leads to a reduction of :

Data from a meta analysis including 10 prospective cohort studies, 3 large international trial and 28 intervention studies

Law et al, British Medical Journal 1994


Fat quality versus quantity

Fat quality versus quantity

USA 2005 dietary recommendations:

“…increasing consensus that it is the quality rather than the quantity of fat that counts….”

Limiting calories is more important to health than cutting fats


Fats fatty acids

D. Mozaffarian JAMA, 2006 Vol 296: 1885-97


Fats fatty acids

D. Mozaffarian JAMA, 2006 Vol 296: 1885-97


Overview of beneficial effects of pufa

Overview of beneficial effects of PUFA

  • Omega 6 (Linoleic acid)

    • Blood lipids: clearly protective

  • Omega 3 (Linolenic acid)

    • Blood lipids: probably similar to linoleic acid

    • Other risk factors: mostly inconsistent

  • Omega 3 (EPA/DHA)

    • Blood lipids: in high dose lowers TG, but LDL up

    • Other risk factors: blood pressure ? reduced thrombosis and likely improved endothelial relaxation, lowers inflammation and risk of fatal cardiac arrhythmias


Fats fatty acids

Design: a follow-up study of 11 pooled American and European cohort studies including 344,696 persons; outcome CHD over a 4–10 yr FU,

5249 coronary events and 2155 coronary deaths occurred Results:

For a 5%lower energy intake from SFAs and a concomitant higher energy intake from PUFAs risk of coronary events HR: 0.87 (95% CI: 0.77-0.97); HR for coronary deaths 0.74 (0.61-0.89).

For a 5% lower energy intake from SFAs and a concomitant higher energy intake from CHO there was a significant association with coronary events (HR 1.07; (CI: 1.01- 1.14); for coronary deaths 0.96 (0.82- 1.13).

MUFA intake was not associated with CHD.

Jakobsen et al Am J Clin Nutr 89:1–8 2009


Fats fatty acids

coronary events

coronary deaths

0.87 (0.77-0.97)

0.74 (0.61-0.89)

Jakobsen et al Am J Clin Nutr 89:1–8 2009


Fats fatty acids

coronary events

coronary deaths

coronary events

coronary deaths

1.07 (1.01-1.14)

0.96 (0.82-1.13)

Jakobsen et al Am J Clin Nutr 89:1–8 2009;.


Fats fatty acids

Coronary Heart Disease

Am J Clin Nutr

doi: 10.3945/ajcn.2009.27725

Risk ratios and 95% CIs for fully adjusted random-effects models examining associations between saturated fat intake in relation to coronary heart disease & stroke

1.07 (0.96, 1.19)P = 0.22

Stroke

0.81 (0.62-1.05)P = 0.11

1.0 (0.89-1.11)P = 0.95

Total CVDs


Fats fatty acids

Am J Clin Nutr 2010;91: 1764–8.

We aimed to investigate the risk of myocardial infarction (MI) associated with a higher energy intake from carbohydrates and a concomitant lower energy intake from SFAs. Carbohydrates with different glycemic index (GI) values were also investigated.

Design: Our prospective cohort study included 53,644 women and men free of MI at baseline.

Conclusion: This study suggests that replacing SFAs with carbohydrates with low-GI values is associated with a lower risk of MI, whereas replacing SFAs with carbohydrates with high-GI values is associated with a higher risk of MI.


Fats fatty acids

Pooled Analysis of 11 Major Cohort Studies

SFA → PUFA

SFA → Carb

SFA → MUFA

*

*

Total of 344,696 individuals with 5,249 CHD events. *p<0.05

Jakobsen et al, AJCN 2009


Fats fatty acids

Saturated Fat vs. CHO Quality

SFA → Low GI CHO

SFA → Med GI CHO

SFA → High GI CHO

*

Risk of CHD among 53,644 adults followed for 12 years. *p<0.05

Jakobsen et al, AJCN 2010


Fats fatty acids

A More Complete Diet-Heart Paradigm


Key messages for health professionals

Key messages for Health Professionals

  • Strong Convincing Evidence that a diet low in saturate and trans fats, and high polyunsaturated fats lowers cholesterol and reduces risk of CVD

  • Diet can reduce LDL - cholesterol up to 30 %

  • Simple dietary changes can make a significant difference to the CVD risk

  • Changes in Diet and Physical activity are the cornerstone of primary prevention of CVDs


Recommendations on pufa and trans

Recommendationson PUFA and trans

  • General international agreement on absolute levels.- Total PUFA: 4-15 en% (8-10 en% most common)- Linoleic acid n-6 :up to 14 en% (8 en% most common)- Linolenic acid n-3:0.2 to 1.0 en%- EPA+DHA : 200-500 mg/day

  • Trans fatty acids: as low as possible, lower than 1-2 %

  • Some give recommendations for omega-6:omega-3 ratio, others do not. Most often not to exceed ~ 5:1

  • In many societies the intake of Omega 3 is lower and that of trans is higher than recommended


Type of fat consumed on bread in north karelia 1972 2000 25 59 year old

Type of Fat Consumed on Bread in North Karelia, 1972–2000 (25–59-year-old)

%

Year


Saturated fat from milk and fat on bread gr day

50

40

North Karelia

Kuopio province

30

Southwest Finland

Helsinki area

20

10

0

1972

1977

1982

1987

1992

Saturated Fat from Milk and Fat on Bread gr/day

Year


Fats fatty acids

Butter & Margarine Consumption Finland 1979–01


Fats fatty acids

Age-adjusted Mortality Rates of CHD in North Karelia and the all of Finland in males aged 35–64 years 1969 to 2002.

69

72

75

78

81

84

87

90

93

96

99

2002

700

start of the North Karelia Project

600

extension of the Project nationally

Mortality per 100 000 population

500

North Karelia

400

300

- 82 %

All Finland

200

- 75%

100

6th ICPC, Iguassy Falls 21.-25.5. 2005 (3.)

Year


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