Professor Dag Steinar Thelle University of Oslo

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ProfessorDag Steinar Thelle University of
Oslo
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Fat and Cardiovascular Diseases October 23, 2008

• Dag S. Thelle
• University of Oslo

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Contents

• A few words about fat and heart disease, the
  Dutch, maybe Englishmen and Scottish sheep,
• the French, Norwegian fish, and surely Søren
  Kierkegaard and how we know what we know

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The basis for our knowledge on fat and heart
disease

• Anecdotal information and observations
• Ecological analyses
• Observational studies, consistencies and
  discrepancies
• Feeding experiments
• Large scale trials
• A comprehensive diet-heart theory from Virchow to
  ?

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Thats what is all about...

• The plaque - why does it occur?
• Why does it rupture?
• It is filled with lipids - fat derived substances
• Highly reactive - inducing inflammatory actions,
  thrombosis
• Questions that have been around for 150 years...

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Three different theories by the end of the 19th
century

• incrustation theory developed by von Rokitansky
  putting most weight upon thrombosis and role of
  platelets,
• irritation theory from von Virchow with emphasis
  on chronic inflammatory processes,
• lipid infiltration theory based upon Anitschkovs
  and Chalatovs feeding experiments on rabbits

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The unsystematic observations

• The Dutch in Java (de Langen 1907)
• Chicken and Noblemen in Russia (Anitschkow 1905)

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Observation (epidemiological) studies

• Ragnar Nicolaysen (1958-60) total cholesterol
• 3751 men aged 40-49 followed for 10 years, 213
  first time MI (Scand Clin Lab Invest suppl 127,
  1972).
• Similar coefficients for total cholesterol and MI
  as in Framingham
• Followed by a large number of similar studies

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Ecological studies Seven Countries, Keys et al
1980
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CHD in 40 Countries in Relation to Milk Intake,
Artaud et al, Circulation 1993
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Association between fat and TC

• Hegsteds formula, followed by a number of similar
  formulas

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Nutritional guidelines

• American Heart Assocations 1970s
• World Health Organisation 1970s
• Nutrition policy- across Europe 1980s

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The Truth

• To whom is anyting true?
• Three scientists in Scotland...

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The 25 year follow-up of the Seven Countries
Study - fats and CHD, Kromhout 1995

• Total fat
• C120, lauric acid
• C140, myristic acid
• C160, palmitic acid
• C180, stearic acid
• C181C, oleic acid

• 0.60
• 0.84
• 0.86
• 0.81
• 0.84
• -0.08
• plt 0.05

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A causal theory should explain

• Acute events
• Long term evolution or pathogenesis
• Rapid changes in CVD and CHD incidence rates
• One single factor (and fat is many!) will not do

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The exceptions to the pattern

• Inuites (Greenland) low CHD, but high on omega -
  3 fatty acids Bang, Dyerberg and Sinclair in
  1976

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The exceptions to the pattern

• Inuites (Greenland) low CHD, but high on omega -
  3 fatty acids Bang, Dyerberg and Sinclair in
  1976
• Crete - low CHD, high total fat intake - mainly
  monounsaturated fatty acids (oliveoil), Katan et
  al 1988

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Metabolic experiments- substitution for saturated
fat , Mensink Katan 1987

• Carbohydrates
• Total cholesterol -down
• LDL cholesterol - down
• HDL cholesterol - down
• Triglycerides - up

• Monounsaturated
• Total cholesterol - flat
• LDL cholesterol - down
• HDL cholesterol - up
• Triglycerides - flat

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The exceptions to the pattern

• Inuites (Greenland) low CHD, but high on omega -
  3 fatty acids Bang, Dyerberg and Sinclair in
  1976
• Crete - low CHD, high total fat intake - mainly
  monounsaturated fatty acids (oliveoil), Katan et
  al 1988
• Masaii people in Kenya, high dairy products, no
  CHD (but they walk and run 20 km/day)

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The Trans Fat Story

• Paul Sabatier develops the hydrogenation
  process.  French chemist,
• Nobel laureate in 1912.

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The Trans Fat Story

• Paul Sabatier develops the hydrogenation
  process.  French chemist,
• Nobel laureate in 1912.
• Used for margarine and shortenings- cheaper than
  butter
• 1950s increasing amounts used in Norway- 3kg
  per personyear

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The Trans Fatty Acid Controversy

• The EURAMIC study - ten centres in Europe from
  Russia to Spain, 671 cases v. 717 controls
• Fat biopsies, OR 0.97 (95 CI 0.56-1.67), but
  the variation in TFA between centres is
  considerable
• Aro et al, Lancet 1995

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Trans fatty acids

• ..replacing saturated and trans unsaturated fats
  with unhydrogenated monounsaturated and
  polyunsaturated fats is more effective in
  preventing coronary heart disease in women than
  reducing overall fat intake.
• Hu et al NEJM 1997

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Animal studies

• Rats on hardened fish oils showed declining total
  cholesterol levels but
• rats differ from humans most of the cholesterol
  is HDL-C

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Epidemiological Research Strategies

• An example from Norway 112 cases acute MI, 107
  controls, Pedersen et al, Eur J Clin Nutr 2000
• Fat biopsies - fatty acids, dietary information

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Different dietary effects

• Butter, C140, LDL
• Meat, beef C160, LDL
• Cocoa butter C180, LDL flat
• Trans fatty acids LDL
  HDL
  down
• Coffee diterpenes (cafestol) LDL
• Genetic constitution (heritability appr. 35-50)

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Some dietary intervention trials

• Open populations
• Oslo Study 1972-77 effect
• Göteborg 1972 no effect
• WHO factory trial no effect
• Multiple Risk Factor Intervention Trial 1973 no
  effect

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Some dietary intervention trials

• Closed populations
• Helsinki mental hospital study 1979- a
  cross-over dietary trial
• The Lyon Diet Heart Study CHD patients

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The source matters

• Milk consumption is associated with decreased CHD
  risk?
• Cheese?
• Fermentation?
• Effects on inflammation?

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A few words about the French and the cholesterol-
saturated fat index

• CSI(1.01 x g saturated fat) (0.05 x mg
  cholesterol)
• Correlation 0.78 with CHD mortality, but France
  has a high CSI and low CHD mortality
• They get their fat from other sources than the
  rest of us...

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So, where do we stand?

• Total fat is not the main issue
• Trans-fatty acids increase the CHD risk
• Myristic, palmitic and lauric acids increase the
  total cholesterol and most likely CHD risk
• The risk may be modified by anti-oxidants - but
  this is still a hypothesis (not shown in vivo)

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So, where do we stand?

• The effect of omega- 3 supplementation is not
  established
• The use of oily fish is recommended
• The use of oleic acid is recommended
• Trans fatty acids should be banned

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Fat and CHD - are related, but

• the exposure is heterogeneous different fatty
  acids with differing biological properties
• and endpoints are a number of phenotypical
  variations with similar clinical
  manifestationsand may have different etiology.

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Increasing life expectancy (Oeppen Vaupel,
Science 20022961029-1031)
The CHD epidemic
The Flu
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Any scientific truth has a limited life span

• Life is understood by its past, and lived into
  the future (Søren Kierkegaard)