Download - Dr Jonathan Morrell - Cholesterol
"I drive way too fast to
worry about cholesterol"
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The evolution of man Human evolution – the shape of things to come?
Lumen
Media:
Smooth muscle cell
Matrix proteins
Internal elastic membrane
Endothelium
Intima:
External elastic membrane
Normal arterial wall
Haemorrhage from plaque microvessels
Rupture of the fibrous cap
Thinning of the fibrous cap
The Unstable Plaque
Intraluminal thrombus
Intraplaque thrombus
Lipid pool
Plaque rupture and thrombus formation
Cerebrovascular disease
Ischaemic stroke
Transient ischaemic attack (TIA)
Peripheral arterial disease (PAD)
Intermittent claudication (IC)
Pain on walking
Acute critical limb ischaemia
Chronic critical limb ischaemia
Rest pain, gangrene, necrosis
Cardiovascular (CV) disease
Myocardial infarction (MI)
Angina (stable/unstable)
Go back!
We ****** up everything!
Outline
• What is cholesterol?
• Why is it so important?
• What can we do about it?
• Reality checking
NHS Health Checks
‘I drive way too fast to worry about my cholesterol’
0 5 10 15 20 25 30
28.7 Atherothrombosis*
17.8 Infectious disease
12.6 Cancer
9.1 Injuries
6 Pulmonary disease
5.1 AIDS
Atherosclerosis is the leading cause
of death worldwide
The World Health Report, 2002, WHO Geneva, 2002
Mortality (%)
Proportion of all deaths (%)
CVD – The biggest killer in the UK
• 191,000 deaths from CVD (heart disease + stroke)
• 88,000 deaths from coronary heart disease (CHD)
• 1 in 5 deaths in men and 1 in 8 women
• 124,000 heart attacks each year
• 152,000 strokes
• 2.7 million people live with heart disease
BHF CHD statistics 2010
BHF statistics 2008
Atherosclerosis
Increasing age
Increasing risk factors
<25y – 22%
25-35y – 47%
>35y – 70%
Nissen S. Am J Cardiol 2001 87 Suppl. 15A
INTERHEART
Risk Factor PAR (%)
Lipids 49.2
Smoking 35.7
Hypertension 17.9
Diabetes 9.9
Abdominal obesity 20.1
Psychosocial 32.5
Lack daily fruit and vegetables 13.7
Lack regular alcohol 6.7
Lack regular physical activity 12.2
What are lipids?
What is cholesterol?
Why do we need cholesterol?
Where does it come from?
How is cholesterol moved around the
body?
The lipoprotein family
Structure of LDL
Murphy HC, et al. Biochemistry. 2000;39:9763-970.
Hydrophobic Core
of Triglyceride and
Cholesteryl Esters
Apo B
Surface
Monolayer of
Phospholipids
and Free
Cholesterol
Slide Source
Lipids Online Slide Library www.lipidsonline.org
Structure of HDL
Rye KA, et al. Atherosclerosis. 1999;145:227-238.
Hydrophobic
Core of Triglyceride
and Cholesteryl
Esters
Surface Monolayer of
Phospholipids and
Free Cholesterol
Apo A-II
Apo A-I
Rianna’s story
Rianna’s story
• Mother and
grandmother on
statins
• Fatty lumps on her
knuckles
• ‘No need to test
yet’
• ‘Pinhole’ arteries
Familial hypercholesterolaemia
• Eliza Parachute 1851
• Autosomal dominant
• 1/500
• 1/1,000,000
FH-natural history
Age
(years)
♂
% CHD
♀
% CHD
40-49 48 7
50-59 80 51
Slack, Lancet.1969;1380-2
Family history
Family history
1 in 106 - Homozygous FH
Brown and Goldstein identified autosomal
dominant LDLR defect in FH fibroblasts in 1974
Family history
?
?
? ? ?
?
?
?
? ?
What are the duties of care for this family?
INTERHEART
Risk Factor PAR (%)
Lipids 49.2
Smoking 35.7
Hypertension 17.9
Diabetes 9.9
Abdominal obesity 20.1
Psychosocial 32.5
Lack daily fruit and vegetables 13.7
Lack regular alcohol 6.7
Lack regular physical activity 12.2
Joint British Societies CVD Risk Predictor Chart
Communicating risk
• Studies show high risk individuals can be motivated
to reduce their risk if their risk status is
communicated effectively
• ‘Your CVD risk is 31% over 10 years’
22nd April 2008 QRisk © 2008 All rights reserved 22nd April 2008 QRisk © 2008 All rights reserved
Communicating risk
• 4/5 people at high-risk are inappropriately optimistic
• 1/5 people at low-risk are inappropriately pessimistic
Van der Weijden T et al. Curr Opin Cardiol 2008;23(5):471-6
Communicating risk – HEART AGE
• Concentrates on the modifiable proportion of risk
• Compares the Heart Age of the subject with a person of the same age whose risk factors are ideal
• For example, a 61 year-old woman has a 10-year CV risk of 10.5%. Her ‘normal’ risk should be 6.7%. The 57% increase in relative risk extrapolates to a Heart Age of 73
Cobain M et al
What are typical cholesterol values
in the UK?
5.3/5.4 mmol/L HSE 2006 (N.B. effect of age and treatment)
Typical LDL-C of people with a heart attack is
3.8 mmol/L
Lowering LDL-C
• 21% reduction in CV ‘events’ when
LDL-C is lowered by 1mmol/L
• 40% for 2mmol/L
Oxford CTTC
Cholesterol targets
Guideline Year
published
LDL-C target
(mmol/l)
TC target
(mmol/l)
ATP 3a 2004 <1.8
ESC/EAS 2011 <1.8
QOF 2003 <5.0
JBS 2 2005 <2.0 <4.0
NICE (20) 2008 <2.0 <4.0
Lower (LDL) cholesterol
Daily Telegraph May 17th 2012
WHO 2002
‘….up to 80% of cases of coronary heart
disease and up to 90% of type 2 diabetes could
be avoided by changing lifestyle factors….’
Predicted (all
risk factors)
Smoking
Blood pressure
Cholesterol
Observed (all risk factors)
Decli
ne i
n m
ort
ality
, %
0
10
20
30
40
50
60 1972 80 76 84 88 92
Year Vartiainen E,
BMJ 1994; 309: 23
Observed &
predicted
decline in CHD
death in
Finnish men,
35 - 64
1. Balance calorie intake and physical activity to
maintain a healthy body weight and shape
2. Limit intake of saturated and trans fats and
cholesterol
3. Substitute saturated and trans fats with unsaturated
fats
4. Increase omega-3 fatty acid consumption
5. Consume a diet rich in fruits and vegetables
10 tips for a healthy lifestyle
6. Choose whole-grain, high fibre foods
7. Choose and prepare foods with little or no salt
8. Consider plant sterols and soy protein as part of a
healthy, balanced diet
9. Consume alcohol in moderation
10. Avoid use of and exposure to, tobacco products
10 tips for a healthy lifestyle
‘The new diet rules’
• Drink full fat milk not skimmed
• Eat full fat cheese/yoghurt
• Eat two eggs a day
• Buy butter not margarine
• Use coconut oil
‘People with high levels of blood cholesterol don’t have
worse health outcomes than those with lower ones.’
The Times March 17th 2012
Just an ordinary café?
It's 10 eggs, 10 bacon, 10 sausage, 10 toast, 5 black
puddings, tomatoes, beans and mushrooms for £10
No chips…..
Eat it all in 20 mins with no drink to wash
it down with and you get it free
The breakfast packs in 5,000 calories
A spokesman for
the British Heart
Foundation said:
"Eating this amount
in one sitting is not
a good idea.".
The heart attack grill
Cholesterol reduction by diet
Dietary component
Dietary change Approximate LDL-C reduction in %
Saturated fat <7% of energy 5-10
Plant sterols 2-2.5 g/day 10
Dietary cholesterol <200 mg/day 5
Viscous fibre 5-10 g/day 5
Soya protein 25 g/day 5
Body weight management
Lose ~5 kg 5
Adapted from Jenkins et al. Curr Opin Lipidol 2000
Mechanism of Action
Competition with cholesterol for solubilisation of
dietary and biliary cholesterol in mixed micelles
Overview of clinical trials assessing
efficacy of plant sterols
-16
-12
-8
-4
0 0.5 1 1.5 2 2.5 3 3.5
plant sterols (g/day)
LD
L c
ho
leste
rol
(% c
han
ge)
41 trials with plant sterols/stanols:
95% CI from meta-analysis LDL cholesterol
2–2.5 g of plant sterols
daily significantly
reduces LDL
cholesterol by ~10%
Katan et al. Mayo Clin Proc 2003
The ‘Portfolio Diet’
• Breakfast oatbran, orange, Metamucil (psyllium), oatbran bread, PS margarine, double fruit jam, soy milk
• Snack almonds, soy milk
• Lunch vegetarian chilli, oatbran bread, PS margarine, soy slices, tomato, orange
• Snack almonds, Metamucil, soy milk
• Dinner vegetable curry, soy burger, beans, barley, okra, aubergine, cauliflower, onions, red pepper
• Snack soy yoghurt, Metamucil, jam
A dietary portfolio effectively
reduces LDL cholesterol levels
#Dietary portfolio = plant sterols, soy protein, viscous fibre, Jenkins et al. AJCN 2005
*Significantly different from control (low saturated fat diet)
-35
-30
-25
-20
-15
-10
-5
0
Week 0 Week 2 Week 4
LD
L c
ho
leste
rol
(% c
han
ge )
Control diet
Control diet + statin
Dietary portfolio#
-8.5%
-29.6%*
-33.3%*
34 adults,
4 week interventions
Tom
• Asymptomatic
• Non-smoker
• 124/62
• Father died MI 49, paternal grandfather sudden death 54
• 2 sons aged 8 and 9
• 2 brothers, 1 sister
TC 9.9 HDL 1.4
Why is cholesterol so important?
• Essential for life
• Key player in the development of arterial disease
• Effects can be modified by diet and drugs
What are YOU going to do about it?