"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?