What you'll learn

• How atherosclerosis develops inside arteries.
• Why blood clotting is normally useful, but can be dangerous in coronary arteries.
• How atheromas, thrombi, heart attacks and strokes are linked.
• How to interpret CVD risk data without overclaiming.

The starting point: the cardiovascular system

Your cardiovascular system is the heart and blood vessels. It transports substances such as oxygen, glucose, carbon dioxide, urea, hormones and heat around the body.

Arteries carry blood away from the heart. They have thick, elastic, muscular walls because blood in arteries is under relatively high pressure. The space inside a blood vessel is called the lumen.

The inner lining of a blood vessel is the endothelium. A healthy endothelium is smooth, so blood flows with low friction and platelets are less likely to stick.

Coronary arteries matter especially

The coronary arteries supply the heart muscle with oxygenated blood. The heart muscle is called the myocardium. Like any muscle, it needs oxygen for aerobic respiration.

If blood flow through a coronary artery is reduced, the myocardium may receive too little oxygen. This is called ischaemia. It can cause chest pain called angina.

If blood flow is completely blocked for long enough, heart muscle cells die. This is a myocardial infarction, commonly called a heart attack.

Blood lipids and lipoproteins

Lipids, including cholesterol, are not very soluble in blood plasma. So they are transported in particles called lipoproteins.

Two important types are:

• Low-density lipoprotein, or LDL: transports cholesterol from the liver to tissues.
• High-density lipoprotein, or HDL: transports cholesterol from tissues back to the liver.

Cholesterol itself is not “bad” — it is needed in cell membranes and is used to make some hormones. The problem is that high concentrations of LDL in the blood are associated with a greater risk of atherosclerosis.

Atherosclerosis: plaques in artery walls

The process usually develops slowly over many years.

How an atheromatous plaque forms

1. The endothelium becomes damaged, for example by high blood pressure, chemicals in cigarette smoke or high blood glucose.
2. LDL particles move into the artery wall.
3. White blood cells called monocytes enter the artery wall and develop into macrophages.
4. Macrophages take up lipids and become foam cells.
5. Foam cells accumulate, forming a fatty streak.
6. Smooth muscle cells and collagen form a fibrous cap over the fatty deposit.
7. This becomes an atheromatous plaque, also called an atheroma.

This diagram shows the contrast between a healthy artery and one affected by atherosclerosis.

Why narrowing the lumen increases risk

When the lumen becomes narrower, there is greater resistance to blood flow. This means less blood can reach tissues downstream of the plaque.

In a coronary artery, this may reduce oxygen delivery to the myocardium. During exercise, the heart needs more oxygen, so symptoms such as angina may become more noticeable.

If the plaque ruptures, it exposes materials that trigger blood clotting. A clot can then form very quickly at the plaque surface.

Blood clotting: normally a protective response

Blood clotting is part of haemostasis, which means stopping blood loss after a vessel is damaged.

When a blood vessel is damaged:

• Platelets stick to exposed collagen in the damaged vessel wall.
• Platelets release chemicals that attract more platelets.
• A temporary platelet plug forms.
• Clotting factors trigger a cascade of enzyme reactions.
• Soluble fibrinogen is converted into insoluble fibrin.
• Fibrin fibres form a mesh that traps red blood cells and platelets, making a stable clot.

The simplified clotting pathway is shown below.

The key biochemical steps

Two proteins are especially important:

• Prothrombin is an inactive plasma protein.
• Thrombin is the active enzyme made from prothrombin.
• Fibrinogen is a soluble plasma protein.
• Fibrin is an insoluble protein that forms fibres.

The pathway can be summarised as:

$$prothrombin\to thrombin$$ $$fibrinogen\to fibrin$$

Thrombin catalyses the conversion of fibrinogen into fibrin. Calcium ions are also required in the clotting process.

When clotting becomes dangerous: thrombosis

A thrombus can partially or completely block blood flow. If it blocks a coronary artery, it can cause a myocardial infarction. If it blocks an artery supplying the brain, it can cause a stroke.

Sometimes part of a clot breaks away and travels in the blood. This moving clot is called an embolus. If it lodges in a narrower vessel, it can block blood flow there.

Linking atherosclerosis to CVD

The chain of events often looks like this:

1. Risk factors damage the endothelium.
2. LDL and immune cells enter the artery wall.
3. An atheromatous plaque forms.
4. The lumen narrows, reducing blood flow.
5. The plaque may rupture.
6. Platelets stick and clotting is triggered.
7. A thrombus forms and may block the artery.
8. Tissue downstream becomes starved of oxygen.

In the heart, this can cause myocardial infarction. In the brain, it can cause stroke.

Risk factors for CVD

Risk factors can be modifiable, meaning you can change them, or non-modifiable, meaning you cannot.

Important modifiable risk factors include:

• smoking
• high blood pressure
• high LDL concentration
• low HDL concentration
• diets high in saturated fat
• high salt intake
• low physical activity
• obesity
• poorly controlled diabetes

Important non-modifiable risk factors include:

• age
• biological sex
• inherited genetic variants
• family history of CVD

Smoking increases CVD risk because chemicals in smoke damage the endothelium, carbon monoxide reduces oxygen transport by haemoglobin, and nicotine can increase heart rate and blood pressure.

High blood pressure increases mechanical stress on artery walls, making endothelial damage more likely. Diabetes increases risk partly because high blood glucose damages blood vessels.

Interpreting CVD risk data

In Biology A, you should be able to interpret evidence about lifestyle, health and risk. Be careful with the difference between correlation and causation.

A correlation means two variables are associated. For example, people with higher LDL concentrations may have higher rates of CVD. This does not automatically prove that LDL is the only cause, because other variables may differ between groups.

A confounding variable is an uncontrolled variable that affects the outcome. For example, if one group smokes more, exercises less and has higher LDL, it is hard to isolate the effect of LDL alone.

Relative risk

Relative risk compares the probability of disease in one group with the probability in another group.

$$relative\; risk=\frac{risk\; in\; exposed\; group}{risk\; in\; comparison\; group}$$

Reducing CVD risk

CVD risk can often be reduced by lifestyle changes and medical treatments.

Lifestyle approaches include:

• stopping smoking
• increasing aerobic physical activity
• reducing saturated fat intake
• increasing intake of fruit, vegetables and fibre
• reducing salt intake to help lower blood pressure
• maintaining a healthy body mass

Medical approaches may include:

• statins, which reduce blood LDL concentration
• antihypertensive drugs, which reduce blood pressure
• antiplatelet drugs, which reduce clot formation risk
• angioplasty and stents, which widen narrowed arteries
• coronary bypass surgery, which diverts blood around a blocked coronary artery

Treatments have benefits and risks, so doctors consider the patient’s overall risk profile rather than one measurement alone.