Atherosclerosis and cardiovascular disease

The Development of Atherosclerosis

Atherosclerosis is the progressive hardening and narrowing of arteries caused by the build-up of fatty deposits called atheromas in the artery wall.

The disease develops in four overlapping stages, each making the next more severe.

1. Endothelial dysfunction The endothelium is the smooth inner lining of an artery. It becomes damaged by high blood pressure, toxins from smoking, or high blood glucose. This damage exposes the underlying tissue and disrupts normal blood flow.

2. Inflammatory response White blood cells leave the blood and move into the damaged artery wall. They accumulate low-density lipoprotein (LDL) cholesterol from the plasma. Loaded with cholesterol, they become foam cells, which build up as a fatty streak.

3. Plaque formation More cholesterol, fibres, and calcium salts accumulate around the foam cells. Together these form a hard atherosclerotic plaque that bulges into the lumen. The artery wall loses elasticity and the lumen becomes narrower.

MisconceptionMany students describe plaque as forming “inside the lumen” or “on top of” the artery wall. Plaque actually forms within the wall itself, between the endothelium and the underlying muscle layer. The lumen narrows because the wall thickens inwards.

Exam TipAlways say plaque forms inside the artery wall, not in the lumen.

4. Raised blood pressure A narrower lumen forces the same volume of blood through a smaller space. This raises blood pressure, which damages the endothelium further. The cycle is therefore self-reinforcing, so atherosclerosis worsens once it begins.

Blood Clotting and Its Role in CVD

Blood clotting is a cascade of reactions that seals damaged blood vessels and prevents excessive blood loss.

When a vessel is damaged, platelets stick to the exposed collagen and release a substance called thromboplastin. The clotting cascade then follows three key steps:

1. Thromboplastin is released from platelets and damaged tissue, triggering the cascade.
2. Thromboplastin, together with calcium ions, converts soluble prothrombin into active thrombin.
3. Thrombin acts as an enzyme that converts soluble fibrinogen into insoluble fibrin.

Fibrin forms a mesh of fibres across the wound. Red blood cells and platelets become trapped in the mesh, forming a clot that seals the damage.

Role in CVD

A clot that forms inside a blood vessel is called a thrombus. Thrombi often form on the rough surface of an atherosclerotic plaque, where the endothelium is damaged.

If a thrombus blocks a coronary artery, the heart muscle beyond it is starved of oxygen, causing a myocardial infarction [heart attack]. If a thrombus blocks an artery supplying the brain, brain tissue dies, causing a stroke.

A clot can also break loose and travel through the circulation, causing blockage elsewhere. This is called an embolism.

Risk Factors for Cardiovascular Disease

Cardiovascular disease (CVD) risk depends on several factors that interact and accumulate over a person’s lifetime.

Some factors are non-modifiable, meaning they cannot be changed. Others are modifiable, meaning they can be reduced through lifestyle change.

These factors do not act in isolation. A smoker who is also inactive and has a high-fat diet has a far greater risk than someone with only one factor.

Examiner InsightVague answers like “smoking is bad for the heart” gain no credit. Examiners reward specific mechanisms. For example, carbon monoxide binds irreversibly to haemoglobin and reduces oxygen delivery to tissues.

Exam TipAlways link a risk factor to a precise biological mechanism.

Antioxidants and Cardiovascular Health

Dietary antioxidants are nutrients that neutralise harmful molecules called free radicals.

Free radicals are unstable molecules with unpaired electrons. They can damage cell membranes, proteins, and DNA, including the endothelium of arteries.

When LDL is oxidised by free radicals, it becomes more readily taken up by white blood cells in the artery wall. This accelerates foam cell and plaque formation.

Antioxidants such as vitamin C, vitamin E, and flavonoids donate electrons to neutralise free radicals before they cause damage. By reducing oxidative damage to the endothelium, antioxidants slow the progression of atherosclerosis.

Diets rich in fruit and vegetables are linked to lower CVD risk in epidemiological studies. However, evidence from supplement trials has been mixed. Whole-food sources of antioxidants appear more effective than isolated supplements.

Investigating Vitamin C Content (Core Practical 2)

This practical determines the vitamin C content of food and drink samples by measuring how much is needed to decolourise the blue dye DCPIP.

DCPIP is blue when oxidised. Vitamin C is a reducing agent, so it reduces DCPIP and turns it colourless. The volume of solution needed to decolourise a fixed volume of DCPIP indicates how concentrated the vitamin C is.

Aim: To determine and compare the vitamin C concentration of different food and drink samples using DCPIP titration.

Method

1. Place 1 cm³ of 1% DCPIP solution into a test tube using a pipette.
2. Fill a graduated syringe (or burette) with a vitamin C standard solution of known concentration, e.g. 1.0 mg/cm³.
3. Add the standard solution drop by drop to the DCPIP, shaking gently after each drop.
4. Stop adding when the DCPIP becomes colourless and remains so for 10 seconds.
5. Record the volume of solution required.
6. Repeat the procedure using each food or drink sample in place of the standard.
7. Calculate the vitamin C concentration of each sample by comparison with the standard.

Variables

• Independent variable (IV): Type of food or drink sample.
• Dependent variable (DV): Volume of sample required to decolourise the DCPIP.
• Control variables (CV): Volume and concentration of DCPIP, temperature of solutions, drop size, end-point judgement, and shaking technique.

Expected results

A smaller volume of sample needed to decolourise DCPIP indicates a higher vitamin C concentration. Citrus juices and blackcurrant typically need very small volumes. Cooked or aged samples need larger volumes because vitamin C degrades with heat and oxygen exposure.

Precaution

End-point judgement is subjective and varies between trials. Place a white tile behind the tube and view from the same angle each time. Vitamin C oxidises in air and is destroyed by heat, so use fresh samples and minimise exposure.