Atherosclerosis and cardiovascular disease

Atherosclerosis develops in four linked stages, with each stage accelerating the next:

1. Endothelial dysfunction
2. Inflammatory response
3. Plaque formation
4. Raised blood pressure

Damage to the endothelium allows white blood cells and LDL cholesterol to enter the artery wall, where they form foam cells and eventually a hardened plaque (atheroma). The narrowed lumen raises blood pressure, which causes further endothelial damage in a self-reinforcing positive feedback cycle.

Blood clotting plays a critical role in CVD. Damage to a plaque exposes collagen and triggers the clotting cascade. Thromboplastin catalyses the conversion of prothrombin to thrombin (in the presence of calcium ions), and thrombin catalyses the conversion of soluble fibrinogen to insoluble fibrin. The fibrin mesh traps blood cells to form a clot (thrombus) that may block a coronary or cerebral artery, causing a heart attack or stroke.

CVD risk depends on a mix of non-modifiable factors (genetics, age, and gender) and modifiable lifestyle factors (diet, smoking, physical inactivity, and high blood pressure). These factors interact, so combining several greatly multiplies the overall risk.

Dietary antioxidants such as vitamin C, vitamin E, and flavonoids neutralise free radicals that would otherwise oxidise LDL and damage the endothelium, helping to slow the progression of atherosclerosis.

Core Practical This chemistry is applied quantitatively to measure the vitamin C content of food and drink using DCPIP titration.

Together, these subtopics tie biochemistry, physiology, and epidemiology into one framework for understanding why CVD is the world's leading killer and how it can be prevented.