L06: Atherosclerosis and Ischaemic Heart Disease

Ischaemia is a reduction in blood supply sufficient to impair tissue function or viability. Infarction is localised ischaemic necrosis resulting from complete or near-complete cessation of blood flow. Ischaemic heart disease (IHD) encompasses the clinical syndromes arising from myocardial ischaemia, the commonest cause of death in developed countries.

Atherosclerosis is the pathological process underlying most IHD. It is a chronic inflammatory disease of large and medium arteries characterised by the formation of atheromatous plaques in the intima. The sequence of events begins with endothelial dysfunction — caused by hyperlipidaemia, hypertension, smoking, diabetes, and haemodynamic stress — which allows low-density lipoprotein (LDL) to enter and accumulate in the intima. LDL is oxidised by reactive oxygen species, becoming a potent stimulus for monocyte recruitment. Monocytes differentiate into macrophages, which engulf oxidised LDL via scavenger receptors and transform into lipid-laden foam cells. Foam cells accumulate to form the fatty streak, the earliest visible lesion.

Over years, a fibrous cap of smooth muscle cells and collagen forms over the lipid core, creating a fibrous plaque (atheroma). Risk factors for atherosclerosis include: hyperlipidaemia (especially elevated LDL), hypertension, smoking, diabetes mellitus, obesity, physical inactivity, and a family history of premature cardiovascular disease. Inflammation (elevated CRP, IL-6) independently predicts cardiovascular risk.

A critical stenosis of 70–75% of the luminal cross-sectional area is required before resting blood flow is significantly impaired. Stable angina results when demand exceeds supply during exertion; it is relieved by rest and nitrates.

Acute coronary syndromes (ACS) result from acute changes in a plaque: fissuring, ulceration, or rupture of the fibrous cap exposes the thrombogenic core, triggering platelet aggregation and thrombus formation. Unstable angina is caused by a non-occlusive thrombus producing transient ischaemia. Myocardial infarction (MI) results when thrombus completely occludes the vessel for more than 30 minutes, causing irreversible myocyte necrosis. STEMI (ST-elevation MI) indicates complete occlusion with transmural ischaemia; NSTEMI (non-ST-elevation MI) indicates partial occlusion or spontaneous reperfusion.

Biochemical markers of MI: troponin I and T are released from necrotic cardiomyocytes and are detectable within 3–6 hours of onset, peaking at 24 hours and remaining elevated for 7–14 days. They are highly sensitive and cardiac-specific. CK-MB rises earlier and clears faster (useful for detecting reinfarction). Troponin elevation without obstructive CAD (type 2 MI or myocarditis) must be distinguished clinically.

Complications of MI: within hours — cardiac arrhythmias (most common cause of early death, including ventricular fibrillation) and cardiogenic shock from extensive necrosis. Days 1–3 — fibrinous pericarditis (Dressler-like but early, from epicardial inflammation). Day 3–7 — risk of myocardial rupture through the softened necrotic zone (causes haemopericardium and cardiac tamponade). Papillary muscle rupture causes acute mitral regurgitation. Weeks — mural thrombus forms on akinetic endocardium (systemic embolisation risk). Ventricular aneurysm from replacement of infarcted muscle with fibrous scar. Chronic IHD progresses to congestive heart failure as surviving myocardium hypertrophies and dilates.