Atherosclerosis and aneurysms

Risk factors

• Non-modifiable: age, male sex, family history of premature disease (male relative under 55, female under 65), genetics (familial hypercholesterolaemia, high lipoprotein(a)), South Asian ethnicity (disease earlier and at lower BMI, so action thresholds are lower: BMI 23 overweight, 27.5 or more obese, smaller waist cut-offs).
• Modifiable: raised LDL, low HDL, hypertension, smoking, diabetes, central obesity, inactivity; also CKD, inflammation (rheumatoid arthritis, SLE, HIV), raised homocysteine.
• LDL is the main atherogenic lipoprotein: it enters the intima and is oxidised. Large chylomicrons and large VLDL particles are too big to enter the intima and contribute less (their smaller remnants are atherogenic).
• Low HDL raises risk because HDL carries cholesterol from plaques back to the liver (reverse cholesterol transport). Drugs that only raise HDL have not cut events, so treat total risk and LDL.
• Lipoprotein(a): an LDL particle carrying apo(a), which resembles plasminogen; it competes with plasminogen and impairs fibrinolysis (prothrombotic) and also delivers cholesterol to the wall.
• Homocystinuria (cystathionine β-synthase deficiency): marfanoid habit, downward lens dislocation, very high homocysteine, which damages endothelium and promotes thrombosis; treat with pyridoxine, folate and B12 (and betaine).

How a plaque forms

• Endothelial dysfunction first, from hypertension, smoking, hyperlipidaemia and hyperglycaemia, especially at branch points with turbulent flow.
• LDL enters the intima and is oxidised; endothelium expresses VCAM-1; monocytes enter and become macrophages that take up oxidised LDL by scavenger receptors, becoming foam cells.
• Fatty streak: the earliest lesion, flat, present from childhood, reversible.
• Growth factors (PDGF, TGF-β) make smooth muscle cells migrate from media to intima and lay down collagen, forming a fibrous cap over a necrotic lipid core (cholesterol crystals, foam cells, debris): the atheroma.
• Sites: abdominal aorta (most severe, especially infrarenal), proximal coronary arteries, popliteal, internal carotid at the bifurcation, circle of Willis, origins of renal and mesenteric arteries. Atherosclerotic renal artery stenosis affects the proximal 2 cm (ostium) in older people; fibromuscular dysplasia affects the distal artery in young women. Veins are spared.

• Other complications: haemorrhage into a plaque, cholesterol embolism (blue toes, renal failure after angiography), calcification, and aneurysm from thinning of the media.

Ischaemic heart disease

• Stable angina: at rest, arterioles beyond an 80% stenosis dilate to keep flow normal; on exertion they are already fully dilated, so the coronary flow reserve is exhausted and demand outstrips supply.
• Vasospastic (Prinzmetal) angina: chest pain at rest, often early morning, with transient ST elevation and no fixed stenosis. Treat with calcium channel blockers and nitrates; avoid beta-blockers, which leave alpha-mediated vasoconstriction unopposed.
• The subendocardium is the most vulnerable layer: it is furthest from the epicardial arteries and is compressed hardest during systole, so global hypotension causes subendocardial infarction.
• Acute coronary syndromes: unstable angina (no necrosis), NSTEMI (subendocardial), STEMI (transmural, occlusive thrombus). For STEMI, primary PCI is preferred if it can open the artery within about 120 minutes (ideally 90); new LBBB with typical pain is treated as STEMI. After a stent for ACS, give dual antiplatelet therapy for about 12 months, then aspirin alone.
• Territories: the LAD is most often occluded (anterior wall, septum, apex; V1–V4); RCA gives inferior infarcts (II, III, aVF) and supplies the SA and AV nodes in most people, so heart block follows; circumflex gives lateral infarcts (I, aVL, V5–V6).

• Other complications: ventricular fibrillation (main early killer), heart failure, cardiogenic shock, ventricular aneurysm (persistent ST elevation), mural thrombus, Dressler syndrome weeks later.

Mesenteric and carotid disease

• Chronic mesenteric ischaemia (abdominal angina): an elderly smoker with pain 15–30 minutes after meals, fear of eating and weight loss; usually the superior mesenteric artery (often with the coeliac axis).
• Acute mesenteric ischaemia: embolus (AF) or thrombosis of an atherosclerotic SMA: severe pain out of proportion to signs, then dark purple bowel at laparotomy; resect dead bowel and revascularise.
• Symptomatic carotid stenosis (TIA or minor stroke in that territory, such as right arm and face weakness with a left internal carotid stenosis) of 70–99% (and selected 50–69%): carotid endarterectomy within 2 weeks, plus antiplatelet, statin and blood pressure control.

Peripheral arterial disease

• Claudication: calf (superficial femoral), thigh and buttock (aortoiliac; Leriche syndrome: buttock claudication, impotence, absent femoral pulses). Critical ischaemia: rest pain at night relieved by hanging the leg down, ulcers, gangrene.
• ABPI: normal 1.0–1.3; claudication 0.5–0.9; critical below 0.5. Above 1.3 in diabetes or CKD means calcified, incompressible arteries (Mönckeberg medial sclerosis), so a high value can hide ischaemia; use toe pressures.

• The six Ps: pain, pallor, pulselessness, paraesthesia, paralysis, perishing cold. Sensory loss and muscle weakness mean a threatened limb that needs revascularisation within hours; less pain may mean dying nerves. Fixed mottling and rigid muscles mean an unsalvageable limb.
• Reperfusion compartment syndrome: hours after embolectomy, severe calf pain on passive toe movement and a tense calf, even with pulses present: four-compartment fasciotomy. Check potassium, creatine kinase and urine myoglobin.
• Diabetic foot: sensory neuropathy removes protective pain, and pressure under the first metatarsal head causes callus and a painless neuropathic ulcer; ischaemia and infection stop it healing. Neuropathic ulcers sit at pressure points, ischaemic ones at toe tips. Offloading is the most important treatment, with debridement, infection control and revascularisation if needed.
• Gangrene: dry (arterial, mummified, clear line), wet (infected, urgent), gas (*C. perfringens*). Progressive bacterial synergistic gangrene (Meleney ulcer) around a suture weeks after laparotomy: a slowly spreading ulcer ringed by purple then red skin, from microaerophilic streptococci with *S. aureus*; wide excision and antibiotics.
• Buerger disease: young heavy smokers; segmental inflammation of small and medium limb arteries and veins; digital gangrene; stopping smoking is essential.

Aneurysms and dissection

• True aneurysms involve all wall layers; false ones (pseudoaneurysms) are contained haematomas after puncture or trauma.

• Aortoenteric fistula after AAA graft repair (usually into the third part of the duodenum): a small herald bleed followed hours or days later by massive haemorrhage; endoscopy may look normal.

Other arterial diseases

• Arteriolosclerosis: hyaline (benign hypertension, diabetes), hyperplastic onion-skin (malignant hypertension).
• Giant cell arteritis: new temporal headache, jaw claudication, visual loss, high ESR: high-dose steroids immediately, then temporal artery biopsy. Granulomatosis with polyangiitis: sinusitis, haemoptysis, haematuria, c-ANCA (anti-PR3). Takayasu (young Asian women), polyarteritis nodosa (HBV), Kawasaki (coronary aneurysms).

Remember Plaques narrow slowly but kill suddenly: a thin cap ruptures and a thrombus closes the artery.

Exam trap The fatty streak is the earliest lesion; myocardial rupture peaks at 3–7 days.

Exam trap An ABPI above 1.3 in a diabetic means calcified arteries, not good circulation.

How FCPS asks about this

• Most affected vessel: abdominal aorta; the LAD is the commonest artery occluded in MI.
• Lipids: LDL is atherogenic; low HDL reduces reverse cholesterol transport; Lp(a) mimics plasminogen; apoE2 gives palmar xanthomas.
• Angina mechanisms: exertional angina exhausts flow reserve; vasospastic angina avoids beta-blockers; subendocardium is most vulnerable.
• Acute limb ischaemia in AF: embolus from the left atrium; sensory loss means threatened limb; fasciotomy for reperfusion compartment syndrome.
• Diabetic foot: neuropathic ulcer under the first metatarsal head; offload it.
• Post-prandial pain and weight loss: superior mesenteric artery stenosis.
• AAA: repair at 5.5 cm; herald bleed after graft repair means aortoenteric fistula.