Vascular Disease & Coronary Artery Disease — USMLE Step 2 CK Notes

Hypertension — pathophysiology & pharmacology

• Primary (essential, ~90%): multifactorial — increased sympathetic tone, RAAS activation, sodium retention and vascular remodelling raise total peripheral resistance (MAP = CO × TPR).
• Secondary causes: renal artery stenosis (fibromuscular dysplasia in young women, atherosclerosis in older adults), primary hyperaldosteronism (hypertension + hypokalaemia), phaeochromocytoma (episodic), Cushing, coarctation, obstructive sleep apnoea, oral contraceptives.
• Hypertensive emergency: severe hypertension with acute end-organ damage (encephalopathy, papilloedema, acute kidney injury, dissection) — lower pressure in a controlled way.
• Drug classes: thiazides (inhibit the Na-Cl cotransporter; hyponatraemia, hypokalaemia, hyperuricaemia), ACE inhibitors/ARBs (block angiotensin II; cough and angioedema with ACE inhibitors, hyperkalaemia, contraindicated in pregnancy and bilateral renal artery stenosis), calcium channel blockers (dihydropyridines dilate arterioles — ankle oedema; verapamil/diltiazem also slow the heart), beta-blockers (reduce rate/contractility and renin), hydralazine (arteriolar dilator; reflex tachycardia, drug-induced lupus), nitroprusside (cyanide toxicity risk).

Hyperlipidaemia signs

• Xanthomas: lipid-laden macrophage deposits in skin or tendon.
• Tendinous xanthoma (Achilles tendon, knuckle extensors) — classic for familial hypercholesterolaemia.
• Eruptive xanthomas (crops of yellow papules) indicate very high triglycerides.
• Xanthelasma (yellow plaques on the eyelids) and corneal arcus (lipid ring at the corneal periphery) — arcus is age-related in older adults but suggests hyperlipidaemia when it appears before ~45.

Atherosclerosis

• Location, commonest first: abdominal aorta > coronary arteries > popliteal > carotid.
• Risk factors: modifiable — smoking, hypertension, diabetes, dyslipidaemia (high LDL, low HDL), obesity; non-modifiable — age, male sex, family history.
• Progression: endothelial injury → LDL enters the intima and is oxidised → monocytes enter and become foam cells → fatty streak → smooth muscle migration with collagen forms a fibrous plaque → complicated plaque with calcification, ulceration and rupture.
• Complications: stenosis with ischaemia (angina, claudication), plaque rupture with thrombosis (infarction), embolisation, aneurysm formation.
• Pharmacology: statins (HMG-CoA reductase; also plaque-stabilising) are first line, plus ezetimibe and PCSK9 inhibitors; antiplatelets prevent thrombosis. Manage blood pressure, diabetes and smoking.

Cholesterol emboli syndrome

• Plaque cholesterol crystals showered downstream, typically after vascular catheterisation or surgery (or spontaneously on anticoagulation).
• Features: livedo reticularis, blue toe syndrome with intact pulses, acute kidney injury, eosinophilia, and Hollenhorst plaques in the retina. Management is supportive with statin therapy.

Arteriolosclerosis

• Hyaline arteriolosclerosis: pink hyaline thickening of small vessels from protein leak — seen in benign hypertension and diabetes (also causes the nodular glomerulosclerosis picture).
• Hyperplastic arteriolosclerosis: concentric "onion-skin" smooth-muscle thickening — seen in malignant (severe) hypertension, sometimes with fibrinoid necrosis.
• Monckeberg medial calcific sclerosis: calcification of the media of medium arteries, does not obstruct flow; a radiological curiosity ("pipestem" arteries).

Aortic aneurysm & dissection

• Abdominal aortic aneurysm: usually below the renal arteries, driven by atherosclerosis and smoking in older men; a pulsatile mass. Rupture gives sudden severe back/abdominal pain with hypotension — a surgical emergency. Repair electively at ~5.5 cm.
• Thoracic aortic aneurysm: from cystic medial degeneration (Marfan, Ehlers-Danlos, bicuspid valve) or tertiary syphilis (vasa vasorum endarteritis, "tree-bark" intima); may cause aortic regurgitation.
• Traumatic aortic rupture: rapid deceleration injury tears the aorta at the isthmus near the ligamentum arteriosum; a widened mediastinum on chest X-ray is the clue.
• Aortic dissection: an intimal tear lets blood track into the media. Sudden tearing chest pain radiating to the back, unequal arm blood pressures. Stanford A (ascending) needs surgery; Stanford B (descending) is managed medically with beta-blockers first, then vasodilators. Risks: hypertension, Marfan, bicuspid valve, pregnancy, cocaine.

Subclavian steal syndrome

• Stenosis of the subclavian artery proximal to the vertebral origin; exercising that arm drops distal pressure and blood is "stolen" by retrograde vertebral flow.
• Gives arm claudication plus posterior circulation symptoms (dizziness, vertigo, syncope) on arm exertion, with a blood pressure difference >15 mmHg between arms. Treat with stenting or bypass.

Coronary artery disease & acute coronary syndromes

• Stable angina: fixed stenosis (~>70%); predictable exertional chest pain relieved by rest or nitrates; ST depression on stress testing, normal troponin.
• Unstable angina: plaque rupture with partial thrombosis — pain at rest or crescendo; ST depression/T-wave inversion, normal troponin.
• NSTEMI: subendocardial infarction — ST depression/T inversion with raised troponin.
• STEMI: transmural infarction from complete occlusion — ST elevation with raised troponin; needs immediate reperfusion.
• Prinzmetal (vasospastic) angina: coronary spasm at rest with transient ST elevation and normal arteries; linked to smoking and cocaine; treat with calcium channel blockers and nitrates (avoid beta-blockers).
• Troponin: rises at 3-4 hours, peaks around 24 hours, stays elevated 7-10 days (so it cannot detect early re-infarction). CK-MB normalises in 48-72 hours and is therefore the marker used for re-infarction.
• Coronary steal: a vasodilator (dipyridamole, adenosine, regadenoson) dilates healthy vessels and diverts flow away from an already maximally dilated stenotic bed — the basis of pharmacological stress testing.
• Myocardial stunning: transient contractile dysfunction after brief ischaemia/reperfusion, recovers in days. Hibernating myocardium: chronically underperfused but viable tissue with reduced function that recovers after revascularisation.
• Sudden cardiac death: death within an hour of symptom onset, usually from ventricular fibrillation; most often due to coronary disease, and in the young to hypertrophic cardiomyopathy or channelopathies.
• Chronic ischaemic heart disease: progressive ischaemic myocardial fibrosis leading to heart failure.

Evolution of a myocardial infarct

• 0-24 hours: early coagulative necrosis with wavy fibres and contraction bands; risk of arrhythmia (the main early killer). Gross: no change, then dark mottling.
• 1-3 days: neutrophil infiltration; risk of fibrinous pericarditis (post-infarction pericarditis).
• 3-14 days: macrophages clear debris then granulation tissue appears — the wall is weakest, so this is when free wall rupture, papillary muscle rupture and septal rupture occur. Gross: yellow-tan centre with a hyperaemic border.
• 2 weeks onward: collagenous scar forms — risk of true ventricular aneurysm, mural thrombus and Dressler syndrome.

ECG localisation of STEMI

• II, III, aVF → inferior wall → right coronary artery (watch for bradycardia/AV block; avoid nitrates if RV involved).
• V1-V2 → septal, V3-V4 → anterior → LAD.
• V5-V6, I, aVL → lateral → left circumflex.
• Posterior → tall R waves and ST depression in V1-V2 (a mirror image) → RCA/LCx. Work through real tracings in the ECGs tab.

Complications of myocardial infarction

• Arrhythmia (commonest cause of early death, especially VF).
• Post-infarction fibrinous pericarditis (days 1-3) and Dressler syndrome (autoimmune, weeks later, with fever and a rub).
• Papillary muscle rupture (3-5 days, posteromedial muscle in inferior MI) → acute severe mitral regurgitation and pulmonary oedema.
• Interventricular septal rupture → new harsh holosystolic murmur with a left-to-right shunt (step-up in oxygen saturation).
• Free wall rupture → tamponade and sudden death; contained rupture forms a pseudoaneurysm (narrow neck, high rupture risk).
• True ventricular aneurysm (weeks-months) — scarred wall, persistent ST elevation, mural thrombus risk, but low rupture risk.

Pharmacology of acute coronary syndromes

• Antiplatelet: aspirin (irreversible COX-1 inhibition) plus a P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel).
• Anticoagulant: heparin (or low-molecular-weight heparin).
• Anti-ischaemic: nitrates (venodilate, reduce preload; avoid in RV infarct, hypotension or recent PDE-5 inhibitor use) and beta-blockers (reduce oxygen demand; avoid in cardiogenic shock or cocaine-induced ischaemia).
• Reperfusion: primary PCI for STEMI (thrombolysis if PCI is unavailable in time).
• Secondary prevention: high-intensity statin, ACE inhibitor (especially with reduced EF), beta-blocker and dual antiplatelet therapy.

High-yield revision notes; verify against a primary source before clinical use.