Vascular development, vasculitis, epidemiology and surgical management

The vascular system begins as blood islands that coalesce into paired dorsal aortae, which fuse below the level of the fourth thoracic segment. Six pairs of aortic arches connect the aortic sac to the dorsal aortae in the pharyngeal arches, and they appear and regress in sequence rather than all at once. The first and second arches largely disappear, leaving the maxillary and stapedial arteries; the third becomes the common carotid and the first part of the internal carotid; the fourth becomes the arch of the aorta on the left and the proximal right subclavian artery on the right; the fifth is rudimentary or absent; the sixth gives the pulmonary arteries, and on the left its distal part persists as the ductus arteriosus. The asymmetry of the arches explains the asymmetric course of the recurrent laryngeal nerves, which hook under the sixth arch derivative: under the ductus arteriosus on the left and, because the distal sixth arch regresses on the right, under the right subclavian artery. In the fetus the placenta is the organ of gas exchange, so three shunts divert blood away from the liver and lungs: the ductus venosus carries oxygenated umbilical blood past the liver to the inferior vena cava, the foramen ovale passes blood from the right atrium to the left, and the ductus arteriosus carries most of the right ventricular output from the pulmonary trunk into the descending aorta. At birth the lungs expand, pulmonary vascular resistance falls, systemic resistance rises when the placenta is removed, left atrial pressure exceeds right and the flap of the foramen ovale closes; rising oxygen tension and falling prostaglandins constrict the ductus arteriosus within hours and it fibroses over weeks into the ligamentum arteriosum, while the ductus venosus becomes the ligamentum venosum and the umbilical vein the ligamentum teres. Failure of these steps and errors of septation and arch formation produce the congenital malformations: patent ductus arteriosus with a continuous machinery murmur and a left-to-right shunt, atrial and ventricular septal defects, coarctation of the aorta near the ligamentum arteriosum with upper-limb hypertension, weak delayed femoral pulses and rib notching, transposition of the great arteries, tetralogy of Fallot, and vascular rings from persistence of arches that normally regress, which can compress the trachea and oesophagus. A persistent left-to-right shunt that raises pulmonary vascular resistance can eventually reverse, producing cyanosis, the Eisenmenger syndrome.

Vasculitis is inflammation of vessel walls, producing ischaemia downstream by narrowing or thrombosis and, where the wall is destroyed, aneurysm or haemorrhage. Its causes are immune mediated, from immune complex deposition (hepatitis B in polyarteritis nodosa, drugs, systemic lupus erythematosus, cryoglobulins), from ANCA, from anti-endothelial antibodies as in Kawasaki disease and from cell-mediated injury; it may also be caused directly by infection of the wall, by bacteria, fungi or rickettsiae, and this distinction matters because immunosuppression would be harmful in infective vasculitis. ANCA are autoantibodies against neutrophil granule enzymes: cytoplasmic ANCA against proteinase-3 accompany granulomatosis with polyangiitis, and perinuclear ANCA against myeloperoxidase accompany microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. They are not innocent markers: they activate primed circulating neutrophils, which adhere to endothelium and degranulate, so ANCA titres often follow disease activity. The classification is by vessel size. Large-vessel disease includes giant cell (temporal) arteritis, a granulomatous arteritis of the branches of the carotid in patients over fifty with headache, scalp tenderness, jaw claudication, a raised erythrocyte sedimentation rate and the risk of sudden blindness from ophthalmic artery involvement, treated urgently with corticosteroids, and Takayasu arteritis, the same histology in young women affecting the aortic arch and its branches with pulseless upper limbs. Medium-vessel disease includes polyarteritis nodosa, a segmental transmural necrotising arteritis with lesions of different ages that spares the lungs and presents with fever, weight loss, renal and gastrointestinal ischaemia, neuropathy and hypertension, associated with hepatitis B in about a third of cases; Kawasaki disease of young children with fever, conjunctivitis, rash, cervical nodes and coronary arteritis that can produce aneurysms; and Buerger disease (thromboangiitis obliterans), a segmental thrombosing inflammation of the distal limb arteries of heavy smokers causing claudication, rest pain and gangrene, in which stopping smoking is the treatment. Small-vessel disease includes granulomatosis with polyangiitis (necrotising granulomas of the upper and lower respiratory tract with glomerulonephritis, c-ANCA), microscopic polyangiitis (lesions all of the same age, p-ANCA, pulmonary-renal syndrome), eosinophilic granulomatosis with polyangiitis (asthma, eosinophilia, granulomas), Henoch-Schönlein purpura with IgA deposition, and hypersensitivity (leukocytoclastic) vasculitis, usually drug-related, with palpable purpura on the legs.

Varicose veins are abnormally dilated and tortuous superficial veins produced by chronically raised intraluminal pressure with loss of support and valvular incompetence; the superficial veins of the leg are affected in perhaps a fifth of adults, more in women, with age, obesity, pregnancy, prolonged standing and family history as risks. Incompetent valves allow reflux, venous pressure in the standing leg stays high, and the sequelae are stasis dermatitis with pigmentation from haemosiderin, induration, poorly healing venous ulcers around the medial malleolus, and superficial thrombophlebitis; embolism from superficial varices is rare. Varices occur at other sites where venous pressure rises: oesophageal varices in portal hypertension, haemorrhoids, and varicocele of the pampiniform plexus. Deep venous thrombosis, by contrast, arises from Virchow triad of stasis, endothelial injury and hypercoagulability, and is the source of clinically important pulmonary embolism. Lymphatic disease follows obstruction or destruction: lymphangitis is acute bacterial inflammation of lymphatics with red streaks and tender nodes; lymphoedema is chronic accumulation of protein-rich interstitial fluid, primary from congenital lymphatic hypoplasia (Milroy disease) or secondary to tumour, surgical node dissection, radiation, fibrosis or filariasis, which in its extreme form is elephantiasis, and long-standing lymphoedema can give rise to lymphangiosarcoma. Tumours of blood vessels form a spectrum. Benign lesions are common and include capillary and cavernous haemangioma, pyogenic granuloma, glomus tumour of the digits, which is characteristically painful, and lymphangioma; these are well circumscribed, composed of recognisable vascular channels lined by regular endothelium, and do not invade. Borderline (intermediate) lesions such as Kaposi sarcoma, driven by human herpesvirus 8 and seen in acquired immunodeficiency and in immunosuppression, and haemangioendothelioma, behave between benign and malignant. Malignant tumours are rare: angiosarcoma, most often of skin, soft tissue, breast or liver, with the classic associations of arsenic, vinyl chloride and thorotrast for hepatic angiosarcoma and of chronic lymphoedema after mastectomy for the cutaneous form, shows cellular atypia, mitoses, invasive irregular channels or solid sheets that need endothelial markers such as CD31 to identify, and it metastasises early with a poor prognosis. The distinguishing criteria are therefore circumscription, cellular atypia, mitotic rate, the regularity of the vascular channels and the presence of invasion.

Cardiovascular disease is the leading cause of death worldwide, accounting for about a third of all deaths, and it is the leading cause of death in Jordan, where the epidemiological transition has been rapid: communicable disease has receded while smoking, obesity, diabetes and physical inactivity have risen sharply, so ischaemic heart disease and stroke now dominate mortality and present at a younger age than in western Europe. Described by person, the incidence rises steeply with age, is higher in men until the menopause and then converges, and is higher in those with a family history, in lower socioeconomic groups and in South Asian populations; by time, rates rose through the twentieth century in industrialised countries and have fallen since the 1970s where risk factors were addressed, while they are still rising in many middle-income countries; by place, they vary with diet, smoking prevalence and health system performance. The identification of the risk factors themselves came largely from the Framingham Heart Study, begun in 1948 in Framingham, Massachusetts, which followed a community cohort for decades and established age, sex, smoking, blood pressure, total and HDL cholesterol and diabetes as independent predictors, gave the term risk factor its currency, and produced the first multivariable risk equations. The modifiable factors are smoking, hypertension, dyslipidaemia, diabetes, obesity, physical inactivity, unhealthy diet and harmful alcohol use, with psychosocial stress; the non-modifiable are age, male sex, family history and ethnicity. Control has two strategies. The high-risk strategy finds and treats individuals at the top of the risk distribution, which is efficient for the individual and well accepted, but it reaches only a minority of future cases, because most events arise from the large number of people at moderate risk, the prevention paradox. The population strategy shifts the entire distribution by a small amount through taxation, legislation, food reformulation, urban design and mass education, which prevents more total events but offers little visible benefit to any one person. The levels of control follow the usual scheme: primordial prevention stops risk factors from appearing at all (tobacco-free environments, school nutrition); primary prevention removes risk factors in people without disease (smoking cessation, blood pressure and lipid control); secondary prevention detects and treats early disease (screening for hypertension and diabetes, aspirin and statins after an event); tertiary prevention limits disability and prevents recurrence (cardiac rehabilitation, adherence programmes). The North Karelia project in Finland, launched in 1972 in the province with the highest coronary mortality in the world, is the standard example of the population approach: a community-wide campaign of smoking cessation, dietary change from dairy fat to vegetable oil and berries, salt reduction, food industry cooperation and lay volunteer networks cut coronary mortality in working-age men by about 80 percent over three decades and was extended nationally.

Surgery treats the mechanical consequences of cardiovascular disease when drugs and risk-factor control are not enough. In coronary artery disease, percutaneous coronary intervention passes a catheter to the lesion, dilates it with a balloon and holds it open with a drug-eluting stent; it is the treatment of choice for acute ST-elevation infarction, where door-to-balloon time determines how much muscle is saved, and for single or two-vessel disease, with in-stent restenosis and stent thrombosis as its characteristic problems, the latter prevented by dual antiplatelet therapy. Coronary artery bypass grafting uses the left internal mammary artery to the anterior descending vessel, with radial artery or saphenous vein grafts to other territories, and is preferred for left main stem disease, three-vessel disease, diabetic patients with multivessel disease and when ventricular function is impaired; the internal mammary graft has much the best long-term patency. Its complications are those of cardiopulmonary bypass and sternotomy: bleeding, atrial fibrillation, stroke, cognitive change, sternal wound infection, graft occlusion and perioperative infarction. The mechanical complications of infarction, free wall rupture, ventricular septal rupture and papillary muscle rupture with acute mitral regurgitation, are surgical emergencies. Valvular disease is corrected when the lesion is severe and symptomatic, or when the ventricle is beginning to decompensate: aortic stenosis is treated by surgical or transcatheter valve replacement, mitral regurgitation increasingly by repair rather than replacement because repair preserves the subvalvar apparatus and avoids anticoagulation, and mitral stenosis by balloon valvotomy or replacement. The choice between a mechanical prosthesis, which lasts for decades but requires lifelong warfarin, and a bioprosthesis, which needs no long-term anticoagulation but degenerates in ten to fifteen years, turns on the patient age, bleeding risk and plans for pregnancy; prosthetic valves carry the risks of thromboembolism, endocarditis, haemolysis and paravalvular leak, and endocarditis prophylaxis applies. In peripheral vascular disease, intermittent claudication is managed first with smoking cessation, supervised exercise, statins and antiplatelet drugs, since exercise develops collaterals, and intervention is reserved for lifestyle-limiting claudication or critical limb ischaemia with rest pain, ulceration or gangrene: angioplasty and stenting for short stenoses, endarterectomy for localised plaque, and bypass grafting (femoropopliteal, femorodistal, aortobifemoral) for long occlusions, with amputation when the limb cannot be salvaged. Carotid endarterectomy reduces stroke in symptomatic severe carotid stenosis, and abdominal aortic aneurysms are repaired, openly or with an endovascular stent graft, when they exceed about five and a half centimetres or enlarge rapidly, because rupture is usually fatal. Acute limb ischaemia from embolism or thrombosis, recognised by the six Ps, is an emergency requiring anticoagulation and embolectomy or bypass within hours.