Cardiovascular pathophysiology


Cardiovascular disease is the biggest killer in the Western world. Ischaemic heart disease is the leading cause of death in the UK, with stroke (after cancer) accounting for the third-highest number of deaths. Cardiovascular disease is an inevitable consequence of the ageing process but is accelerated by the following risk factors (male gender, smoking, ethnicity: Indian subcontinent ethnicity is associated with an increased risk, diabetes: especially with poor glycaemic control, dyslipidaemia: high LDL cholesterol, low HDL cholesterol and high triglycerides; there may be a familial tendency, obesity, family history: close relative with premature cardiovascular disease).




Hypertension (Chapter 32)


This is a key cardiovascular disease and is a risk factor for developing ischaemic heart disease and chronic heart failure.



Ischaemic heart disease


Ischaemic heart disease (IHD) may manifest as either angina or myocardial infarction (MI) and is an important cause of chronic heart failure. In both cases, IHD is generally associated with atherosclerosis within the coronary arteries, leading to impaired blood flow or thromboembolic occlusion. In angina, the reductions in coronary blood flow mean that perfusion does not match demand, leading to ischaemia, which provokes the symptoms. Stable angina is characterised by chest pain (which may radiate down the left arm and to the jaw), which appears on exertion but is relieved by rest and/or the nitrate glyceryl trinitrate (GTN) given as a spray. Diagnosis may be based on symptoms and on ST-depression on the electrocardiogram (ECG) during an attack. Patients with stable angina receive beta-blockers (or rate-limiting calcium channel blockers), which reduce cardiac work and by increasing the time for diastole (when coronary flow occurs) increase coronary blood flow. GTN is used to relieve attacks and releases nitric oxide, which causes vasorelaxation, specifically venorelaxation, and this decreases venous return to the heart and so reduces cardiac work. Interventions include angioplasty with stenting (see below) or coronary artery bypass grafting (CABG), in which a donor artery (e.g. internal mammary artery) is used to surgically restore the blood flow by bypassing the diseased artery.


Unstable angina is generally due to plaque rupture and the for­mation of a non-occlusive thromboembolism, or, vasospasm.


In myocardial infarction (MI) there is often thromboembolic occlusion of a coronary artery. The cessation of blood flow results in damage or infarction of the cardiac muscle starved of blood. MI may lead to acute left ventricular failure and/or arrhythmias, which are the leading cause of early mortality. The initial management of MI is now emergency angioplasty, in which a balloon is advanced into the coronary atery to open up the blockage and restore blood flow. This is followed by insertion of a stent (a metal cage) to prevent reformation of the narrowing (restenosis). Other treatments include the use of ‘clot-busting’ drugs or thrombolytic agents that activate the plasma protein plasminogen to plasmin, which degrades fibrin that forms the clot, resulting in reperfusion. Following an MI, patients are often prescribed the combination of a beta-blocker, an ACE inhibitor, a statin and an antiplatelet drug (e.g. low-dose aspirin) for secondary prevention.


Ischaemic heart disease is often due to atheroscelerosis result­­ing from atherogenesis (Figure 35.1). The formation of changes to the intimal wall of the blood vessel begin in early adulthood with the formation of fatty streaks, and this process, over time, leads to the formation of cholesterol-rich atherosclerotic plaques which lead to partial occlusion of the artery (leading to angina) or they may rupture, leading to thrombus formation (leading to an MI in the coronary artery or stroke in the cerebral circulation). Atherogenesis is regarded as an inflammatory process and when injury occurs (as promoted by smoking, hypertension and possibly infection) activated monocytes and macrophages generate free radicals, which oxidise LDL cholesterol, which in turn damages its receptor and this leads to cholesterol being deposited at the point of the lesion. To slow down atherosclerosis the key approach is reduction of cardiovascular risk through lifestyle changes. Patients who have an elevated cardiovascular risk are prescribed statins.


Statins are cholesterol-lowering drugs that inhibit the endogenous production of cholesterol in the liver by inhibiting the enzyme hydroxyl-methylglutaryl coenzyme A reductase (HMG-CoA reductase), which catalyses the first committed step of cholesterol synthesis. This reduces cholesterol levels by reducing its synthesis and also leads to an upregulation of LDL cholesterol receptors, which promotes the uptake of cholesterol into liver cells. In addition to reducing cholesterol levels, statins may also stabilise cholesterol within the plaques, reducing the chances of a cardiovascular event.


Although total cholesterol should ideally be <5 mmol/L, statins are prescribed in relation to overall cardiovascular risk and are of benefit in patients with ‘normal’ cholesterol levels.

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Apr 22, 2017 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Cardiovascular pathophysiology

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