What is the cause of ischemic heart disease (IHD)?

Causes of Ischaemic Heart Disease

Ischaemic heart disease results from inadequate coronary blood flow to meet myocardial oxygen demands, caused by both obstructive coronary atherosclerosis and multiple non-obstructive mechanisms including coronary microvascular dysfunction, vasospasm, and conditions that create supply-demand mismatch. 1

Primary Pathophysiological Mechanisms

Obstructive Coronary Artery Disease

• Atherosclerotic plaque formation in epicardial coronary arteries remains the most recognized cause, creating fixed stenotic lesions that limit coronary blood flow, particularly during increased myocardial oxygen demand 1
• Plaque rupture with superimposed thrombosis can acutely compromise coronary flow, leading to acute myocardial ischaemic syndromes 1
• The severity and distribution of coronary stenoses directly influence prognosis and symptom burden 1

Non-Obstructive Mechanisms

• Coronary microvascular dysfunction (CMD) represents a major cause of ischaemia in patients without obstructive epicardial disease, involving functional and structural alterations in the coronary microcirculation 1, 2
• Nearly half of patients with stable angina undergoing invasive angiography demonstrate no obstructive coronary disease, with CMD frequently responsible for their ischaemia 3
• Coronary vasospasm can cause transient flow limitation even in arteries without significant atherosclerosis 2, 4

Conditions That Precipitate or Exacerbate Ischaemia

Increased Myocardial Oxygen Demand

• Hyperthermia, particularly when accompanied by volume contraction, substantially increases oxygen requirements 1, 5
• Hyperthyroidism elevates metabolic rate and cardiac workload 1
• Sympathomimetic toxicity from cocaine or methamphetamine abuse increases demand while simultaneously inducing coronary vasospasm 1
• Severe uncontrolled hypertension increases left ventricular wall tension and oxygen consumption 1
• Tachyarrhythmias (ventricular or supraventricular) dramatically increase myocardial oxygen requirements 1
• Left ventricular hypertrophy from hypertrophic cardiomyopathy or aortic stenosis increases baseline oxygen demand 1, 6
• Emotional stress and anger trigger tachycardia and hypertension, creating critical supply-demand mismatch in patients with underlying coronary disease 7

Decreased Myocardial Oxygen Supply

• Anaemia reduces oxygen-carrying capacity; cardiac output rises when haemoglobin drops below 9 g/dL, with ST-T wave changes occurring at levels below 7 g/dL 1
• Hypoxaemia from pulmonary diseases (pneumonia, asthma, chronic obstructive pulmonary disease, pulmonary hypertension, interstitial fibrosis, obstructive sleep apnoea) limits oxygen availability 1
• Severe dehydration reduces coronary perfusion pressure through volume contraction, particularly affecting subendocardial blood flow 5
• Increased blood viscosity from polycythaemia, leukaemia, thrombocytosis, or hypergammaglobulinaemia decreases coronary artery blood flow 1, 5
• Significant aortic stenosis limits coronary perfusion, especially during diastole 1

Risk Factors Contributing to Disease Development

Modifiable Risk Factors

• Smoking directly damages endothelium and accelerates atherosclerosis 1
• Hyperlipidaemia (historically defined as total cholesterol >250 mg/dL) promotes plaque formation 1
• Diabetes mellitus significantly increases IHD probability and is associated with silent ischaemia due to autonomic neuropathy 1
• Hypertension contributes to both atherosclerosis and left ventricular hypertrophy 1
• Obesity and metabolic syndrome create multiple cardiovascular risk pathways 1
• Physical inactivity independently increases cardiovascular risk 1

Non-Modifiable Risk Factors

• Age and sex: Risk increases substantially with age; men have higher risk at younger ages than women 1
• Family history of premature IHD (onset in first-degree male relative before age 55 or female relative before age 65) indicates genetic predisposition 1

Important Clinical Considerations

• Silent ischaemia occurs in a sizeable proportion of patients, particularly those with diabetes and autonomic neuropathy, where ischaemic episodes produce no anginal symptoms 1
• The pathophysiology is dynamic and multifactorial, with atherosclerosis representing just one component of a complex disease process that can be modified by lifestyle, pharmacological therapies, and revascularization 8
• Conditions causing increased oxygen demand can precipitate angina even in the absence of significant anatomic coronary obstruction when severe enough 1, 5
• Coexisting conditions like heart failure, peripheral arterial disease, cerebrovascular disease, chronic kidney disease, and inflammatory conditions (rheumatoid arthritis, systemic lupus erythematosus) worsen prognosis 1