Coronary atherosclerotic heart disease (coronary artery disease, CAD; or coronary heart disease, CHD) is heart disease caused by atherosclerosis of the coronary arteries, which leads to narrowing or occlusion of the vessel lumen, resulting in myocardial ischemia, hypoxia, or necrosis. It is also known as ischemic heart disease (IHD).
CAD is the most common type of organ damage caused by atherosclerosis and poses a significant threat to human health. The disease predominantly affects adults over 40 years old, with males developing it earlier than females. Its prevalence is higher in economically developed countries. In recent years, there has been a trend toward younger onset of the disease.
Clinical Classification
Due to differences in pathological anatomy and pathophysiology, CAD manifests in various clinical forms. In 1979, the World Health Organization (WHO) classified CAD into five types:
- Silent or asymptomatic CAD
- Angina pectoris
- Myocardial infarction (MI)
- Ischemic cardiomyopathy
- Sudden cardiac death (SCD)
In recent years, CAD has been more commonly divided into two categories based on its clinical presentation and treatment principles:
- Chronic coronary syndrome (CCS)
- Acute coronary syndrome (ACS)
Chronic coronary syndrome, also known as chronic coronary disease (CCD), may involve obstructive or non-obstructive coronary lesions. CCS includes the following scenarios:
- Patients with suspected CAD presenting with stable angina symptoms and/or dyspnea
- Patients with suspected CAD presenting with new-onset heart failure or left ventricular dysfunction
- Patients who are asymptomatic or have stable symptoms within one year after ACS or recent revascularization
- Patients with a first diagnosis of CAD or more than one year after revascularization, whether asymptomatic or symptomatic
- Patients with suspected vasospastic or microvascular angina
Asymptomatic CAD can be detected during screening.
Acute coronary syndrome includes unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), ST-segment elevation myocardial infarction (STEMI), and sudden cardiac death, with the latter being the most severe clinical manifestation of CAD. Pathologically, ACS is most caused by thrombosis and/or spasm secondary to atherosclerotic lesions in the coronary arteries. In a small proportion of cases, myocardial infarction occurs without obstructive coronary artery disease (MINOCA), which may result from spasm, spontaneous coronary artery dissection (SCAD), intramural hematoma, embolism, or microvascular disease.
CCS and ACS represent different stages in the progression of CAD. Clinical presentation primarily depends on the stability of atherosclerotic plaques. CAD can remain stable for a long period; however, the risk of cardiovascular events may change over time. If risk factors are poorly controlled, lifestyle modifications and/or pharmacological treatments are inadequate, or revascularization is unsuccessful, plaque rupture or erosion may lead to acute thrombotic events, transitioning CCS into ACS.
Pathogenesis
Myocardial ischemia and hypoxia occur when there is an imbalance between coronary blood supply and myocardial oxygen demand. Temporary ischemia and hypoxia cause angina, while prolonged and severe ischemia and hypoxia result in myocardial necrosis, i.e., myocardial infarction.
The myocardium requires a significant oxygen supply to produce energy, extracting 65%-75% of the oxygen in the blood, which is much higher than other tissues. Under normal conditions, the myocardium is already extracting oxygen near its maximum capacity. When oxygen demand increases, the myocardium cannot extract significantly more oxygen from the blood and must rely on increased coronary blood flow to meet its needs.
The coronary circulation has substantial reserve capacity under normal circumstances. Coronary blood flow is dynamically regulated by neural and humoral mechanisms to match myocardial oxygen demand. During intense physical activity, coronary arteries dilate appropriately, increasing blood flow by 6-7 times compared to resting levels.
The primary factors determining myocardial oxygen consumption are heart rate, myocardial contractility, and ventricular wall tension. Clinically, myocardial oxygen consumption is often estimated using the formula "heart rate x systolic blood pressure." Since coronary perfusion primarily occurs during diastole, an increased heart rate (shortening diastole) or reduced diastolic pressure significantly impairs coronary perfusion. Fixed coronary stenosis or increased microvascular resistance can also reduce coronary blood flow. When coronary artery stenosis reaches 50%-75%, blood flow may be sufficient at rest but becomes inadequate during physical exertion, tachycardia, or emotional stress, leading to transient myocardial oxygen supply-demand imbalance. This is the primary mechanism of most CCS cases.
In other cases, unstable atherosclerotic plaques may rupture, erode, or hemorrhage, triggering platelet aggregation or thrombosis, leading to a sudden increase in stenosis severity or coronary artery spasm. These events significantly reduce myocardial oxygen supply and are the primary causes of ACS. Additionally, myocardial oxygen supply may be significantly reduced in cases of severe anemia, even if coronary perfusion is normal. In many cases, myocardial ischemia or necrosis results from a combination of increased oxygen demand and reduced oxygen supply.
During myocardial ischemia, hypoxia inhibits oxidative metabolism, depleting high-energy phosphate reserves and altering cellular function. The direct cause of angina pain is likely the accumulation of metabolic byproducts in the myocardium under ischemic and hypoxic conditions, such as lactic acid, pyruvic acid, phosphates, and peptide-like substances similar to kinins. These substances stimulate the afferent nerve endings in the myocardium, transmitting pain signals via the sympathetic ganglia (T1-T5) and corresponding spinal segments to the brain, where the sensation of pain is perceived.
This pain is referred to areas innervated by the same spinal segments as the autonomic nerves, such as the retrosternal region, the anterior-medial aspects of both arms, and the little fingers, particularly on the left side.
To be continued