Pathogenesis of Coronary Artery Disease
Coronary artery disease (CAD) is defined as myocardial ischemia resulting from the narrowing of the coronary arteries. The main cause of this narrowing is atherosclerosis, although other mechanisms can also lead to it, such as vascular spasm or inflammatory processes in the arterial wall.
Atherosclerosis develops in stages: first, vascular endothelial injury occurs, then monocytes infiltrate the subendothelial space of the intima, transform into macrophages, and accumulate lipids, forming foam cells. Next, destruction of elastic fibers, calcification, and the formation of an atherosclerotic plaque take place, which, upon progression, can lead to thrombosis.
The arterial wall consists of three main layers: tunica intima, tunica media, and tunica adventitia. The inner surface of the intima is lined with endothelium.
Role of the Endothelium and Nitric Oxide
The endothelium performs not only a barrier function but also participates in hemostasis, metabolic processes, and the regulation of vascular tone. A key role in tone regulation is played by nitric oxide released by the endothelium, which causes dilation of the coronary arteries.
Coronary artery dilation increases myocardial perfusion — meaning the volume of blood supplied to the heart muscle increases without raising the total circulating blood volume, achieved by widening the vessel lumen. This is a physiological mechanism also utilized for diagnostic purposes, particularly in pharmacological stress tests.
Risk Factors and Sex Differences
CAD ranks first in mortality among cardiovascular diseases. When evaluating patients of the same age with identical risk factors (smoking, lack of physical activity), men should be prioritized for a more thorough examination first, because women before the onset of menopause are protected by the effects of estrogens, which reduce the risk of atherosclerosis.
Among significant predictors of CAD development identified in the discussed clinical cases are:
- diabetes mellitus
- hypercholesterolemia
- arterial hypertension
- history of long-term smoking
Diagnostic Methods for CAD
The diagnostic algorithm for suspected CAD is built on the principle of sequential exclusion: from simple non-invasive methods to invasive ones.
- Resting ECG is the first and most accessible method, which may be uninformative outside of an acute episode
- Treadmill test (exercise stress test on a treadmill) is contraindicated in recent surgeries, bleeding, and conditions limiting physical exertion
- Echocardiography evaluates myocardial contractility and valve structure, but is informative primarily when myocardial damage is already present
- Myocardial scintigraphy is a radioisotope method in which a radiopharmaceutical is administered intravenously and accumulates throughout the body; imaging is performed in several stages (at rest and under stress) with an interval of tens of minutes, allowing evaluation of myocardial blood supply dynamics. Areas with insufficient blood flow do not accumulate the tracer and are not visualized
- Coronary angiography is the invasive gold standard for CAD diagnosis, associated with a risk of complications; it is performed only when clear indications are present (acute coronary syndrome, pathological changes in cardiac biomarkers)
The choice of method is determined by the clinical picture and the patient's condition: for example, in recent abdominal surgery, a treadmill test and gastroscopy are undesirable, making the pharmacological stress test the optimal choice.
Pharmacological Stress Tests
When a physical exercise test cannot be performed, a pharmacological stress test is used. One option is the administration of dobutamine, which has a positive inotropic effect: the drug enhances myocardial contractility, increasing its oxygen demand. In the presence of coronary disease, this manifests as signs of ischemia on the ECG and a worsening of the clinical presentation.
Another option is the dipyridamole test, a phosphodiesterase inhibitor used primarily as an antiplatelet agent for the prevention of angina and stroke. Upon diagnostic administration, dipyridamole causes coronary artery dilation, which can provoke coronary steal syndrome: blood is predominantly redistributed through the main dilated vessel, whereas myocardial areas supplied via small collaterals in the stenotic zone receive less blood. This leads to increased ischemia and the appearance of ST-segment depression on the ECG in the affected vascular bed.
Pharmacological tests are potentially hazardous in severe stenosis as they can provoke myocardial infarction, and therefore they are performed exclusively in an inpatient setting.
Differential Diagnosis in Clinical Cases
During the review of a case involving a patient with abdominal pain that worsens with walking and dyspnea that subsides at rest, the importance of differentiating from angina pectoris was emphasized: the association of pain with physical exertion is not characteristic of gastritis or peptic ulcer disease. The clinical picture of an ulcer features aching or sharp dagger-like epigastric pain unrelated to exertion, potentially accompanied by hematemesis.
It is important to consider that myocardial necrosis upon complete cessation of blood flow develops almost instantaneously, unlike the intestine, which can tolerate ischemia for several hours. Rupture of an atherosclerotic plaque can lead to acute coronary syndrome and myocardial infarction accompanied by characteristic sharp, unremitting pain and ECG changes.
The role of Prinzmetal's angina was highlighted separately—a specific variant associated with coronary artery spasm that occurs predominantly in the morning hours and is independent of physical exertion, which distinguishes it from classic stable effort angina.
Key points
- CAD is myocardial ischemia most commonly caused by coronary atherosclerosis
- The endothelium regulates vascular tone by releasing nitric oxide, which induces arterial dilation
- Men face a higher risk of CAD compared to premenopausal women due to the protective effect of estrogens
- The diagnostic algorithm for CAD follows a sequential approach: ECG, stress tests, echocardiography, scintigraphy, coronary angiography
- Pharmacological tests with dobutamine or dipyridamole are used when physical exercise is contraindicated
- Coronary steal syndrome occurs during vasodilator administration and leads to impaired blood flow in the stenosis zone due to blood redistribution
- Myocardial necrosis upon cessation of blood flow develops almost immediately
- Differential diagnosis of angina requires ruling out gastroenterological pathology and other causes of pain