Ischemic Heart Disease: Pathophysiology
Cardiac Ischemia:
Cardiac ischemia occurs when coronary blood flow doesn't keep up with the metabolic needs of the heart; ultimately, mechanical and/or electrical functions are impaired.
Ischemia can be caused by:
Extravascular events, such as increased intramyocardial pressure or reduced diastolic filling time
Coronary vascular dysfunction
Acute coronary syndrome is an umbrella term for events that occur as the result of sudden cardiac ischemia, including unstable
angina,
heart attack, and sudden cardiac death.
Ischemic heart disease is the leading cause of death in both men and women.
Sex and racial differences in pathology and symptoms may delay diagnosis and treatment, leading to poor health outcomes for some populations (particularly women).
Risk factors for ischemic heart disease include:
Family history, increasing age, smoking, hypertension, diabetes, hyperlipidemia, obesity, low physical activity levels, early menopause, gestational diabetes and gestational hypertension, and, chronic inflammatory rheumatoid diseases.
Notice that several of these risk factors are related to metabolic and/or inflammatory conditions.
Studies suggest that many of these variables are even stronger risk factors in women than in men.
Coronary blood supply:
We show the
heart, and the major vessels on its superior surface: the superior vena cava, aorta, and pulmonary trunk.
The epicardial coronary arteries are those that run along the surface of the heart: the left and right coronary arteries and their branches.
The microvasculature of the heart comprises the prearterioles, arterioles, and capillaries that run through the deeper cardiac tissues.
Recall that prearterioles and arterioles provide resistance to and regulation of blood flow.
With this in place, let's learn about four conditions that can produce ischemic heart disease via the epicardial arteries and microvasculature; as we'll see, some of these conditions may overlap.
Obstructive Coronary Artery Disease
Characterized by atherosclerotic plaques that obstruct 50% or more of the lumen of an epicardial artery.
This condition is primarily seen in men over 45 years of age, though women over 55 years of age are at elevated risk.
In addition to blocking blood flow through the arteries, these
plaques can rupture or erode, producing
thrombi that lead to acute coronary events.
Be aware that, although coronary artery disease was long held as the model for ischemic heart disease,
up to half of patients who undergo angiogram have no significant coronary obstruction.
Ischemia and No Obstructive Coronary Artery Disease (INOCA):
Characterized by smaller plaques that block less than 50% of the lumen, and, therefore, do not significantly obstruct blood flow.
INOCA is particularly common in women, and is present in roughly 30% of men.
Formerly thought to be a benign condition, we now know that INOCA is associated with an elevated risk of Major Adverse Cardiovascular Events (MACE), particularly in younger women.
Ischemia may be due to plaque erosion, microvascular disease and/or vasospasm, which we'll learn about in a moment.
Angina and other symptoms of ischemia without vessel obstruction require further investigation.
Plaque rupture and erosion
Associated with Acute Coronary Syndrome in both obstructive and nonobstructive coronary artery disease.
Plaque rupture occurs when tears in the fibrous caps release thrombogenic contents into the lumen of the vessel.
These plaques are characterized by lipid cores, thin caps, and produces fibrin-rich "red thrombi".
Historically, plaque rupture was an important cause of thrombus and ischemia.
However, due to reductions in atherosclerosis associated with hyperlipidemia (thanks to
statins and other drugs), plaque rupture is less often implicated in acute coronary syndrome than it was in the past.
Unfortunately, reducing atherosclerosis and hyperlipidemia does not reduce the occurrence plaque erosion.
Plaque erosion is an increasingly significant cause of acute coronary syndrome.
Plaque erosion occurs more often in women, and is associated with young age, smoking, and diabetes.
Plaque erosion occurs when a plaque with a thick cap produces a white thrombus rich in platelets.
In plaque erosion, the vessel endothelium is fractured or absent, which suggests that a dysfunctional endothelium is an
important component of these plaques.
Though omitted for simplicity, be aware that there are other compositional differences between plaques that rupture and plaques that erode, including the types of white blood cells and amount of smooth muscle cells.
Coronary Microvasculature Dysfunction
This is a significant cause of Ischemia & No Obstructive Coronary Artery Disease, though it can also co-exist with Obstructive Coronary Artery Disease.
Associated with elevated risk of Major Adverse Cardiovascular Events.
Although early studies indicated that coronary microvascular dysfunction was more common in women, more recent studies show that it
affects both sexes in near-equal proportions.
Coronary microvascular dysfunction can be attributed to structural and/or functional mechanisms:
Arteriole remodeling, which occurs dynamically in response to various stimuli, can produce microvessels with thicker medial and intimal walls, and with a reduced wall:lumen ratio; consequently, coronary blood flow is reduced. This kind of defect is diffuse in the myocardium, and produces patchy areas of ischemia, as opposed to the localized lesions associated with obstruction in the epidcardial arteries.
Functional mechanisms of microvascular dysfunction include impaired vasodilation, which can be due to endothelial dysfunction and/or other causes, and, vasospasms.
Extravascular mechanisms, including those we mentioned at the beginning of the tutorial, can impair coronary microcirculation.
Occur in the epicardial coronary arteries and in the microvasculature.
Occur in the presence or absence of stenosis.
Vasospasm can be induced via a variety of mechanisms, including:
Enhanced autonomic nervous system activity, endothelial dysfunction (especially via reduced levels of nitric oxide), oxidative stress and inflammation that cause damage and constriction, vascular smooth muscle hyperactivity, and, substances such as nicotine, cocaine, and vasoconstricting medications.
Vasospasms cause angina at rest (including variant and microvascular angina) as opposed to effort angina, which we'll learn more about elsewhere.
They can also trigger acute coronary syndrome.
