Category: Causes

  • What is Atherosclerosis

    What is Atherosclerosis

    Overview

    Atherosclerosis is a chronic, slowly progressing disease where fatty and/or fibrous material builds up in the inner layer of your arteries, called the intima. This build-up forms what are known as atherosclerotic plaques or atheromas, a term derived from a Greek word, reflecting the appearance of the lipid material at the core of these plaques. Over time, these plaques can become more fibrous and accumulate calcium.

    This condition can have serious consequences by impeding blood flow, leading to ischemia (insufficient blood supply to tissues). Plaques can also break open, triggering the formation of a thrombus (blood clot) that can block the artery, causing acute ischemia.

    Coronary artery disease (CVD) is a leading cause of vascular disease and death worldwide, significantly contributing to conditions like heart attacks and strokes. Despite advancements in medical care, it remains a major global health challenge.

    In Details

    First: Key Characteristics of Atherosclerosis

    • Build up of fatty and fibrous material: Occurs in the inner lining of arteries.
    • Formation of plaques (atheromas): These are the distinctive lesions of the disease.
    • Narrowing of arteries: Advanced plaques can reduce the space for blood flow.
    • Risk of blood clot formation: Plaques can rupture or erode, leading to clots that block blood flow.
    • Involves Low-Density Lipoprotein (LDL): A key factor in plaque development.
    • Inflammation and other risk factors: Play significant roles in its development.

    Initiation of Atherosclerosis

    Atherosclerosis often begins as early as childhood, though symptoms may not appear for decades. The process is thought to start with damage or injury to the inner layer of an artery, called the endothelium. This damage can be caused by various factors, including high blood pressure, high cholesterol, high triglycerides (another type of fat in the blood), smoking or other tobacco use, diabetes, insulin resistance, obesity, and inflammation. When the artery wall is damaged, low-density lipoprotein (LDL) particles – which transport cholesterol through the blood – can accumulate in the intima, the innermost layer of the artery

    Research strongly suggests that atherosclerosis would likely not occur if LDL-C (low-density lipoprotein cholesterol) concentrations did not exceed the body’s physiological needs. Prolonged exposure to high LDL-C levels over many years is a primary driver of the disease’s initiation and progression. For instance, individuals with familial hypercholesterolaemia (a genetic condition causing very high LDL-C from an early age) develop premature atherosclerotic CVD, highlighting LDL’s causal role.

    Progression of Atherosclerosis

    In its early stages, atherosclerotic plaques often expand outwards, away from the arterial lumen (the hollow centre where blood flows), which helps preserve the artery’s width. However, eventually, the growing plaque begins to encroach upon the arterial lumen, leading to stenosis (narrowing) and potentially flow-limiting lesions. This reduced blood flow can cause symptoms like angina pectoris (chest pain from insufficient blood to the heart) during physical exertion.

    Complications of Atherosclerosis

    The most severe complications of atherosclerosis often arise from the disruption of plaques. The most common trigger for acute coronary syndromes, such as a myocardial infarction (heart attack), is the rupture of an atherosclerotic plaque.

    These “vulnerable plaques” typically have a large lipid core covered by a thin fibrous cap (a layer of fibrous tissue). When this cap breaks, the plaque’s thrombogenic (clot-forming) contents are exposed to the blood, rapidly triggering thrombosis (blood clot formation), which can completely block the artery.

    Another mechanism, increasingly recognized, is plaque erosion, where lesions without a thin cap or much lipid can also lead to clot formation, particularly in the current era of effective anti-atherosclerotic therapies. These clots can lead to acute ischemic events like heart attacks or strokes.

    Other Similar Questions

    What are the common symptoms of atherosclerosis?

    Mild atherosclerosis often causes no symptoms for many years. Symptoms usually only appear when an artery is significantly narrowed or blocked, or when a blood clot forms. Symptoms vary depending on which arteries are affected. For example, chest pain (angina) if it’s in heart arteries, sudden weakness or trouble speaking if it’s in brain arteries (like a stroke), or leg pain when walking (claudication) if it’s in leg arteries.

    Is atherosclerosis curable?

    While atherosclerosis is a chronic and progressive disease, its progression can often be prevented, and in some cases, even reversed, through lifestyle changes and medical treatments. Current treatments aim to manage the disease and prevent its serious complications like heart attacks and strokes.

    How is atherosclerosis diagnosed?

    The diagnosis of atherosclerosis often involves imaging tests that can directly visualise the plaques or assess if there is reduced blood flow to organs. Non-invasive tests include ultrasonography (using sound waves) and CT angiography (a type of X-ray scan).

    More invasive procedures like invasive angiography (using a dye to visualize arteries) might be used to guide treatments.

    Resources

    • “Atherosclerosis” by Peter Libby, Julie E. Buring, Lina Badimon, Göran K. Hansson, John Deanfield, Márcio Sommer Bittencourt, Lale Tokgözoğlu and Eldrin F. Lewis.
    • Arteriosclerosis / atherosclerosis
  • What causes Coronary Artery disease ?

    What causes Coronary Artery disease ?

    Overview

    For many years, doctors and scientists thought that What causes Coronary Artery disease (CAD), often called “heart artery disease,” was mainly too much cholesterol building up in your blood vessels. While cholesterol certainly plays a role, our understanding has changed a lot. We now know that CAD is fundamentally an inflammatory condition, almost like an ongoing battle inside your arteries. This inflammation is crucial at every stage of the disease, from its very beginning to its progression, and even contributes to serious events like heart attacks

    .

    This new understanding means that managing CAD isn’t just about clearing blockages; it’s also about calming the widespread inflammation that affects your arteries. This inflammatory process can even make non-obstructive plaques, which might not cause symptoms, very dangerous

    In Details

    The inflammatory process in your arteries starts when the inner lining of these blood vessels, called the endothelium, encounters various “risk factors”. These can include high levels of unhealthy fats like LDL cholesterol, hormones linked to high blood pressure, substances associated with high blood sugar (like in diabetes), or even inflammatory signals from excess body fat. When the artery lining senses these stressors, it becomes “sticky,” expressing molecules that act like hooks. These hooks then grab white blood cells, such as immune cells called monocytes and T lymphocytes, which are circulating in your blood. Once attached, these white blood cells are drawn into the inner layer of the artery wall.

    Once inside the artery wall, these immune cells don’t just sit there; they become active participants in a complex inflammatory “conversation” with your artery’s own cells, like endothelial cells and smooth muscle cells. They exchange molecular messages, releasing various inflammatory mediators. These include small fatty molecules (like prostanoids and leukotrienes), other locally acting substances (like histamine), and particularly proteins called cytokines and complement components. These mediators further amplify the inflammatory response, turning it into a persistent state of irritation within the artery.

    A major consequence of this ongoing inflammation is the migration of smooth muscle cells (SMCs) from a deeper layer of the artery (the tunica media) into the inner lining. These SMCs then multiply and lay down a complex network of structural materials, forming what becomes part of the atherosclerotic plaque. In response to inflammatory signals, these cells also secrete enzymes called matrix metalloproteinases (MMPs), which can remodel or even break down parts of the artery’s structure. Components of this newly formed plaque can bind to lipoproteins, like cholesterol, making them more susceptible to damage, such as oxidation. These damaged lipoprotein products, in turn, continue to fuel and spread the inflammatory response, creating a self-perpetuating cycle of disease. As the plaque grows, dead, lipid-filled immune cells can accumulate, forming a soft, fatty core within the plaque.

    This inflammatory process isn’t just confined to one area; recent research shows that it’s often widespread throughout the arteries of individuals who experience acute coronary syndromes (like heart attacks). While some plaques grow inwards and create noticeable blockages, many others grow outwards, a process called “compensatory enlargement”. This outward growth means that a significant amount of disease can be present without causing narrowing that would be visible on standard angiography.

    These “hidden” lesions, particularly those with a thin outer fibrous cap and a large lipid core, are very prone to rupture. When such a plaque disrupts, it can trigger blood clot formation, leading to sudden events even if it hadn’t caused any symptoms before. Markers of inflammation, such as myeloperoxidase, have been found to be elevated even in areas of the heart not directly affected by a heart attack, indicating a widespread inflammatory state. This shifts our view from focusing solely on a single “vulnerable plaque” to considering the “vulnerable patient” with diffuse inflammation

    Other similar questions

    How do specific risk factors, like high blood pressure or diabetes, contribute to inflammation in arteries?

    When the inner lining of arteries, the endothelium, encounters risk factors such as high blood pressure (due to vasoconstrictor hormones) or high blood sugar (products of glycoxidation), these cells increase the expression of adhesion molecules

    What are the differences between a stable plaque and a “vulnerable” plaque, and how does inflammation play a role?

    Stable plaques, often those that cause significant narrowing (stenosis), typically have smaller lipid cores, more fibrous tissue, calcification, and thick fibrous caps2. In contrast, “vulnerable” plaques, which are prone to rupture and cause acute coronary syndromes (ACS), generally have large lipid cores, thin fibrous caps, and are populated by numerous inflammatory cells while lacking relatively in smooth muscle cells (SMCs)

    How do medications, such as statins, help by targeting inflammation, not just cholesterol levels?

    Statins and similar lipid-lowering therapies contribute to reducing recurrent coronary events by influencing the biology of the plaque, in addition to lowering cholesterol8. These successful therapeutic strategies appear to exert their benefit, at least in part, by combating inflammation8. Specifically, statins can reduce the blood levels of inflammatory markers like C-reactive protein

    Resources

    The information provided in this summary is based on the following scientific article:

    • Libby, P., & Theroux, P. (2005). Pathophysiology of Coronary Artery Disease. Circulation, 111(24), 3481–3488.

    This article provides a comprehensive review of the evolution in understanding the mechanisms of coronary artery disease. It is a valuable resource for deeper scientific understanding.