Atherosclerosis
Disease Details
Family Health Simplified
- Description
- Atherosclerosis is a condition characterized by the buildup of plaque within the arterial walls, leading to narrowed and hardened arteries which can impede blood flow.
- Type
- Atherosclerosis is a complex, multifactorial disease primarily characterized by the buildup of plaques in the arterial walls, leading to narrowing and hardening of the arteries. It is influenced by genetic factors but is not transmitted in a simple Mendelian pattern. Instead, it exhibits polygenic inheritance, where multiple genes, in combination with environmental factors such as diet and lifestyle, contribute to the risk of developing the disease.
- Signs And Symptoms
- Atherosclerosis is asymptomatic for decades because the arteries enlarge at all plaque locations, thus there is no effect on blood flow. Even most plaque ruptures do not produce symptoms until enough narrowing or closure of an artery, due to clots, occurs. Signs and symptoms only occur after severe narrowing or closure impedes blood flow to different organs enough to induce symptoms. Most of the time, patients realize that they have the disease only when they experience other cardiovascular disorders such as stroke or heart attack. These symptoms, however, still vary depending on which artery or organ is affected.Early atherosclerotic processes likely begin in childhood. Fibrous and gelatinous lesions have been observed in the coronary arteries of children. Fatty streaks have been observed in the coronary arteries of juveniles.While coronary artery disease is more prevalent in men than women, atherosclerosis of the cerebral arteries and strokes equally affect both sexes.Marked narrowing in the coronary arteries, which are responsible for bringing oxygenated blood to the heart, can produce symptoms such as chest pain of angina and shortness of breath, sweating, nausea, dizziness or lightheadedness, breathlessness or palpitations. Abnormal heart rhythms called arrhythmias—the heart beating either too slowly or too quickly—are another consequence of ischemia.Carotid arteries supply blood to the brain and neck. Marked narrowing of the carotid arteries can present with symptoms such as: a feeling of weakness; being unable to think straight; difficulty speaking; dizziness; difficulty in walking or standing up straight; blurred vision; numbness of the face, arms and legs; severe headache; and loss of consciousness. These symptoms are also related to stroke (death of brain cells). Stroke is caused by marked narrowing or closure of arteries going to the brain; lack of adequate blood supply leads to the death of the cells of the affected tissue.Peripheral arteries, which supply blood to the legs, arms and pelvis, also experience marked narrowing due to plaque rupture and clots. Symptoms of the narrowing are numbness within the arms or legs, as well as pain. Another significant location for plaque formation is the renal arteries, which supply blood to the kidneys. Plaque occurrence and accumulation lead to decreased kidney blood flow and chronic kidney disease, which, like in all other areas, is typically asymptomatic until late stages.In 2004, US data indicated that in ~66% of men and ~47% of women, the first symptom of atherosclerotic cardiovascular disease was a heart attack or sudden cardiac death (defined as death within one hour of onset of the symptom).Case studies have included autopsies of U.S. soldiers killed in World War II and the Korean War. A much-cited report involved the autopsies of 300 U.S. soldiers killed in Korea. Although the average age of the men was 22.1 years, 77.3 percent had "gross evidence of coronary arteriosclerosis".
- Prognosis
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Atherosclerosis is a chronic condition characterized by the buildup of plaque within the arterial walls, which can lead to restricted blood flow. The prognosis for individuals with atherosclerosis varies based on several factors, including the extent of arterial blockage, the specific arteries affected, and the presence of other health conditions such as diabetes or hypertension.
1. **Early Detection and Management:** If detected early and managed effectively through lifestyle changes, medications, and sometimes surgical interventions, the progression of atherosclerosis can be slowed, and complications can be minimized.
2. **Complications:** Untreated or severe cases can lead to serious complications such as heart attack, stroke, peripheral artery disease, and aneurysms, significantly impacting prognosis.
3. **Lifestyle Modifications:** Adopting a heart-healthy lifestyle—such as maintaining a balanced diet, exercising regularly, quitting smoking, and managing stress—can improve outcomes.
4. **Medical Interventions:** Medications like statins to lower cholesterol, antihypertensives to control blood pressure, and antiplatelet agents to prevent blood clots play critical roles in managing the disease. In some cases, surgical procedures like angioplasty or bypass surgery may be necessary.
Overall, while atherosclerosis is a serious and potentially life-threatening condition, early and proactive management can lead to a better prognosis and improved quality of life. - Onset
- Atherosclerosis is a progressive condition that typically begins in childhood and adolescence, often without symptoms. The disease can take decades to develop, with noticeable symptoms usually appearing in middle age or later. The exact onset can vary based on factors like genetics, lifestyle, and underlying health conditions.
- Prevalence
- Atherosclerosis is a common condition globally, especially prevalent in developed countries. It primarily affects older adults, with a higher prevalence seen in individuals over 65 years of age. The incidence of atherosclerosis increases with age, and it is more common in men than in women until women reach menopause, after which the gender difference diminishes. Key risk factors include high blood pressure, high cholesterol, smoking, diabetes, obesity, and a sedentary lifestyle.
- Epidemiology
- Cardiovascular disease, which is predominantly the clinical manifestation of atherosclerosis, is one of the leading causes of death worldwide.Almost all children older than age 10 in developed countries have aortic fatty streaks, with coronary fatty streaks beginning in adolescence.In 1953, a study was published which examined the results of 300 autopsies performed on U.S. soldiers who had died in the Korean War. Despite the average age of the soldiers being just 22 years old, 77% of them had visible signs of coronary atherosclerosis. This study showed that heart disease could affect people at a younger age and was not just a problem for older individuals.In 1992, a report had shown that microscopic fatty streaks were seen in the left anterior descending artery in over 50% of children aged 10–14 and 8% had even more advanced lesions with more accumulations of extracellular lipid.In a 2005 report of a study done between 1985 and 1995, it was found that around 87% of aortas and 30% of coronary arteries in age group 5–14 years had fatty streaks which increased with age.
- Intractability
- Atherosclerosis is generally not considered fully intractable, as it can be managed and its progression slowed through a combination of lifestyle changes, medication, and in some cases, medical procedures. However, it is a chronic condition that currently cannot be completely cured. Effective management includes a healthy diet, regular exercise, quitting smoking, controlling blood pressure and cholesterol levels, and the use of medications such as statins. In advanced cases, procedures like angioplasty or surgery may be necessary.
- Disease Severity
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Atherosclerosis is a progressive disease characterized by the hardening and narrowing of the arteries due to the buildup of plaque. Its severity can vary widely:
1. **Mild Atherosclerosis**: Often asymptomatic, detected incidentally during routine check-ups.
2. **Moderate Atherosclerosis**: May cause symptoms such as chest pain (angina) or shortness of breath, especially during physical activity.
3. **Severe Atherosclerosis**: Can lead to significant health issues like heart attack, stroke, or peripheral artery disease due to greatly reduced blood flow.
It's important for individuals to manage risk factors, such as hypertension, high cholesterol, smoking, and diabetes, to prevent progression and complications. - Healthcare Professionals
- Disease Ontology ID - DOID:1936
- Pathophysiology
- Atherogenesis is the developmental process of atheromatous plaques. It is characterized by a remodeling of arteries leading to subendothelial accumulation of fatty substances called plaques. The buildup of an atheromatous plaque is a slow process, developed over a period of several years through a complex series of cellular events occurring within the arterial wall and in response to a variety of local vascular circulating factors. One recent hypothesis suggests that, for unknown reasons, leukocytes, such as monocytes or basophils, begin to attack the endothelium of the artery lumen in cardiac muscle. The ensuing inflammation leads to the formation of atheromatous plaques in the arterial tunica intima, a region of the vessel wall located between the endothelium and the tunica media. The bulk of these lesions is made of excess fat, collagen, and elastin. At first, as the plaques grow, only wall thickening occurs without any narrowing. Stenosis is a late event, which may never occur and is often the result of repeated plaque rupture and healing responses, not just the atherosclerotic process by itself.
- Carrier Status
- Atherosclerosis is not an infectious disease, so there is no concept of carrier status associated with it. It is a condition characterized by the buildup of plaques in the arterial walls, which can lead to serious cardiovascular problems.
- Mechanism
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Atherosclerosis is a condition characterized by the buildup of plaques within the arterial walls, leading to narrowed and hardened arteries.
### Mechanism
1. **Endothelial Injury:** The process begins with damage to the endothelial lining of the artery. This can be caused by factors such as high blood pressure, smoking, or high levels of LDL cholesterol.
2. **Lipid Accumulation:** Damaged endothelial cells become more permeable, allowing low-density lipoprotein (LDL) cholesterol to penetrate the artery wall.
3. **Inflammation:** The retained LDL cholesterol is oxidized, triggering an inflammatory response. Monocytes are attracted to the site, migrate into the intima, and transform into macrophages that engulf the oxidized LDL, becoming foam cells.
4. **Plaque Formation:** Foam cells accumulate to form fatty streaks. Smooth muscle cells proliferate and migrate to the intima, secreting extracellular matrix proteins, which stabilize the plaque but also contribute to its growth.
5. **Fibrous Cap Formation:** A fibrous cap of smooth muscle cells and collagen forms over the lipid core, stabilizing the plaque but potentially leading to lumen narrowing.
6. **Plaque Rupture:** Over time, the plaque can become unstable and rupture, leading to the formation of a thrombus (blood clot) that can occlude the artery, resulting in conditions like myocardial infarction or stroke.
### Molecular Mechanisms
1. **Endothelial Dysfunction:** Involves reduced production of nitric oxide (NO), a critical molecule for maintaining vascular homeostasis and inhibiting inflammation and platelet aggregation.
2. **Oxidative Stress:** Reactive oxygen species (ROS) produced in endothelial cells oxidize LDL, which is critical for foam cell formation.
3. **Inflammatory Pathways:** Activation of nuclear factor kappa B (NF-κB) and other transcription factors in endothelial cells and macrophages upregulates pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF-α) and adhesion molecules (e.g., VCAM-1, ICAM-1), facilitating monocyte adhesion and migration.
4. **Macrophage Differentiation:** Monocytes differentiate into macrophages upon entering the intima, driven by factors like macrophage colony-stimulating factor (M-CSF).
5. **Foam Cell Formation:** Macrophages uptake oxidized LDL via scavenger receptors such as CD36 and SR-A, leading to foam cell formation.
6. **Extracellular Matrix Remodeling:** Metalloproteinases (MMPs) produced by macrophages and smooth muscle cells degrade extracellular matrix components, contributing to plaque instability.
7. **Smooth Muscle Cell (SMC) Proliferation and Migration:** Growth factors such as platelet-derived growth factor (PDGF) promote SMC proliferation and migration to the intima, contributing to plaque growth.
8. **Apoptosis:** Cell death within the plaque can destabilize it. Macrophage apoptosis and defective efferocytosis (clearance of apoptotic cells) contribute to necrotic core formation, increasing rupture risk.
Understanding these mechanisms helps in the development of therapeutic strategies to prevent or treat atherosclerosis. - Treatment
- Treatment of established disease may include medications to lower cholesterol such as statins, blood pressure medication, or medications that decrease clotting, such as aspirin. A number of procedures may also be carried out such as percutaneous coronary intervention, coronary artery bypass graft, or carotid endarterectomy.Medical treatments often focus on alleviating symptoms. However measures which focus on decreasing underlying atherosclerosis—as opposed to simply treating symptoms—are more effective. Non-pharmaceutical means are usually the first method of treatment, such as stopping smoking and practicing regular exercise. If these methods do not work, medicines are usually the next step in treating cardiovascular diseases and, with improvements, have increasingly become the most effective method over the long term.The key to the more effective approaches is to combine multiple different treatment strategies. In addition, for those approaches, such as lipoprotein transport behaviors, which have been shown to produce the most success, adopting more aggressive combination treatment strategies taken on a daily basis and indefinitely has generally produced better results, both before and especially after people are symptomatic.
- Compassionate Use Treatment
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Compassionate use treatments for atherosclerosis allow patients with severe or life-threatening conditions to access investigational drugs outside of clinical trials. These treatments are typically reserved for those who have exhausted all other available medical options.
Off-label or experimental treatments for atherosclerosis may include:
1. **PCSK9 Inhibitors**: While primarily approved for lowering cholesterol, these drugs (e.g., alirocumab and evolocumab) are sometimes used off-label for more aggressive lipid control in atherosclerosis.
2. **Stem Cell Therapy**: Experimental treatments involving stem cells aim to repair damaged blood vessels and improve cardiovascular outcomes in atherosclerosis patients.
3. **Gene Therapy**: This is still largely experimental and involves altering genes to reduce atherosclerosis risk factors or directly repair damaged tissues.
4. **Anti-inflammatory Medications**: Certain drugs, such as colchicine, initially used for treating gout, are being investigated for their potential to reduce inflammation in blood vessels, thereby treating atherosclerosis.
These treatments are at various stages of research and are not yet established as standard care for atherosclerosis. - Lifestyle Recommendations
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Lifestyle recommendations for atherosclerosis:
1. **Diet**:
- Increase intake of fruits, vegetables, whole grains, and lean proteins.
- Reduce saturated and trans fats, added sugars, and sodium.
- Consider a Mediterranean or DASH (Dietary Approaches to Stop Hypertension) diet.
2. **Physical Activity**:
- Aim for at least 150 minutes of moderate-intensity exercise per week, such as brisk walking or cycling.
- Include muscle-strengthening activities at least two days per week.
3. **Weight Management**:
- Achieve and maintain a healthy weight through a balanced diet and regular exercise.
- Seek guidance from a healthcare provider to set realistic goals.
4. **Smoking Cessation**:
- Quit smoking and avoid exposure to secondhand smoke.
- Seek support through counseling, medications, or nicotine replacement therapies if needed.
5. **Alcohol Consumption**:
- Limit alcohol intake to moderate levels (up to one drink per day for women and two for men).
6. **Stress Management**:
- Practice stress-reducing techniques such as meditation, yoga, or deep breathing exercises.
- Ensure adequate sleep and manage work-life balance.
7. **Regular Health Check-ups**:
- Monitor blood pressure, cholesterol levels, and blood glucose regularly.
- Follow medical advice and take prescribed medications to control hypertension, hyperlipidemia, and diabetes.
These lifestyle changes can help manage and potentially reduce the progression of atherosclerosis. - Medication
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Atherosclerosis is a condition where arteries become narrowed and hardened due to a buildup of plaque. Medications used to treat atherosclerosis include:
1. **Statins (e.g., atorvastatin, simvastatin)** - These lower cholesterol levels and stabilize plaque.
2. **Antiplatelet agents (e.g., aspirin, clopidogrel)** - These reduce the risk of blood clots.
3. **Angiotensin-converting enzyme (ACE) inhibitors (e.g., enalapril, lisinopril)** - These lower blood pressure and provide cardiovascular protection.
4. **Beta-blockers (e.g., metoprolol, atenolol)** - These help manage blood pressure and reduce the heart's workload.
5. **Calcium channel blockers (e.g., amlodipine, diltiazem)** - These help lower blood pressure and improve blood flow.
6. **Niacin (vitamin B3)** - This can also help to improve cholesterol levels.
Lifestyle changes, such as diet and exercise, are often recommended alongside medication. - Repurposable Drugs
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Repurposable drugs for atherosclerosis include:
- **Metformin**: Primarily used for type 2 diabetes, it has anti-inflammatory and anti-oxidative properties that may benefit cardiovascular health.
- **Colchicine**: Used for gout, it has anti-inflammatory effects that can reduce cardiovascular events.
- **Ezetimibe**: Initially for lowering cholesterol, it can be used alongside statins to reduce plaque buildup.
- **SGLT2 inhibitors**: Used in diabetes, they have shown potential in reducing cardiovascular events.
- **PCSK9 inhibitors**: Though primarily designed to lower cholesterol, they can also reduce arterial plaque.
These repurposed drugs are being investigated for their potential benefits beyond their original indications, specifically in the context of atherosclerosis treatment and management. - Metabolites
- In atherosclerosis, key metabolites include lipids such as cholesterol and triglycerides, as well as inflammatory markers like C-reactive protein (CRP). Additionally, glucose and homocysteine levels can also be important. These metabolites can indicate the extent of lipid metabolism dysfunction and inflammation, both of which are central to the development and progression of atherosclerosis.
- Nutraceuticals
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Nutraceuticals, such as omega-3 fatty acids, fiber, antioxidants (e.g., vitamins C and E), and plant sterols, may help in managing atherosclerosis by reducing inflammation, improving lipid profiles, and decreasing oxidative stress. However, their efficacy can vary, and they should complement, not replace, conventional treatments.
The field of nanotechnology (nan) offers potential innovations for atherosclerosis treatment. Nanoparticles can be used for targeted drug delivery, ensuring that therapeutic agents reach atherosclerotic plaques more effectively while minimizing side effects. Nanotechnology also holds promise in diagnostic imaging, allowing for earlier detection and monitoring of plaque formation.
Both nutraceuticals and nanotechnology are adjuncts and require further research to fully understand their benefits and application in atherosclerosis. - Peptides
- Peptides and nanotechnology have shown promise in the diagnosis and treatment of atherosclerosis. Peptides can target specific molecules involved in the disease process, potentially helping to reduce plaque accumulation or inflammation. Nanotechnology, on the other hand, allows for the creation of nanoparticles that can deliver drugs directly to atherosclerotic plaques, improving the efficacy and reducing side effects of treatments. Both approaches are under active research to develop more effective strategies for managing atherosclerosis.