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Peripheral Vascular Disease

Disease Details

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Description: Peripheral Vascular Disease (PVD) is a circulatory condition where narrowed blood vessels reduce blood flow to the limbs.
Type: Peripheral vascular disease (PVD) is primarily an acquired condition rather than a genetic one. However, when genetic factors are involved, there is no single mode of transmission; it can be influenced by multiple genetic and environmental factors. It is generally associated with risk factors like diabetes, hypertension, and high cholesterol, which can have genetic predispositions.
Signs And Symptoms: The signs and symptoms of peripheral artery disease are based on the part of the body that is affected. About 66% of patients affected by PAD either do not have symptoms or have atypical symptoms. The most common presenting symptom is intermittent claudication (IC), which typically refers to lower extremity skeletal muscle pain that occurs during exercise. IC presents when there is insufficient oxygen delivery to meet the metabolic requirements of the skeletal muscles. IC is a common manifestation of peripheral arterial disease (PAD). The pain is usually located in the calf muscles of the affected leg and is relieved by rest. This occurs because during exercise, the muscles require more oxygen. Normally, the arteries would be able to increase the amount of blood flow and therefore increase the amount of oxygen going to the exercised muscle. However, in PAD, the artery is unable to respond appropriately to the increased demand for oxygen from the muscles, and as a result, the muscles are deprived of oxygen, leading to muscle pain that subsides with rest.Other symptoms may include:
Pain, aches, and/or cramps in the buttocks, hip, or thigh
Muscle atrophy (muscle loss) of the affected limb
Hair loss of the affected limb
Skin that is smooth, shiny, or cool to the touch in the affected area
Decreased or absent pulse in the feet
Cold and/or numbness in the toes
Sores/ulcers on the affected limb that do not healIn individuals with severe PAD, complications may arise, including critical limb ischemia and gangrene. Critical limb ischemia occurs when the obstruction of blood flow in the artery is compromised to the point where the blood is unable to maintain oxygenation of the tissue at rest. This can lead to pain at rest, a feeling of coldness, or numbness in the affected foot and toes. Other complications of severe PAD include lower limb tissue loss (amputation), arterial insufficiency ulcers, erectile dysfunction, and gangrene. People with diabetes are affected by gangrene of the feet at a rate that is 30 times higher than the unaffected population. Many of these severe complications, such as those leading to amputation, are irreversible.
Prognosis: Individuals with PAD have an "exceptionally elevated risk for cardiovascular events and the majority will eventually die of a cardiac or cerebrovascular etiology". Prognosis is correlated with the severity of the PAD as measured by an ABI. Large-vessel PAD increases mortality from cardiovascular disease significantly. PAD carries a greater than "20% risk of a coronary event in 10 years".The risk is low that an individual with claudication will develop severe ischemia and require amputation, but the risk of death from coronary events is three to four times higher than matched controls without claudication. Of patients with intermittent claudication, only "7% will undergo lower-extremity bypass surgery, 4% major amputations, and 16% worsening claudication", but stroke and heart attack events are elevated, and the "5-year mortality rate is estimated to be 30% (versus 10% in controls)".
Onset: Peripheral Vascular Disease (PVD) typically has a gradual onset, often developing over many years. It is commonly due to atherosclerosis, where fatty deposits build up in the arterial walls. This slow progression can result in symptoms appearing in middle or older age. Factors such as smoking, diabetes, hypertension, and high cholesterol can expedite the onset. Symptoms might not be noticeable until the condition has significantly advanced.
Prevalence: Peripheral vascular disease (PVD) refers to disorders of blood vessels outside the heart and brain. It is estimated to affect around 5-10% of individuals in the general population, with the prevalence increasing to 20-30% in people over the age of 70. Risk factors include smoking, diabetes, hypertension, and high cholesterol.
Epidemiology: The prevalence of PAD in the general population is 3–7%, affecting up to 20% of those over 70; 70%–80% of affected individuals are asymptomatic; only a minority ever require revascularization or amputation. Peripheral artery disease affects one in three diabetics over the age of 50. In the US, it affects 12–20 percent of Americans age 65 and older. Around 10 million Americans have PAD. Despite its prevalence and implications for cardiovascular risk, there are still low levels of awareness of risk factors and symptoms, with 26% of the population in the US reported to have knowledge of PAD.In 2000, among people aged 40 years and older in the United States, rates of PAD were 4.3%. Rates were 14.5% for people aged 70 years or over. Within age groups, rates were generally higher for women than men. Non-Hispanic blacks had a rate of 7.9% compared to 4.4% in Non-Hispanic whites and 3.0% (1.4%–4.6%) in Mexican Americans.The incidence of symptomatic PAD increases with age, from about 0.3% per year for men aged 40–55 years to about 1% per year for men aged over 75 years. The prevalence of PAD varies considerably depending on how PAD is defined and the age of the population being studied. People diagnosed with PAD have a greater risk of a MACE (Major Adverse Cardiac Event) and stroke. Their risk of developing a reinfarction, stroke, or transient ischemic attack within one year following a heart attack increases to 22.9%, compared to 11.4% for those without PAD.The Diabetes Control and Complications Trial and the UK Prospective Diabetes Study trials in people with type 1 and type 2 diabetes, respectively, demonstrated that glycemic control is more strongly associated with microvascular disease than macrovascular disease. Pathologic changes occurring in small vessels may be more sensitive to chronically elevated glucose levels than atherosclerosis occurring in larger arteries.
Intractability: Peripheral vascular disease (PVD) can vary in its intractability. Early stages may be managed effectively with lifestyle changes, medications, and minimally invasive interventions. However, advanced cases, particularly those involving severe atherosclerosis or extensive damage to blood vessels, can be more challenging to treat and may require surgical interventions. In some instances, despite aggressive treatment, the disease may remain difficult to manage, making it functionally intractable.
Disease Severity: Peripheral vascular disease (PVD) covers a range of disorders, and its severity can vary significantly among individuals. Severity is often classified based on symptoms and diagnostic findings:

1. **Mild:** May present with intermittent claudication (pain in the legs during exercise that subsides with rest). Physical examination might show diminished pulses in the affected extremities.

2. **Moderate:** Patients might experience pain at rest, particularly at night, along with significant reduction in limb function. There may also be signs of tissue damage, such as changes in skin color or texture.

3. **Severe:** Includes critical limb ischemia, where the blood flow is insufficient to sustain the tissues, leading to sores, ulcers, or gangrene that don't heal. Patients often have constant pain and significant functional impairment.

The severity of PVD is assessed using various tests, including the Ankle-Brachial Index (ABI), ultrasound, and angiography, to determine the extent of the arterial blockage.
Healthcare Professionals: Disease Ontology ID - DOID:341
Pathophysiology: Peripheral vascular disease (PVD), also known as peripheral artery disease (PAD), involves the narrowing or blockage of the peripheral arteries, primarily affecting the legs. Its pathophysiology is usually rooted in atherosclerosis, a process where plaque—a mixture of fat, cholesterol, and other substances—builds up on the arterial walls. This plaque buildup reduces blood flow and can lead to ischemia, causing pain, cramping, and in severe cases, tissue damage. Risk factors include smoking, diabetes, high blood pressure, and high cholesterol.
Carrier Status: Peripheral Vascular Disease (PVD) is not typically associated with a carrier status because it is not a genetic disorder that is inherited in the same way as conditions like cystic fibrosis or sickle cell anemia. Instead, PVD primarily results from factors such as atherosclerosis, smoking, diabetes, high blood pressure, and high cholesterol.
Mechanism: Peripheral vascular disease (PVD) primarily involves the obstruction or narrowing of peripheral arteries, most commonly in the legs. The primary mechanism underlying PVD is atherosclerosis, which is the buildup of atherosclerotic plaques within the arterial walls. These plaques are composed of lipids, cholesterol, calcium, and cellular debris, leading to reduced blood flow and oxygen delivery to the affected tissues.

**Molecular Mechanisms:**

1. **Endothelial Dysfunction:**
- The inner lining of blood vessels, called the endothelium, becomes dysfunctional due to factors like high blood pressure, smoking, and elevated cholesterol levels.
- Inflammation, oxidative stress, and the presence of modified low-density lipoprotein (LDL) particles lead to the expression of adhesion molecules, attracting monocytes to the endothelium.

2. **Lipid Accumulation and Foam Cell Formation:**
- LDL particles infiltrate the endothelial layer and become oxidized (ox-LDL).
- Monocytes differentiate into macrophages and engulf ox-LDL, transforming into foam cells, which are lipid-laden cells that contribute to plaque formation.

3. **Smooth Muscle Cell Migration and Proliferation:**
- Smooth muscle cells (SMCs) from the arterial media layer migrate to the intima layer.
- These cells proliferate and secrete extracellular matrix components like collagen, which stabilize the plaque but also narrow the vessel lumen.

4. **Chronic Inflammation:**
- Persistent inflammation within the arterial wall promotes the progression of the atherosclerotic plaque.
- Cytokines and chemokines are involved in the recruitment of additional inflammatory cells, perpetuating the inflammatory response.

5. **Calcification and Plaque Destabilization:**
- Over time, plaques may become calcified, further stiffening the artery.
- Plaques can become unstable and rupture, exposing thrombogenic material to the bloodstream, leading to clot formation and potential acute ischemic events.

Understanding these molecular mechanisms provides insights into the progression and potential therapeutic targets for managing peripheral vascular disease.
Treatment: Depending on the severity of the disease, these steps can be taken, according to these guidelines:
Compassionate Use Treatment: For peripheral vascular disease (PVD), compassionate use treatment and off-label or experimental treatments include several options:

1. **Stem Cell Therapy**: Experimental treatments using stem cells aim to promote angiogenesis (the formation of new blood vessels) to improve blood flow to affected areas. This therapy is still in clinical trial phases and is not widely available.

2. **Gene Therapy**: Experimental gene therapies seek to introduce genes that encourage blood vessel growth or improve blood flow. For example, therapies involving the VEGF (vascular endothelial growth factor) gene are under investigation.

3. **Drug-eluting Stents**: While stents are commonly used to treat blockages in arteries, drug-eluting stents release medication that can prevent the artery from becoming blocked again (restenosis). Some of these uses can be considered off-label depending on the specific context.

4. **Hyperbaric Oxygen Therapy (HBOT)**: Although primarily used for wound healing, HBOT has been used off-label to enhance oxygen delivery to affected tissues in PVD patients.

5. **Anticoagulant and Antiplatelet Drugs**: Some medications, such as cilostazol or pentoxifylline, are used off-label to manage symptoms and improve blood flow.

6. **Prostanoids (e.g., Iloprost)**: These drugs can be used off-label to treat severe cases of PVD by dilating blood vessels and inhibiting platelet aggregation.

Patients seeking these treatments should consult with their healthcare providers to understand the potential benefits, risks, and availability, as many of these options are still under research and not part of standard care protocols.
Lifestyle Recommendations: For peripheral vascular disease (PVD), several lifestyle recommendations can help manage the condition and improve overall vascular health:

1. **Quit Smoking:** Smoking is a major risk factor for PVD. Quitting can improve symptoms and overall vascular health.
2. **Exercise Regularly:** Aim for at least 30 minutes of moderate-intensity exercise, such as walking, most days of the week to improve blood flow.
3. **Healthy Diet:** Eat a balanced diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats. Limit saturated fats, trans fats, cholesterol, sodium, and added sugars.
4. **Weight Management:** Maintain a healthy weight to reduce the strain on blood vessels.
5. **Control Blood Pressure and Cholesterol:** Keep blood pressure and cholesterol levels within recommended ranges through diet, exercise, and medication if prescribed.
6. **Manage Diabetes:** Keep blood sugar levels under control if you have diabetes.
7. **Limit Alcohol:** Drink alcohol in moderation. Follow guidelines of up to one drink per day for women and up to two drinks per day for men.
8. **Foot Care:** Proper foot care is essential to prevent complications, especially if you have diabetes. Avoid walking barefoot, check your feet daily, and wear properly fitting shoes.

Implementing these lifestyle changes can help slow the progression of PVD and reduce the risk of complications.
Medication: Management of diabetes
Management of hypertension
Management of high cholesterol, and antiplatelet drugs such as aspirin and clopidogrel. Statins reduce clot formation and cholesterol levels, respectively, and can help with disease progression and address the other cardiovascular risks that the affected person is likely to have.According to guidelines, taking aspirin or clopidogrel is recommended to reduce AMI ("heart attack"), stroke, and other causes of vascular death in people with symptomatic peripheral artery disease. It is recommended that aspirin and clopidogrel be taken alone and not in conjunction with one another (i.e., not as dual antiplatelet therapy). The recommended daily dosage of aspirin for treating PAD is between 75 and 325 mg, while the recommended daily dosage for clopidogrel is 75 mg. The effectiveness of both aspirin and clopidogrel to reduce the risk of cardiovascular ischemic events in people with symptomatic PAD is not well established. Research also suggests that low-dose rivaroxaban plus aspirin is effective as a new anti-thrombotic regimen for PAD.Cilostazol can improve symptoms in some people. Pentoxifylline is of unclear benefit. Cilostazol may improve walking distance for people who experience claudication due to peripheral artery disease, but no strong evidence suggests that it improves the quality of life, decreases mortality, or decreases the risk of cardiovascular events.Treatment with other drugs or vitamins is unsupported by clinical evidence, "but trials evaluating the effect of folate and vitamin B12 on hyperhomocysteinemia, a putative vascular risk factor, are near completion".
Repurposable Drugs: For Peripheral Vascular Disease (PVD), some repurposable drugs include:

1. **Statins**: Originally used for lowering cholesterol, statins also help improve endothelial function and reduce inflammation.
2. **ACE Inhibitors**: Commonly used for hypertension and heart failure, ACE inhibitors may improve blood flow and reduce disease progression.
3. **Antiplatelet Agents**: Drugs like aspirin and clopidogrel, primarily used to prevent heart attacks and strokes, can reduce blood clotting risk in PVD.
4. **Phosphodiesterase inhibitors**: Cilostazol is used to treat intermittent claudication by widening blood vessels and decreasing the clotting ability of platelets.

These drugs can help manage symptoms and improve overall vascular health in patients with PVD. Always consult a healthcare provider for personalized medical advice.
Metabolites: Peripheral Vascular Disease (PVD) is associated with a variety of metabolic changes. Some key metabolites often associated with PVD include:

1. **Lipid Metabolism Changes**:
- Elevated levels of LDL cholesterol (Low-Density Lipoprotein)
- Lower levels of HDL cholesterol (High-Density Lipoprotein)
- Increased triglycerides

2. **Amino Acids**:
- Elevated homocysteine levels, which can contribute to endothelial damage and inflammation.

3. **Glucose Metabolism**:
- Insulin resistance, leading to increased blood glucose levels.

These metabolites play a role in the development and progression of PVD by affecting blood vessel integrity, promoting atherosclerosis, and contributing to overall vascular inflammation and damage.
Nutraceuticals: Nutraceuticals for peripheral vascular disease (PVD) can include supplements like omega-3 fatty acids, which may help improve blood flow and reduce inflammation. Other beneficial nutraceuticals include antioxidants like vitamins C and E, as well as L-arginine and coenzyme Q10, which support vascular health. Always consult a healthcare provider before starting any new supplement regimen for PVD.
Peptides: Peripheral vascular disease (PVD) involves the narrowing of blood vessels outside the heart and brain, usually due to atherosclerosis. Peptides and nanotechnology are emerging areas of research in the treatment and diagnosis of PVD. Peptides can be designed to enhance angiogenesis or inhibit inflammatory pathways, potentially improving blood flow and alleviating symptoms. Nanotechnology could offer targeted drug delivery systems, improve imaging for better diagnosis, or aid in the development of advanced stents and grafts. These innovations aim to enhance therapeutic efficacy and minimize side effects.