Atherosclerosis – Symptoms, Causes, Treatment

Introduction of Atherosclerosis:

Atherosclerosis (or arteriosclerotic vascular disease) is a condition where the arteries become narrowed and hardened due to an excessive buildup of plaque around the artery wall. Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood. Over time, plaque hardens and narrows arteries. The disease disrupts the flow of blood around the body, posing serious cardiovascular complications. Atherosclerosis can lead to serious problems, including heart attack, stroke, or even death.

Healthy arteries are flexible and elastic, but over time, the walls in arteries can harden, a condition commonly called hardening of the arteries. The word atherosclerosis is of Greek origin and means focal accumulation of lipid and thickening of arterial intima (sclerosis [hardening]).

Atherosclerosis can affect any artery in the body, including arteries in the heart, brain, arms, legs, pelvis, and kidneys. As a result, different diseases may develop based on which arteries are affected.

Arteriosclerosis is the stiffening or hardening of the artery walls. Atherosclerosis is the narrowing of the artery because of plaque build-up.

All patients with atherosclerosis have arteriosclerosis, but those with arteriosclerosis might not necessarily have atherosclerosis. However, the two terms are frequently used with the same meaning.

Differences between normal and atherosclerosis artery
Fig: Differences between normal and atherosclerosis artery

Causes of Atherosclerosis:

Atherosclerosis can begin in the late teens, but it usually takes decades to cause symptoms. Some people experience rapidly progressing atherosclerosis during their thirties, others during their fifties or sixties.

Certain factors that can damage the inner area of the artery (endothelium) and can trigger atherosclerosis include:

  • High blood pressure
  • High levels of cholesterol
  • Smoking
  • High levels of sugar in the blood

Areas of the artery that are damaged are likely to have plaque buildup which can eventually break open. When the plaque breaks open, blood cell fragments called thrombocytes (or platelets) accumulate in the affected area. These fragments can then stick together, forming blood clots.

High triglycerides:

 Most fat in food and the body takes the form of triglycerides. Blood triglyceride levels above 400 mg/dL have been linked to coronary artery disease in some people. Triglycerides, however, are not nearly as harmful as LDL cholesterol.

Diabetes:

Patients with poorly controlled diabetes, who frequently have excess blood glucose levels, are much more likely to develop atherosclerosis.

Genetics:

 People with a parent or sibling who has/had atherosclerosis and cardiovascular disease have a much higher risk of developing atherosclerosis than others.

Obesity:

 Excess weight increases the strain on the heart and increases the risk of developing atherosclerosis even if no other risk factors are present.

Mechanism of atherosclerosis
Fig: Mechanism of atherosclerosis

Pathophysiology of Atherosclerosis:

 Very low-density lipoprotein (VLDL) is produced by the liver and is changed into LDL using lipoprotein lipase. This process removes triglycerides from VLDL by hydrolysis, releasing fatty acids and leaving greater numbers of cholesterol, thus increasing the density of the molecule.

The LDL crosses the endothelium and moves into the extracellular matrix where it is oxidized (by the aforementioned steps above), and forms oxidized LDL (OxLDL).

OxLDL is a cause of inflammation and signals monocytes (white blood cells) to enter the arterial wall to fix the inflammation. As monocytes enter the arterial wall, they transform into macrophages.

Since the LDL is now oxidized due to aldehydes and lipid hydroperoxides, the modified apolipoprotein B in LDL attaches to macrophage scavenger receptor cells. At this stage, OxLDL has a very high number of cholesterol and cholesterol esters, since it lost antioxidants, triglycerides, and fatty acids in previous steps. Macrophages are supposed to remove cholesterol by use of high-density lipoprotein (HDL) particles, but if there is too much excess cholesterol, it causes the macrophages to enlarge and fill with lipids.

Eventually, the macrophages build up and convert into lipid-laden foam cells (a collection of fatty materials and cholesterol) which die and become part of the plaque that causes atherosclerosis.

As this process continues, more and more LDL becomes trapped within the tunica intima (the innermost layer of the arterial wall) creating a pool of cholesterol called a fatty streak.

The smooth muscle cells move from the tunica media (the thickest layer of the artery) to the tunica intima and become proliferated by way of released cytokines (proteins that help with immunity) within the macrophages. Major atherosclerosis causing plaque has a fibrous cap, which sticks out into the artery, causing vasoconstriction, and blocking blood flow (the plaque always forms in the lumen, which is between the intima and the musculature of the wall.

Atherosclerosis

Symptoms of Atherosclerosis:

Atherosclerosis does not usually produce symptoms until blood circulation becomes restricted or blocked, leading to cardiovascular disease (CVD).

The type of cardiovascular disease and its associated symptoms depends on, where the blockage occurs. The first signs of atherosclerosis can begin to develop during adolescence, with streaks of white blood cells appearing on the artery wall. The symptoms of the disease depend on, which arteries are affected.

Carotid Arteries:

These arteries provide blood to the brain. When the blood supply is limited, patients can suffer a stroke and may experience:

  • Weakness
  • Difficulty in breathing
  • Headache
  • Facial numbness
  • Paralysis

Coronary Arteries:

 These arteries provide blood to the heart, when the blood supply to the heart is limited, it can cause angina and heart attack. Symptoms include:

  • Vomiting
  • Extreme anxiety
  • Chest pain
  • Coughing
  • Feeling faint

Heart attack:

 If one of the plaques in coronary arteries ruptures, it could create a blood clot. If the blood clot blocks the supply of blood to the heart, it will cause to have a heart attack. Symptoms of a heart attack include:

  • Chest pain – usually located in the center of the chest and giving the sensation of pressure, tightness, or squeezing.
  • Pain in other parts of the body that can feel as though it is traveling from chest to arms. (usually, the left arm, although both arms can be affected), jaw, neck, back, and abdomen.
  • An overwhelming sense of anxiety.
  • (Similar to a panic attack), Shortness of breath, feeling sick, lightheadedness, coughing, vomiting, wheezing.

Aneurysm:

If atherosclerosis weakens the walls of blood vessels, it can lead to the formation of an aneurysm (a bulge in a blood vessel).

If the aneurysm grows too large, there is a danger. It will rupture, which can cause potentially fatal internal bleeding and organ damage.

An aneurysm can develop anywhere in the body, but the two most common types of aneurysm are:

  • A brain aneurysm (also known as a cerebral aneurysm), which develops inside the brain.
  • An aortic aneurysm, which develops inside the aorta (a large blood vessel that runs down the abdomen and transports blood away from the heart).

If an aortic aneurysm ruptures, the person will experience sudden and severe pain in the middle or side abdomen. In men, the pain can spread down into the scrotum (the sac containing the testicles).

Symptoms of a ruptured brain aneurysm usually begin with a sudden and severe headache, which has been described as being hit on the head.

Renal arteries:

These supply blood to the kidneys; if the blood supply becomes limited, there is a serious risk of developing chronic renal failure, and the patient may experience:

  • Loss of appetite.
  • Swelling of the hands and feet.
  • Difficulty in concentrating.

Peripheral arterial disease:

The arteries to the limbs, usually the legs, are blocked. The most common symptom is leg pain, either in one or both legs, usually in the calves, thighs or hips. The pain may be described as one of heaviness, cramp, or dullness in the leg muscles. Other symptoms may include:

  • Hair loss on legs or feet
  • Male impotence (erectile dysfunction)
  • Numbness in the legs
  • The colour of the skin on the legs change
  • The toenails get thicker
  • Weakness in the legs

Table: Location of atherosclerosis and its symptoms

Location of the atherosclerosisSymptoms
In the coronary (heart) arteriesChest pain, heart attack, or sudden death
In the carotid (brain) arteriesweakness, loss of speech, or blindness
In the femoral (leg) arteriesDiseases of the blood vessels in the outer parts of the body (peripheral vascular disease) causer-scraping and fatigue in the calves when walking.
In the renal (kidney) arteries, in the arteries leading to genitalsHigh blood pressure that is difficult to treat, pain during sex. Sometimes, atherosclerosis can cause erectile dysfunction in men. In women, high blood pressure can reduce blood flow to the vagina, making sex less pleasurable

Diagnosis of Atherosclerosis:

Physicians may be able to make a diagnosis of atherosclerosis during a physical exam using a stethoscope and gentle probing of the arteries with the hand (palpation) to find signs of narrowed, enlarged or hardened arteries, including A weak or absent pulse below the narrowed area of the artery. Decreased blood pressure in an affected limb. Whooshing sounds (bruits) over arteries, heard using a stethoscope. Signs of a pulsating bulge (aneurysm) in the abdomen or behind the knee. Evidence of poor wound healing in the area where blood flow is restricted.

Depending on the results of the physical exam, more diagnostic tests, including:

Blood tests:

 Blood tests can detect increased levels of cholesterol and blood sugar that may increase the risk of atherosclerosis.

Doppler ultrasound:

 It is a special ultrasound device (Doppler ultrasound) used to measure blood pressure at various points along the arm or leg. These measurements can help the doctor to measure the degree of any blockages, as well as the speed of blood flow in arteries.

Ankle-brachial index:

 This test can reveal atherosclerosis in the arteries in the legs and feet. The doctor may compare the blood pressure in the ankle with the blood pressure in the arm. This is known as the ankle-brachial index. An abnormal difference may indicate peripheral vascular disease, which is usually caused by atherosclerosis.

More definite tests are:

 Electrocardiography (ECG):

 An electrocardiogram measures the electrical activity of the heart. This test can measure how well the heart is functioning and can often detect the presence of heart disease.

Stress test:

 A stress test also called an exercise stress test, is used to gather information about how well the heart works during physical activity. Because exercise makes the heart pump harder and faster than it does during most daily activities, an exercise stress test can reveal problems within a heart that might not be noticeable otherwise. An exercise stress test usually involves walking on a treadmill or riding a stationary bike while heart rhythm, blood pressure and breathing are monitored.

Cardiac catheterization and angiogram:

This test can show if coronary arteries are narrowed or blocked. A liquid dye is injected into the arteries of the heart through a long, thin tube (catheter) that is fed through an artery, usually in the leg, to the arteries in the heart. As the dye fills arteries, the arteries become visible on X-ray, revealing areas of blockage.

Ultrasound:

 An ultrasound scanner uses sound waves to build up a picture of the inside of the body. This can be used to measure blood pressure at different points in the body. Any variation in pressure could point to the site of a blockage in arteries. Ultrasound tests can also be used to study the larger arteries.

Computerized tomography scan:

 A computerized tomography (CT) scan takes a series of X-ray images and uses a computer to assemble them into a more detailed three-dimensional image. It can often detect narrowing or hardening in the larger arteries.

Treatment of Atherosclerosis:

 Lifestyle changes:

 The changes will focus on weight management, physical activity and a healthy diet. The doctor may recommend eating foods high in soluble fiber and limiting the intake of saturated fats, sodium, and alcohol.

Medication:

 The medications may be prescribed:

  • To prevent the deposition of plaque or blood clots using antiplatelet agents or Thrombolytic agents.
  • To lower cholesterol such as statins.
  • To lower blood pressure such as Angiotensin-converting enzyme (ACE) inhibitors, Diuretics (Water pills).

Surgery:

Severe cases of atherosclerosis may be treated by surgical procedures, such as angioplasty or coronary artery bypass grafting (CABG).

Angioplasty involves expanding the artery and opening the blockage so that the blood can flow through properly again. CABG is another form of surgery that can improve blood flow to the heart by using arteries from other parts of the body to bypass a narrowed coronary artery.

Angioplasty and stent placement:

 Angioplasty is a procedure in which a tiny device is inserted into narrowed blood vessels that supply blood to the heart. This device widens the arteries and increases blood flow.

Balloon angioplasty:

Balloon angioplasty also known as percutaneous transluminal coronary angioplasty (PTCA), uses a small, thin tube (called a catheter) with a tiny balloon at its tip. The tube is inserted into the bloodstream through a large vessel in the arm or leg. By watching the progress of the tube on an X-ray, the cardiologist guides the tube into the heart, where it is inserted into a narrowed coronary artery. The tiny balloon is then inflated to widen the narrowed area.

Balloon angioplasty
Fig: Balloon angioplasty

During most of these procedures, cardiologists also insert a metal wire frame that serves as a scaffolding to help keep the artery open. This device is called a stent. A blocked artery is less likely to close up if a stent is in place

There are two types of stents:

  • Bare metal stents
  • Drug coated stents

Endarterectomy:

 In some cases, fatty deposits must be surgically removed from the walls of a narrowed artery. When the procedure is done on arteries in the neck (the carotid arteries), it is called a carotid endarterectomy.

Bypass surgery:

 In this, a graft bypass may be created using a vessel from another part of the body or a tube made of synthetic fabric. This allows blood to flow around the blocked or narrowed artery.

Stent with balloon angioplasty
Fig: Stent with balloon angioplasty

Table: Drugs used in the treatment of atherosclerosis

Statins to lower bad cholesterol (LDL)Lovastatin, Simvastatin, Pravastatin, Flu vastatin, Atorvastatin, Rosuvastatin
Fibrates to reduce TriglyceridesGemfibrozil, Fenofibrate
Reducing triglycerides and LDL. It also increases HDL.Nicotinic acid.
Other drugs for atherosclerosisCholestyramine, Colestipol, Colesevelam
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