Atherosclerosis

Atherosclerosis is a subtype of arteriosclerosis. Arteriosclerosis is a general term for the hardening of arteries and, in its progression, the walls of arteries become thick and stiff, sometimes preventing the flow of blood to organs and tissues. Atherosclerosis is a disease in which fatty substances, cholesterol, cellular waste products, calcium and some other substances accumulate in the inner lining (intima) of artery. Collectively, the accumulated substances are referred to as plaque. Over time, plaque continues to accumulate, hardens and eventually narrows the lumen of arteries. Ischaemia or reduced blood flow can lead to serious problems, depending on the specific artery affected.


The typical progression of atherosclerosis begins when tears or fatty streaks in the inner lining of blood vessels attract monocytes (type of white blood cell) and stimulate the cellular immune response. Advanced lesions (any abnormality of tissue in any area of the body) develop when cholesterol, calcium crystals, and cellular debris builds up within the inner lining (intima). The increase in size of the affected intima narrows the lumen of the vessel. Clotting factors (substances produced in response to injury) and platelets (smallest type of blood cell) are activated by contact with the lesions. Thrombi (blood clots) may build on lesions or move downstream, potentially blocking the artery.
A condition or disease masy result due to the advanced progression of atherosclerosis in particular areas of the body. For instance:

• Peripheral arterial disease develops when arteries supplying the limbs are affected, consequently circulation problems in the arms and legs may occur.
  
• Coronary artery disease develops when arteries supplying the heart are affected and there’s a possibility of experiencing chest pain (angina) or a heart attack (myocardial infarction).
  
• Transient ischemic attack or stroke arises when arteries supplying blood to the brain are affected.
  

Also, atherosclerosis can possibly also lead to a bulge in the wall of an artery, which may be referred to as an aneurysm.

Signs & Symptoms
Atherosclerosis usually doesn’t show signs or symptoms until it progresses to a point where an artery is partially or fully blocked. In most cases, it takes a medical emergency to give an indication of progressing atherosclerosis. Otherwise, the signs and symptoms experienced depend on which arteries are severely affected. For instance:

• Obstruction of arteries supplying the brain, i.e. carotid arteries in the neck, may cause symptoms of a stroke, such as dizziness, sudden numbness or weakness.


• Obstruction of arteries to the heart (coronary arteries) may cause symptoms of a heart attack, e.g. angina pectoris (chest pain which is normally relieved after a few minutes of rest, in contrast to a heart attack in which the pain is more intense and is not relieved by rest.)


• Obstruction of the arteries supplying the arms and legs may cause symptoms of peripheral arterial disease, such as leg pain when walking, numbness or sometimes serious infections.

Men may go through sexual dysfunction because of hardening of the arteries.

Causes and Associated Risks

Although the exact cause of atherosclerosis is unknown, it is suspected to begin with damage to the inner layer of an artery. The damage may be as a result of high blood pressure, high cholesterol, an irritant such as nicotine or certain diseases like diabetes. Thus, the risk factors of atherosclerosis include high blood pressure, high cholesterol, diabetes, obesity, smoking and having a family history of an aneurysm or early heart disease.

Screening and Diagnosis

Diagnosis is normally based on three (3) things:

• your medical and family histories


• risk factors


• results of a physical exam and dianostic tests.

During a physical exam, signs of narrowed, enlarged or hardened arteries may be found. These signs may include:

• Whooshing sounds over arteries, heard with a stethoscope.


• Evidence of poor wound healing in the area where blood flow is being restricted.


• A weak or absent pulse below the narrowed area of the artery.


• Decreased blood pressure in an affected limb.


• Signs of a pulsating bulge (aneurysm) in the abdomen or behind the knee.

Depending or the results of a physical exam, one or more diagnostic tests may be performed, including:

1. Angiogram - a special dye may be injected into the arteries before a chest x-ray is done to give an indication of how blood is flowing through the vessels and whether there are any blockages.

2. Ankle-Brachial Index - used to compare the blood pressure in the ankle to that in the arm. Any abnormal difference may indicate peripheral vascular disease.

3. Blood tests - increased levels of cholesterol, blood sugar and other substances that may increase the risks of atherosclerosis may be detected.

4. Doppler Ultrasound - a special ultrasound device is used to measure blood pressure at various points of the arms and legs to determine the degree of any blockages, as well asthe speed of blood flow in the arteries.

5. Electrocardiogram (ECG/EKG) – records electrical signals as they move through the heart. It can give an indication of how nerve impulses pass through the heart and whether a myocardial infarction is progressing or has occurred recently.

6. Other imaging tests – can also be used to study the arteries, such as an ultrasound, computerized tomography (CT) scan or a magnetic resonance angiogram (MRA).

Treatment
The main treatment for atherosclerosis is lifestyle changes. Medicines and medical procedures may also be required. Treatment seeks to: relieve any symptoms; reduce risk factors in an effort to slow, stop or reverse the build-up of plaque; lower the risk of blood clots forming; widen or bypass clogged arteries; prevent diseases related to atherosclerosis.

Lifestyle changes can promote healthier arteries. Sometimes, these changes may be the only treatment necessary. Otherwise, medication or surgical procedures may be recommended as well.

Medication

• Anticoagulants – such as heparin, can aid in blood thinning to prevent clots from forming.
  
• Anti-platelet medications – such as aspirin, can lessen the likelihood of platelets clumping in narrowed arteries.
  
• Blood pressure medications – can help slow the progression of atherosclerosis.
  
• Cholesterol medications – (see post on high cholesterol)
• Other medications – can be used to control specific risk factors or treat symptoms of atherosclerosis.
  

Procedures
In severe cases, any one of the following procedures may be necessary:

1. Angioplasty – a long, thin tube (catheter) is inserted into the narrowed part of the artery. Then a wire with a deflated balloon is passed through the catheter to the narrowed area. The balloon is inflated, compressing the deposits against the artery walls in the hopes of reopening the artery, if blocked.

2. Bypass surgery – a graft bypass using a vessel from another part of the body or a tube made of synthetic fabric is created to give rise to an alternate path for blood to flow.

3. Endarterectomy – fatty deposits are surgically removed from the walls of a narrowed artery.

4. Thrombolytic therapy - a clot-dissolving drug may be inserted into the artery to break up a blood clot blocking the artery.

High Cholesterol (Hypercholesterolemia)

Cholesterol

Cholesterol is a sterol (a group of unsaturated alcohols of the steroid group) present in cell membranes, the brain and lipoproteins. It can be utilized to produce all the steroids of the body. About 1g of cholesterol is synthesized per day in humans. Cholesterol is normally converted into bile salts, vitamin D3 and steroid hormones, which includes testosterone, estrogen and progesterone. Cholesterol is mainly excreted in the form of bile salts in stool. Free cholesterol is transported by lipoproteins in the circulation. Cholesterol ester is a storage form of cholesterol found in most tissues. Cholesterol esters are formed by the esterification of cholesterol to fatty acids. This esterification occurs in the body by transfer of PUFA (polyunsaturated fatty acids). This step is important in the regulation of cholesterol level. The normal blood level is 150-220 mg/dL. Increased cholesterol levels lead to atherosclerosis as cholesterol accumulates in the arteries causing narrowing of blood vessels. Dietary intake of polyunsaturated fatty acids help in the transport and metabolism of cholesterol and, in so doing, prevents atherosclerosis.

Note that hypercholesterolemia is more common in men younger than 55 and in women older than 55 years. The risk for high cholesterol increases with age.

Causes

With more than enough cholesterol in the bloodstream, which is usually due to an unbalanced diet, cholesterol is carried throughout the blood bound to proteins along with a few other substances, e.g fatty acids, and is called a lipoprotein. Lipoproteins can directly contribute to atherosclerosis progression. The main types of lipoproteins are: Low-density lipoprotein (LDL), which is also known as 'bad cholesterol' and is responsible for transporting cholesterol throughout the body, and High-density lipoprotein (HDL), which transports cholesterol from the bodily tissues back to the liver for excretion. With an adequately balanced diet, the HDL and LDL levels can be altered to maintain acceptable cholesterol levels. Increasing the intake of linoleic acid (and other related polyunsaturated fatty acids) lowers cholesterol levels, although not as significantly as saturated fatty acids raise it.

Other factors that influence the amount of 'bad cholesterol' in the blood include genetics, body weight, viscous dietary fiber, soy protein, plant sterols, antioxidants and flavonoids (fat-soluble antioxidants). In a rare cholesterol disorder, the NPC(Neiman-Pick type C)1 gene malfunctions impairing the normal movement of cholesterol within cells. The genetic makeup of a person may change the way LDL cholesterol is removed or cause the liver to produce too much cholesterol. Being overweight tends to increase cholesterol and so, losing weight can help lower LDL and total cholesterol levels, as well as raise HDL and lower triglyceride levels. Oxygen free radicals (hydrogen peroxide, superoxide, etc) are sometimes generated by cellular activities of the body. These compounds bring about damage to blood vessels by oxidizing/altering lipids (primarily LDL) and turning certain cells called macrophages into foam cells, which contribute to plaque formation in blood vessels. Water-soluble antioxidants, e.g Vitamin C, and fat-soluble antioxidants protect against free radicals.

Risk Factors

• Cigarette smoking damages the walls of blood vessels making them more susceptible/vulnerable to fatty deposit accumulation. Smoking may also lower HDL cholesterol levels, which is the 'good cholesterol'.


• High blood pressure can damage arteries, contributing to the rate of fatty deposit accumulation.


• High blood sugar alters LDL and HDL cholesterol levels (LDL cholesterol becomes high while HDL cholesterol becomes low). High blood sugar can also damage the lining of arteries.

Treatment

After having a blood test to determine a complete lipid profile, which measures total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, and hypercholesterolemia is evident, the choices of medication include:

• Statins - prevent the liver from making cholesterol and with this cholesterol is depleted in the liver cells, allowing them to take up cholesterol for excretion. They may also aid in reabsorbing fatty deposits that may have accumulated in the wall of arteries.

Examples: atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Altoprev, Mevacor), pravastatin (Pravachol), rosuvastatin (Crestor) and simvastatin (Zocor).

• Bile-acid-binding resins -binds to bile acids produced by the liver, preventing them from being recycled. This causes cholesterol to be taken up by the liver cells to be converted to bile acids, reducing blood cholesterol levels in the process.

Examples: Cholestyramine (Prevalite, Questran), colesevelam (Welchol) and colestipol (Colestid).

• Cholesterol absorption inhibitors- prevents the absorption of cholesterol by the small intestine.

Example: ezetimibe (Zetia), which can be used in combination with any of the statin drugs.

For high triglycerides:

• Fibrates- decrease triglycerides by reducing the production of very-low-density lipoprotein (VLDL), precursor to LDL (meaning that VLDL is used to make LDL), and by speeding up the removal of triglycerides from the blood. Triglycerides are the major component of VLDL.


• Niacin (Niaspan)- decreases triglycerides by limiting the production of VLDL and LDL by the liver.

Most medications do not cause complications. However, the most common side effects are constipation, diarrhea, stomach pain and nausea.

Why Is A Change In Lifestyle Important?

Lifestyle changes can improve your cholesterol level significantly. Regular physical activity can help raise HDL and lower LDL and is especially important for those with high triglyceride and/or low HDL levels who are overweight with a large waist. Weight management plays a central role in prevention of cardiovascular diseases. Dietary recommendations include saturated and trans fatty acid intake less than or equal to 8% of total calories; cholesterol intake less than 300 mg/day; at least 2 servings of fish per week; a diet which includes fruits,vegetables, and whole grains; limiting sodium intake to less than 2300mg/day; limiting alcohol to 2 drinks or less per day for men and 1 drink per day for women; and limiting added sugar. This healthy eating pattern should assist in acheiving desirable body weight, cholesterol and lipoprotein profile and blood pressure. Lifestyle changes can reduce excessive LDL concentrations by 20-40%. For this reason, lifestyle changes are essential in the treatment process.