Atherosclerosis

DEFINITION: Atherosclerosis is the hardening of a blood vessel from a buildup of arterial plaque. Plaque is made of fatty deposits, cholesterol, and calcium. It builds on the inside lining of arteries. This causes the artery to narrow and harden. It affects large and medium-sized arteries.

As plaque builds up, it can slow and even stop blood flow. This means the tissue supplied by the affected artery is cut off from its blood supply. This often leads to pain or decreased function. This condition can cause a number of serious health problems. Depending on the location of the blockage, it can cause coronary heart disease (a loss of blood to areas of the heart), stroke (a loss of blood to areas of the brain), and/or peripheral vascular disease, characterized by leg pain with walking. In addition, a hardened artery is more likely to be damaged. Repeated damage to the inner wall of an artery causes blood clots to form. The clots are called thrombi. They can lead to a further decrease in blood flow. In some cases, a thrombus may become so large that it completely closes off the artery. It could also break into clumps, called emboli. These clumps travel through the bloodstream and lodge in smaller arteries, blocking them off. In these cases, the tissue supplied by the artery receives no oxygen and quickly dies. When this occurs in the heart, it is called a heart attack. In the brain, it is called a stroke. Long-term atherosclerosis can also cause arteries to weaken. In response to pressure, they may bulge. This bulge is called an aneurysm. If untreated, aneurysms can rupture and bleed.

Risk Factors

There are two types of factors that increase an individual’s chance of atherosclerosis: risk factors the individual cannot control and risk factors the individual can control.

The National Heart, Lung, and Blood Institute states that some of the risk factors that cannot be controlled as having a father or brother who developed complications of atherosclerosis before age fifty-five or having a mother or sister who developed complications of atherosclerosis before age sixty-five, men forty-five years of age or older, and women fifty-five or older, are also at risk. Men have a greater risk of heart attack than women.

Risk factors that can be controlled include having high levels of low-density lipoprotein (LDL), or “bad” cholesterol, and low levels of high-density lipoprotein (HDL), or “good” cholesterol; having high blood pressure; cigarette smoking; diabetes type I and type II; being overweight or obese; and a lack of physical activity.

Metabolic syndrome is a combination of three out of the following five findings: low HDL cholesterol (also called “good” cholesterol), high triglycerides, elevated blood sugar, elevated blood pressure, and an increased waist circumference (greater than forty inches in men and thirty-five inches in women).

Etiology and Genetics

Multiple environmental and genetic factors play a contributing part in atherosclerosis. Some individuals are genetically predisposed to developing the condition, yet a detailed genetic analysis and prediction of inheritance patterns are not possible since so many different genes seem to be implicated. According to a 2020 article in Circulation Research, 163 gene loci may be involved in atherosclerosis in humans.

One gene with a clear association with atherosclerosis is APOE, found on the long arm of chromosome 19 at position 19q13.2. APOE encodes the protein apolipoprotein E, which functions to carry excess cholesterol from the blood to on the surface of cells in the liver. Some mutations in the gene lead to altered protein products that lack the ability to bind to the receptors, resulting in a marked increase in an individual’s blood cholesterol.

Studies using deoxyribonucleic acid (DNA) microarray analyses have implicated another gene, EGR1 (early growth response gene 1), as a contributor to some cases of atherosclerosis. Found on the long arm of chromosome 5 at 5q23–q31, this gene encodes a protein that is an important part of the body’s vascular repair system. When inappropriately active in coronary arteries, the effect is the slow closure of the arteries, leading to angina and possible starvation of heart muscle. This important discovery opened new avenues of research designed to develop drugs targeted to inhibit EGR1 gene expression.

A 2016 study by Washington University in St. Louis found that a malfunction in the immune system's waste disposal mechanisms leading to protein buildup also played a role in atherosclerosis.

In 2024, a study conducted by researchers at Vanderbilt University Medical Center found that smooth muscle cells in blood vessels with atherosclerosis actually change their identities and act like cancer cells. The researchers also found that treatment with an anticancer drug slowed progression of the disease, a breakthrough that promised to open the door for new methods of treating and preventing atherosclerosis.

Symptoms

There are no symptoms in early atherosclerosis. As the arteries become harder and narrower, symptoms may begin to appear. If a clot blocks a blood vessel or a large embolus breaks free, symptoms can occur suddenly.

Symptoms depend on which arteries are affected. For example, coronary (heart) arteries may cause symptoms of heart disease, such as chest pain; arteries in the brain may cause symptoms of a stroke, such as weakness or dizziness; and arteries in the lower extremities may cause pain in the legs or feet and trouble walking.

Screening and Diagnosis

Most patients are diagnosed after they develop symptoms. However, patients can be screened and treated for risk factors.

A patient who has symptoms will be asked questions by his or her doctor; these questions will help to determine which arteries might be affected. The doctor will also need to know a patient’s full medical history, and a physical exam will be conducted. Tests will depend on which arteries may be involved; these tests will be decided based on the patient’s symptoms, physical exam, and/or risk factors.

Many of these tests detect problems with the tissue that is not getting enough blood. Two common tests that directly evaluate the atherosclerotic arteries are angiography and ultrasonography. In angiography, a tube-like instrument is inserted into an artery. Dye is injected into the vessel to help determine the degree of blood flow. When done in the heart, this test is called cardiac catheterization. An ultrasound is a test that uses sound waves to examine the inside of the body. In this case, the test examines the size and shape of arteries.

Treatment and Therapy

An important part of treatment for atherosclerosis is reducing risk factors. Beyond that, treatment depends on the area of the body most affected.

Treatment may include medications, such as drugs to interfere with the formation of blood clots, like aspirin or clopidogrel (Plavix); drugs to control blood pressure, if elevated; drugs to lower cholesterol, if elevated; and drugs that improve the flow of blood through narrowed arteries, such as cilostazol (Pletal) or pentoxifylline (Trental).

Procedures involving a thin tube, called a catheter, can also be used. The catheter is inserted into an artery. Catheter-based procedures are most often done for arteries in the heart; they may be used to treat atherosclerosis elsewhere in the body. These procedures include balloon angioplasty, in which a balloon-tipped catheter is used to press plaque against the walls of the arteries, increasing the amount of space for the blood to flow.

Stents are usually done after angioplasty. In this procedure, a wire mesh tube is placed in a damaged artery; it will support the arterial walls and keep them open.

In an atherectomy, instruments are inserted via a catheter. They are used to cut away and remove plaque so that blood can flow more easily. This procedure is not often performed.

Surgical options include endarterectomy—removal of the lining of an artery obstructed with large plaques. This procedure is often done in the carotid arteries of the neck; these arteries bring blood to the brain.

Arterioplasty can repair an aneurysm; it is usually done with synthetic tissue. Bypass is the creation of an alternate route for blood flow using a separate vessel.

Prevention and Outcomes

There are a number of ways to prevent as well as reverse atherosclerosis. They include eating a healthy diet that should be low in saturated fat and cholesterol and rich in whole grains, fruits, and vegetables. Patients should exercise regularly, maintain a healthy weight, and lose weight if they are overweight. They should not smoke; if they smoke, they should quit. Patients should also control their diabetes, if present.

If a doctor recommends it, a patient should take medication to reduce his or her risk factors. This may include medicine for high blood pressure or high cholesterol. Patients should also talk to their doctors about screening tests for atherosclerotic disease of the heart (coronary artery disease) if they have risk factors.

Bibliography

Aherrahrou, Redouane, et.al. "Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells." Circulation Research, vol. 127, no. 12, 12 Oct. 2022, doi.org/10.1161/CIRCRESAHA.120.317415. Accessed 29 Aug. 2024.

American Association for Clinical Chemistry. "APOE Genotyping, Cardiovascular Disease." Lab Tests Online. Amer. Assn. for Clinical Chemistry, 18 Mar. 2014. Web. 22 July 2014.

"Atherosclerosis." MedlinePlus. Natl. Inst. of Health, 1 Dec. 2015. Web. 15 Jan. 2016.

"Atherosclerosis is Alzheimer’s Disease of Blood Vessels, Study Suggests." Bioscience Technology. Advantage Business Media, 13 Jan. 2016. Web. 15 Jan. 2016.

Ballantyne, Christie M., James H. O’Keefe, and Antonio M. Gotto. Dyslipidemia and Atherosclerosis Essentials. 4th ed. Sudbury: Jones, 2009. Print.

Beers, Mark H., ed. The Merck Manual of Medical Information. 3rd home ed. Whitehouse Station: Merck Research Laboratories, 2009. Print.

Kohlstadt, Ingrid, ed. Food and Nutrients in Disease Management. 2nd ed. Boca Raton: CRC, 2012. Print.

National Heart, Lung, and Blood Institute. "Atherosclerosis." National Institutes of Health. US Dept. of Health and Human Services, 1 July 2011. Web. 22 July 2014.

Pan, Huize, et al. "Atherosclerosis Is a Smooth Muscle Cell–Driven Tumor-Like Disease." Circulation, vol. 18, no. 24, 30 Apr. 2024, doi.org/10.1161/CIRCULATIONAHA.123.067587. Accessed 29 Aug. 2024.

Roberts, Robert, Ruth McPherson, and Alexandre F. R. Stewart. “Genetics of Atherosclerosis.” Cardiovascular Genetics and Genomics. Ed. Dan Roden. Hoboken: Wiley-Blackwell, 2009. Print.

Rosenbaum, Laurie. "Atherosclerosis." Health Library. EBSCO, 2 May 2014. Web. 14 July 2014.

Stephenson, Frank H. “Atherosclerosis.” DNA: How the Biotech Revolution Is Changing the Way We Fight Disease. Amherst: Prometheus, 2007. Print.

Stylianou, Ioannis M., Robert C. Bauer, Muredach P. Reilly, and Daniel J. Rader. "Genetic Basis of Atherosclerosis: Insights from Mice and Humans." Circulation Research 110 (2012): 337–55. PDF file.

Wang, Hong, and Cam Patterson. Atherosclerosis: Risks, Mechanisms, and Therapies. Hoboken: Wiley, 2015. Print.