Arteries are the blood vessels that carry nutrient-rich and oxygenated blood from the heart to all tissues of the body. Sometimes, fatty and waxy material builds up inside the walls of arteries causing narrowing of arteries and hinders the normal circulation of blood. This buildup of substances is called atherosclerosis or plaque formation leading to the hardening of arteries(Weaver, 2013). Sometimes it is important to remove plaque from arteries to prevent serious health issues. Plaque is usually made up of substances that enter the bloodstream, including cholesterol, fat, calcium, waste products from cells, and clotting agent (Insull, 2009).
Atherosclerosis occurs at susceptible sites in major arteries and is one of the leading causes of global disease burden and mortality (Murray & Lopez, 2013). The process of plaque is caused as a result of various chemical activities, including oxidation, lipid retention, increased concentration of lipoproteins containing apolipoprotein B, mainly LDL (low-density lipoprotein). As it is a multifactorial disease, many other factors like hypertension, diabetes mellitus, smoking, etc. also facilitate its progression, making the treatment of the disease difficult (Bentzon, Otsuka, Virmani, & Falk, 2014). Clumping of platelets at the site of injury can also form clots that narrow down the arteries. Inflammation can also occur as a result of the immune system attacking the cholesterol by the white blood cells after sensing an extra layering or buildup as a problem or threat.
Although not all the plaques are dangerous, some of the vulnerable plaques can rupture, causing blot clot formation and restriction in blood flow. Atherosclerotic lesions can cause blockage of major arteries to the heart, brain, legs, or other organs. These artery-clogging plaques can lead to stroke or heart attack under serious circumstances (The Society for Cardiovascular Angiography and Interventions, 2017).
Multifaceted mechanisms of plaque formation are triggered by various factors such as inflammatory cell recruitment, lipoprotein retention, apoptosis or necrosis, angiogenesis, smooth muscle cell proliferation, calcification, arterial remodeling, and thrombosis. Each plaque leads to a different outcome depending on the morphology, rate of progression associated with neo-angiogenesis, site of formation as some of them remain asymptomatic while some become obstructive (Bentzon, Otsuka, Virmani, & Falk, 2014).
Complete removal of plaque from the arteries is nearly impossible after it has set in, but it can be reversed to some extent with the help of pharmacological intervention. The best alternative is to slow down or prevent any further plaque buildup. Measuring the plaques activity in the at-risk populations can help initiate preventive therapies on an individual level (Sillesen & Falk, 2011).
The strategy for plaque removal or preventive therapy depends on the type of arteries that have been affected and the associated symptoms, although they don’t become apparent until the condition has worsened. The arteries most affected by plaques are coronary arteries that supply blood to the heart with symptoms, including angina, arrhythmias, and shortness of breath. Carotid artery disease occurs when plaques narrow down the arteries supplying blood to the brain, ultimately leading to a stroke. Symptoms might be a sudden weakness, dizziness, paralysis, loss of consciousness, headaches, etc. If plaque formation occurs in major arteries providing blood to the arms, legs, or pelvis, it is referred to as peripheral artery disease, while chronic kidney disease can result from narrowing or blockage of renal arteries supplying blood to the kidney (NHLBI, NIH, 2019).
Electrocardiogram, X-ray, Echo test, computed tomography (CT) scan are some of the diagnostic methods used by physicians to diagnose atherosclerosis. Sometimes, angiography is performed to assess the site and severity of the blockage. Right and timely diagnosis is a vital part of plaque removal or disease treatment. Major courses of action that can be taken for plaque removal from arteries are lifestyle changes, use of medication, or surgical interventions.
Some of the major changes needed to be made in living style are eating healthy and balanced diets that have controlled levels of cholesterol and ultimately lesser fat or plaque deposition, physical activity, and proper stress management, maintaining a healthy weight and avoiding smoking as it could worsen the disease.
Mediterranean diets rich in fruits, vegetables, olive oil, fish, etc. reduce the risk of heart disease by around 30%. Lesser use of processed meat and a controlled quantity of cheese are other necessary changes required for reduction in plaques (Harvard Health Publishing, 2019). Eating unsaturated foods like walnuts, olives, vegetables, and drinking herbal teas also helps to reduce the LDL levels that might contribute to plaque regression or prevention (Nettleton, Brouwer, Geleijnse, & Hornstra, 2017).
Regular exercise keeps the blood pressure under control and helps in lowering the blood sugar level. Burning the body fat via rigorous aerobic exercises or maintaining a healthy body mass index is useful. The lining of arteries is also disrupted by smoking. Hence quitting smoking also elevates the HDL levels in the blood and reduces the LDL responsible for the aggravation of plaque formation.
If preventive therapies fail, medical intervention is usually required to halt the further buildup of plaque and alleviate the harmful effects of clogged arteries. Atherosclerosis reduction up to 20-40% can be achieved with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, i.e., statin treatment. Statins are the most commonly used drugs for the reduction of LDL cholesterol as they block the enzymes responsible for cholesterol production. The drugs are Rosuvastatin (Crestor) and Atorvastatin (Lipitor), and sometimes Ezetimibe (Zetia) is also given to patients to reduce the cholesterol absorption in the digestive tract (Harvard Health Publishing, 2019).
The use of statin medications helps to reduce the chances of having a heart attack or stroke. Along with statins, medicines to lower the blood pressure are also used, such as the diuretics, calcium channel blockers, and angiotensin receptor blockers. ACE inhibitors are used to slow down the progression of the atherosclerotic plaque and reduce the chances of recurrent heart attacks. Beta-blockers are commonly given to patients having coronary artery disease to lower the amount of pressure on the heart and also to lower the heart rate (Mayo Clinic, 2018). Metformin might help to lower the blood sugar levels to keep the plaque formation in check.
Lipid treatments have proved to be effective in the measurement of the plaque size and its chemical composition, the risk of disease progression, and inflammation-based clinical activities (Insull, 2009). Inflammatory processes are also among the potential targets of atherosclerotic therapies. Anti-inflammatory drugs, as well as anti-platelets drugs such as Aspirin, may be given under certain conditions to limit the clumping of platelets, and exert its anti-inflammatory properties to control blood clots formation and further blockage of arteries, along with the help of statins (Paoletti, GottoJr, & Hajjar, 2014).
When medications and lifestyle changes fail to halt the plaques formation and its harmful effects, surgical intervention may be deemed necessary to counter progressive atherosclerosis. Some of the procedures commonly done include angioplasty.
Angioplasty, also known as percutaneous transluminal coronary angioplasty (PTCA), is performed to remove the plaque from arteries. In this process, a small incision is made on the skin, and a long tube called catheter is inserted into the affected vessel. As soon as the tube reaches the place where the artery is blocked, the balloon attached at the tip of the tube is inflated, which compresses the plaque against the vessel wall. The inflation and deflation may be repeated several times as required along with placement of a stent (a metal tube) to keep the artery open and prevent the clogging of this artery again that might cause a heart attack or stroke(Byrne, Stone, Ormiston, & Kastrati, 2017).
Around one-third of patients go through angioplasty and arterial scaffolding using the stent implantation (Michaels & Chatterjee, 2002). A stent is generally a small tube made of high-grade stainless steel and is used to prevent any chances of the closure of the artery after angioplasty. Usually placed at the narrow end of the artery, it is pressed against the wall of the artery and is permanently placed. The practice of stent placement was initiated because of re-stenosis occurring in patients whose arteries had previously been opened via angioplasty. They not only prevent the re-occlusion of arteries with plaques but also reduce ischemia and recurrent heart attacks. Primary PTCA alone cannot provide long term benefits. Hence adjunct stent implantation improves the outcomes of this surgical procedure(Brancati, Burzotta, Trani, Leonzi, Cuccia, & Crea, 2017).
Percutaneous coronary intervention (PCI) has been successful because of advanced technology in intracoronary imaging, and pharmacotherapy to complement the surgical procedures. It is also supplemented with antithrombotic therapy for enhanced efficacy and reaching desired results (Cuisset, Verheugt, & Mauri, 2017). Although rare, coronary stent infections can occur and have a high mortality rate necessitating the use of alternate procedures wherever applicable.
For patients who have more than 40-50% of their artery clogged with lesser chances of improvement via angioplasty or stents, coronary artery bypass graft (CABG) surgery is performed. Also known as open-heart surgery, it is done in about 10% of the coronary artery disease (CAD) patients in which two or three arteries are blocked (Graham, Ghali, Faris, Galbraith, Norris, & Knudtson, 2002).In CABG, surgeons take a healthy vessel from another part of the patients’ body and create a bypass or a detour for the blood to pass around the clogged area of a coronary artery. During this procedure, while the surgeons are operating, an artificial heart and lung machine is used to maintain the circulation (Harris, Croce, & Tian, 2013). It is performed under general anesthesia and takes 3-6 months for proper recovery from the surgery.
Directional coronary atherectomy (DCA) is a minimally invasive procedure that has been used to yield synergistic results for plaque excision and ease the pain due to blocked vessels (Sato, Kijima, Ichimura, Yaegashi, & Anzai et al., 2019). A catheter with a deflated balloon is inserted through an incision to the narrowed end of the artery. The balloon is inflated to unblock the vessel. And a blade inside the catheter rotates to remove any plaque left behind. The material left behind is around 10µm in diameter and is usually removed in circulation. The DCA was considered superior to primary stent implantation based on clinical outcomes reported in randomized clinical trials (Tsuchikane, Sumitsuji, Awata, Nakamura, & Kobayashi et al., 1999). But as the stent technique is continuously being improved, DCA had to compete with angioplasty and stenting.
Sometimes, a rotational device is a good tool to remove plaques from arteries. It is used at high speed to widen the narrowed down artery and break down the calcified plaques. It is referred to as rotational atherectomy and differentially cuts and drills through the hardened atherosclerotic plaque and calcium while keeping the elastic arterial structure intact (Patel, Rafeedheen, & Helmy, 2018).
Carotid endarterectomy (CEA) is a procedure to remove plaque from the carotid arteries in the neck region. It is carried out to prevent the stroke or death in patients suffering from carotid artery disease (Saha, Saha, & Vyas, 2015). Surgeons cut the affected artery and remove the plaque through this incision. Temporarily a flexible tube may be inserted to allow the blood flow during the removal of plaque in arteries. This surgery is usually complicated due to the sensitivity of the organs that could be affected by it.
Peripheral vessel disease (PVD) occurs when vessels outside of the heart and brain get clogged due to plaque formation. Intermittent claudication, pain in leg or arm due to blocked artery, is the major symptom of PVD along with numbness, weakness, and atrophy. It is usually managed with anti-coagulant and anti-platelet medications or drugs to lower cholesterol. Cilostazol (Pletal) is a medicine causing dilation of the arteries. It is given to relieve claudication and enable people to increase their physical activity, allowing them to walk a longer distance without pain in the arm or affected leg(Stöppler, 2019). Bypass surgery or endarterectomy may be performed in cases where medications are unable to control the disease.
The calcium buildup inside the arteries leads to calcified plaques formation and can prove to be harmful if not taken care of timely. The osteoblasts promote this process of calcium-driven atherosclerosis. A drug to activate PPARγ (peroxisome proliferator-activated receptor-gamma) mediates the formation and increased infiltration of osteoclasts into the plaques instead of osteoblasts and reverse the blood vessels calcium accumulation. This also provides insight into a new therapeutic target to halt the atherosclerosis progression and severity of symptoms (Weaver, 2013).
Moreover, newer treatment options are also being tested to remove atherosclerotic plaques. Targeted Nanotherapy with synthesized peptide nanofiber along with ApoA reported showing efficient results in the aortic root (Mansukhani et al., 2018). These could also be given via intravenous injections causing the cholesterol to dissolve. New targets and therapeutic strategies are also being identified and are in the process to be approved after improved efficacy results of randomized clinical trials as compared to previously available treatments.
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