Atherosclerosis Artery Hardening Fatty Deposits Biology Essay

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Atherosclerosis is the hardening of the artery wall by accumulation of fatty deposits in the lining of the arteries. The damage of the lining of the arteries may lead to the plaque formation that caused by factors such as high blood pressure and chemicals from cigarettes. Cholesterol: your guide for a healthy heart A simple plaque can also grow into a more complicated one when calcium accumulates and hardens the plaque, and when blood clot develop. The narrow coronary arteries causes the blood flow to heart can slow down or stop. This can cause chest pain (angina), shortness of breath, heart attack (myocardial infarction), and other symptoms.

Atherosclerosis can affect many different organs, including the heart, brain, and limbs. In USA, it caused almost one million deaths in 1996 and affects 4.6 million people in USA. http://www.sunstar.com.ph/static/bag/2007/10/18/oped/dr..victor.dumaguing.to.your.health.html It occurs in the arteries because the blood flows rapidly under high pressure in the arteries. Smokers and overweight people have greater risk to get atherosclerosis rather than the normal people. In the meantime, atherosclerosis cannot be cured, but it can be treated by using many different ways. Therefore, what are the current treatments that used nowadays to treat this disease?

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Figure 1 Normal artery vs artery with atherosclerosis

http://www.treehugger.com/files/2007/07/diesel_and_your_heart.php

http://ebsco.smartimagebase.com/progression-of-atherosclerosis-in-the-coronary-arteries/view-item?ItemID=16390

A Possible Solution

STATIN DRUGS

Statins are widely prescribed for treating atherosclerosis. The usage of statin drugs has increasing as they possess relatively various pleiotropic effects in reducing atherosclerosis disease. Recent clinical studies confirm that statins decreases low density lipoprotein (LDL) cholesterol to well below 100 mg/dL in high risk patients.

http://www.health-news.org/images/full_size/study-crestor-side-effects-deemed-worse.jpg

Statin drugs work by inhibiting a key enzyme, HMG-CoA (3-hydroxy-3-methyglutaryl COA) reductase which catalyzes the conversion of HMG-CoA to mevalonate. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2703237/ Mevalonate is used as building block for cholesterol biosynthesis. It interferes with its production by acting as a reversible competitive inhibitor for HMG-CoA which binds to the HMG-CoA reductase. . http://en.wikipedia.org/wiki/Lovastatin It inhibits the synthesis of LDL which causes an increase in the number of the LDL receptors on the surface of liver cells. As a result, more cholesterol being removed from the bloodstream thus reduces the risk of high-cholesterol related diseases. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896785/

Article Title:

The Effects of Statins on the Progression of Atherosclerotic Renovascular Disease.

Source:

Nephron Clinical Practice, Oct2007, Vol. 107 Issue 2, pc35-c42, 1p, 6 charts, 1 graph

Graph; found on pc37

The major pleiotropic effects of statins are considered to be: attenuation of the inflammatory process, improvement of endothelial function and normalization of the coagulationfibrinolysis system

Statin drugs are able to lower LDL levels from 18% - 55% and to raise HDL levels 5% - 15%. Studies have shown that statin drugs can help the body reabsorb cholesterol that has accumulated on the artery walls. According to the Mayo Clinic, raising HDL cholesterol level 1 milligram per deciliter (mg/dL) of blood can reduce the heart attack risk by 3%. Therefore, the usage of statin in treating atherosclerosis is beneficial to improve the balance of LDLs to HDLs and reduce the inflammation in the lining of the arteries, thus reducing the risk of atherosclerosis.

Statins could restore endothelial function by lowering serum low-density-lipoprotein cholesterol (LDL-C) levels Pleiotropic Effects of Statins Statins have been shown to improve endothelial function in patients with atherosclerosis. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896785/

Lipid lowering by statins contributes to plaque stability due to the decreased in inflammatory activity, with a decrease in the expression of matrix metalloproteinase, a family of highly homologous protein-degrading zinc dependent enzymes endopeptidases, by reducing plaque size or by modifying the physiochemical properties of the lipid core.

There are many types of statins, including lovastatin, fluvastatin, pravastatin, rosuvastatin, atorvastatin, pitavastatin, and simvastatin. Lovastatin, fluvastatin, and pravastatin are indicated for slowing coronary atherosclerosis in patients with coronary heart disease. Rosuvastatin is indicated for slowing the progression of atherosclerosis both in patients with and without coronary heart disease. Atorvastatin works by inhibiting enzymes that make cholesterol in the liver. Pitavastatin is indicated for hypercholesterolaemia and for the prevention of cardiovascular disease. Simvastatin inhibits the progression of atherosclerosis by decreasing low density lipoprotein (LDL) levels in the patient's body.

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Lovastatin is an inhibitor of HMG-CoA reductase, an enzyme which catalyzes the conversion of HMG-CoA to mevalonate. Mevalonate is used as building block for cholesterol biosynthesis. It interferes with its production by acting as a reversible competitive inhibitor for HMG-CoA which binds to the HMG-CoA reductase. Lovastatin is inactive in the the form in which it is administered, while active when it is hydrolysed to the β-hydroxy acid form in the body. http://en.wikipedia.org/wiki/Lovastatin

The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) examined the effects of lovastatin on the incidence of a first major coronary event in 5608 men and 997 women with average total cholesterol and LDL cholesterol and below-average HDL cholesterol levels. A statistically significant 37% reduction in the incidence of the first major coronary event (4% vs 6.8%) occurred after an average of 5.2 years http://emedicine.medscape.com/article/150916-treatment

Fluvastatin has a hypocholesterolaemic effect as well as a protective effect on low-density lipoprotein (LDL) from oxidation, which can protect plasma LDL from oxidative modification and, thereby, prevent cholesterol accumulation in macrophages and endothelial dysfunction in blood vessels. This anti-oxidative effect of fluvastatin may be beneficial for preventing the progression of atherosclerosis. http://www.ncbi.nlm.nih.gov/pubmed/10831243

Pravastatin, as with all HMG-CoA reductase inhibitor drugs, blocks the normal production of cholesterol in the body. It reduces the production of LDL cholesterol by blocking the action of the enzyme HMG-CoA reductase in the liver that is responsible for its production. This decreases the amount of cholesterol in the liver cells, causing them to take up LDL cholesterol from the blood. The decreased cholesterol production and increased removal of LDL cholesterol from the blood ultimately results in lowered blood cholesterol levels.

The West of Scotland Coronary Prevention Study (WOSCOPS) examined the effects of pravastatin on the incidence of nonfatal myocardial infarction and coronary mortality rates in 6595 men with moderate hypercholesterolemia and no prior history of coronary heart disease. A statistically significant 29% reduction in nonfatal myocardial infarction (4.6% vs 6.5%) and a 30% reduction in death from all cardiovascular causes (1.6% vs 2.3%) occurred after an average of 4.9 years of follow-up http://emedicine.medscape.com/article/150916-treatment

Rosuvastatin is an antilipemic agent and a competitive HMG-CoA reductase inhibitor effective in lowering LDL cholesterol and triglycerides. It is used to treat primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb).

These study results were similar in demonstrating that rosuvastatin produced a greater LDL-cholesterol reduction and target achievement in comparison with the other agents.

Atorvastatin is a synthetic lipid-lowering agent that inhibits HMG-CoA reductase and cholesterol synthesis in the liver. It increases the number of LDL receptors in the liver to enhance absorption and breakdown of LDL which, in turn, lowers blood cholesterol levels. There is also increasing evidence that statins affect blood vessel walls through a complex series of actions that ultimately stabilize plaque, prevent rupture, and possibly act to prevent blood clotting. http://www.ems1.com/ems-products/Ambulance-Disposable-Supplies/articles/409082-Atorvastatin-Drug-Whys/

http://www.cholesterol-hdl-ldl.com/atherosclerosis-treatment.html (statin action)

http://www.jfponline.com/pages.asp?id=8062

Figure 1 Least-squares mean percentage change from baseline in LDL-C, HDL-C, and triglycerides with 10-mg statin doses from the STELLAR trial

Treatment with rosuvastatin resulted in significantly greater reductions in LDL-C, as compared with atorvastatin, simvastatin, and pravastatin. The efficacy of rosuvastatin in reducing LDL-C may make it particularly useful in high-risk patients who need to achieve low LDL-C targets.

http://journals.prous.com/journals/mf/20022409/html/mf240593/images/FIGURE1.gif

figure Chemical structures of several types of statins

Strong evidence supports the management of atherosclerosis with statins, according to Dr. Subodh Verma, MD, PhD, a cardiac surgeon at St. Michael's Hospital, University of Toronto and the Canada Research Chair in Atherosclerosis. He pointed to a recent study involving more than 90,000 participants that indicated for every slight reduction (1 millimole per litre) in low-density lipoprotein (LDL) cholesterol, there was also reduction of about 23 percent in the risk of heart attacks or coronary-related mortality, a 24 percent reduction in the need for coronary revascularization, and a 17 percent reduction in the rate of fatal or non-fatal stroke.

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Social & Economic Implication

http://sloanreview.mit.edu/the-magazine/articles/1995/summer/3642/economic-consequences-of-illness-in-the-workplace/

In 1994, U.S. health care expenditures approached $1 trillion, of which private businesses paid a substantial portion. While the debates on regulatory measures to contain these costs have not been resolved, the market has responded decisively to pressures from increased health care spending, evidenced by the broad shift to managed care. This trend has moved decision-making authority from providers and recipients of health care goods and services. Increasingly, those who pay for health care, including insurers, managed care organizations, and employers, are asserting their influence over the way treatment decisions are ultimately made.1

If more effective management can curtail cost escalation in health care, an employer can channel some resources otherwise allocated to health care for other uses. To capitalize on this opportunity, some employers have attempted to intervene directly in the workplace to address health care issues, which requires a clear understanding of the costs they currently bear. Whereas employers routinely calculate and report out-of-pocket health care costs, they generally do not understand the opportunity costs associated with health care decisions. Our purpose is to illustrate the importance of the "indirect" costs of illness in the workplace, especially the effects of impaired functioning on the job as well as absenteeism. Without paying proper attention to these additional costs, employers are unlikely to make the best health care expenditure decisions, from a systemwide perspective.2

Costs of Illness in the Workplace

Cost-of-illness analysis requires a specific vantage point. For example, we can examine the costs of a particular illness - direct and indirect - with respect to an individual sufferer. Alternatively, we can explore society's stake in the illness using a slight variant of the same methodology. While direct costs include all the out-of-pocket expenditures incurred for treatment, indirect costs include the lost output that results from illness. This latter category includes, but may not be limited to, lost resources due to premature death.

Although this type of analysis usually takes the perspective of the individual or of society, we can focus on the vantage point of other agents or groups of interested parties as well. Our discussion takes the perspective of employers who want to ascertain the cumulative resource depletion from illness in the workplace. A specific firm can easily develop a simple extension of the same analysis, based on that company's unique features and the demographics of its workforce. Alternatively, a company can apply a similar approach to a range of...

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Benefits and Risks

According to the research, statin drugs have lower LDL levels from 18% - 55% and to raise HDL levels 5% - 15%. Besides that, statin drugs have anti-inflammatory properties, which help in stabilising the lining of blood vessels. This would make plaques less likely to rupture and subsequently reduce the risk of blood clot. Statins also help in relaxing the blood vessels. http://www.mayoclinic.com/health/statins/CL00010/NSECTIONGROUP=2 As a result, the blood pressure is lowered thus reducing the inflammation as well as the plaque formation. Statins act directly on blocking the pathway for synthesizing cholesterol in the liver by inhibiting the enzyme (HMG-CoA) reductase. Consequently, the blood cholesterol level will fall as liver can no longer produce cholesterol. http://en.wikipedia.org/wiki/Statin#Mechanism_of_action It was assumed that statin-mediated reductions of blood cholesterol levels would be associated with corresponding reductions in the risks of atherosclerosis-mediated diseases.

In spite of reducing the blood cholesterol level, statin also imposses several side effects to human health. The most serious side effects are liver failure and rhabdomyolysis (muscle damage). http://www.medicinenet.com/statins/page2.htm The chance of experiencing myopathies (inflammation of the muscles) is depending on an individual's age, the dose of statins taken, and the interaction of statins with other medications. These symptoms will usually appear within four months after the statin therapy. www.statinssideeffects.net/ Besides that, the other common side effects are constipation, diarrhea, and nausea. http://www.mayoclinic.com/health/statins/CL00010 Some statins are known to interact adversely with other drugs. http://meddesktop.blogspot.com/2008/05/control-your-cholestrol-with-statins.html As the intake of statins may lead to several side effects; therefore the patients need to be monitored by their physician regularly. Lowering the dose may help in reducing the side effects.

Statins are relatively safe for most people, but some can respond differently to the drugs. Certain people may have fewer side effects with one statin drug than another.

http://themissingfacts.com/statins.html

http://www.mayoclinic.com/health/statin-side-effects/MY00205

http://encyclopedia.thefreedictionary.com/atherosclerosis

Alternative Solution

Natural remedies

Since oxidised LDL is involved in the formation of plaques which clog the arteries thus fighting off free radicals will consequently prevent many sequences of events that contribute to atherosclerosis. Antioxidants provide several heart-protecting benefits, including reducing LDL level. Antioxidants are compounds that help to neutralize free radicals and protect the body against destructive effects, which means that it can protect the arteries from oxidized LDL. Therefore, several natural remedies can be used as an alternative to treat atherosclerosis as they have high antioxidant content.

http://thaimangosteen.net/mangosteen-facilitate-for-atherosclerosis

Mangosteen

Gamma mangostin, a xanthone found in mangosteen is a powerful antioxidant. It can prevent the oxidation of low-density lipoprotein (LDL) by free radicals. It also helps in raising the levels of high-density lipoprotein (HDL) and the overall levels of cholesterol without the potentially serious side effects of anti-cholesterol drugs. Besides that, polyphenols in mangosteen were found to be five times more effective than vitamin C as antioxidant. http://thaimangosteen.net/mangosteen-facilitate-for-atherosclerosis The supplementation of mangosteen, coupled with a good diet, avoidance of smoking, and regular exercise, show remarkable results on the patients with atherosclerosis.

Oxygen Radical Absorbance Capacity (ORAC) test done in laboratory shows that an ounce of mangosteen has 20 to 30 more times more capable of absorbing free radicals than other fruits and vegetables of the same amount.

http://thaimangosteen.net/mangosteen-facilitate-for-atherosclerosis

Pomegranate Juice

Pomegranate juice could block or slow the buildup of cholesterol in the arteries due to its high antioxidant content. The study showed that the antioxidant level in pomegranate juice was higher than that found in other fruit juices, including blueberries, strawberries, and even oranges. http://www.webmd.com/food-recipes/news/20050321/pomegranate-juice-may-clear-clogged-arteries

Antioxidant levels of fruits and vegetables

http://www.aromatherapy4moms.com/chinese-wolfberry-juice.html

Pomegranate juice is rich in antioxidants, especially polyphenols rather than other fruit juices. Researchers found that pomegranate juice is able to prevent hardening of the arteries by improving the blood flow of atherosclerosis patient which causes the reduction of blood vessel damage. Due to the high antioxidant content; this juice may also reverse the progression of atherosclerosis. http://www.webmd.com/food-recipes/news/20050321/pomegranate-juice-may-clear-clogged-arteries

Pomegranate juice also shown to reduce the stress effects on human blood vessel cells by stimulating the production of nitric oxide, a substance that keep the arteries open and keep blood flowing smoothly by inhibiting LDL oxidation.

In a study, researchers tested the effects of pomegranate juice on samples of human cells that line blood vessels. The cells were exposed to excessive physical stress, such as might occur with high blood pressure. Cells that were treated with pomegranate juice had less evidence of damage from the stress.

In addition, tests on mice showed that pomegranate juice significantly slowed hardening of the arteries that developed from high cholesterol. Researchers say pomegranate juice may be useful in both prevention and treatment of heart disease if further studies show those results in humans

Dark chocolate

The results of a study suggest that regular consumption of nutritional doses of cocoa may have an effect on all initial phases of the atherosclerotic process in subjects at high risk of coronary heart disease. These anti-inflammatory effects, together with other previously reported effects, including those of antioxidant, anti-platelelet, and positive vascular effects, may contribute to the overall benefits of cocoa consumption against atherosclerosis. The study appears in the American Journal of Clinical Nutrition.

Dark chocolate provides health benefits due to the high flavanols-content found in cocoa. Flavanols are a class of flavonoids, which is an antioxidant found in cocoa beans. They can increase blood flow to the brain and have supporting roles in disease prevention by protecting the blood vessels from undergoing oxidative changes that result in certain diseases. Consequently, this will strengthen the capillaries and other connective tissue which leads to enhanced health and wellness. http://ezinearticles.com/?The-Benefits-of-Dark-Chocolate-May-Surprise-You&id=938700

Dark chocolate has better antioxidant properties as well.

http://www.ellaneblog.net/2009/11/10/whats-sooo-good-about-chocolate/

Dark chocolate able to lower high blood pressure, say Dirk Taubert, MD, PhD, and colleagues at the University of Cologne, Germany. Their report appears in the Aug. 27 issue of The Journal of the American Medical Association.

Dark chocolate is a potent antioxidant, report Mauro Serafini, PhD, of Italy's National Institute for Food and Nutrition Research in Rome, and colleagues. Their report appears in the Aug. 28 issue of Nature. Antioxidants gobble up free radicals, destructive molecules that are implicated in heart disease and other ailments.

http://chocolate-news.org/articles/Dark_Chocolate_is_Healthy_chocolate.pdf

Dark Chocolate Is Healthy Chocolate

Dark Chocolate Has Health Benefits Not Seen in Other Varieties

Aug. 27, 2003

The benefits of dark chocolate have been reported in many scientific journals in recent years. One of these was the study by Grassi, Lippi, Necozione, and Desideri in the American Journal of Clinical Nutrition, 2005. These researchers found that dark chocolate decreased blood pressure and had a positive impact on insulin sensitivity in healthy persons.

. These benefits were first seen in the Kuna Indian population living in the San Blas Islands off the coast of Panama. This population has a very low incidence of cardiovascular disease and diabetes. They also consume high quantities of cocoa-rich beverages. This led researchers to study the link between cocoa and their health. They observed definite links between the cocoa and their low incidence of certain diseases.

Antioxidants block free radicals that can damage the arterial wall and act as a stimulant to get into a good mood and help to prevent heart attacks.

fights atherosclerosis (flavonoids play a role in protecting circulating lipids from oxidation which is part of the process that creates the plaque that clogs arteries)

"In their protection of body cells, the antioxidants transfer free radicals that develop on the walls of blood vessels and can cause cancer, aging and atherosclerosis," Rast says. "It is known that the antioxidant concentration is higher in dark chocolate than in food like grapes, nuts and green tea."

Alternative therapies combining with a range of physical and psychological approaches can halt and even reverse atherosclerosis. Particularly successful seem to be those involving a healthy diet with food supplements, exercise, yoga, massage, and relaxation therapy, counseling and other "talking therapies" linked to close social support.

The study was a randomized, double-blind, placebo-controlled design conducted over a 2 week period in 21 healthy adult subjects. Subjects were randomly assigned to daily intake of high-flavonoid (213 mg procyanidins, 46 mg epicatechin) or low-flavonoid dark chocolate bars (46 g, 1.6 oz).

Results: High-flavonoid chocolate consumption improved endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (mean change = 1.3 ± 0.7%) as compared to low-flavonoid chocolate consumption (mean change = -0.96 ± 0.5%) (p = 0.024).

http://www.jacn.org/cgi/content/full/23/3/197?maxtoshow=&hits=10&RESULTFORMAT=&andorexacttitle=and&titleabstract=dark+chocolate&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&fdate=1/1/2000&resourcetype=HWCIT

Fig. 1. Flow-mediated dilation (FMD %) of the brachial artery in the low-flavonoid and high-flavonoid dark chocolate groups.

http://www.jacn.org/cgi/content/full/23/3/197/F1

Angioplasty

Angioplasty is an alternative in the coronary artery patient. Angioplasty is the technique of mechanically widening narrowed or obstructed arteries by using a catheter to inflate a balloon at the blockage site with water pressure, squashing and cracking the plaque to create a wider channel. http://en.wikipedia.org/wiki/Angioplasty & buku Tony Smith

http://www.medicinenet.com/coronary_angioplasty/article.htm

Angioplasty is safer than bypass surgery and according to statistics less than 1% of people die from complications after this procedure. http://en.wikipedia.org/wiki/Angioplasty Patients who had surgery had a significantly higher risk of stroke of about two per cent versus nearly zero risk for patients who had an angioplasty. Coronary angioplasty, using special drug-coated stents, is as safe as bypass surgery in treating very complex coronary artery disease. Dr Haizal Haron Kamar 

Consultant Cardiologist Tropicana Medical Centrehttp://www.mmail.com.my/content/balloon-angioplasty-versus-bypass

Patients with stents are usually prescribed clopidogrel which is taken together with acetylsalicylic acid. These medications are prescribed to prevent blood clots and they are usually taken for at least in first months after the procedure is performed. http://en.wikipedia.org/wiki/Angioplasty

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