Coronary artery disease 5876 223910862 2008-07-06T13:43:34Z DOI bot 6652755 Citation maintenance. Formatted: title. Initiated by [[User:RDBrown|RDBrown]]. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. {{Infobox_Disease | Name = Coronary artery disease | Image = | Caption = | DiseasesDB = | ICD10 = {{ICD10|I|20||i|20}}-{{ICD10|I|25||i|20}} | ICD9 = {{ICD9|410}}-{{ICD9|414}}, {{ICD9|429.2}} | ICDO = | OMIM = | MedlinePlus = | eMedicineSubj = radio | eMedicineTopic = 192 | MeshID = D003324 | }} '''Coronary artery disease''' (CAD) (or '''[[atherosclerosis|atherosclerotic]] [[heart disease]]''') is the end result of the accumulation of [[atheroma|atheromatous plaques]] within the walls of the [[Coronary circulation|arteries]] that supply the [[myocardium]] (the muscle of the [[heart]]) with oxygen and nutrients. It is sometimes also called '''[[coronary heart disease]]''' (CHD), but although CAD is the most common cause of CHD, it is not the only cause. CAD is the leading cause of death in the U.S. While the symptoms and signs of coronary artery disease are noted in the advanced state of disease, most individuals with coronary artery disease show no evidence of disease for decades as the disease progresses before the first onset of symptoms, often a "sudden" [[myocardial infarction|heart attack]], finally arise. After decades of progression, some of these [[atheroma|atheromatous plaques]] may rupture and (along with the activation of the [[blood clot]]ting system) start limiting [[blood flow]] to the [[cardiac muscle|heart muscle]]. The disease is the most common cause of [[cardiac arrest|sudden death]]<ref>{{cite journal |author=Thomas AC, Knapman PA, Krikler DM, Davies MJ |title=Community study of the causes of "natural" sudden death |journal=BMJ |volume=297 |issue=6661 |pages=1453–6 |year=1988 |month=December |pmid=3147014 |pmc=1835183 |doi= |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1835183}}</ref>, and is also the most common reason for death of men and women over 20 years of age<ref name="AHA">American Heart Association: [http://www.americanheart.org/presenter.jhtml?identifier=3000090 Heart Disease and Stroke Statistics]-2007 Update. AHA, Dallas, Texas, 2007</ref>. According to present trends in the United States, half of healthy 40-year-old males will develop CAD in the future, and one in three healthy 40-year-old women.<ref>{{cite journal |author=Rosamond W, Flegal K, Friday G, ''et al'' |title=Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee |journal=Circulation |volume=115 |issue=5 |pages=e69–171 |year=2007 |month=February |pmid=17194875 |doi=10.1161/CIRCULATIONAHA.106.179918 |url=http://circ.ahajournals.org/cgi/content/full/115/5/e69/TBL3179728}}</ref> According to the [[Guinness Book of Records]], [[Northern Ireland]] is the country with the most occurrences of CAD. By contrast, the [[Maasai]] of Africa have almost no heart disease. As the degree of coronary artery disease progresses, there may be near-complete obstruction of the [[lumen]] of the coronary artery, severely restricting the flow of oxygen-carrying blood to the myocardium. Individuals with this degree of coronary artery disease typically have suffered from one or more [[myocardial infarction]]s (heart attacks), and may have signs and symptoms of chronic coronary ischemia, including symptoms of [[Angina pectoris|angina]] at rest and flash [[pulmonary edema]]. A distinction should be made between myocardial ischemia and myocardial infarction. Ischemia means that the amount of oxygen supplied to the tissue is inadequate to supply the needs of the tissue. When the myocardium becomes ischemic, it does not function optimally. When large areas of the myocardium becomes ischemic, there can be impairment in the relaxation and contraction of the myocardium. If the blood flow to the tissue is improved, myocardial ischemia can be reversed. Infarction means that the tissue has undergone irreversible death due to lack of sufficient oxygen-rich blood. An individual may develop a rupture of an atheromatous plaque at ''any'' stage of the spectrum of coronary artery disease. The acute rupture of a plaque may lead to an acute [[myocardial infarction]] (heart attack). ==Pathophysiology== Limitation of blood flow to the heart causes [[ischemia]] (cell starvation secondary to a lack of oxygen) of the myocardial cells. When myocardial cells die from lack of [[oxygen]], this is called a [[myocardial infarction]] (commonly called a heart attack). It leads to [[cardiac muscle|heart muscle]] damage, [[cardiac muscle|heart muscle]] death and later scarring without [[cardiac muscle|heart muscle]] regrowth. Myocardial infarction usually results from the sudden occlusion of a coronary artery when a plaque ruptures, activating the clotting system and [[atheroma]]-clot interaction fills the lumen of the artery to the point of sudden closure. The [[stenosis|narrowing]] of the lumen of the [[coronary artery|heart artery]] before sudden closure is often not severe, according to clinical research completed in the late 1990s and using [[IVUS]] examinations within 6 months prior to a [[myocardial infarction|heart attack]]. High grade [[stenosis|stenoses]] as such exceeding 75% blockage, such as detected by [[Cardiac stress test|stress testing]] while carrying much higher individual risk for sudden closure, were found to be responsible for only 14% of acute [[myocardial infarction|heart attack]]s because they are rarer compared to less severe narrowings. The events leading up to plaque rupture are not understood despite many theories. [[Myocardial infarction]] is almost never caused by temporary spasm of the artery wall occluding the lumen, a condition also associated with [[atheroma]]tous plaque and CAD. CAD is associated with [[Tobacco smoking|smoking]], [[diabetes]], and [[hypertension]]. A family history of early CAD is one of the less important predictors of CAD. Most of the familial association of coronary artery disease are related to common dietary habits. Screening for CAD includes evaluating [[High density lipoprotein|high-density]] and [[Low density lipoprotein|low-density lipoprotein]] ([[cholesterol]]) levels and [[triglyceride]] levels. Despite much press, most of the alternative risk factors including homocysteine, C-reactive protein (CRP), Lipoprotein (a), coronary calcium and more sophisticated lipid analysis have added little if any additional value to the conventional risk factors of smoking, diabetes and hypertension. ==Angina== [[Angina pectoris|Angina]] that occurs regularly with activity, after heavy meals, or at other predictable times is termed stable angina and is associated with high grade [[stenosis|narrowings]] of the [[heart]] [[artery|arteries]]. The symptoms of angina are often treated with betablocker therapy such as metoprolol or atenolol. Nitrate preparations such as [[Glyceryl trinitrate (pharmacology)|nitroglycerin]], which come in short-acting and long-acting forms are also effective in relieving symptoms but are not known to reduce the chances of future heart attacks. Many other more effective treatments, especially of the underlying [[atheroma]]tous disease, have been developed. Angina that changes in intensity, character or frequency is termed unstable. Unstable angina may precede myocardial infarction, and requires urgent medical attention. It may be treated with oxygen, intravenous nitroglycerin, and aspirin. Interventional procedures such as [[angioplasty]] may be done. == Sex characteristics of coronary artery disease == === Special Pathophysiology === Typically, [[coronary artery disease]] occurs when part of the smooth, elastic lining inside a [[coronary artery]] (the arteries that supply blood to the heart muscle) develops [[atherosclerosis]]. With atherosclerosis, the artery's lining becomes hardened, stiffened, and swollen with all sorts of "grunge" - including calcium deposits, fatty deposits, and abnormal inflammatory [[cell]]s - to form a [[plaque]]. Plaques can be thought of as large "pimples" that protrude into the channel of an artery, causing a partial obstruction to blood flow. Patients with coronary artery disease might have just one or two [[plaque]]s, or might have dozens distributed throughout their [[coronary arteries]]. However, there is a term in medicine called ''“'''Cardiac Syndrome X'''”'', which describes chest pain ([[Angina pectoris]]) and chest discomfort in people who do not show signs of blockages in the larger [[coronary arteries]] of their hearts when an [[angiogram]] (coronary angiogram) is being performed<ref>{{cite journal |author=Lanza GA |title=Cardiac syndrome X: a critical overview and future perspectives |journal=Heart |volume=93 |issue=2 |pages=159–66 |year=2007 |month=February |pmid=16399854 |doi=10.1136/hrt.2005.067330 |url=}}</ref>. No one knows exactly what causes “Cardiac Syndrome X” and it is unlikely to have a single cause. Today, we speculate that the major contributing factor to “Cardiac Syndrome X” is ''“'''microvascular dysfunction'''”'': The term “microvascular” refers to very small blood vessels and, in this case, very small [[arteries]] ([[arterioles]], [[capillaries]]) of the [[heart]]. Studies have also shown that people with “Cardiac Syndrome X” have enhanced [[pain]] perception, meaning they feel chest pain more intensely than the average person. The large majority of women have the garden variety of coronary artery disease. Rarely, women with “Cardiac Syndrome X” have typical anginal syndromes that are not associated with the presence of atherosclerotic plaques; that is, the localized blockages are absent. Scientists speculate that the blood vessels in these women are diffuse abnormal. Some have falsely claim that the entire lining of the [[artery]] becomes thickened throughout, making the [[plaque]]s flush with the wall of the [[artery]] without any scientific proof. On [[cardiac catheterization]] their [[coronary arteries]] appear smooth-walled and normal, though they may look "small" in diameter. By the way: in general, female [[coronary arteries]] (like all arteries) are somewhat smaller than in males.[[Image:Coro Man.jpg|thumb|Coronary angiogram of a man]][[Image:Coro Woman.jpg|thumb|Coronary angiogram of a woman]] “Cardiac Syndrome X” have never been shown to cause acute heart attacks ([[myocardial infarction]]) despite much speculation. The prognosis with syndrome-X coronary artery disease is also known to be better than with typical [[coronary artery disease]], but this is not a benign condition since it can be quite disabling. It is not completely clear why women are more likely than men to suffer from "Syndrome X"; however, [[hormone]]s and other risk factors unique to women may play a role<ref>{{cite journal |author=Kaski JC |title=Pathophysiology and management of patients with chest pain and normal coronary arteriograms (cardiac syndrome X) |journal=Circulation |volume=109 |issue=5 |pages=568–72 |year=2004 |month=February |pmid=14769677 |doi=10.1161/01.CIR.0000116601.58103.62 |url=}}</ref>. Women’s blood vessels are exposed to changing levels of [[oestrogen]] throughout their lives, first during regular menstrual cycles and later during and after [[menopause]] as [[oestrogen]] levels decline with age. [[Oestrogen]] affects how blood vessels narrow and widen and how they respond to injury, so changes in [[oestrogen]] levels mean changes in the reactivity of the blood vessels. Women’s vessels may be “programmed” for more changes than men’s vessels, which could increase the risk of having problems in the lining of the [[arteries]] ([[endothelial cells]]) and the [[smooth muscle]] cells in the walls of the arteries. The endothelial dysfunction is likely to be multifactorial in these patients and it is conceivable that risk factors such as [[hypertension]], [[hypercholesterolemia]], [[diabetes mellitus]] and smoking can contribute to its development. Most patients with female-pattern coronary artery disease are postmenopausal women and [[oestrogen]] deficiency has been therefore proposed as a pathogenic factor in female patients. In addition to changing hormone levels, there are several other risk conditions for blood vessel problems that are unique to women, such as [[preeclampsia]] (a problem caused by high blood pressure during pregnancy) and delivering a low-birth weight baby. Of course, despite these issues women, the female gender as a whole is protective against coronary artery disease. === Symptoms === Cardiac Syndrome X often is a diagnosis of exclusion where the presence of '''typical''' chest pains is not accompanied by coronary artery narrowings on angiography. In considering Syndrome-X, it is important to understand that about 80% of chest pains have nothing to do with the heart. Therefore, the characteristics of typical chest pains must be carefully documented to avoid unnecessary labelling patients with heart disease: * Chest pain or [[Angina]] with physical stress; the [[pain]] may spread to the left arm or the neck, back, throat, or jaw. There might be present a numbness ([[paresthesia]]) or a loss of feeling in the arms, shoulders, or wrists. * [[Coronary angiography]] demonstrates “normal” coronary arteries, i. e. no blockages or stenoses can be detected in the larger [[epicardial]] vessels. * No inducible coronary artery [[spasm]] present during [[cardiac catheterization]]. * Characteristic [[ischemic]] [[ECG]] changes during exercise testing. * [[ST segment]] depression and angina in the presence of left ventricular wall perfusion abnormalities during thallium or other stress perfusion test. * Consistent response to sublingual [[nitrate]]s. * Postmenopausal or [[menopausal]] status. The diagnosis of “Cardiac Syndrome X” - the rare coronary artery disease that is more common in women, as mentioned, an “exclusion” diagnosis. Therefore, usually the same tests are used as in any patient with the suspicion of coronary artery disease: * Baseline ECG * Exercise ECG – Stress test * Exercise radioisotope test (nuclear stress test, myocardial [[scintigraphy]]). * [[Echocardiography]] (including stress echocardiography). * [[Coronary angiography]]. * [[Intravascular ultrasound]]. * [[MRI]] scan. ===Therapy=== A variety of drugs are used in the attempt to treat the Syndrome-X coronary artery disease: [[nitrate]]s, [[calcium channel antagonist]]s, [[ACE-inhibitor]]s, [[statin]]s, imipramin ([[analgesia]]), [[aminophylline]], hormone replacement therapy ([[oestrogen]]), even electrical [[spinal cord stimulation]] are tried to overcome the symptomatology -all with mixed results. Quite often the quality of life for these women remains poor. While not enough is known about Syndrome-X coronary artery disease to list specific [[prevention]] techniques, adopting heart-healthy habits can be a good start. These include monitoring [[cholesterol]] and [[blood pressure]] levels, maintaining a low-fat [[diet]], exercising regularly, quitting smoking, avoiding recreational drugs, and moderating alcohol intake. It is also important to remember that garden variety coronary atherosclerosis remains a much, much larger threat to women then Syndrome-X. == Risk factors == '''The following are confirmed [[independent risk factors]] for the development of CAD:''' # [[Hypercholesterolemia]] (specifically, serum [[LDL]] concentrations) # [[Tobacco smoking|Smoking]] # [[Diabetes]] # [[Hypertension]] (high systolic pressure seems to be most significant in this regard) # [[Type A personality|Type A Behavioural Patterns, TABP]]. Added in 1981 as an independent risk factor after a majority of research into the field discovered that TABP's were twice as likely to exhibit CAD than any other personality type.{{Fact|date = June 2008}} '''Significant, but indirect risk factors include:''' * Lack of [[exercise]] * Stress * Diet rich in [[saturated fat]]s * [[Obesity]] * Men over 60; Women over 65<ref>http://findarticles.com/p/articles/mi_m0857/is_n6_v13/ai_17942856</ref> '''Risk factors can be classified as''' #Fixed (minor importance): age, sex, family history #Modifiable (major importance): smoking, hypertension, diabetes mellitus, obesity, etc. == Prevention == Coronary artery disease is the most common form of heart disease in the Western world. Prevention centers on the modifiable risk factors, which include decreasing [[cholesterol]] levels, addressing [[obesity]] and [[hypertension]], avoiding a [[sedentary lifestyle]], making healthy dietary choices, and [[smoking cessation|stopping smoking]]. There is some evidence that lowering [[homocysteine]] levels may contribute to more heart attacks (NORVIT trial). In [[diabetes mellitus]], there is little evidence that very tight [[blood sugar]] control actually improves cardiac risk although improved sugar control appears to decrease other undesirable problems like kidney failure and blindness. Some recommend a diet rich in omega-3 fatty acids and [[vitamin C]]. The [[World Health Organization]] (WHO) recommends "low to moderate alcohol intake" to reduce risk of coronary artery disease although this remains without scientific cause and effect proof.<ref>{{cite web |url=http://www.who.int/nutrition/topics/5_population_nutrient/en/index12.html |title=5. Population nutrient intake goals for preventing diet-related chronic diseases |format= |publisher=WHO |accessdate=}}</ref> An increasingly growing number of other [[physiological]] markers and [[homeostatic]] mechanisms are currently under scientific investigation. Patients with CAD and those trying to prevent CAD are advised to avoid fats that are readily oxidized (e.g., saturated fats and [[trans-fats]]), there is no proof of any kind that carbohydrates and processed sugars increases production of [[Low density lipoprotein]]s while increasing [[High density lipoprotein]]s. It is also important to keep [[blood pressure]] normal, exercise and stop smoking. These measures reduces the development of heart attacks. Recent studies have shown that dramatic reduction in LDL levels can cause regression of coronary artery disease in as many as 2/3 of patients after just one year of sustained treatment. Despite much initial enthusiasm, vitamin therapies including various forms of [[Vitamin A|A]] (beta [[carotene]] included), [[B Vitamins|B]] ([[folate]] included), [[Vitamin C|C]], [[Vitamin E|E]] or [[Vitamin K|K]] have not demonstrated any significant effect in reducing coronary artery disease. In fact, excessive amount of vitamin B may lead to more heart attacks while large doses of beta carotene or Vitamin E appears to lead to increases in cancer. The entire theory of anti-oxidant therapy upon which some of these is based has never been proved and remains areas of basic research. == Exercise == Separate to the question of the benefits of exercise; it is unclear whether doctors should spend time counseling patients to exercise. The [http://www.ahrq.gov/clinic/uspstfix.htm U.S. Preventive Services Task Force (USPSTF)], based on a [[systematic review]] of [[randomized controlled trials]], found 'insufficient evidence' to recommend that doctors counsel patients on exercise, but "it did not review the evidence for the effectiveness of physical activity to reduce chronic disease, morbidity and mortality", it only examined the effectiveness of the counseling itself.<ref name="pmid12160370">{{cite journal |author= |title=Behavioral counseling in primary care to promote physical activity: recommendation and rationale |journal=Ann. Intern. Med. |volume=137 |issue=3 |pages=205–7 |year=2002 |pmid=12160370 |doi=}}</ref> However, the [[American Heart Association]], based on a non-systematic review, recommends that doctors counsel patients on exercise <ref name="pmid12821592">{{cite journal |author=Thompson PD, Buchner D, Pina IL, ''et al'' |title=Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity) |journal=Circulation |volume=107 |issue=24 |pages=3109–16 |year=2003 |pmid=12821592 |doi=10.1161/01.CIR.0000075572.40158.77}} http://www.ngc.gov/summary/summary.aspx?ss=15&doc_id=5360&string=#s23</ref> == Preventive diets == {{POV-section|date=December 2007}} {{main|Diet and Heart Disease}} It has been suggested that coronary artery disease is partially reversible using an intense dietary regimen coupled with regular cardio exercise.<ref name="Ornish-1990">{{cite journal | author= Ornish D, Brown SE, Scherwitz LW, Billings JH, Armstrong WT, Ports TA, McLanahan SM, Kirkeeide RL, Brand RJ, Gould KL. | title=Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial | journal=Lancet | year=1990 | volume=336 | issue=8708 | pages=129–33 | pmid=1973470 | doi=10.1016/0140-6736(90)91656-U}}</ref> *Vegetarian diet: [[Vegetarianism|Vegetarians]] have been shown to have a 24% reduced risk of dying of heart disease.<ref name="Key-1998">{{cite journal | author=Key TJ, Fraser GE, Thorogood M, Appleby PN, Beral V, Reeves G, Burr ML, Chang-Claude J, Frentzel-Beyme R, Kuzma JW, Mann J, McPherson K | title=Mortality in vegetarians and non-vegetarians: a collaborative analysis of 8300 deaths among 76,000 men and women in five prospective studies | journal=Public Health Nutr | year=1998 | volume=1 | issue=1 | pages=33–41 | pmid=10555529 | doi=10.1079/PHN19980006}}</ref> *Cretan [[Mediterranean diet]]: The Seven Country Study found that [[Cretan]] men had exceptionally low death rates from heart disease, despite moderate to high intake of fat. The Cretan diet is similar to other traditional Mediterranean diets: consisting mostly of [[olive oil]], bread, abundant fruit and vegetables, a moderate amount of wine and fat-rich animal products such as lamb, sausage and [[goat cheese]].<ref name="Willett-1995">{{cite journal | author=Willett WC, Sacks F, Trichopoulou A, Drescher G, Ferro-Luzzi A, Helsing E, Trichopoulos D. | title=Mediterranean diet pyramid: a cultural model for healthy eating | journal=Am J Clin Nutr | year=1995 | volume=61 | issue= 6 Suppl| pages=1402S–1406S | pmid=7754995}}</ref><ref>Perez-Llamas, F., et.al., ''J Hum Nutr Diet'', Dec 1996, 9:6:463-471</ref><ref name="Alberti-Fidanza-1994">{{cite journal | author=Alberti-Fidanza A, Paolacci CA, Chiuchiu MP, Coli R, Fruttini D, Verducci G, Fidanza F. | title=Dietary studies on two rural Italian population groups of the Seven Countries Study. 1. Food and nutrient intake at the thirty-first year follow-up in 1991 | journal=Eur J Clin Nutr | year=1994 | volume=48 | issue=2 | pages=85–91 | pmid=8194497}}</ref> However, the Cretan diet consisted of less fish and wine consumption than some other Mediterranean-style diets, such as the diet in [[Corfu]], another region of Greece, which had higher death rates.{{Fact|date=February 2007}} The consumption of [[trans fat]] (commonly found in [[hydrogenated]] products such as [[margarine]]) has been shown to cause the development of [[endothelial dysfunction]], a precursor to [[atherosclerosis]].<ref name="Lopez-Garcia-2005">{{cite journal | author=Lopez-Garcia E, Schulze MB, Meigs JB, Manson JE, Rifai N, Stampfer MJ, Willett WC, Hu FB. | title=Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction | journal=J Nutr | year=2005 | volume=135 | issue=3 | pages=562–6 | pmid=15735094}}</ref>The consumption of trans fatty acids has been shown to increase the risk of coronary artery disease<ref>{{cite journal |author=Mozaffarian D, Katan MB, Ascherio A, Stampfer MJ, Willett WC |title=Trans fatty acids and cardiovascular disease |journal=N. Engl. J. Med. |volume=354 |issue=15 |pages=1601–13 |year=2006 |month=April |pmid=16611951 |doi=10.1056/NEJMra054035 |url=}}</ref> Foods containing [[fiber]], [[potassium]], [[nitric oxide]] (in green leafy vegetables), [[monounsaturated fat]], [[polyunsaturated fat]], [[saponin]]s, or [[lecithin]] are said to lower cholesterol levels. Foods high in [[grease]], [[salt]], [[trans fat]], or [[saturated fat]] are said to raise cholesterol levels. == Aspirin == Aspirin, in doses of less than 75 to 81 mg/d<ref name="pmid17488967">{{cite journal |author=Campbell CL, Smyth S, Montalescot G, Steinhubl SR |title=Aspirin dose for the prevention of cardiovascular disease: a systematic review |journal=JAMA |volume=297 |issue=18 |pages=2018–24 |year=2007 |pmid=17488967 |doi=10.1001/jama.297.18.2018}}</ref>, can reduce the incidence of cardiovascular events.<ref name="pmid16418466">{{cite journal |author=Berger J, Roncaglioni M, Avanzini F, Pangrazzi I, Tognoni G, Brown D |title=Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials |journal=JAMA |volume=295 |issue=3 |pages=306–13 |year=2006 |pmid=16418466 | url=http://jama.ama-assn.org/cgi/content/full/294/1/47 |doi=10.1001/jama.295.3.306}}</ref> The [http://www.ahrq.gov/clinic/uspstfix.htm U.S. Preventive Services Task Force] 'strongly recommends that clinicians discuss aspirin chemoprevention with adults who are at increased risk for coronary artery disease'.<ref name="pmid11790071">{{cite journal |author= |title=Aspirin for the primary prevention of cardiovascular events: recommendation and rationale |journal=Ann Intern Med |volume=136 |issue=2 |pages=157–60 |year=2002 |pmid=11790071 | url=http://www.annals.org/cgi/content/full/136/2/157}}</ref> The Task Force defines increased risk as 'Men older than 40 years of age, postmenopausal women, and younger persons with risk factors for coronary artery disease (for example, hypertension, diabetes, or smoking) are at increased risk for heart disease and may wish to consider aspirin therapy'. More specifically, high-risk persons are 'those with a 5-year risk ≥ 3%'. A risk calculator is available.<ref>[http://www.med-decisions.com/ Welcome to Med-decisions!<!-- Bot generated title -->]</ref> Regarding healthy women, the more recent [[Women's Health Study]] [[randomized controlled trial]] found [[statistical significance|insignficant]] benefit from aspirin in the reduction of cardiac events; however there was a [[statistical significance|signficant]] reduction in [[stroke]].<ref name="pmid15753114">{{cite journal |author=Ridker P, Cook N, Lee I, Gordon D, Gaziano J, Manson J, Hennekens C, Buring J |title=A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women |journal=N Engl J Med |volume=352 |issue=13 |pages=1293–304 |year=2005 |pmid=15753114 | rul=http://content.nejm.org/cgi/content/full/352/13/1293 | doi=10.1056/NEJMoa050613}}</ref> [[Subgroup analysis]] showed that all benefit was confined to women over 65 years old.<ref name="pmid15753114" /> In spite of the [[statistical significance|insignficant]] benefit for women < 65 years old, recent [[Clinical practice guideline|practice guidelines]] by the [[American Heart Association]] recommend to 'consider' aspirin in 'healthy women' <65 years of age 'when benefit for ischemic stroke prevention is likely to outweigh adverse effects of therapy'.<ref>[http://circ.ahajournals.org/cgi/content/abstract/CIRCULATIONAHA.107.181546v1 Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women: 2007 Update - Mosca et al., 10.1161/CIRCULATIONAHA.107.181546 - Circulation<!-- Bot generated title -->]</ref> == Omega-3 fatty acids == The benefit of fish oil is controversial with conflicting conclusions reached by a negative [[meta-analysis]]<ref name="pmid16565093">{{cite journal |author=Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, Worthington HV, Durrington PN, Higgins JP, Capps NE, Riemersma RA, Ebrahim SB, Davey Smith G |title=Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review |journal=BMJ |volume=332 |issue=7544 |pages=752–60 |year=2006 |pmid=16565093 |doi=10.1136/bmj.38755.366331.2F}}</ref> of [[randomized controlled trials]] by the international [[Cochrane Collaboration]] and a partially positive [[systematic review]]<ref name="pmid16825676">{{cite journal |author=Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J |title=n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review |journal=Am. J. Clin. Nutr. |volume=84 |issue=1 |pages=5–17 |year=2006 |pmid=16825676 |doi=}} http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1a.chapter.38290</ref> by the [[Agency for Healthcare Research and Quality]]. Since these two reviews, a [[randomized controlled trial]] reported a reduction on coronary events in Japanese hypercholesterolemic patients.<ref name="pmid17398308">{{cite journal |author=Yokoyama M, Origasa H, Matsuzaki M, ''et al'' |title=Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis |journal=Lancet |volume=369 |issue=9567 |pages=1090–8 |year=2007 |pmid=17398308 |doi=10.1016/S0140-6736(07)60527-3}}</ref> [[Omega 3|Omega-3]] fatty acids are also found in some plant sources including [[flax seed oil]], [[hemp seed oil]], and [[walnut]]s. Plant sources may be safer as fish products have been shown to contain heavy metals and other fat soluble pollutants. == Secondary prevention == Secondary prevention is preventing further sequelae of already established disease. Regarding coronary artery disease, this can mean risk factor management that is carried out during cardiac rehabilitation, a 4-phase process beginning in hospital after MI, angioplasty or heart surgery and continuing for a minimum of three months. Exercise is a main component of cardiac rehabilitation along with diet, smoking cessation, and blood pressure and cholesterol management. Beta blockers may also be used for this purpose.<ref>{{cite book |last=Awtry |first=Eric H. |coauthors=Joseph Loscalzo |title=Cecil Essentials of Medicine |pages=87-108 |chapter=Coronary Heart Disease |year=2004 |edition=6 |publisher=Saunders |location=Philadelphia, PA |isbn=978-0-7216-0147-2}}</ref> ====Anti-platelet therapy==== A [[meta-analysis]] of [[randomized controlled trials]] by the international [[Cochrane Collaboration]] found "that the use of clopidogrel plus aspirin is associated with a reduction in the risk of cardiovascular events compared with aspirin alone in patients with acute non-ST coronary syndrome. In patients at high risk of cardiovascular disease but not presenting acutely, there is only weak evidence of benefit and hazards of treatment almost match any benefit obtained.".<ref name="pmid17636787">{{cite journal |author=Keller T, Squizzato A, Middeldorp S |title=Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease |journal=Cochrane database of systematic reviews (Online) |volume= |issue=3 |pages=CD005158 |year=2007 |pmid=17636787 |doi=10.1002/14651858.CD005158.pub2}}</ref> == Therapy - Principles of Treatment == Therapeutic options for coronary artery disease<ref>Kasper, D.L., Braunwald, E., Fauci, A.S., Hauser, S.L., Longo, D.L., Jameson, J.L. (Eds.): Harrison's principles of internal medicine. 16th edition, McGraw-Hill, New York, 2005</ref> today are based on three principles: 1. Medical treatment - drugs (e.g. cholesterol lowering medications, beta-blockers, nitroglycerin, calcium antagonists, etc.); 2. Coronary interventions as [[angioplasty]] and stent-implantation; 3. Coronary artery bypass grafting (CABG - [[coronary artery bypass surgery]]). Recent research efforts focus on new angiogenic treatment modalities ([[angiogenesis]]) and various (adult) [[stem cell]] therapies. == Recent research == {{further|[[atheroma]] and [[atherosclerosis]]}} A 2006 study by the [[Cleveland Clinic]] found a region on Chromosome 17 was confined to families with multiple cases of myocardial infarction.<ref name="Farrall-2006">{{cite journal | author=Farrall M, Green FR, Peden JF, Olsson PG, Clarke R, Hellenius ML, Rust S, Lagercrantz J, Franzosi MG, Schulte H, Carey A, Olsson G, Assmann G, Tognoni G, Collins R, Hamsten A, Watkins H, on behalf of the PROCARDIS Consortium | title=Genome-Wide Mapping of Susceptibility to Coronary Artery Disease Identifies a Novel Replicated Locus on Chromosome 17 | journal=PLoS Genetics | year=2006 | volume=2 | issue=5 | pages=e72 | url=http://genetics.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pgen.0020072 | pmid=16710446 | doi=10.1371/journal.pgen.0020072}}</ref> A more controversial link is that between ''[[Chlamydophila pneumoniae]]'' infection and atherosclerosis.<ref name="Saikku-1992">{{cite journal | author=Saikku P, Leinonen M, Tenkanen L, Linnanmaki E, Ekman MR, Manninen V, Manttari M, Frick MH, Huttunen JK. | title=Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study | journal=Ann Intern Med | year=1992 | volume=116 | issue=4 | pages=273–8 | pmid=1733381}}</ref> While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor.{{Fact|date=February 2007}} Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.<ref name="Andraws-2005">{{cite journal | author=Andraws R, Berger JS, Brown DL. | title=Effects of antibiotic therapy on outcomes of patients with coronary artery disease: a meta-analysis of randomized controlled trials | journal=JAMA | year=2005 | volume=293 | issue=21 | pages=2641–7 | pmid=15928286 | doi=10.1001/jama.293.21.2641}}</ref> Since the 1990s the search for new treatment options for coronary artery disease patients, particularly for so called "no-option" coronary patients, focused on usage of [[angiogenesis]]<ref>{{cite journal |author=Simons M, Bonow RO, Chronos NA, ''et al'' |title=Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert panel summary |journal=Circulation |volume=102 |issue=11 |pages=E73–86 |year=2000 |month=September |pmid=10982554 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10982554}}</ref> and (adult) [[stem cell]] therapies. Numerous clinical trials were performed, either applying [[protein]] (angiogenic [[growth factor]]) therapies, such as [[FGF-1]] or [[VEGF]], or cell therapies using different kinds of adult [[stem cell]] populations. Research is still going on - with first promising results particularly for [[FGF-1]]<ref>Stegmann, T.J.: A human growth factor in the induction of neoangiogenesis. Exp.Opin.Invest.Drugs 7: 2011-2015, 1998</ref><ref>Wagoner, L.E., Merrill, W., Jacobs, J., Conway, G., Boehmer, J., Thomas, K., Stegmann, T.J.: Angiogenesis Protein Therapy With Human Fibroblast Growth Factor (FGF-1): Results Of A Phase I Open Label, Dose Escalation Study In Subjects With CAD Not Eligible For PCI Or CABG. Circulation 116: 443, 2007 </ref> and utilization of endothelial [[progenitor cells]]. ==References== {{reflist|2}} ==See also== *[[Diet and Heart Disease]] *[[ApoA-1 Milano]] *[[Endothelium-derived relaxing factor]] == External links == * [http://www.americanheart.org/presenter.jhtml?identifier=3003499 Risk Assessment of having a heart attack or dying of coronary artery disease], from the American Heart Association. * [http://www.invisionguide.com/heart The InVision Guide to a Healthy Heart] An interactive website on the development and function of the cardiovascular system and cardiovascular diseases and consequences. The website also features treatment options and preventative measures for maintaining a healthy heart. {{Circulatory system pathology}} [[Category:Aging-associated diseases]] [[Category:Cardiovascular diseases]] [[Category:Ischemic heart diseases]] {{Link FA|pt}} [[zh-min-nan:Koan-chōng tōng-me̍h sim-chōng-pēⁿ]] [[ca:Malaltia coronària]] [[de:Koronare Herzkrankheit]] [[el:Στεφανιαία καρδιακή νόσος]] [[es:Cardiopatía isquémica]] [[eu:Kardiopatia iskemiko]] [[fa:بیماری شریان‌های کرونری]] [[fr:Cardiopathie coronarienne]] [[it:Coronaropatia]] [[he:מחלת לב כלילית]] [[lv:Išēmiskā sirds slimība]] [[ms:Penyakit koronary jantung]] [[nl:Ischemische hartklachten]] [[pt:Aterosclerose coronariana]] [[qu:Sunqu sirk'a unquy]] [[simple:coronary heart disease]] [[sr:Коронарна болест срца]] [[fi:Sepelvaltimotauti]] [[vi:Bệnh tim mạch vành]] [[tr:Koroner arter hastalığı]]