Coronary artery disease (CAD) also known as atherosclerotic heart disease,coronary heart disease, or ischemic heart disease (IHD), is the most common type of heart disease and cause of heart attacks. The disease is caused by plaque building up along the inner walls of the arteries of the heart, which narrows the arteries and reduces blood flow to the heart.
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" heart attack, finally arises. Symptoms of stable ischaemic heart disease include angina (characteristic chest pain on exertion) and decreased exercise tolerance. Unstable IHD presents itself as chest pain or other symptoms at rest, or rapidly worsening angina. The risk of artery narrowing increases with age, smoking, high blood cholesterol, diabetes, high blood pressure, and is more common in men and those who have close relatives with CAD. Other causes include coronary vasospasm, a spasm of the blood vessels of the heart, it is usually called Prinzmetal's angina.
It was as of 2012 the most common cause of death in the world, and a major cause of hospital admissions. There is limited evidence for population screening, but prevention (with a healthy diet and sometimes medication for diabetes, cholesterol and high blood pressure) is used both to prevent IHD and to decrease the risk of complications.
Angina (chest pain) that occurs regularly with activity, after heavy meals, or at other predictable times is termed stable angina and is associated with high grade narrowings of the heartarteries. The symptoms of angina are often treated with betablocker therapy such as metoprolol or atenolol. Nitrate preparations such as 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 atheromatous disease, have been developed.
Angina that changes in intensity, character or frequency is termed unstable. Unstable angina may precede myocardial infarction. About 80% of chest pains have nothing to do with the heart.
Risk factors can be classified as: fixed (such as age, sex, family history) and modifiable (such as smoking, hypertension, diabetes mellitus, obesity, etc.)
There are various risk assessment systems for determining the risk of coronary artery disease, with various emphasis on different variables above. A notable example is Framingham Score, used in the Framingham Heart Study. It is mainly based on age, gender, diabetes, total cholesterol, HDL cholesterol, tobacco smoking and systolic blood pressure.
Job stress appears to play a minor role accounting for about 3% of cases. In one study, women who were free of stress from work life saw an increase in the diameter of their blood vessels, leading to decreased progression of atherosclerosis. Contrastingly, women who had high levels of work-related stress experienced a decrease in the diameter of their blood vessels and significantly increased disease progression. Also, having a type A behavior pattern, a group of personality characteristics including time urgency, competitiveness, hostility, and impatience  is linked to an increased risk of coronary disease.
Hemostatic factors: High levels of fibrinogen and coagulation factor VII are associated with an increased risk of CAD. Factor VII levels are higher in individuals with a high intake of dietary fat. Decreased fibrinolytic activity has been reported in patients with coronary atherosclerosis.
High levels of Lipoprotein(a), a compound formed when LDL cholesterol combines with a substance known as Apoliprotein (a).
Illustration depicting atherosclerosis in coronary artery.
Illustration depicting coronary artery disease
Limitation of blood flow to the heart causes ischemia (cell starvation secondary to a lack of oxygen) of the myocardial cells. Myocardial cells may die from lack of oxygen and this is called a myocardial infarction (commonly called a heart attack). It leads to heart muscle damage, heart muscle death and later myocardial scarring without heart muscle regrowth. Chronic high-grade stenosis of the coronary arteries can induce transient ischemia which leads to the induction of a ventricular arrhythmia, which may terminate into ventricular fibrillation leading to death.
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 "gunge" - including calcium deposits, fatty deposits, and abnormal inflammatory cells - to form a plaque. Deposits of calcium phosphates (hydroxyapatites) in the muscular layer of the blood vessels appear to play not only a significant role in stiffening arteries but also for the induction of an early phase of coronary arteriosclerosis. This can be seen in a so-called metastatic mechanism of calcification as it occurs in chronic kidney disease and haemodialysis (Rainer Liedtke 2008). Although these patients suffer from a kidney dysfunction, almost fifty percent of them die due to coronary artery disease. 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 plaques, 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.
For symptomatic patients, stress echocardiography can be used to make a diagnosis for obstructive coronary artery disease. The use of echocardiography is not recommended on individuals who are exhibiting no symptoms and are otherwise at low risk for developing coronary disease.
CAD has always been a tough disease to diagnose without the use of invasive or stressful activities. The development of the Multifunction Cardiogram (MCG) has changed the way CAD is diagnosed. The MCG consists of a 2 lead resting EKG signal is transformed into a mathematical model and compared against tens of thousands of clinical trials to diagnose a patient with an objective severity score, as well as secondary and tertiary results about the patients condition. The results from MCG tests have been validated in 8 clinical trials which resulted in a database of over 50,000 patients where the system has demonstrated accuracy comparable to coronary angiography (90% overall sensitivity, 85% specificity). This level of accuracy comes from the application of advanced techniques in signal processing and systems analysis combined with a large scale clinical database which allows MCG to provide quantitative, evidence-based results to assist physicians in reaching a diagnosis. The MCG has also been awarded a Category III CPT code by the American Medical Association in the July 2009 CPT update.
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:
The diagnosis of coronary disease underlying particular symptoms depends largely on the nature of the symptoms. The first investigation is an electrocardiogram (ECG/EKG), both for "stable" angina and acute coronary syndrome. An X-ray of the chest and blood tests may be performed.
Diagnosis of acute coronary syndrome generally takes place in the emergency department, where ECGs may be performed sequentially to identify "evolving changes" (indicating ongoing damage to the heart muscle). Diagnosis is clear-cut if ECGs show elevation of the "ST segment", which in the context of severe typical chest pain is strongly indicative of an acute myocardial infarction (MI); this is termed a STEMI (ST-elevation MI), and is treated as an emergency with either urgent coronary angiography and percutaneous coronary intervention (angioplasty with or without stent insertion) or with thrombolysis ("clot buster" medication), whichever is available. In the absence of ST-segment elevation, heart damage is detected by cardiac markers (blood tests that identify heart muscle damage). If there is evidence of damage (infarction), the chest pain is attributed to a "non-ST elevation MI" (NSTEMI). If there is no evidence of damage, the term "unstable angina" is used. This process usually necessitates admission to hospital, and close observation on a coronary care unit for possible complications (such as cardiac arrhythmias – irregularities in the heart rate).
Depending on the risk assessment, stress testing or angiography may be used to identify and treat coronary artery disease in patients who have had an NSTEMI or unstable angina.
In diabetes mellitus, there is little evidence that very tight blood sugar control improves cardiac risk although improved sugar control appears to decrease other problems like kidney failure and blindness. 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.
It has been suggested that coronary artery disease is partially reversible using an intense dietary regimen coupled with regular cardiovascular exercise. A high fiber diet appears to lower the risk.
Vegetarian diet: Vegetarians have been shown to have a 24% reduced risk of dying of heart disease.
Avoiding fats that are readily oxidized (e.g., trans-fats), and limiting carbohydrates and processed sugars may reduce low density lipoproteins, triacylglycerol and apolipoprotein-B thus decreasing the risk.
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.
There are three main treatment options for coronary artery disease:
Avoiding the consumption of trans fats (in hydrogenated oils)
Exercise Aerobic exercise, like walking, jogging, or swimming, can help decrease blood pressure and the amount of blood cholesterol(LDL) over time. It also increases HDL cholesterol which is considered as a " good cholesterol " 
In people with coronary artery disease, aerobic exercise can reduce the risk of mortality. Separate to the question of the benefits of exercise; it is unclear whether doctors should spend time counseling patients to exercise. The U.S. Preventive Services Task Force, 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. The American Heart Association, based on a non-systematic review, recommends that doctors counsel patients on exercise.
Statins, which reduce cholesterol, reduce risk of coronary disease 
In those with no other heart problems aspirin decreases the risk of a myocardial infarction in men but not women and increases the risk of bleeding, most of which is from the stomach. It does not affect the overall risk of death in either men or women. It is thus only recommended in adults who are at increased risk for coronary artery disease where increased risk is defined as 'men older than 90 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%'.
Clopidogrel plus aspirin reduces cardiovascular events more than aspirin alone in those with an STEMI. In others at high risk but not having an acute event the evidence is weak.
CAD as of 2010 was the leading cause of death globally resulting in over 7 million deaths. This is up from 5.2 million deaths in 1990. It may affect individuals at any age but becomes dramatically more common at progressively older ages, with approximately a tripling with each decade of life. Males are affected more often than females.
Coronary heart disease (CHD) is the leading cause of death for both men and women and accounts for approximately 600,000 deaths in the United States every year. 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. It is the most common reason for death of men and women over 20 years of age in the United States. The Maasai of Africa have almost no heart disease.
Recent research efforts focus on new angiogenic treatment modalities (angiogenesis) and various (adult) stem cell therapies.
A region on Chromosome 17 was confined to families with multiple cases of myocardial infarction.
A more controversial link is that between Chlamydophila pneumoniae infection and atherosclerosis. While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor. Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.
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 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 and utilization of endothelial progenitor cells.
^ abcFinegold JA, Asaria P, Francis DP (4 December 2012). "Mortality from ischaemic heart disease by country, region, and age: Statistics from World Health Organisation and United Nations". International journal of cardiology168 (2): 934–45. doi:10.1016/j.ijcard.2012.10.046. PMID23218570.
^World Health Organization Department of Health Statistics and Informatics in the Information, Evidence and Research Cluster (2004). The global burden of disease 2004 update. Geneva: WHO. ISBN92-4-156371-0.
Douglas PS, Garcia MJ, Haines DE, Lai WW, Manning WJ, Patel AR, Picard MH, Polk DM, Ragosta M, Ward RP, Weiner RB (2011). "ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 Appropriate Use Criteria for Echocardiography". Journal of the American College of Cardiology57 (9): 1126–1166. doi:10.1016/j.jacc.2010.11.002. PMID21349406.
Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS, Ferguson TB, Fihn SD, Fraker TD, Gardin JM, O'Rourke RA, Pasternak RC, Williams SV (2003). "ACC/AHA 2002 guideline update for the management of patients with chronic stable angina—summary article". Journal of the American College of Cardiology41 (1): 159–168. doi:10.1016/S0735-1097(02)02848-6. PMID12570960.
Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA, Foster E, Hlatky MA, Hodgson JM, Kushner FG, Lauer MS, Shaw LJ, Smith SC, Taylor AJ, Weintraub WS, Wenger NK, Jacobs AK, Smith SC, Anderson JL, Albert N, Buller CE, Creager MA, Ettinger SM, Guyton RA, Halperin JL, Hochman JS, Kushner FG, Nishimura R, Ohman EM, Page RL, Stevenson WG, Tarkington LG, Yancy CW (2010). "2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults". Journal of the American College of Cardiology56 (25): e50–103. doi:10.1016/j.jacc.2010.09.001. PMID21144964.
^Naci, H.; Ioannidis, J. P. A. (1 October 2013). "Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study". BMJ347 (oct01 1): f5577–f5577. doi:10.1136/bmj.f5577.
^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 (1998). "Mortality in vegetarians and non-vegetarians: a collaborative analysis of 8300 deaths among 76,000 men and women in five prospective studies". Public Health Nutr1 (1): 33–41. doi:10.1079/PHN19980006. PMID10555529.
^Willett WC, Sacks F, Trichopoulou A, Drescher G, Ferro-Luzzi A, Helsing E, Trichopoulos D (1995). "Mediterranean diet pyramid: a cultural model for healthy eating". Am J Clin Nutr61 (6 Suppl): 1402S–1406S. PMID7754995.
^Lopez-Garcia E, Schulze MB, Meigs JB, Manson JE, Rifai N, Stampfer MJ, Willett WC, Hu FB (2005). "Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction". J Nutr135 (3): 562–6. PMID15735094.
^Mozaffarian D, Katan MB, Ascherio A, Stampfer MJ, Willett WC (April 2006). "Trans fatty acids and cardiovascular disease". N. Engl. J. Med.354 (15): 1601–13. doi:10.1056/NEJMra054035. PMID16611951.
^Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS (September 2012). "Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events A Systematic Review and Meta-analysis". JAMA308 (10): 1024–1033. doi:10.1001/2012.jama.11374. PMID22968891.
^Kwak SM, Myung SK, Lee YJ, Seo HG (2012-04-09). "Efficacy of Omega-3 Fatty Acid Supplements (Eicosapentaenoic Acid and Docosahexaenoic Acid) in the Secondary Prevention of Cardiovascular Disease: A Meta-analysis of Randomized, Double-blind, Placebo-Controlled Trials". Archives of Internal Medicine172 (9): 686–94. doi:10.1001/archinternmed.2012.262. PMID22493407.
^Gutierrez J, Ramirez G, Rundek T, Sacco RL (25 June 2012). "Statin therapy in the prevention of recurrent cardiovascular events: a sex-based meta-analysis". Archives of Internal Medicine172 (12): 909–19. doi:10.1001/archinternmed.2012.2145. PMID22732744.
^Wolff T, Miller T, Ko S (17 March 2009). "Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S. Preventive Services Task Force". Annals of internal medicine150 (6): 405–10. doi:10.7326/0003-4819-150-6-200903170-00009. PMID19293073.
^Keller TT, Squizzato A, Middeldorp S (2007). "Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease". In Squizzato, Alessandro. Cochrane database of systematic reviews (Online) (3): CD005158. doi:10.1002/14651858.CD005158.pub2. PMID17636787.
^Stergiopoulos K, Boden WE, Hartigan P, Möbius-Winkler S, Hambrecht R, Hueb W, Hardison RM, Abbott JD, Brown DL (2014). "Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: a collaborative meta-analysis of contemporary randomized clinical trials". JAMA Intern Med174 (2): 232–40. doi:10.1001/jamainternmed.2013.12855. PMID24296791.
^Sipahi I, Akay MH, Dagdelen S, Blitz A, Alhan C (2014). "Coronary artery bypass grafting vs percutaneous coronary intervention and long-term mortality and morbidity in multivessel disease: meta-analysis of randomized clinical trials of the arterial grafting and stenting era". JAMA Intern Med174 (2): 223–30. doi:10.1001/jamainternmed.2013.12844. PMID24296767.
^Sipahi I, Akay MH, Dagdelen S, Blitz A, Alhan C (Feb 1, 2014). "Coronary artery bypass grafting vs percutaneous coronary intervention and long-term mortality and morbidity in multivessel disease: meta-analysis of randomized clinical trials of the arterial grafting and stenting era.". JAMA internal medicine174 (2): 223–30. doi:10.1001/jamainternmed.2013.12844. PMID24296767.
^ abLozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, et al. (15 December 2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. PMID23245604.
^Saikku P, Leinonen M, Tenkanen L, Linnanmäki E, Ekman MR, Manninen V, Mänttäri M, Frick MH, Huttunen JK (1992). "Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study". Ann Intern Med116 (4): 273–8. doi:10.7326/0003-4819-116-4-273. PMID1733381.
^Andraws R, Berger JS, Brown DL (2005). "Effects of antibiotic therapy on outcomes of patients with coronary artery disease: a meta-analysis of randomized controlled trials". JAMA293 (21): 2641–7. doi:10.1001/jama.293.21.2641. PMID15928286.
^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
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.