Coronary artery disease

Coronary artery disease
File:Blausen 0257 CoronaryArtery Plaque.png
Illustration depicting atherosclerosis in a coronary artery.
Classification and external resources
ICD-10 I20-I25
ICD-9 410-414, 429.2
MedlinePlus 007115
eMedicine radio/192
NCI Coronary artery disease
Patient UK Coronary artery disease
MeSH D003324

Coronary artery disease (CAD), also known as ischemic heart disease (IHD),[1] atherosclerotic heart disease,[2] atherosclerotic cardiovascular disease,[3] and coronary heart disease,[4] is a group of diseases that includes: stable angina, unstable angina, myocardial infarction, and sudden coronary death.[5] It is within the group of cardiovascular diseases of which it is the most common type.[6] A common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw.[7] Occasionally it may feel like heartburn.[7] Usually symptoms occur with exercise or emotional stress, last less than a few minutes, and gets better with rest.[7] Shortness of breath may also occur and sometimes no symptoms are present.[7] The first sign is occasionally a heart attack.[8] Other complications include heart failure or an irregular heartbeat.[8]

Risk factors include: high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, and excessive alcohol, among others.[9][10] Other risks include depression.[11] The underlying mechanism involves atherosclerosis of the arteries of the heart.[10] A number of tests may help with diagnoses including: electrocardiogram, cardiac stress testing, and coronary angiogram among others.[12]

Prevention is by eating a healthy diet, regular exercise, maintaining a healthy weight and not smoking.[13] Sometimes medication for diabetes, high cholesterol, or high blood pressure are also used.[13] There is limited evidence for screening people who are at low risk and do not have symptoms.[14] Treatment involves the same measures as prevention.[15][16] Additional medications such as aspirin, beta blockers, or nitrogylcerin may be recommended.[16] Procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) may be used in severe disease.[16][17] In those with stable CAD it is unclear if PCI or CABG in addition to the other treatments improve life expectancy or decreases heart attack risk.[18]

In 2013 CAD was the most common cause of death globally, resulting in 8.14 million deaths (16.8%) up from 5.74 million deaths (12%) in 1990.[6] The risk of death from CAD for a given age has decreased between 1980 and 2010 especially in the developed world.[19] The number of cases of CAD for a given age has also decreased between 1990 and 2010.[20] In the United States in 2010 about 20% of those over 65 had CAD, while it was present in 7% of those 45 to 64, and 1.3% of those 18 to 45.[21] Rates are higher among men than women of a given age.[21]

Signs and symptoms

Chest pain that occurs regularly with activity, after eating, or at other predictable times is termed stable angina and is associated with narrowings of the arteries of the heart.

Angina that changes in intensity, character or frequency is termed unstable. Unstable angina may precede myocardial infarction. In adults who go to the emergency with an unclear cause of pain, about 30% have pain due to coronary artery disease.[22]

Risk factors

Coronary artery disease has a number of well determined risk factors. The most common risk factors include smoking, family history, hypertension, obesity, diabetes, lack of exercise, stress, and high blood lipids.[23] Smoking is associated with about 36% of cases and obesity 20%.[24] Lack of exercise has been linked to 7–12% of cases.[24][25]

Job stress appears to play a minor role accounting for about 3% of cases.[24] 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.[26] 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.[26] Also, having a type A behavior pattern, a group of personality characteristics including time urgency, competitiveness, hostility, and impatience[27] is linked to an increased risk of coronary disease.[28]

Risk factors can be classified as: fixed (such as age, sex, family history) and modifiable (such as smoking, hypertension, diabetes mellitus, obesity, etc.)

Blood fats

Dietary cholesterol does not appear to have a significant effect on blood cholesterol and thus recommendations about its consumption may not be needed.[34]


  • Type A personality.Type A behaviour is associated with competitive drive, restlessness,hostility & a sense of impatience. 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 as any other personality type (very controversial due to tobacco industry funding of these researches).[citation needed]
  • Hemostatic factors:[35] 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[citation needed]. Decreased fibrinolytic activity has been reported in patients with coronary atherosclerosis.
  • Low hemoglobin[36]* Men over 45; Women over 55[37]


File:RCA atherosclerosis.jpg
Micrograph of a coronary artery with the most common form of coronary artery disease (atherosclerosis) and marked luminal narrowing. Masson's trichrome.
File:Blausen 0259 CoronaryArteryDisease 02.png
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 calciphylaxis 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.[38]

No one knows exactly what causes cardiac syndrome X. One explanation is microvascular dysfunction.[39] It is not completely clear why women are more likely than men to have it; however, hormones and other risk factors unique to women may play a role.[40]


File:Coro Man.jpg
Coronary angiogram of a man
File:Coro Woman.jpg
Coronary angiogram of a woman

For symptomatic patients, stress echocardiography can be used to make a diagnosis for obstructive coronary artery disease.[41] The use of echocardiography, stress cardiac imaging, and/or advanced non-invasive imaging is not recommended on individuals who are exhibiting no symptoms and are otherwise at low risk for developing coronary disease.[41][42]

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 patient's condition. The results from MCG tests have been validated in 8 clinical trials[citation needed] 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[citation needed].

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.

Stable angina

Main article: Angina pectoris

In "stable" angina, chest pain with typical features occurring at predictable levels of exertion, various forms of cardiac stress tests may be used to induce both symptoms and detect changes by way of electrocardiography (using an ECG), echocardiography (using ultrasound of the heart) or scintigraphy (using uptake of radionuclide by the heart muscle). If part of the heart seems to receive an insufficient blood supply, coronary angiography may be used to identify stenosis of the coronary arteries and suitability for angioplasty or bypass surgery.

Acute coronary syndrome

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.

Risk assessment

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.[43]


Prevention involves: exercise, decreasing obesity, treating hypertension, a healthy diet, decreasing cholesterol levels, and stopping smoking. Medications and exercise are roughly equally effective.[44]

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.[45]


A diet high in fruits and vegetables decreases the risk of cardiovascular disease and death.[46] Vegetarians have a lower risk of heart disease,[47][48] possibly due to their greater consumption of fruits and vegetables.[49] Evidence also suggests that the Mediterranean diet[50] and a high fiber diet lower the risk.[51]

The consumption of trans fat (commonly found in hydrogenated products such as margarine) has been shown to cause a precursor to atherosclerosis[52] and increase the risk of coronary artery disease.[53]

Evidence does not support a beneficial role for omega-3 fatty acid supplementation in preventing cardiovascular disease (including myocardial infarction and sudden cardiac death).[54][55] There is tentative evidence that menaquinone (Vitamin K2), but not phylloquinone (Vitamin K1), intake may reduce the risk of CAD mortality.[56]

Secondary prevention

Secondary prevention is preventing further sequelae of already established disease. Lifestyle changes that have been shown to be effective to this goal include:

  • Weight control
  • Smoking cessation
  • Avoiding the consumption of trans fats (in partially hydrogenated oils)
  • Exercise. In people with coronary artery disease, aerobic exercise, like walking, jogging, or swimming, can reduce the risk of mortality.[57] Aerobic exercise can help decrease blood pressure and the amount of blood cholesterol (LDL) over time. It also increases HDL cholesterol which is considered as "good cholesterol".[58][59] 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.[60] The American Heart Association, based on a non-systematic review, recommends that doctors counsel patients on exercise.[61]


There are a number of treatment options for coronary artery disease:[63]

  1. Lifestyle changes
  2. Medical treatment - drugs (e.g. cholesterol lowering medications, beta-blockers, nitroglycerin, calcium antagonists, etc.);
  3. Coronary interventions as angioplasty and coronary stent;
  4. Coronary artery bypass grafting (CABG)


It is recommended that blood pressure typically be reduced to less than 140/90 mmHg.[65] The diastolic blood pressure however should not be lower than 60 mmHg. Beta blockers are recommended first line for this use.[65]


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.[66] It is thus only recommended in adults who are at increased risk for coronary artery disease[67] 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%'.[citation needed]

Anti-platelet therapy

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.[68] In those who have had a stent more than 12 months of clopidogrel plus aspirin does not affect the risk of death.[69]


Revascularization for acute coronary syndrome has a mortality benefit.[70] Revascularization for stable ischaemic heart disease does not appear to have benefits over medical therapy alone.[71] In those with disease in more than one artery coronary artery bypass grafts appear better than percutaneous coronary interventions.[72][73]


File:Ischaemic heart disease world map - DALY - WHO2004.svg
Disability-adjusted life year for ischaemic heart disease per 100,000 inhabitants in 2004.[74]
  no data

CAD as of 2010 was the leading cause of death globally resulting in over 7 million deaths.[75] This is up from 5.2 million deaths in 1990.[75] 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.[76] Males are affected more often than females.[76]

It is estimated that 60% of the world's cardiovascular disease burden will occur in the South Asian subcontinent despite only accounting for 20% of the world's population. This may be secondary to a combination of genetic predisposition and environmental factors. Organizations such as the Indian Heart Association are working with the World Heart Federation to raise awareness about this issue.[77]

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.[78] According to present trends in the United States, half of healthy 40-year-old men will develop CAD in the future, and one in three healthy 40-year-old women.[79] It is the most common reason for death of men and women over 20 years of age in the United States.[80] The Maasai of Africa have almost no heart disease.

Society and culture

Other terms sometimes used for this condition are "hardening of the arteries" and "narrowing of the arteries".[81]


Further information: atheroma and atherosclerosis

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.[82]

A more controversial link is that between Chlamydophila pneumoniae infection and atherosclerosis.[83] While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor.[citation needed] Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.[84]

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[85] 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[86][87] and utilization of endothelial progenitor cells.

Myeloperoxidase has been proposed as a biomarker.[88]


  1. ^ Bhatia, Sujata K. (2010). Biomaterials for clinical applications (Online-Ausg. ed.). New York: Springer. p. 23. ISBN 9781441969200. 
  2. ^ "Coronary heart disease - causes, symptoms, prevention". Southern Cross Healthcare Group. Retrieved 15 September 2013. 
  3. ^ Faxon, D. P. (1 June 2004). "Atherosclerotic Vascular Disease Conference: Executive Summary: Atherosclerotic Vascular Disease Conference Proceeding for Healthcare Professionals From a Special Writing Group of the American Heart Association". Circulation 109 (21): 2595–2604. doi:10.1161/01.CIR.0000128517.52533.DB. 
  4. ^ "Coronary heart disease". ADAM. Retrieved 15 September 2013. 
  5. ^ Wong, ND (May 2014). "Epidemiological studies of CHD and the evolution of preventive cardiology.". Nature reviews. Cardiology 11 (5): 276–89. PMID 24663092. doi:10.1038/nrcardio.2014.26. 
  6. ^ a b GBD 2013 Mortality and Causes of Death, Collaborators (17 December 2014). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.". Lancet 385: 117–171. PMC 4340604. PMID 25530442. doi:10.1016/S0140-6736(14)61682-2. 
  7. ^ a b c d "What Are the Signs and Symptoms of Coronary Heart Disease?". September 29, 2014. Retrieved 23 February 2015. 
  8. ^ a b "Coronary Artery Disease (CAD)". March 12, 2013. Retrieved 23 February 2015. 
  9. ^ Mehta, PK; Wei, J; Wenger, NK (16 October 2014). "Ischemic heart disease in women: A focus on risk factors.". Trends in Cardiovascular Medicine 25: 140–151. PMID 25453985. doi:10.1016/j.tcm.2014.10.005. 
  10. ^ a b Mendis, Shanthi; Puska, Pekka; Norrving, Bo (2011). Global atlas on cardiovascular disease prevention and control (PDF) (1st ed. ed.). Geneva: World Health Organization in collaboration with the World Heart Federation and the World Stroke Organization. pp. 3–18. ISBN 9789241564373. 
  11. ^ Charlson, FJ; Moran, AE; Freedman, G; Norman, RE; Stapelberg, NJ; Baxter, AJ; Vos, T; Whiteford, HA (26 November 2013). "The contribution of major depression to the global burden of ischemic heart disease: a comparative risk assessment.". BMC medicine 11: 250. PMID 24274053. doi:10.1186/1741-7015-11-250. 
  12. ^ "How Is Coronary Heart Disease Diagnosed?". September 29, 2014. Retrieved 25 February 2015. 
  13. ^ a b "How Can Coronary Heart Disease Be Prevented or Delayed?". Retrieved 25 February 2015. 
  14. ^ Desai, CS; Blumenthal, RS; Greenland, P (April 2014). "Screening low-risk individuals for coronary artery disease.". Current atherosclerosis reports 16 (4): 402. PMID 24522859. doi:10.1007/s11883-014-0402-8. 
  15. ^ Boden, WE; Franklin, B; Berra, K; Haskell, WL; Calfas, KJ; Zimmerman, FH; Wenger, NK (October 2014). "Exercise as a therapeutic intervention in patients with stable ischemic heart disease: an underfilled prescription.". The American Journal of Medicine 127 (10): 905–11. PMID 24844736. doi:10.1016/j.amjmed.2014.05.007. 
  16. ^ a b c "How Is Coronary Heart Disease Treated?". September 29, 2014. Retrieved 25 February 2015. 
  17. ^ Deb, S; Wijeysundera, HC; Ko, DT; Tsubota, H; Hill, S; Fremes, SE (20 November 2013). "Coronary artery bypass graft surgery vs percutaneous interventions in coronary revascularization: a systematic review.". JAMA 310 (19): 2086–95. PMID 24240936. doi:10.1001/jama.2013.281718. 
  18. ^ Rezende, PC; Scudeler, TL; da Costa, LM; Hueb, W (16 February 2015). "Conservative strategy for treatment of stable coronary artery disease.". World journal of clinical cases 3 (2): 163–70. PMID 25685763. doi:10.12998/wjcc.v3.i2.163. 
  19. ^ Moran, AE; Forouzanfar, MH; Roth, GA; Mensah, GA; Ezzati, M; Murray, CJ; Naghavi, M (8 April 2014). "Temporal trends in ischemic heart disease mortality in 21 world regions, 1980 to 2010: the Global Burden of Disease 2010 study.". Circulation 129 (14): 1483–92. PMID 24573352. doi:10.1161/circulationaha.113.004042. 
  20. ^ Moran, AE; Forouzanfar, MH; Roth, GA; Mensah, GA; Ezzati, M; Flaxman, A; Murray, CJ; Naghavi, M (8 April 2014). "The global burden of ischemic heart disease in 1990 and 2010: the Global Burden of Disease 2010 study.". Circulation 129 (14): 1493–501. PMID 24573351. doi:10.1161/circulationaha.113.004046. 
  21. ^ a b Centers for Disease Control and Prevention, (CDC) (14 October 2011). "Prevalence of coronary heart disease--United States, 2006-2010.". MMWR. Morbidity and mortality weekly report 60 (40): 1377–81. PMID 21993341. 
  22. ^ Kontos, MC; Diercks, DB; Kirk, JD (Mar 2010). "Emergency department and office-based evaluation of patients with chest pain.". Mayo Clinic proceedings 85 (3): 284–99. PMID 20194155. doi:10.4065/mcp.2009.0560. 
  23. ^ "Causes". Coronary artery disease. Mayo Foundation for Medical Education and Research. 29 June 2012. DS00064. 
  24. ^ a b c Kivimäki M, Nyberg ST, Batty GD, Fransson EI, Heikkilä K, Alfredsson L, Bjorner JB, Borritz M, Burr H, Casini A, Clays E, De Bacquer D, Dragano N, Ferrie JE, Geuskens GA, Goldberg M, Hamer M, Hooftman WE, Houtman IL, Joensuu M, Jokela M, Kittel F, Knutsson A, Koskenvuo M, Koskinen A, Kouvonen A, Kumari M, Madsen IE, Marmot MG, Nielsen ML, Nordin M, Oksanen T, Pentti J, Rugulies R, Salo P, Siegrist J, Singh-Manoux A, Suominen SB, Väänänen A, Vahtera J, Virtanen M, Westerholm PJ, Westerlund H, Zins M, Steptoe A, Theorell T (October 2012). "Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data". Lancet 380 (9852): 1491–7. PMC 3486012. PMID 22981903. doi:10.1016/S0140-6736(12)60994-5. 
  25. ^ Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT (July 2012). "Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy". Lancet 380 (9838): 219–29. PMC 3645500. PMID 22818936. doi:10.1016/S0140-6736(12)61031-9. 
  26. ^ a b Wang HX, Leineweber C, Kirkeeide R, Svane B, Schenck-Gustafsson K, Theorell T, Orth-Gomér K (March 2007). "Psychosocial stress and atherosclerosis: family and work stress accelerate progression of coronary disease in women. The Stockholm Female Coronary Angiography Study". J. Intern. Med. 261 (3): 245–54. PMID 17305647. doi:10.1111/j.1365-2796.2006.01759.x. 
  27. ^ Andreassi, John L. (2000). Psychophysiology : human behavior and physiological response. Mahwah NJ: L. Erlbaum. p. 287. 
  28. ^ McCann S.J.H. (November 2001). "The precocity-longevity hypothesis: earlier peaks in career achievement predict shorter lives". Pers Soc Psychol Bull 27 (11): 1429–39. doi:10.1177/01461672012711004. 
    Rhodewalt; Smith (1991). "Current issues in Type A behaviour, coronary proneness, and coronary heart disease". In Snyder, C.R.; Forsyth, D.R. Handbook of social and clinical psychology: the health perspective. New York: Pergamon. pp. 197–220. ISBN 0080361285. 
  29. ^ Underwood and Cross, James, (2009). General ans Systematic Pathology. London: Churchhill livingstone. p. 279. 
  30. ^ Kannel, WB; Vasan, RS (Jul 2009). "Triglycerides as vascular risk factors: new epidemiologic insights.". Current opinion in cardiology 24 (4): 345–50. PMC 3012388. PMID 19424059. doi:10.1097/HCO.0b013e32832c1284. 
  31. ^ Danesh J, Collins R, Peto R (2000). "Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies". Circulation 102 (10): 1082–5. PMID 10973834. doi:10.1161/01.CIR.102.10.1082. 
  32. ^ Smolders B, Lemmens R, Thijs V (2007). "Lipoprotein (a) and stroke: a meta-analysis of observational studies". Stroke 38 (6): 1959–66. PMID 17478739. doi:10.1161/STROKEAHA.106.480657. 
  33. ^ Schreiner PJ, Morrisett JD, Sharrett AR, Patsch W, Tyroler HA, Wu K, Heiss G (1993). "Lipoprotein(a) as a risk factor for preclinical atherosclerosis" (PDF). Arterioscler. Thromb. 13 (6): 826–33. PMID 8499402. doi:10.1161/01.ATV.13.6.826. 
  34. ^ "Scientific Report of the 2015 Dietary Guidelines Advisory COmmittee" (PDF). Feb 2015. p. 17. 
  35. ^ Smith FB, Lee AJ, Fowkes FG, Price JF, Rumley A, Lowe GD (November 1997). "Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study". Arterioscler Thromb Vasc Biol. 17 (11): 3321–5. PMID 9409328. doi:10.1161/01.ATV.17.11.3321. 
  36. ^ Padmanaban P, Toora BD. Hemoglobin: Emerging marker in stable coronary artery disease. Chron Young Sci [serial online] 2011 [cited 2011 Jul 24];2:109-10. Available from:
  37. ^ "Women and heart disease | Health News | Find Articles at BNET". [dead link]
  38. ^ Lanza GA (February 2007). "Cardiac syndrome X: a critical overview and future perspectives". Heart 93 (2): 159–66. PMC 1861371. PMID 16399854. doi:10.1136/hrt.2005.067330. 
  39. ^ Jones E, Eteiba W, Merz NB (August 2012). "Cardiac syndrome X and microvascular coronary dysfunction". Trends in Cardiovascular Medicine 22 (6): 161–8. PMC 3490207. PMID 23026403. doi:10.1016/j.tcm.2012.07.014. 
  40. ^ Kaski JC (February 2004). "Pathophysiology and management of patients with chest pain and normal coronary arteriograms (cardiac syndrome X)". Circulation 109 (5): 568–72. PMID 14769677. doi:10.1161/01.CIR.0000116601.58103.62. 
  41. ^ a b American Society of Echocardiography. "Five Things Physicians and Patients Should Question". Choosing Wisely: an initiative of the ABIM Foundation (American Society of Echocardiography). Retrieved 27 February 2013 , citing
    • 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 Cardiology 57 (9): 1126–1166. PMID 21349406. doi:10.1016/j.jacc.2010.11.002. 
    • 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 Cardiology 41 (1): 159–168. PMID 12570960. doi:10.1016/S0735-1097(02)02848-6. 
    • 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 Cardiology 56 (25): e50–103. PMID 21144964. doi:10.1016/j.jacc.2010.09.001. 
  42. ^ American College of Cardiology (September 2013), "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation (American College of Cardiology), retrieved 10 February 2014 
  43. ^ > Coronary Heart Disease (10-year risk)(based on Wilson, D'Agostino, Levy et al. 'Prediction of Coronary Heart Disease using Risk Factor Categories', Circulation 1998)
  44. ^ Naci, H.; Ioannidis, J. P. A. (1 October 2013). "Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study". BMJ 347 (oct01 1): f5577–f5577. doi:10.1136/bmj.f5577. 
  45. ^ "5. Population nutrient intake goals for preventing diet-related chronic diseases". WHO. 
  46. ^ Wang, X; Ouyang, Y; Liu, J; Zhu, M; Zhao, G; Bao, W; Hu, FB (Jul 29, 2014). "Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies.". BMJ (Clinical research ed.) 349: g4490. PMID 25073782. doi:10.1136/bmj.g4490. 
  47. ^ Li, D (30 January 2014). "Effect of the vegetarian diet on non-communicable diseases.". Journal of the science of food and agriculture 94 (2): 169–73. PMID 23965907. doi:10.1002/jsfa.6362. 
  48. ^ Huang, T; Yang, B; Zheng, J; Li, G; Wahlqvist, ML; Li, D (2012). "Cardiovascular disease mortality and cancer incidence in vegetarians: a meta-analysis and systematic review.". Annals of nutrition & metabolism 60 (4): 233–40. PMID 22677895. doi:10.1159/000337301. 
  49. ^ Ginter, E (2008). "Vegetarian diets, chronic diseases and longevity.". Bratislavske lekarske listy 109 (10): 463–6. PMID 19166134. 
  50. ^ Walker C, Reamy BV (April 2009). "Diets for cardiovascular disease prevention: what is the evidence?". Am Fam Physician 79 (7): 571–8. PMID 19378874. 
  51. ^ Threapleton DE, Greenwood DC, Evans CE, Cleghorn CL, Nykjaer C, Woodhead C, Cade JE, Gale CP, Burley VJ (2013). "Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis". BMJ 347: f6879. PMC 3898422. PMID 24355537. doi:10.1136/bmj.f6879. 
  52. ^ 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 Nutr 135 (3): 562–6. PMID 15735094. 
  53. ^ 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. PMID 16611951. doi:10.1056/NEJMra054035. 
  54. ^ 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". JAMA 308 (10): 1024–1033. PMID 22968891. doi:10.1001/2012.jama.11374. 
  55. ^ 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 Medicine 172 (9): 686–94. PMID 22493407. doi:10.1001/archinternmed.2012.262. 
  56. ^ Erkkilä AT, Booth SL (2008). "Vitamin K intake and atherosclerosis". Curr. Opin. Lipidol. 19 (1): 39–42. PMID 18196985. doi:10.1097/MOL.0b013e3282f1c57f. 
  57. ^ Swardfager W, Herrmann N, Cornish S, Mazereeuw G, Marzolini S, Sham L, Lanctôt KL (2012). "Exercise intervention and inflammatory markers in coronary artery disease: a meta-analysis". Am Heart J 163 (4): 666–676. PMID 22520533. doi:10.1016/j.ahj.2011.12.017. 
  58. ^
  59. ^ "Coronary Heart Disease (CHD)". Penguin Dictionary of Biology. 2004. 
  60. ^ "Behavioral counseling in primary care to promote physical activity: recommendation and rationale". Ann. Intern. Med. 137 (3): 205–7. 2002. PMID 12160370. doi:10.7326/0003-4819-137-3-200208060-00014. 
  61. ^ Thompson PD, Buchner D, Pina IL, Balady GJ, Williams MA, Marcus BH, Berra K, Blair SN, Costa F, Franklin B, Fletcher GF, Gordon NF, Pate RR, Rodriguez BL, Yancey AK, Wenger NK (2003). "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)". Circulation 107 (24): 3109–16. PMID 12821592. doi:10.1161/01.CIR.0000075572.40158.77. 
    Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease. Major Recommendations
  62. ^ Linden W, Stossel C, Maurice J (April 1996). "Psychosocial interventions for patients with coronary artery disease: a meta-analysis". Arch. Intern. Med. 156 (7): 745–52. PMID 8615707. doi:10.1001/archinte.1996.00440070065008. 
  63. ^ Jameson JN, Kasper DL, Harrison TR, Braunwald E, Fauci AS, Hauser SL, Longo DL. (2005). Harrison's principles of internal medicine (16th ed.). New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-140235-7. OCLC 54501403. 
  64. ^ 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 Medicine 172 (12): 909–19. PMID 22732744. doi:10.1001/archinternmed.2012.2145. 
  65. ^ a b Rosendorff, C; Lackland, DT; Allison, M; Aronow, WS; Black, HR; Blumenthal, RS; Cannon, CP; de Lemos, JA; Elliott, WJ; Findeiss, L; Gersh, BJ; Gore, JM; Levy, D; Long, JB; O'Connor, CM; O'Gara, PT; Ogedegbe, O; Oparil, S; White, WB (31 March 2015). "Treatment of Hypertension in Patients With Coronary Artery Disease: A Scientific Statement From the American Heart Association, American College of Cardiology, and American Society of Hypertension.". Circulation. PMID 25829340. 
  66. ^ 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 medicine 150 (6): 405–10. PMID 19293073. doi:10.7326/0003-4819-150-6-200903170-00009. 
  67. ^ U.S. Preventive Services Task Force*, (15 January 2002). "Aspirin for the primary prevention of cardiovascular events: recommendation and rationale". Ann Intern Med 136 (2): 157–60. PMID 11790071. doi:10.7326/0003-4819-136-2-200201150-00015. 
  68. ^ Keller TT, Squizzato A, Middeldorp S (2007). Squizzato, Alessandro, ed. "Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease". Cochrane database of systematic reviews (Online) (3): CD005158. PMID 17636787. doi:10.1002/14651858.CD005158.pub2. 
  69. ^ Elmariah, Sammy; Mauri, Laura; Doros, Gheorghe; Galper, Benjamin Z; O'Neill, Kelly E; Steg, Philippe Gabriel; Kereiakes, Dean J; Yeh, Robert W (November 2014). "Extended duration dual antiplatelet therapy and mortality: a systematic review and meta-analysis". The Lancet 385: 792–798. doi:10.1016/S0140-6736(14)62052-3. 
  70. ^ Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE, Steward DE, Theroux P, Gibbons RJ, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Smith SC (October 2002). "ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina)". Circulation 106 (14): 1893–900. PMID 12356647. doi:10.1161/01.CIR.0000037106.76139.53. 
  71. ^ 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 Med 174 (2): 232–40. PMID 24296791. doi:10.1001/jamainternmed.2013.12855. 
  72. ^ 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 Med 174 (2): 223–30. PMID 24296767. doi:10.1001/jamainternmed.2013.12844. 
  73. ^ 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 medicine 174 (2): 223–30. PMID 24296767. doi:10.1001/jamainternmed.2013.12844. 
  74. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. Retrieved 11 November 2009. 
  75. ^ a b Lozano 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". Lancet 380 (9859): 2095–128. PMID 23245604. doi:10.1016/S0140-6736(12)61728-0. 
  76. ^ a b Finegold 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 cardiology 168 (2): 934–45. PMID 23218570. doi:10.1016/j.ijcard.2012.10.046. 
  77. ^ Indian Heart Association Why South Asians Facts Web. 29 April 2015. <>
  78. ^ "Kochanek KD, Xu JQ, Murphy SL, Miniño AM, Kung HC." (PDF). Retrieved 25 March 2013. 
  79. ^ Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y (February 2007). "Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee". Circulation 115 (5): e69–171. PMID 17194875. doi:10.1161/CIRCULATIONAHA.106.179918. 
  80. ^ American Heart Association:Heart Disease and Stroke Statistics-2007 Update. AHA, Dallas, Texas, 2007
  81. ^ "Other Names for Coronary Heart Disease". September 29, 2014. Retrieved 23 February 2015. 
  82. ^ 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 (2006). "Genome-Wide Mapping of Susceptibility to Coronary Artery Disease Identifies a Novel Replicated Locus on Chromosome 17". PLoS Genetics 2 (5): e72. PMC 1463045. PMID 16710446. doi:10.1371/journal.pgen.0020072. 
  83. ^ 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 Med 116 (4): 273–8. PMID 1733381. doi:10.7326/0003-4819-116-4-273. 
  84. ^ 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". JAMA 293 (21): 2641–7. PMID 15928286. doi:10.1001/jama.293.21.2641. 
  85. ^ Simons M, Bonow RO, Chronos NA, Cohen DJ, Giordano FJ, Hammond HK, Laham RJ, Li W, Pike M, Sellke FW, Stegmann TJ, Udelson JE, Rosengart TK (September 2000). "Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert panel summary". Circulation 102 (11): E73–86. PMID 10982554. doi:10.1161/01.CIR.102.11.e73. 
  86. ^ Stegmann TJ (December 1998). "FGF-1: a human growth factor in the induction of neoangiogenesis". Expert Opin Investig Drugs. 7 (12): 2011–5. PMID 15991943. doi:10.1517/13543784.7.12.2011. 
  87. ^ Wagoner L.E., Merrill W., Jacobs J., Conway G., Boehmer J., Thomas K., Stegmann T.J. (2007). "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. 
  88. ^ Loria V, Dato I, Graziani F, Biasucci LM (2008). "Myeloperoxidase: a new biomarker of inflammation in ischemic heart disease and acute coronary syndromes". Mediators Inflamm. 2008: 135625. PMC 2276594. PMID 18382609. doi:10.1155/2008/135625. 

External links