Coronary heart disease

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Coronary heart disease (CHD), also called coronary artery disease (CAD), is caused by abnormalities the arteries that supply the heart with blood. Those arteries are called the coronary arteries and the usual cause of coronary artery disease is athersosclerosis. Atherosclerosis is a degenerative disease of the arterial walls, in which the normal elastic walls of the arteries become thickened and replaced with deposits of fatty material, including cholesterol. As the walls of the affected arteries thicken, the hollow lumen at the center of each, that conduit through which oxygen enriched blood normally pulses, becomes narrower and, eventually, the flow of blood within it is decreased. With narrowing of the artery's lumen and reduced flow comes the risk of sudden occlusion of the artery, especially if the lining is abnormally roughened by deposits of irregular plaques of minerals and fats.

Etiology/cause

The cause and manifestation of coronary heart disease is multifactorial. About 3/4 of the risk of coronary heart disease is due to three risk factors: hypercholesterolemia (total cholesterol > 182 mg/dL [4.71 mmol/L]), hypertension (diastolic blood pressure > 90 mm Hg), and cigarette smoking.[1]

Inflammation may underlay the association between elevated C-reactive protein levels and coronary heart disease. Periodontal disease may contribute to this inflammation.[2]

The role of emotional stress was supported in a study of the incidence of coronary events in the Munich area during the 2006 World Cup Football (soccer) championship.[3] The incidence of coronary events was higher during the match, especially for people who had pre-existing coronary disease. Stress, via increases in unhealthy behaviors, was also identified as more important than hypertension or C-reactive protein level in predicting coronary events.[4]

Atherosclerotic obstruction

About 10% of patients with chronic angina have left main disease.[5][6] In males over age 70 with definite angina, almost 50% have obstruction of the left main coronary artery.[6] The extent of coronary obstructions can be quantified with the Duke Coronary Artery Disease Index.[7]

Coronary vasospasm

Approximately 15% of NSTEMI and 2% of STEMI patients have no obstruction of coronary arteries and in about half of these patients, spasm of a coronary artery can be induced.[8]

Syndrome X

Cardiac syndrome X is the presence of typical angina, abnormal exercise-test results, and normal coronary arteries (including no vasospasm).[9] Syndrome X may be caused by subendocardial hypoperfusion that can be demonstrated by cardiovascular magnetic resonance imaging during the administration of adenosine.[9]

Diagnosis

History, physical examination, and risk factors

Angina pectoris, or simply angina, is the chest pain due to coronary heart disease; however, most patients do not report angina.[10] The nature of the chest pain affects the probability of underlying coronary disease.[11]

The Pryor nomogram, a clinical prediction rule, can help diagnose patients with suspected chest pain in a non emergent setting.[12][13]

Cardiac stress test

For more information, see: Stress test.
Sensitivity and specificity of cardiac stress tests[14]
  Sensitivity Specificity
Exercise electrocardiography 68% 77%
Stress echocardiography 76% 88%
Myocardial perfusion imaging
thallium planar 		79% 73%
Myocardial perfusion imaging
single-photon emission computed tomography (SPECT) 		88% 77%
Positron emission tomography (PET), 68% 77%

The sensitivity and specificity of the various cardiac stress tests have been summarized.[14]

Exercise treadmill test

The exercise treadmill test (ETT) can help diagnose and prognose patients with suspected CHD. The likelihood of a positive treadmill test depends on the severity of the underlying coronary disease.[5] For example, 87% of patients with obstruction of the left main coronary artery will have a positive treatmill test, whereas only 57% of patients with obstructions of one or two of the other coronaries will have a positive treadmill test. The treadmill can help predict the location of coronary stenoses.[15]

Stress myocardial perfusion imaging

Stress echocardiography

Stress ventriculography

X-ray computed tomography

There are two types of computed tomography used for noninvasive coronary arteriography.

Electron beam computed tomography

Electron beam computed tomography (EBCT) is also called ultrafast CT.

Cardiac computed tomographic angiography

For more information, see: Computed tomographic cardiac angiography.

Computed tomographic cardiac angiography (CT cardiac angiography) uses multidetector spiral computed tomography.[16][17][18] The physiologic significance of obstructions estimated to be 60% to 80% is difficult to predict.[19]

The accuracy using 64-row CT for detecting stenoses of 50% is:[20]

Coronary calcium score

Both types of computed tomography, electron beam computed tomography (EBCT) and multidetector spiral computed tomography, can measure the amount of calcium in the walls of the coronary arteries in order to diagnose coronary heart diease.

Treatment

Medications

Invasive treatments

For more information, see: myocardial revascularization.

Patient who have a left ventricular ejection fraction above 50%, no angina or their angina is controlled with medicines, do not benefit from either percutaneous transluminal coronary angioplasty (PCI)[21] or from coronary artery bypass grafting surgery[22].

Regarding patients who must undergo invasive treatment, a systematic review comparing percutaneous coronary interventions and coronary artery bypass grafting (CABG) surgery found that CABG was more effective but was more likely to be complicated by stroke.[23]

Percutaneous cardiac intervention

Patient who have a stable angina and left ventricular ejection fraction above 35% do not reduce mortality from percutaneous transluminal coronary angioplasty (PCI)[21] although there is some reduction in angina for the first three years after procedure[24].

Patients are more likely to benefit from PCI when clinical practice guidelines are followed.[25]

Stents

Meta-analysisMeta-anlayses have found that the rate of late thrombosis was <2% between years 1 and 4.[26][27][28]

Coronary artery bypass graftiing

Major randomized controlled trials of surgery for chronic stable angina
Trial results
Veterans Administration cooperative study
1977
686 patients[29]		 3 year survival was 87% of the medical group and 88% of the surgical group. No significant difference.
Coronary Artery Surgery Study
(CASS)
1984
780 patients[22]		 The 5 year survival 92% with medical therapy and 95% with surgery (not significant). "The likelihood of nonfatal Q-wave myocardial infarction was 11 and 14 per cent, respectively (not significant). The five-year probability of remaining alive and free of infarction was 82 per cent in the patients assigned to medical therapy and 83 per cent in the patients assigned to surgery (not significant)."
European Coronary Surgery Study
1988
767 patients[30]		 5 year survival was 92% with surgery and 83% with medical therapy.
Pooled results[31] Surgery fared better except for patients with one or two vessel disease with neither vessel being the LAD or left main.

Patient who have a left ventricular ejection fraction between 35 and 49 percent benefit from coronary artery bypass surgery if they have disease of three coronary arteries.[22].

Complications

Acute coronary syndrome

For more information, see: Acute coronary syndrome.

Prognosis

Framingham risk

The Framingham risk uses clinical risk factors that are combined in an equation developed from the Framingham Heart Study to calculate prognosis. An online calculator is available at http://hp2010.nhlbihin.net/atpiii/calculator.asp.

Reynolds Score

The Reynolds score has been proposed as an improvement to the Framingham risk by incorporating the c-reactive protein.[32][33] An online calculator is at http://www.reynoldsriskscore.org/.

Coronary calcium score

Coronary calcium score for predicting myocardial infarction or death from coronary heart disease amond 6814 persons without known cardiovascular disease[34]
Score Number of patients Hazard ratio
0 8/3409 1.0
1-100 25/1728 3.9
101-300 24/752 7.1
> 300 32/833 6.8

Both types of computed tomography, electron beam computed tomography (EBCT) and multidetector spiral computed tomography, can measure the amount of calcium in the walls of the coronary arteries in order to estimate prognosis. The calcium score improves upon using clinical risk factors for prognosticating. [34] Using clinical risk factors alone, the area under the receiver operating-characteristic curve (AUC) was 0.79 while the AUC rose to 0.83 when the calcium score was added. The clinical importance of this rise is not clear.[35]

C-reactive protein

For more information, see: C-reactive protein.

Abnormal high sensitivity C-reactive protein (CRP) values may assist in assessing cholesterol measurements in apparently healthy people due to the theory that chronic inflammation precedes atherosclerosis.[36]

The CRP is part of the Reynolds score.

Cardiac stress test

Various cardiac stress tests are available.

Exercise treadmill test

The exercise treadmill test (ETT) can help diagnose and prognose patients with suspected CHD. Clinical prediction rules are available to help interpret the results of the ETT. These rules are the Duke Treadmill score[37] and the newer Cleveland Clinic model[38]. The Duke score has been more extensively studied; however, in a direct comparison by the authors of the Cleveland Clinic model, the latter performed better.[38]

The ETT adds to clinical risk factors in prediction complications. The area under the receiver-operator-characteristics-curve (AUC) for clinical data alone is 0.798 and rises to 0.857 when the ETT is added.[37]

The ETT also adds to the cardiac catheterization in prognosticating[39][40][41] although some researchers have questioned the extent of information provided by the treadmill test[42]. However, in one study among information available from cardiac catheterization, only the left ventricular ejection fraction contributed to the ETT in predicting complications[41] whereas in another study, both the left ventricular ejection fraction and the number of stenoses aided prediction[39].

Cardiac catheterization

Rates of occlusion after 4-5 years[43]
Severity of original stenosis Rate of subsequent occlusion
No stenosis 0.7%
5% to 49% 2.3%
50% to 80% 10.1%
81% to 95% 23.6%

Much research has addressed the association between severity of coronary obstructions and subsequent complications such as myocardial infarctions. Coronary obstructions are more likely to progress or occlude within 4-5 years if the obstructions are severe according to the CASS investigation.[43] 23% of subsequent occlusions were associated with a myocardial infarction. The cholesterol level or the exercise test did not improve the ability to prediction occlusion in the CASS investigation.

Surprisingly, while patients with more severe stenoses are more likely to develop occlusions predicting the exact site of furture occlusions is very difficult. Most subsequent occlusions occur in arteries that originally did not have severe stenoses and were originally not the most severely stenotic arteries in a patient.[44][45][46][47]

In addition, when occlusions develop in severely stenotic vessels, these occlusions may be less likely to cause a myocardial infarction.[47]

In summary, the concept of which coronary stenoses are vulnerable to subsequent plaque rupture and occlusion many be more important that the degree of stenosis of a vessel.[48]

Prevention

Coronary heart 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 stopping smoking. There is some evidence that lowering uric acid and homocysteine levels may contribute. In diabetes mellitus, there is little evidence that blood sugar control actually improves cardiac risk. 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 heart disease.[49]

An increasingly growing number of other physiological markers and homeostatic mechanisms are currently under scientific investigation. Among these markers are low density lipoprotein and asymmetric dimethylarginine. Patients with CHD and those trying to prevent CHD are advised to avoid fats that are readily oxidized (e.g., saturated fats and trans-fats), limit carbohydrates and processed sugars to reduce production of Low density lipoproteins while increasing High density lipoproteins, keeping blood pressure normal, exercise and stop smoking. These measures limit the progression of the disease. Recent studies have shown that dramatic reduction in LDL levels can cause mild regression of coronary heart disease.

Exercise

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 (USPSTF), based on a systematic review of randomized controlled trials, found 'insufficient evidence' to recommend that doctors counsel patients on exercise.[50] However, the American Heart Association, based on a non-systematic review, recommends that doctors counsel patients on exercise [51]

Preventive diets

Dietary changes can potentially lead to large changes in the cholesterol.[52]

Aspirin

Aspirin, in doses of less than 75 to 81 mg/d[53], can reduce the incidence of cardiovascular events.[54] The U.S. Preventive Services Task Force 'strongly recommends that clinicians discuss aspirin chemoprevention with adults who are at increased risk for coronary heart disease'.[55] The Task Force defines increased risk as 'Men older than 40 years of age, postmenopausal women, and younger persons with risk factors for coronary heart 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.[56]

Regarding healthy women, the more recent Women's Health Study randomized controlled trial found insignficant benefit from aspirin in the reduction of cardiac events; however there was a signficant reduction in stroke.[57] Subgroup analysis showed that all benefit was confined to women over 65 years old.[57] In spite of the insignficant benefit for women < 65 years old, recent 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'.[58]

Antilipemic drugs

The U.S. Preventive Services Task Force (USPSTF) estimated that after 5 to 7 years of treatment with statins, the relative risk reduction of coronary heart disease events is decreased by approximately 30%[59][60]. More recently, a meta-analysis reported an almost identical relative risk reduction of 29.2% in low risk patients treated for 4.3 years [61]. A relative risk reduction of 19% in coronary mortality was found in a meta-analysis of patients at all levels of risk.[62]

Various clinical practice guidelines have addressed the treatment of hypercholesterolemia. The American College of Physicians has addressed hypercholesterolemia in patients with diabetes [63]. Their recommendations are:

  • Recommendation 1: Lipid-lowering therapy should be used for secondary prevention of cardiovascular mortality and morbidity for all patients (both men and women) with known coronary artery disease and type 2 diabetes.
  • Recommendation 2: Statins should be used for primary prevention against macrovascular complications in patients (both men and women) with type 2 diabetes and other cardiovascular risk factors.
  • Recommendation 3: Once lipid-lowering therapy is initiated, patients with type 2 diabetes mellitus should be taking at least moderate doses of a statin (the accompanying evidence report states "simvastatin, 40 mg/d; pravastatin, 40 mg/d; lovastatin, 40 mg/d; atorvastatin, 20 mg/d; or an equivalent dose of another statin")[64].
  • Recommendation 4: For those patients with type 2 diabetes who are taking statins, routine monitoring of liver function tests or muscle enzymes is not recommended except in specific circumstances.

The National Cholesterol Education Program revised their guidelines[65]; however, their 2004 revisions have been criticized for use of nonrandomized, observational data.[66]

Omega-3 fatty acids (fish oil)

For more information, see: Fish oil.


Homocysteine lowering

A meta-analysis concluded that lowering homocysteine with folic acid and other supplements may reduce stroke.[67] However, the two largest randomized controlled trials included in the meta-analysis had conflicting results. Lonn reported positive results[68]; whereas the trial by Toole was negative.[69]

Since the meta-analysis, two additional trials have shown no reduction in cardiovascular endpoint despite successfully lowering the plasma homocysteine level.[70][71]

References

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  2. ↑ Humphrey LL, Fu R, Buckley DI, Freeman M, Helfand M (December 2008). "Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis". J Gen Intern Med 23 (12): 2079–86. DOI:10.1007/s11606-008-0787-6. PMID 18807098. Research Blogging.
  3. ↑ Wilbert-Lampen U, Leistner D, Greven S, et al (2008). "Cardiovascular events during World Cup soccer". N. Engl. J. Med. 358 (5): 475–83. DOI:10.1056/NEJMoa0707427. PMID 18234752. Research Blogging.
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  42. ↑ Weiner DA, Ryan TJ, McCabe CH, et al (August 1979). "Exercise stress testing. Correlations among history of angina, ST-segment response and prevalence of coronary-artery disease in the Coronary Artery Surgery Study (CASS)". N. Engl. J. Med. 301 (5): 230–5. PMID 449990. [e]
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