Coronary artery disease (CAD) is the most common manifestation of atherosclerotic disease. It results from an atherosclerotic plaque in the coronary vasculature that leads to an imbalance between myocardial oxygen demand and supply leading to accumulation of waste products and ischemic injury. Coronary artery disease can be classified into Stable angina pectoris and acute coronary syndromes. Other adverse effects of atherosclerosis are ischemic stroke and peripheral vascular disease.
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Image: “Calcificatio atherosclerotica” by Kwz~commonswiki. License: Public Domain


Atherosclerotic plaque

Atherosclerosis is a chronic inflammatory process characterized by accumulation of lipids, fibrous material, and minerals in arteries. It is derived from the words athero meaning lipid accumulation and sclerosis meaning thickening of the vessel intima. This is known as a plaque which is a sticky deposit formed in vessels to cause occlusion of the vessel.

Plaque formation

The process begins with endothelial damage secondary to

  • smoking,
  • diabetes,
  • homocysteine increase,
  • chronic inflammation, and
  • hemodynamic compromise

which lead to a dysfunctional endothelium symbolized by reduced nitric oxide (NO) levels from the vessel wall.

This is followed by entrance and accumulation of Low density lipoproteins that accumulate in the dysfunctional vessel.

Later, oxidation of the lipoproteins takes place from the macrophages and smooth muscle cells of the endothelium. This causes increased permeability of the vessel. Moreover, the permeability is coupled with the increased release of VCAM-1, ICAM-1and chemokines such as monocyte chemoattractant protein (MCP-1).

The above factors lead to mobilization of an inflammatory infiltrate into the dysfunctional endothelium. The activated cells trigger a further release of growth factors, cytokines and upregulation of adhesive molecules leading to further monocyte attraction and macrophage recruitment to the site.

Plaque growth

As macrophages enter the site, they engulf fat molecules and form foam cells that accumulate in the plaque forming the lipid core.

Smooth muscle cells on the other hand are recruited to increase growth of the plaque and they help to stabilize the plaque by forming the fibrous cap.

Plaque rupture

Increase inflammatory infiltrate into a stable plaque, smooth muscle cell apoptosis, and proteolytic degradation of the matrix lead to formation of a vulnerable plaque by destruction of the fibrous capsule stabilizing the plaque.

The vulnerable plaque has an increased risk of disruption/rupture that leads to formation of a thrombus secondary to platelet activation and this leads to vascular occlusion and clinical symptoms as ischemic injury.

The formed thrombus may also rupture further to cause emboli formation in the systemic circulation.

The six areas of consensus in coronary artery disease

Evidence-based treatment

Evidence-based treatment with medicines is effective in the treatment of coronary artery disease.

Recent studies in the treatment of coronary artery disease suggest that the standard treatment for these patients should include:

Lipid lowering drugs (atorvastatin, simvastatin)

  • These drugs are administered with a target serum LDL of 70–100 mg/dl in patients with coronary artery disease to avoid further growth of the atherosclerotic plaque. The drugs work by limiting the cholesterol synthesis and increase in LDL metabolism. Common adverse effects of the drugs include rhabdomyolysis, myalgia, and renal injury.
  • Once the target LDL is achieved the next step is to raise the HDL levels by administration of nicotinic acid which raises HDL by 15–30 % in addition to lowering the LDL.
  • Other drugs used to lower the levels of lipids include ezetimibe and fibrates.
  • Lipid lowering reduces the risk of death by more than 15 % in primary patients and by up to 40 % in patients with old MI. They also reduce the rate of occurrence of MI by greater than 35 % and 50 %, respectively.

Antihypertensive medications (Angiotensin converting enzyme inhibitors and angiotensin receptor blockers)

  • The joint national committee (JNC) on prevention, detection, evaluation, and treatment of hypertension advocates for lowering of blood pressure to a goal of less than 140/90 or 130/80 as recommended by the American heart association. These classes of drugs work by reducing the myocardial oxygen demand which is the main pathologic process. They include:
  • Cardio selective β blockers (atenolol, bisoprolol) which decrease the heart rate and rate of contraction thus reduce myocardial oxygen demand. Thus, they have a negative ionotropic and chronotropic cardiac effect. Have been shown to be effective in primary patients and those with prior MI.
  • ACEIs and ARBs which exert their effects of the renin angiotensin aldosterone pathway and inhibit angiotensin II receptors, thus, cause reduced vasoconstriction and reduced blood pressure. ARBs are known to cause cough and both classes can lead to deranged potassium levels.
  • A 20 % reduction in mortality has been recorded especially with the use of ACEIs in patients with MI, coronary artery disease and reduced ejection fraction.

Antiplatelet therapy

  • After injury of the vulnerable plaque platelets are activated leading to formation of a thrombus at the site. This can be avoided by administration of antiplatelet therapy such as:
  • Aspirin that inhibits COX-1 and COX-2, thus, reducing prostaglandins and thromboxane A2 production and hence reduced platelet aggregation. The effect is more pronounced in the elderly with aspirin reducing the vasoocclusive events by 20 % in the elderly as opposed to 10 % in those younger than 65 years.

All the above methods help in the reduction of major ischemic coronary events (MACE) as well as reduction in the morbidity and mortality from the disease.

In disabling unstable angina with persistence of medical symptoms despite therapy, coronary revascularization is the method of choice for treatment of the disease.

The use of glycoprotein receptor antagonist prior to the procedure helps to improve its efficacy and reduce mortality.

Smoking

Smoking is an important risk factor in the causation of coronary artery disease but it can be controlled.

Smoking causes damage to the endothelium which is the initial event that leads to a plaque formation. The risk of developing coronary artery disease in a smoker rises to 6 times in the first 5 years. This risk levels decrease rapidly with cessation of smoking with a 50 % reduction of the risk experienced in the first year and the risk levels fall to the level of a non-smoker in 15 years.

The toxins in cigarette smoke work by decreasing the level of the most important/only antioxidant in the body (vitamin C), thus, increased oxidation into toxic metabolites.

Smoking cessation can be achieved by acceptance and seeking psychological counselling which is later coupled with nicotine replacement therapy such as varenicline/bupropion. The replacement therapy provides a baseline nicotine level in circulation for those who are addicted to smoking while at the same time sparing the patient the adverse effects of other smoke components such as tar and carbon monoxide smoke.

The likelihood of getting coronary artery disease

The likelihood of getting coronary artery disease can be predicted.

Recent studies show that the occurrence of coronary artery disease can be predicted by scoring the patient based on various risk factors. This can be done with certainty but not accuracy. The risk factors include:

  • Conventional risk factors such as advanced age >45 years, family history of heart diseases, and African-American descent.
  • Modifiable risk factors such as increased blood cholesterol, increased blood pressure, cigarette smoking, diabetes mellitus, obesity, inactivity, and mental stress.
  • Non-traditional risk factors such as increase in CRP, lipoprotein a, homocysteine, fibrinogen, BNP, chronic inflammatory conditions, left ventricular hypertrophy, and abnormal ankle-brachial index.

Trend towards improvement

There is a trend towards improvement of mortality in coronary artery disease patients.

Due to the aggressive nature and efficacy of medications the burden of coronary artery disease has been on a sharp decline. The coronary artery disease associated deaths in in 1970 were in the ranges of 448 per 100,000 people which has since fallen to 144 deaths per 100000 people in 2005.

Moreover, an interesting change in statistics is that coronary artery disease was the leading cause of cardiac disease related deaths as at 1970 which is no longer the case in 2005. This change is directly attributed to:

  • Primary and secondary control of atherosclerotic risk factors.
  • Introduction of evidence-based treatment with the three major classes of drugs, i.e., lipid lowering drugs, antihypertensive and antiplatelet drugs.
  • Lifestyle changes such as dietary modification, increase of exercise activities and cessation of smoking.

In several autopsy studies done, there has been a disappearance of coronary artery disease cases as shown:

  • Korean war (1957–1963) 77 % of autopsies had mild coronary artery disease and a mere 10 % had severe form of the disease.
  • Vietnam war (1968–1978) 45 % of all autopsies had mild coronary artery disease and 5 % had severe disease.
  • Autopsies from the Iraq-Afghanistan war had 8.5 % coronary artery disease lesions with 2.3 % having severe form of the disease.

Timely intervention

Timely intervention can save coronary artery disease patients.

The efficacy of all interventions, i.e., prevention or treatment is based on the physician’s aggressiveness and patients’ adherence to the interventions. The doctor should advocate for cessation of smoking, increase in exercise activities and lifestyle modifications as an addition to prescribing appropriate medications to cater for the disease.

Cardiac rehabilitation

Cardiac rehabilitation improves outcomes for coronary artery disease patients and has been recommended.

The American heart association recommends cardiac rehabilitation with coordinated, multifaceted interventions designed to optimize a cardiac patient’s physical, psychological, and social functioning in addition to slowing or reversing the progress of the disease altogether. The events that entail rehabilitation include:

  1. Baseline patient assessment.
  2. Nutritional counselling and dietary modification.
  3. Aggressive risk factor management with control of hypertension, diabetes, and smoking.
  4. Psychological and vocational counselling.
  5. Exercises.

Class 1 indications for patient’s cardiac rehabilitation include:

  • Myocardial infarction.
  • Percutaneous coronary intervention.
  • Coronary bypass graft.
  • Chronic stable angina.
  • Heart failure.
  • Cardiovascular prevention in women.

The four areas of controversy in coronary artery disease

The efficacy of revascularization

The efficacy of revascularization in saving patients with coronary artery disease has been controversial:

Studies show that revascularization is the only effective therapy in patients with 3 vessel coronary artery disease and left ventricular dysfunction or left main coronary artery disease.

Coronary artery bypass graft is the only procedure shown to prolong life and reduce mortality. This is because angioplasty has not shown similar efficacy creating a controversy.

However, the BARI trial showed that both interventions have similar efficacy and can be used to reduce mortality from coronary artery disease. Moreover, the COURAGE study showed equal efficacy in medical therapy and revascularization, thus, the three alternatives can be considered effective in the management of coronary artery disease.

Cardiac catheter insertion

Cardiac catheter insertion should be done in all patients with coronary artery disease.

The bias towards revascularization as the most effective therapy led to a creation of the second controversy that in all patients with coronary artery disease a catheter should be inserted in anticipation for revascularization.

However, the correct position is that even medical therapy is effective in the management of coronary artery disease more so in patients with left ventricular dysfunction and stable anginas. There is no urgency to institute catheter placement.

Revascularization

Revascularization is contraindicated in older patients:

The assumption that revascularization is the most effective intervention and that in older patients the risks of the procedure outweighs the benefits has led to withholding of the procedure in older patients which is not the correct position.

Studies have shown that elderly people respond well if not better to revascularization. Thus, the restoration of cardiac function is more important than age. Moreover, studies have shown that there are even lower mortality rates with CABG in the elderly population compared to other interventions.

The change of coronary artery distribution

The change of coronary artery distribution against age:

Chronic coronary artery disease was initially thought to be a disease of the elderly. Recent autopsies have shown a changing trend with younger people acquiring the disease. The disease is now common in young males.

Conclusion

In conclusion, coronary artery disease is the leading cause of death in the world affecting people of all sexes, races, and ages.

The deaths arising from this condition can be controlled since it is a highly preventable disease with primary and secondary intervention that reduces morbidity and mortality.

Effective therapy and lifestyle modification achieve further control to give patients with coronary artery disease a longer and productive life.

Elderly patients should also be treated with similar methods as the young generation as recent studies show efficacy of the methods in all populations.

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