Coronary Artery Disease

Coronary artery atherosclerosis

 The pathologic process affecting the coronary arteries

 Coronary artery atherosclerosis is the single largest killer of men and women in the United States

Background

The word atherosclerosis is of Greek origin and literally means focal accumulation of lipid (ie, athere [gruel]) and
thickening of arterial intima (ie, sclerosis [hardening])

Atherosclerosis is a disease of large and medium-sized muscular arteries and is characterized by the following:

 Endothelial dysfunction
 Vascular inflammation
 Buildup of lipids, cholesterol, calcium, and cellular debris within the intima of the vessel wall

Atherosclerotic buildup results in the following:

 Plaque formation
 Vascular remodeling
 Acute and chronic luminal obstruction
 Abnormalities of blood flow
 Diminished oxygen supply to target organs

By impairing or obstructing normal blood flow, atherosclerotic buildup causes myocardial ischemia.

Silent Ischemia

In most cases, a temporary blood shortage to the heart causes the pain of angina pectoris. But in other cases, there is
no pain. These cases are called silent ischemia.

Silent ischemia may also disturb the heart’s rhythm. Abnormal rhythms such as ventricular tachycardia or
ventricular fibrillation can interfere with the heart’s pumping ability and can cause fainting or even sudden cardiac
death.

Signs and symptoms

 Chest pain
 Shortness of breath
 Weakness, tiredness, reduced exertional capacity
 Dizziness, palpitations
 Leg swelling
 Weight gain
 Diaphoresis
  Stable angina pectoris
 Intermittent claudication
 Mesenteric angina
 Tachycardia: Common in persons with acute coronary syndrome (ACS) and acute myocardial infarction (AMI)
 High or low blood pressure
 S4 gallop: A common early finding
 S3 gallop: An indication of reduced left ventricular function
 Heart murmurs
 Tachypnea
 Xanthelasmas

Risk Factors

 Age
o Simply getting older increases your risk of damaged and narrowed arteries.
 Sex
o Men are generally at greater risk of coronary artery disease.
o The risk for women increases after menopause.
 Family history
o A family history of heart disease is associated with a higher risk of coronary artery disease,
especially if a close relative developed heart disease at an early age.
o Your risk is highest if your father or a brother was diagnosed with heart disease before age 55 or if
your mother or a sister developed it before age 65.
 Smoking
o People who smoke have a significantly increased risk of heart disease.
o Exposing others to your secondhand smoke also increases their risk of coronary artery disease.
 High blood pressure
o Uncontrolled high blood pressure can result in hardening and thickening of your arteries,
narrowing the channel through which blood can flow.
 High blood cholesterol levels
o High levels of cholesterol in your blood can increase the risk of formation of plaque and
atherosclerosis.
o High cholesterol can be caused by a high level of low-density lipoprotein (LDL) cholesterol, known
as the "bad" cholesterol.
o A low level of high-density lipoprotein (HDL) cholesterol, known as the "good" cholesterol, can
also contribute to the development of atherosclerosis.
 Diabetes
o Diabetes is associated with an increased risk of coronary artery disease.
 Overweight or obesity
o Excess weight typically worsens other risk factors.
 Physical inactivity
o Lack of exercise also is associated with coronary artery disease
 High stress
o Unrelieved stress in your life may damage your arteries as well as worsen other risk factors for
coronary artery disease.
 Unhealthy diet
o Eating too much food that has high amounts of saturated fat, trans fat, salt and sugar can increase
your risk of coronary artery disease.
  Sleep apnea
o This disorder causes you to repeatedly stop and start breathing while you're sleeping.
o Sudden drops in blood oxygen levels that occur during sleep apnea increase blood pressure and
strain the cardiovascular system, possibly leading to coronary artery disease.
 Preeclampsia
o This condition that can develop in women during pregnancy causes high blood pressure and a
higher amount of protein in urine.
o It can lead to a higher risk of heart disease later in life.
 Alcohol use
o Heavy alcohol use can lead to heart muscle damage.
o It can also worsen other risk factors of coronary artery disease.
 Autoimmune diseases
o Conditions such as rheumatoid arthritis and lupus (and other inflammatory rheumatologic
conditions) have an increased risk of atherosclerosis.

Plaque growth and vascular remodeling

 Hemodynamic factors interact with the activated vascular endothelium.

 Fluid shear stresses generated by blood flow influence the phenotype of the endothelial cells
 Atherosclerotic plaques
o occur in regions of branching and marked curvature
 where blood undergoes sudden changes in velocity and direction of flow.
 The earliest pathologic lesion of atherosclerosis is the fatty streak
o observed in the aorta and coronary arteries of most individuals by age 20 years
o result of focal accumulation of serum lipoproteins within the intima of the vessel wall
o microscopy reveals lipid-laden macrophages, T lymphocytes, and smooth muscle cells in varying
proportions
o may progress to form a fibrous plaque
 Result of progressive lipid accumulation
 Growth of the fibrous plaque results in
o vascular remodeling
o progressive luminal narrowing
o blood-flow abnormalities
o compromised oxygen supply to the target organ
 Human coronary arteries enlarge in response to plaque formation
 Positive remodeling is an outward compensatory remodeling
o arterial wall bulges outward
o lumen remains uncompromised
o usually do not cause angina, because they do not become hemodynamically significant for a long
time
o form the bulk of the vulnerable plaques, grow for years, and are more prone to result in plaque
rupture and ACS
 Negative remodeling causes narrowing of the vascular lumen
o usually lead to the development of stable angina
o also vulnerable to plaque rupture and thrombosis
Plaque rupture

 Denudation of the overlying endothelium or rupture of the protective fibrous cap

o exposure of the thrombogenic contents of the core of the plaque to the circulating blood
 advanced or complicated lesion
o Occurs due to weakening of the fibrous cap
o T lymphocytes elaborate interferon gamma, an important cytokine that impairs vascular smooth
muscle cell proliferation and collagen synthesis
o Activated macrophages degrade collagen
 A plaque rupture may result in
o thrombus formation
o partial or complete occlusion of the blood vessel
o progression of the atherosclerotic lesion
 Main event that causes acute presentations

Diagnostics/Approach

 Routine blood tests include complete blood count (CBC), chemistry panel, lipid profile, and thyroid function
tests
 Routine measurement of blood glucose and hemoglobin A1C is appropriate in patients with DMII
 Fasting lipid profile

o Total cholesterol level

o LDL cholesterol level

 o HDL cholesterol level

o Triglyceride level

 Specific lipid studies

o VLDL-C level

o Lipoprotein (a) level

o Apoprotein profile

 Troponin I
 CKMB
 High sensitivity C-reactive protein
o High sensitivity C-reactive protein (hs-CRP) is a normal protein that appears in higher amounts
when there's inflammation somewhere in your body.
o High hs-CRP levels may be a risk factor for heart disease.
o It's thought that as coronary arteries narrow, you'll have more hs-CRP in your blood.
 Homocysteine
o Homocysteine is an amino acid your body uses to make protein and to build and maintain tissue.
o But high levels of homocysteine may increase your risk of coronary artery disease.
 Electrocardiogram (ECG)
o Records electrical signals as they travel through your heart.
o Can often reveal evidence of a previous heart attack or one that's in progress.

 Holter monitoring

o Portable monitor for 24 hours as you go about your normal activities.

o Certain abnormalities may indicate inadequate blood flow to your heart.

 Echocardiogram
o Uses sound waves to produce images of your heart.
o Determine whether all parts of the heart wall are contributing normally to your heart's pumping
activity.
o Parts that move weakly may have been damaged during a heart attack or be receiving too little
oxygen.
o May indicate coronary artery disease or various other conditions.
 Stress test
o Exercise Tolerance Test
 Walk on a treadmill or ride a stationary bike during an ECG
o Stress echocardiogram
 Echocardiogram before and after you exercise on a treadmill or bike
o Pharmacologic nuclear stress test
 Adenosine or Dobutamine
 Measures blood flow to your heart muscle at rest and during stress.
 Similar to a routine exercise stress test but with images in addition to an ECG
 A tracer is injected into your bloodstream, and special cameras can detect areas in your
heart that receive less blood flow.
 Cardiac catheterization and angiogram
o Dye is injected into the arteries of the heart through a long, thin, flexible tube (catheter) that is
threaded through an artery, usually in the leg, to the arteries in the heart.
 o Dye outlines narrow spots and blockages on the X-ray images
 If a blockage that requires treatment
 a balloon can be pushed through the catheter and inflated to improve the blood
flow in the coronary arteries
 a mesh tube (stent) may then be used to keep the dilated artery open.
 Heart scan
o Computerized tomography (CT) technologies can help to see calcium deposits in your arteries that
can narrow the arteries
o A CT coronary angiogram, in which you receive a contrast dye injected intravenously during a CT
scan, also can generate images of your heart arteries.

Treatment of Angina

 Beta-blockers
o Inhibit sympathetic stimulation of the heart
 reducing heart rate and contractility
o Can decrease myocardial oxygen demand and thus prevent or relieve angina in patients with CAD.
o Since beta-blockers reduce the heart rate–blood pressure product during exercise, the onset of
angina or the ischemic threshold during exercise is delayed or avoided.
 Calcium channel blockers
o Prevent calcium entry into vascular smooth muscle cells and myocytes
 leads to coronary and peripheral vasodilatation, decreased atrioventricular (AV)
conduction, and reduced contractility
o These effects result in decreased coronary vascular resistance and increased coronary blood flow.
 Nitrates
o effective in the treatment of acute anginal symptoms
o usually given sublingually
o primary anti-ischemic effect of nitrates is to decrease myocardial oxygen demand by producing
systemic vasodilation
o improves exercise tolerance, time to onset of angina, and ST-segment depression during exercise
testing
o particularly effective in combination with beta-blockers or calcium-channel blockers.

 Ranolazine
o believed to relieve ischemia by reducing myocardial cellular sodium and calcium overload via
inhibition of the late sodium current of the cardiac action potential.

Surgical Revascularization
 Coronary Artery Bypass Grafting (CABG)
o Better long-term patency rates and improved late survival were achieved by using the LIMA than
by using SVGs.
o Guidelines for CABG
 Class I indications
 Left main coronary artery disease (LMCAD) with 50% or greater narrowing
  Anatomically equivalent LMCAD with 70% or greater narrowing in both the
proximal left anterior descending (LAD) coronary artery and the left circumflex
artery
 Three-vessel coronary artery disease (CAD), particularly in the setting of an
impaired left ventricular ejection fraction (LVEF)
 Class II indications
 Proximal LAD coronary artery stenosis (impaired LVEF becomes a class I
indication)
 One-vessel or two-vessel CAD that does not involve the proximal LAD coronary
artery if a moderate area of viable myocardium is at risk
 Class III indications
 One-vessel or two-vessel CAD that does not involve the proximal LAD coronary
artery
 One-vessel or two-vessel CAD that does not involve the proximal LAD coronary
artery with only a small area of viable myocardium
 Percutaneous Coronary Intervention (PCI)
o Balloon angioplasty
o Coronary stenting are the mainstays of PCI
o Other technologies include
 devices that ablate plaque (atherectomy)
 devices that remove clots from vessels (thrombectomy)
 devices that capture and remove embolic debris (embolic protection).
o Guidelines for PCI
 Class I indications
 Patients with class II-IV angina or acute coronary syndrome with one or more
significant lesions in one or more coronary arteries suitable for PCI
 Patients with acute ST-segment elevation myocardial infarction (STEMI) who can
undergo angioplasty of the infarct artery within 12 hours of symptom onset or
patients who have recurrent ischemia or infarction (rescue PCI)
 Patients older than 75 years who develop cardiogenic shock within 36 hours of
an acute STEMI
 Patients with early ischemia (usually within 30 days) after CABG
 Class II indications
 Patients with focal saphenous vein graft (SVG) lesions or multiple stenosis who
are poor candidates for reoperation
 The presence of one or more lesions with reduced likelihood of success, or vessel
or vessels subtending a less-than-moderate area of viable myocardium
 Patients with STEMI in whom thrombolytic therapy is contraindicated
 Patients with STEMI who experience cardiogenic shock or hemodynamic
instability after thrombolysis
 Patients with ischemia occurring 1-3 years postoperatively and preserved left
ventricular function with discrete lesions in graft conduits
 Patients with disabling angina secondary to new disease in a native coronary
circulation
 Class III indications
 Patients with no evidence of myocardial injury or ischemia on objective testing
who have not undergone a trial of medical therapy, who have a small amount of
salvageable myocardium, or who are at high risk of procedural success or
morbidity or mortality
  Patients with insignificant coronary stenosis
 Patients with significant left main coronary artery disease (CAD) who are
candidates for coronary artery bypass grafting (CABG)
 Patients who opt for elective PCI of a non–infarct-related artery at the time of
myocardial infarction (MI)
 Patients with no evidence of myocardial ischemia after 12 hours of MI or routine
PCI of the infarct artery after thrombolytic therapy
 Patients with total vein graft occlusions

Patient Education

 The most effective and cost-efficient means of reducing the burden of disease secondary to atherosclerosis in
the general population is primary prevention.
 The role of diet and exercise in the prevention of atherosclerotic cardiovascular disease has been well
established.
 Education of the general population regarding healthy dietary habits and regular exercise will reduce the
prevalence of multiple coronary heart disease risk factors.
 For patients with risk factors refractory to lifestyle interventions, education can enhance compliance with
prescribed therapy.