Acute coronary syndrome (ACS) is usually one of three diseases involving

the coronary arteries: ST elevation myocardial infarction (30%), non ST elevation

myocardial infarction (25%), or unstable angina (38%).
These types are named according to the appearance of
the electrocardiogram (ECG/EKG) asnon-ST segment elevation myocardial
infarction (NSTEMI) and ST segment elevation myocardial infarction (STEMI). There
can be some variation as to which forms of MI is classified under acute coronary
syndrome.
ACS should be distinguished from stable angina, which develops during exertion and
resolves at rest. In contrast with stable angina, unstable angina occurs suddenly, often
at rest or with minimal exertion, or at lesser degrees of exertion than the individual's
previous angina ("crescendo angina"). New onset angina is also considered unstable
angina, since it suggests a new problem in a coronary artery.
Though ACS is usually associated with coronary thrombosis, it can also be associated
with cocaine use. Cardiac chest pain can also be precipitated
by anemia, bradycardias (excessively slow heart rate) or tachycardias (excessively fast
heart rate)
Signs and symptoms
The cardinal sign of decreased blood flow to the heart is chest pain experienced as
tightness around the chest and radiating to the left arm and the left angle of the jaw.
This may be associated with diaphoresis (sweating), nausea and vomiting, as well
as shortness of breath. In many cases, the sensation is "atypical", with pain
experienced in different ways or even being completely absent (which is more likely in
female patients and those with diabetes). Some may report palpitations, anxiety or a
sense of impending doom and a feeling of being acutely ill.
The description of the chest discomfort as a pressure has little utility in aiding a
diagnosis as it is not specific for ACS.

Diagnosis
Classification of acute coronary syndromes.

Electrocardiogram
In the setting of acute chest pain, the electrocardiogram is the investigation that most
reliably distinguishes between various causes.[7] If this indicates acute heart damage
(elevation in the ST segment, new left bundle branch block), treatment for a heart attack
in the form of angioplasty or thrombolysis is indicated immediately (see below). In the
absence of such changes, it is not possible to immediately distinguish between unstable
angina and NSTEMI.
Imaging and blood tests
As it is only one of the many potential causes of chest pain, the patient usually has a
number of tests in the emergency department, such as a chest X-ray, blood
tests(including myocardial markers such as troponin I or T, and a D-dimer if
a pulmonary embolism is suspected), and telemetry (monitoring of the heart rhythm).
Prediction scores
The ACI-TIPI score can be used to aid diagnosis; using 7 variables from the admission
record, this score predicts crudely which patients are likely to have myocardial ischemia.
[8]
For example according to a randomized controlled trial, males having chest pain with
normal or non diagnostic ECGare at higher risk for having acute coronary syndrome
than women.[9] In this study, the sensitivity was 65.2% and specificity was 44%. This
particular study had an 8.4% prevalence of acute coronary syndrome, which means
the positive predictive value of being a male with chest pain and having coronary
syndrome is 9.6% and negative predictive value is 93.2% ( click here to adjust these
results for patients at higher or lower risk of acute coronary syndrome).
In a second cohort study, exercise electrocardiography was similarly found to be a poor
predictor of acute coronary syndrome at follow-up.[10]Of the patients who had a coronary
event at 6 years of follow up, 47% had a negative ECG at the start of the study. With an
average follow up of 2.21 years the receiver operating characteristic curves gave resting
ECG a score of 0.72 and exercise ECG a score of 0.74.
Prevention

Acute coronary syndrome often reflects a degree of damage to the coronaries

by atherosclerosis. Primary prevention of atherosclerosis is controlling the risk factors:
healthy eating, exercise, treatment for hypertension and diabetes, avoiding smoking and
controlling cholesterollevels; in patients with significant risk factors, aspirin has been
shown to reduce the risk of cardiovascular events. Secondary prevention is discussed
in myocardial infarction.
After a ban on smoking in all enclosed public places was introduced in Scotland in
March 2006, there was a 17 percent reduction in hospital admissions for acute coronary
syndrome. 67% of the decrease occurred in non-smokers.[11]
Treatment

People with presumed ACS are typically treated with aspirin, nitroglycerin, and if the
chest discomfort persists morphine.[12] Otheranalgesics such as nitrous oxide are of
unknown benefit.
STEMI
If the ECG confirms changes suggestive of myocardial infarction (ST elevations in
specific leads, a new left bundle branch block or a true posterior MI
pattern), thrombolytics may be administered or primary coronary angioplasty may be
performed. In the former, medication is injected that stimulates fibrinolysis, destroying
blood clots obstructing the coronary arteries. In the latter, a flexible catheter is passed
via the femoral or radial arteries and advanced to the heart to identify blockages in the
coronaries. When occlusions are found, they can be intervened upon mechanically
with angioplasty and usually stent deployment if a lesion, termed the culprit lesion, is
thought to be causing myocardial damage. Data suggest that rapid triage, transfer and
treatment is essential.[13] The time frame for door-to-needle thrombolytic administration
according to American College of Cardiology (ACC) guidelines should be within 30
minutes, whereas the door-to-balloon Percutaneous Coronary Intervention (PCI) time
should be less than 90 minutes. It was found that thrombolysis is more likely to be
delivered within the established ACC guidelines among patients with STEMI as
compared to PCI according to a case control study .

NSTEMI and NSTE-ACS

If the ECG does not show typical changes, the term "non-ST segment elevation ACS" is
applied. The patient may still have suffered a "non-ST elevation MI" (NSTEMI). The
accepted management of unstable angina and acute coronary syndrome is therefore
empirical treatment withaspirin, heparin (usually a low-molecular weight heparin such
as enoxaparin) and clopidogrel, with intravenous glyceryl trinitrate and opioids if the
pain persists.
A blood test is generally performed for cardiac troponins twelve hours after onset of the
pain. If this is positive, coronary angiography is typically performed on an urgent basis,
as this is highly predictive of a heart attack in the near-future. If the troponin is negative,
a treadmill exercise test or a thallium scintigram may be requested.
If there is no evidence of ST segment elevation on the electrocardiogram, delaying
urgent angioplasty until the next morning is not inferior to doing so immediately.[15]
In a cohort study comparing NSTEMI and STEMI, patients with NSTEMI had statistically
similar mortality at one year after PCI as compared to patients with STEMI (3.4% vs
4.4%).[16] However, NSTEMI had significantly more "major cardiac events"
(death, myocardial infarction, disabling stroke, or requiring revascularization) at one
year (24.0% vs 16.6%).
Cocaine associated ACS should be managed in a manner similar to other patients with
acute coronary syndrome except beta blockersshould not be used
and benzodiazepines should be administered early.[17]
Prognosis

TIMI score
The TIMI risk score can identify high risk patients[18] and has been independently
validated.[19][20]
Biomarkers for diagnosis
The aim of diagnostic markers is to identify patients with ACS even when there is no
evidence of heart muscle damage.

 Ischemia-Modified Albumin (IMA) - In cases of Ischemia - Albumin undergoes a

conformational change and loses its ability to bind transitional metals (copper or
cobalt). IMA can be used to assess the proportion of modified albumin in ischemia.
Its use is limited to ruling out ischemia rather than a diagnostic test for the
occurrence of ischemia.
 Myeloperoxidase (MPO) - The levels of circulating MPO, a leukocyte enzyme,
elevate early after ACS and can be used as an early marker for the condition.
  Glycogen Phosphorylase Isoenzyme BB-(GPBB) is an early marker of cardiac
ischemia and is one of three isoenzyme of Glycogen Phosphorylase.

 Troponin is a late cardiac marker of ACS

Biomarkers for Risk Stratification

The aim of prognostic markers is to reflect different components of pathophysiology of
ACS. For example:

 Natriuretic peptide - Both B-type natriuretic peptide (BNP) and N-terminal Pro
BNP can be applied to predict the risk of death and heart failure following ACS.
 Monocyte chemo attractive protein (MCP)-1 - has been shown in a number of
studies to identify patients with a higher risk of adverse outcomes after ACS.

Pathophysiology
Myocardial ischemia is most often due to atherosclerotic plaques, which reduce the
blood supply to a portion of myocardium. Initially, the plaques allow sufficient blood flow
to match myocardial demand. When myocardial demand increases, the areas of
narrowing may become clinically significant and precipitate angina. Angina that is
reproduced by exercise, eating, and/or stress and is subsequently relieved with rest,
and without recent change in frequency or severity of activity that produce symptoms, is
called chronic stable angina. Over time, the plaques may thicken and rupture, exposing
a thrombogenic surface upon which platelets aggregate and thrombus forms. The
patient may note a change in symptoms of cardiac ischemia with a change in severity or
of duration of symptoms. This condition is referred to as unstable angina.

Patients with STEMI have a high likelihood of a coronary thrombus occluding the infarct
artery. Angiographic evidence of coronary thrombus formation may be seen in more
than 90% of patients with STEMI but in only 1% of patients with stable angina and about
35-75% of patients with unstable angina or NSTEMI. However, not every STEMI
evolves into a Q-wave myocardial infarction (MI); likewise, a patient with NSTEMI may
develop Q waves.

The excessive mortality rate of coronary heart disease is primarily due to rupture and
thrombosis of the atherosclerotic plaque. Inflammation plays a critical role in plaque
destabilization and is widespread in the coronary and remote vascular beds. Systemic
inflammatory, thrombotic, and hemodynamic factors are relevant to the outcome.
Evidence indicates that platelets contribute to promoting plaque inflammation as well as
thrombosis. A new theory of unbalanced cytokine-mediated inflammation is emerging,
providing an opportunity for intervention.

A less common cause of angina is dynamic obstruction, which may be caused by

intense focal spasm of a segment of an epicardial artery (Prinzmetal angina). Coronary
vasospasm is a frequent complication in patients with connective tissue disease. Other
causes include arterial inflammation and secondary unstable angina. Arterial
inflammation may be caused by or related to infection. Secondary unstable angina
occurs when the precipitating cause is extrinsic to the coronary arterial bed, such as
fever, tachycardia, thyrotoxicosis, hypotension, anemia, or hypoxemia. Most patients
who experience secondary unstable angina have chronic stable angina as a baseline
medical condition.

Spontaneous and cocaine-related coronary artery dissection remains an unusual cause

of ACS and should be included in the differential diagnosis, especially when a younger
female or cocaine user is being evaluated. An early clinical suspicion of this disease is
necessary for a good outcome. Cardiology consultation should be obtained for
consideration for urgent percutaneous coronary intervention.

Although rare, pediatric and adult ACS may result from the following (see Myocardial
Infarction in Childhood):

• ACS may occur with Marfan syndrome; Kawasaki disease; Takayasu arteritis; or
cystic medial necrosis with aortic root dilatation, aneurysm formation, and
dissection into the coronary artery.
• Anomalous origin of the left coronary artery from the pulmonary artery may occur
as unexplained sudden death in a neonate.
• Coronary artery ostial stenosis may occur after repair of a transposition of the
great arteries in the neonatal period.
• An aberrant left main coronary artery with its origin at the right sinus of Valsalva
may cause ACS, especially with exertion.
• Traumatic myocardial infarction can occur in patients at any age.
• Accelerated atherosclerosis is known to occur in cardiac transplant recipients on
immunosuppressive therapy.
• ACS may occur with progeria.

Irrespective of the cause of unstable angina, the result of persistent ischemia is MI.

Frequency
United States
Although the exact incidence of ACS is difficult to ascertain, hospital discharge data
indicate that 1,680,000 unique discharges for ACS occurred in 2001.

International
In Britain, annual incidence rate of angina is estimated at 1.1 cases per 1000 males and
0.5 cases per 1000 females aged 31-70 years. In Sweden, chest pain of ischemic origin
is thought to affect 5% of all males aged 50-57 years. In industrialized countries, annual
incidence rate of unstable angina is approximately 6 cases per 10,000 people.

Mortality/Morbidity
When the only therapy for angina was nitroglycerin and limitation of activity, patients
with newly diagnosed angina had a 40% incidence of MI and a 17% mortality rate within
3 months. A recent study shows that the 30-day mortality rate from ACS has decreased
as treatment has improved, a statistically significant 47% relative decrease in 30-day
mortality rate among newly diagnosed ACS from 1987-2000. This decrease in mortality
rate is attributed to aspirin, glycoprotein (GP) IIb/IIIa blockers, and coronary
revascularization via medical intervention or procedures.

Clinical characteristics associated with a poor prognosis include advanced age, male
sex, prior MI, diabetes, hypertension, and multiple-vessel or left-mainstem disease.

Sex
Incidence is higher in males among all patients younger than 70 years. This is due to
the cardioprotective effect of estrogen in females. At 15 years postmenopause, the
incidence of angina occurs with equal frequency in both sexes. Evidence exists that
women more often have coronary events without typical symptoms, which might explain
the frequent failure to initially diagnose ACS in women.

Age
ACS becomes progressively more common with increasing age. In persons aged 40-70
years, ACS is diagnosed more often in men than in women. In persons older than 70
years, men and women are affected about equally.