Common side effects include headache and low blood pressure. The low blood pressure can be severe. It is unclear if use in pregnancy is safe for the fetus. It should not be used together with medications within the PDE5 inhibitor family such as sildenafil due to the risk of low blood pressure. Nitroglycerin is in the nitrate family of medications. While it is not entirely clear how it works, it is believed to function by dilating blood vessels.
History, society and culture
Nitroglycerin was written about as early as 1846 and came into medical use in 1878. The drug nitroglycerin is a dilute form of the same chemical used as the explosive, nitroglycerin. Dilution makes it non-explosive. In 2021, it was the 174th most commonly prescribed medication in the United States, with more than 2million prescriptions.
Medical uses
Three different forms of nitroglycerin: intravenous, sublingual spray, and the nitroglycerin patch.
Glyceryl trinitrate is useful in decreasing angina attacks, perhaps more so than reversing angina once started, by supplementing blood concentrations of NO, also called endothelium-derived relaxing factor,
before the structure of NO as the responsible agent was known. This led
to the development of transdermal patches of glyceryl trinitrate,
providing 24-hour release. However, the effectiveness of glyceryl trinitrate is limited by development of tolerance/tachyphylaxis
within 2–3 weeks of sustained use. Continuous administration and
absorption (such as provided by daily pills and especially skin patches)
accelerate onset of tolerance and limit the usefulness of the agent.
Thus, glyceryl trinitrate works best when used only in short-term, pulse
dosing. Glyceryl trinitrate is useful for myocardial infarction (heart attack) and pulmonary edema, again working best if used quickly, within a few minutes of symptom onset, as a pulse dose.It
may also be given as a sublingual or buccal dose in the form of a
tablet placed under the tongue or a spray into the mouth for the
treatment of an angina attack.
Other uses
Tentative evidence indicates efficacy of glyceryl trinitrate in the treatment of various tendinopathies, both in pain management and acceleration of soft tissue repair.
Glyceryl trinitrate is also used in the treatment of anal fissures, though usually at a much lower concentration than that used for angina treatment.
Glyceryl trinitrate has been used to decrease pain associated with dysmenorrhea.
Glyceryl trinitrate was once researched for the prevention and treatment of osteoporosis; however, the researcher Sophie Jamal was found to have falsified the findings, sparking one of the largest scientific misconduct cases in Canada.
Tolerance
After long-term use for chronic conditions, nitrate tolerance—tolerance
to agents such as glyceryl trinitrate— may develop in a patient,
reducing its effectiveness. Tolerance is defined as the loss of
symptomatic and hemodynamic effects of glyceryl trinitrate and/or the
need for higher doses of the drug to achieve the same effects, and was first described soon after the introduction of glyceryl trinitrate in cardiovascular therapy. Studies have shown that nitrate tolerance is associated with vascular abnormalities which have the potential to worsen patients' prognosis. These include endothelial and autonomic dysfunction.
The mechanisms of nitrate tolerance have been investigated over
the last 30 years, and several hypotheses to explain tolerance have been
offered, including:
plasma volume expansion
impaired transformation of glyceryl trinitrate into NO or related species
counteraction of glyceryl trinitrate vasodilation by neurohormonal activation
oxidative stress
Adverse events
Glyceryl trinitrate can cause severe hypotension, reflex tachycardia,
and severe headaches that necessitate analgesic intervention for pain
relief, the painful nature of which can have a marked negative effect on
patient compliance.
Glyceryl trinitrate transdermal patches should be removed before defibrillation due to the risk of explosion and/or burns,but investigations have concluded that glyceryl trinitrate patch explosions during defibrillation were due to the breakdown voltage of the metal mesh in some patches.
Mechanism of action
Glyceryl trinitrate is a prodrug which must be denitrated, with the nitrite anion or a related species further reduced to produce the active metabolite nitric oxide (NO). Organic nitrates that undergo these two steps within the body are called nitrovasodilators,
and the denitration and reduction occur via a variety of mechanisms.
The mechanism by which such nitrates produce NO is widely disputed. Some
believe that organic nitrates produce NO by reacting with sulfhydryl groups, while others believe that enzymes such as glutathione S-transferases, cytochrome P450 (CYP), and xanthine oxidoreductase are the primary source of glyceryl trinitrate bioactivation. In recent years, a great deal of evidence has been produced
that supports the conclusion that glyceryl trinitrate's clinically
relevant denitration and reduction produce 1,2-glyceryl dinitrate (GDN)
and NO, and that this reaction is catalysed by mitochondrial aldehyde dehydrogenase (ALDH2 or mtALDH).
It was known almost from the time of the first synthesis of glyceryl trinitrate by Ascanio Sobrero in 1846 that handling and tasting of nitroglycerin could cause sudden intense headaches, which suggested a vasodilation effect (as suggested by Sobrero). Constantine Hering
developed a form of nitroglycerin in 1847 and advocated for its dosing
as a treatment of a number of diseases; however, its use as a specific
treatment for blood pressure and chest pain was not among these. This is
primarily due to his deep rooted focus in homeopathy.
Following Thomas Brunton's discovery that amyl nitrite could be used to treat chest pain, William Murrell experimented with the use of nitroglycerin to alleviate angina and reduce blood pressure, and showed that the accompanying headaches occurred as a result of overdose.
Murrell began treating patients with small doses of glyceryl trinitrate
in 1878, and the substance was widely adopted after he published his
results in The Lancet in 1879.
The medical establishment used the name "glyceryl trinitrate" or
"trinitrin" to avoid alarming patients, because of a general awareness
that nitroglycerin was explosive.
There is a relationship between severity of angina and degree of oxygen deprivation
in the heart muscle. However, the severity of angina does not always
match the degree of oxygen deprivation to the heart or the risk of a heart attack
(myocardial infarction). Some people may experience severe pain even
though there is little risk of a heart attack whilst others may have a
heart attack and experience little or no pain.
In some cases, angina can be quite severe. Worsening angina attacks,
sudden-onset angina at rest, and angina lasting more than 15 minutes are
symptoms of unstable angina (usually grouped with similar conditions as the acute coronary syndrome).
As these may precede a heart attack, they require urgent medical
attention and are, in general, treated similarly to heart attacks.
In the early 20th century, severe angina was seen as a sign of impending death. However, modern medical therapies have improved the outlook substantially. Middle-age patients who experience moderate to severe angina (grading by classes II, III, and IV) have a five-year survival rate of approximately 92%.
Classification
Stable angina
Also known as 'effort angina', this refers to the classic type of angina related to myocardial ischemia.
A typical presentation of stable angina is that of chest discomfort and
associated symptoms precipitated by some activity (running, walking,
etc.) with minimal or non-existent symptoms at rest or after
administration of sublingualnitroglycerin.
Symptoms typically diminish several minutes after activity and recur
when activity resumes. In this way, stable angina may be thought of as
being similar to intermittent claudication symptoms. Other recognized precipitants of stable angina include cold weather, heavy meals, and emotional stress.
it occurs at rest (or with minimal exertion), usually lasting more than 10 minutes
it is severe and of new-onset (i.e., within the prior 4–6 weeks)
it occurs with a crescendo pattern (i.e., distinctly more severe, prolonged, or frequent than before).
UA may occur often unpredictably and even at rest, which may be a
serious indicator of an impending heart attack. The primary factor
differentiating unstable angina from stable angina (other than symptoms)
is the underlying pathophysiology of the atherosclerosis. The pathophysiology of unstable angina is the reduction of coronary blood flow due to transient platelet aggregation on apparently normal endothelium, coronary artery spasms, or coronary thrombosis.
The process starts with atherosclerosis, progresses through
inflammation to yield an active unstable plaque, which undergoes
thrombosis and results in acute myocardial ischemia, which, if not
reversed, results in cell necrosis (infarction). Studies show that 64% of all unstable anginas occur between 22:00 and 08:00 when patients are at rest.
In stable angina, the developing atheroma (a fatty plaque) is protected with a fibrous cap. This cap may rupture in unstable angina, allowing blood clots to precipitate and further decrease the area of the coronary vessel's lumen
or the interior open space within an artery. This explains why, in
many cases, unstable angina develops independently of activity.
Microvascular angina, also known as cardiac syndrome X,
is characterized by angina-like chest pain, in the context of normal
epicardial coronary arteries (the largest vessels on the surface of the
heart, prior to significant branching) on angiography.
The original definition of cardiac syndrome X also mandated that
ischemic changes on exercise (despite normal coronary arteries) were
displayed, as shown on cardiac stress tests.
The primary cause of microvascular angina is unknown, but factors
apparently involved are endothelial dysfunction and reduced flow
(perhaps due to spasm) in the tiny "resistance" blood vessels of the
heart. Since microvascular angina is not characterized by major arterial blockages, it is harder to recognize and diagnose.
Microvascular angina was previously considered a rather benign
condition, but more recent data has changed this attitude. Studies,
including the Women's Ischemia Syndrome Evaluation (WISE), suggest that
microvascular angina is part of the pathophysiology of ischemic heart
disease, perhaps explaining the higher rates of angina in females than
in males, as well as their predilection towards ischemia and acute coronary syndromes in the absence of obstructive coronary artery disease.
Signs and symptoms
Diagram of discomfort caused by coronary artery disease. Pressure,
fullness, squeezing or pain in the center of the chest. Discomfort can
also be felt in the neck, jaw, shoulders, back or arms.
Angina pectoris can be quite painful, but many patients with angina
complain of chest discomfort rather than actual pain: the discomfort is
usually described as a pressure, heaviness, tightness, squeezing,
burning, or choking sensation. Apart from chest discomfort, anginal
pains may also be experienced in the epigastrium (upper central abdomen), back, neck area, jaw, or shoulders. This is explained by the concept of referred pain
and is because the spinal level that receives visceral sensation from
the heart simultaneously receives cutaneous sensation from parts of the
skin specified by that spinal nerve's dermatome,
without an ability to discriminate the two. Typical locations for
referred pain are arms (often inner left arm), shoulders, and neck into
the jaw. Angina is typically precipitated by exertion or emotional
stress. It is exacerbated by having a full stomach and by cold
temperatures. Pain may be accompanied by breathlessness, sweating, and
nausea in some cases. In this case, the pulse rate and the blood
pressure increases. Chest pain lasting only a few seconds is normally
not angina (such as precordial catch syndrome).
Myocardial ischemia
comes about when the myocardium (the heart muscle) receives
insufficient blood and oxygen to function normally either because of
increased oxygen demand by the myocardium or because of decreased supply
to the myocardium. This inadequate perfusion
of blood and the resulting reduced delivery of oxygen and nutrients are
directly correlated to blocked or narrowed blood vessels.
A variant form of angina—Prinzmetal's angina—occurs in patients with normal coronary arteries or insignificant atherosclerosis. It is believed caused by spasms of the artery. It occurs more in younger women.
Coital angina, also known as angina d'amour, is angina subsequent to sexual intercourse. It is generally rare, except in patients with severe coronary artery disease.
Routine counseling of adults by physicians to advise them to improve
their diet and increase their physical activity has, in general, been
found to induce only small changes in actual behavior. Therefore, as of
2012, The U.S. Preventive Services Task Force
does not recommend routine lifestyle counseling of all patients without
known cardiovascular disease, hypertension, hyperlipidemia, or
diabetes, and instead recommends selectively counseling only those
patients who seem most ready to make lifestyle changes and using
available time with other patients to explore other types of
intervention that would be more likely to have a preventative impact.
One study found that smokers with coronary artery disease had a significantly increased level of sympathetic nerve
activity when compared to those without. This is in addition to
increases in blood pressure, heart rate, and peripheral vascular
resistance associated with nicotine, which may lead to recurrent angina
attacks. In addition, the Centers for Disease Control and Prevention (CDC) reports that the risk of CHD (Coronary heart disease), stroke, and PVD (Peripheral vascular disease)
is reduced within 1–2 years of smoking cessation. In another study, it
was found that, after one year, the prevalence of angina in smokingmales
under 60 after an initial attack was 40% less in those having quit
smoking compared to those that continued. Studies have found that there
are short-term and long-term benefits to smoking cessation.
a reduction of blood flow to the heart that can be caused by stenosis, spasm, or acute occlusion (by an embolus) of the heart's arteries.
resistance of the blood vessels. This can be caused by narrowing of the blood vessels; a decrease in radius. Blood flow is proportional to the radius of the artery to the fourth power.
reduced oxygen-carrying capacity of the blood, due to several
factors such as a decrease in oxygen tension and hemoglobin
concentration. This decreases the ability of hemoglobin to carry oxygen to myocardial tissue.
Atherosclerosis is the most common cause of stenosis
(narrowing of the blood vessels) of the heart's arteries and, hence,
angina pectoris. Some people with chest pain have normal or minimal
narrowing of heart arteries; in these patients, vasospasm is a more likely cause for the pain, sometimes in the context of Prinzmetal's angina and syndrome X.
Myocardial ischemia also can be the result of factors affecting
blood composition, such as the reduced oxygen-carrying capacity of blood, as seen with severe anemia (low number of red blood cells), or long-term smoking.
Pathophysiology
Angina
results when there is an imbalance between the heart's oxygen demand
and supply. This imbalance can result from an increase in demand (e.g.,
during exercise) without a proportional increase in supply (e.g., due to
obstruction or atherosclerosis of the coronary arteries).
However, the pathophysiology of angina in females varies significantly as compared to males. Non-obstructive coronary disease is more common in females.
Diagnosis
Angina should be suspected in people presenting tight, dull, or heavy chest discomfort that is:
Retrosternal or left-sided, radiating to the left arm, neck, jaw, or back.
Associated with exertion or emotional stress and relieved within several minutes by rest.
Precipitated by cold weather or a meal.
Some people present with atypical symptoms, including breathlessness,
nausea, or epigastric discomfort, or burning. These atypical symptoms
are particularly likely in older people, women, and those with diabetes.
Anginal pain is not usually sharp or stabbing or influenced by respiration. Antacids and simple analgesics
do not usually relieve the pain. If chest discomfort (of whatever site)
is precipitated by exertion, relieved by rest, and relieved by glyceryl
trinitrate, the likelihood of angina is increased.
In angina patients momentarily not feeling any chest pain, an electrocardiogram
(ECG) is typically normal unless there have been other cardiac problems
in the past. During periods of pain, depression, or elevation of the ST segment may be observed. To elicit these changes, an exercise ECG test
("treadmill test") may be performed, during which the patient exercises
to his/her maximum ability before fatigue, breathlessness, or pain
intervenes; if characteristic ECG changes are documented (typically more
than 1 mm of flat or downsloping ST depression), the test is considered
diagnostic for angina. Even constant monitoring of the blood pressure
and the pulse rate can lead to some conclusions regarding angina. The
exercise test is also useful in looking for other markers of myocardial
ischemia: blood pressure response (or lack thereof, in particular, a
drop in systolic blood pressure), dysrhythmia, and chronotropic
response. Other alternatives to a standard exercise test include a thallium scintigram or sestamibi scintigram (in patients unable to exercise enough for the treadmill tests, e.g., due to asthma or arthritis or in whom the ECG is too abnormal at rest) or stress echocardiography.
In patients in whom such noninvasive testing is diagnostic, a coronary angiogram is typically performed to identify the nature of the coronary lesion, and whether this would be a candidate for angioplasty, coronary artery bypass graft
(CABG), treatment only with medication, or other treatments. In
hospitalized patients with unstable angina (or the newer term of
"high-risk acute coronary syndromes"), those with resting ischaemic ECG
changes or those with raised cardiac enzymes such as troponin may undergo coronary angiography directly.
Angina pectoris occurs as a result of coronary blood flow
insufficiency in the face of increased oxygen demand. The principal goal
in the prevention and relief of angina is to limit the oxygen
requirement of the heart so it can meet the inadequate oxygen supply
derived through the blood supplied from the stenosed or constricted
arteries. The main goals of treatment in angina pectoris are relief of
symptoms, slowing progression of the disease, and reduction of future
events, especially heart attacks and death. Beta blockers (e.g., carvedilol, metoprolol, propranolol)
have a large body of evidence in morbidity and mortality benefits
(fewer symptoms, less disability, and longer life) and short-acting nitroglycerin medications have been used since 1879 for symptomatic relief of angina.
There are differing course of treatments for the patient depending on
the type of angina the patient has. However, this second can provide a
brief overview of the types of medications provided for angina and the
purpose by which they are prescribed.
Beta blockers,
specifically B1 adrenergic blockers without intrinsic sympathomimetic
activity, are preferred for angina treatment, out of B1 selective and
non-selective as well as B1 ISA agents. B1 blockers are cardioselective
blocking agents (such as nevibolol, atenolol, metoprolol, bisoprolol,
etc.) which result in blocking cAMP in the heart muscle cells. cAMP,
which plays a vital role in phosphorylating the ryanodine receptor and
LTCC, will usually increase Ca+2 levels in the heart muscle
cells, blocking contraction. Therefore, B1 blockade decreases the HR and
contraction of the heart muscle, making it demand less oxygen. An
important thing to note is that the B1 cardioselective blockers are
cardioselective and not cardio-specific. This means that if the
beta-adrenergic antagonist is prescribed in higher doses, it can lose
the selectivity aspect and begin causing hypertension from B2 adrenergic
stimulation of smooth muscle cells. This is why in therapy for patients
with angina, the vasodilatory organonitrates complement the use of
B-blockers when prescribed the use of angina. The preference for Beta-1
cardioselective blockers is for B1 cardioselective blockers without
instrinsic sympathetic activity. Beta blockers with intrinsic
sympathetic activity will still do the beta blockade of the heart muscle
cells and have a decreased ionotrophic and chronotropic effect, but
this effect will be to a lesser extent than if the beta blocker did not
have the instrinsic sympathetic activity. A common beta-blocker with ISA
prescribed for the treatment of angina is Acebutolol.
Non-selective beta-adrenergic antagonists will yield the same
action on B1 receptors, however will also act on B2 receptors. These
medications, such as Propranolol and Nadolol, act on B1 receptors on
smooth muscle cells as well. B1 blockade occurs in the smooth muscle
cells. Specifically cAMP is responsible for inhibiting Myosin Light
Kinase, the enzyme responsible for acting on Actin-Myosin. The
inhibition of B1 will result in decreased levels of cAMP which will lead
to increased levels of Myosin Light Chain Kinase in the smooth muscle
cells, the enzyme responsible for acting on Actin-Myosin and leading to
contraction of the smooth muscle cell. This increased contraction of the
smooth muscle cell from B1 blockade is not desirable since it explains
the hypertension that may arise with patients taking that medication.
Calcium channel blockers act to decrease the heart's workload,
and thus its requirement for oxygen by blocking the calcium channels of
the heart muscle cell. With decreased intracellular calcium, the
calcium-troponin complex does not form in the heart muscle cell and it
does not contract, therefore reducing the need for oxygen.
The other class of medication that can be used to treat angina
are the organic nitrates. Organic nitrates are used extensively to treat
angina. They improve coronary blood flow of the coronary arteries
(arteries which supply blood to the heart muscle) by reversing and
preventing vasospasm, which increases the blood flow to the heart,
improving perfusion and oxygen delivery to the heart associated with the
pain of angina. These drugs also reduce systemic vascular resistance,
of both veins and arteries but the veins to a greater extent. The
decrease in the resistance of the arteries and veins decreases the
myocardial oxygen demand, which also reduces myocardial oxygen demand. Nitroglycerin is a potent vasodilator
that decreases myocardial oxygen demand by decreasing the heart's
workload. Nitroglycerin should not be given if certain inhibitors such
as sildenafil, tadalafil, or vardenafil have been taken within the previous 12 hours as the combination of the two could cause a serious drop in blood pressure.
Treatments for angina are balloon angioplasty, in which the balloon is inserted at the end of a catheter and inflated to widen the arterial lumen. Stents to maintain the arterial widening are often used at the same time. Coronary bypass surgery involves bypassing constricted arteries with venous grafts. This is much more invasive than angioplasty.
Calcium channel blockers (such as nifedipine (Adalat) and amlodipine), isosorbide mononitrate and nicorandil are vasodilators commonly used in chronic stable angina. A new therapeutic class, called If inhibitor, has recently been made available: Ivabradine provides heart rate reduction without affecting contractility leading to major anti-ischemic and antianginal efficacy. ACE inhibitors are also vasodilators with both symptomatic and prognostic benefit. Statins are the most frequently used lipid/cholesterol modifiers, which probably also stabilize existing atheromatous plaque. Low-dose aspirin
decreases the risk of heart attack in patients with chronic stable
angina, and was part of standard treatment. However, in patients without
established cardiovascular disease, the increase in hemorrhagic stroke
and gastrointestinal bleeding offsets any benefits and it is no longer
advised unless the risk of myocardial infarction is very high.
Exercise is also a very good long-term treatment for the angina
(but only particular regimens – gentle and sustained exercise rather
than intense short bursts), probably working by complex mechanisms such as improving blood pressure and promoting coronary artery collateralisation.
The calcium channel blocker nifedipine
prolongs cardiovascular event- and procedure-free survival in patients
with coronary artery disease. New overt heart failures were reduced by
29% compared to placebo; however, the mortality rate difference between
the two groups was statistically insignificant.
Microvascular angina in women
Women
with myocardial ischemia often have either no or atypical symptoms,
such as palpitations, anxiety, weakness, and fatigue. Additionally, many
females with angina are found to have cardiac ischemia, yet no evidence
of obstructive coronary artery disease on cardiac catheterization.
Evidence is accumulating that nearly half of females with myocardial
ischemia have coronary microvascular disease, a condition often called
microvascular angina (MVA). Small intramyocardial arterioles constrict
in MVA causing ischemic pain that is less predictable than with typical
epicardial coronary artery disease (CAD).
The pathophysiology is complex and still being elucidated, but
there is strong evidence that endothelial dysfunction, decreased
endogenous vasodilators, inflammation, changes in adipokines, and
platelet activation are contributing factors. The diagnosis of MVA may
require catheterization during which there is an assessment of the
microcirculatory response to adenosine or acetylcholine and measurement
of coronary and fractional flow reserve. New techniques include positron
emission tomography (PET) scanning, cardiac magnetic resonance imaging
(MRI), and transthoracic Doppler echocardiography.
Managing MVA can be challenging, for example, females with this
condition have less coronary microvascular dilation in response to
nitrates than do those without MVA. Females with MVA often have
traditional risk factors for CAD such as obesity, dyslipidemia,
diabetes, and hypertension. Aggressive interventions to reduce
modifiable risk factors are an important component of management,
especially smoking cessation, exercise, and diabetes management. The
combination of non-nitrate vasodilators, such as calcium channel
blockers and angiotensin-converting enzyme (ACE) inhibitors along with
HMG-CoA reductase inhibitors (statins), also is effective in many women,
and new drugs, such as Ranolazine and Ivabradine, have shown promise in
the treatment of MVA. Other approaches include spinal cord stimulators,
adenosine receptor blockade, and psychiatric intervention.
Suspected angina
Hospital
admission for people with the following symptoms is recommended, as
they may have unstable angina: pain at rest (which may occur at night),
pain on minimal exertion, angina that seems to progress rapidly despite
increasing medical treatment. All people with suspected angina should be
urgently referred to a chest pain evaluation service, for confirmation
of the diagnosis and assessment of the severity of coronary heart
disease.
Epidemiology
As of 2010, angina due to ischemic heart disease
affects approximately 112 million people (1.6% of the global
population) being slightly more common in males than females (1.7% to
1.5%).
In the United States, 10.2 million are estimated to experience angina with approximately 500,000 new cases occurring each year.
Angina is more often the presenting symptom of coronary artery disease
in females than in men. The prevalence of angina rises with increasing
age, with a mean age of onset of 62.3 years.
After five years post-onset, 4.8% of individuals with angina
subsequently died from coronary heart disease. Males with angina were
found to have an increased risk of subsequent acute myocardial
infarction and coronary heart disease related death than women. Similar
figures apply in the remainder of the Western world. All forms of
coronary heart disease are much less-common in the Third World, as its risk factors are much more common in Western and Westernized countries; it could, therefore, be termed a disease of affluence.
History
The condition was named "hritshoola" in ancient India and was described by Sushruta (6th century BC).
The first clinical description of angina pectoris was by a British physician Dr. William Heberden in 1768.
Acute coronary syndrome (ACS) is a syndrome (a set of signs and symptoms) due to decreased blood flow in the coronary arteries such that part of the heart muscle is unable to function properly or dies. The most common symptom is centrally located pressure-like chest pain, often radiating to the left shoulder or angle of the jaw, and associated with nausea and sweating.
Many people with acute coronary syndromes present with symptoms other
than chest pain, particularly women, older people, and people with diabetes mellitus.
ACS should be distinguished from stable angina, which develops during physical activity or stress 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.
Signs and symptoms
Symptoms of the acute coronary syndromes are similar. The cardinal symptom of critically decreased blood flow to the heart is chest pain, experienced as tightness, pressure, or burning.
Localisation is most commonly around or over the chest and may radiate
or be located to the arm, shoulder, neck, back, upper abdomen, or jaw. This may be associated with sweating, nausea, or shortness of breath.Previously, the word "atypical" was used to describe chest pain not
typically heart-related, however this word is not recommended and has
been replaced by "noncardiac" to describe chest pain that indicate a low
likelihood of heart-related pain.
In unstable angina, symptoms may appear on rest or on minimal exertion. The symptoms can last longer than those in stable angina, can be resistant to rest or medicine, and can get worse over time.
In those who have ACS, atheroma rupture is most commonly found 60% when compared to atheroma erosion (30%), thus causes the formation of thrombus which block the coronary arteries. Plaque rupture is responsible for 60% in ST elevated myocardial infarction
(STEMI) while plaque erosion is responsible for 30% of the STEMI and
vice versa for Non ST elevated myocardial infarction (NSTEMI). In plaque
rupture, the content of the plaque is lipid rich, collagen poor, with
abundant inflammation which is macrophage predominant, and covered with a thin fibrous cap. Meanwhile, in plaque erosion, the plaque is rich with extracellular matrix, proteoglycan, glycoaminoglycan, but without fibrous caps, no inflammatory cells, and no large lipid core. After the coronary arteries are unblocked, there is a risk of reperfusion injury due spreading inflammatory mediators throughout the body. Investigations is still underway on the role of cyclophilin D in reducing the reperfusion injury.
Other, less common, causes of acute coronary syndrome include spontaneous coronary artery dissection,
ischemia in the absence of obstructive coronary artery disease (INOCA),
and myocardial infarction in the absence of obstructive coronary artery
disease (MINOCA).
Diagnosis
Classification of acute coronary syndromes.
Electrocardiogram
In the setting of acute chest pain, the electrocardiogram (ECG or EKG) is the investigation that most reliably distinguishes between various causes. The ECG should be done as early as practicable, including in the ambulance if possible. ECG changes indicating acute heart damage include: ST elevation, new left bundle branch block and ST depression amongst others. The absence of ECG changes does not immediately distinguish between unstable angina and NSTEMI.
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 cholesterol levels; 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% reduction in
hospital admissions for acute coronary syndrome. 67% of the decrease
occurred in non-smokers.
If the ECG confirms changes suggestive of myocardial infarction (ST elevation in specific leads, a new left bundle branch block or a true posterior MI pattern), thrombolytics may be administered or percutaneous coronary intervention 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 artery and advanced to the heart to identify blockages in the coronary arteries. 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. 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 2009 case control study.
NSTEMI and NSTE-ACS
If
the ECG does not show typical changes consistent with STEMI, the term
"non-ST segment elevation ACS" (NSTE-ACS) may be used and encompasses
"non-ST elevation MI" (NSTEMI) and unstable angina.
The accepted management of unstable angina and acute coronary syndrome is therefore empirical treatment with aspirin, a second platelet inhibitor such as clopidogrel, prasugrel or ticagrelor, and heparin (usually a low-molecular weight heparin), with intravenous nitroglycerin and opioids if the pain persists. The heparin-like drug known as fondaparinux appears to be better than enoxaparin.
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. Using statins in the first 14 days after ACS reduces the risk of further ACS.
Cocaine-associated ACS should be managed in a manner similar to other patients with acute coronary syndrome except beta blockers should not be used and benzodiazepines should be administered early.
Prognosis
Prediction scores
The TIMI risk score can identify high risk patients in ST-elevation and non-ST segment elevation MI ACS and has been independently validated.
Based on a global registry of 102,341 patients, the GRACE risk scoreestimates in-hospital, 6 months, 1 year, and 3-year mortality risk after a heart attack. It takes into account clinical (blood pressure, heart rate, EKG findings) and medical history.
Nowadays, GRACE risk score is also used within non-ST elevation ACS
patients as a high-risk criteria(GRACE score > 140), which may favor
early invasive strategy within 24 hours of the heart attack.
Biomarkers
Coronary CT angiography combined with troponin levels is also helpful to triage those who are susceptible to ACS. F-fluoride positron emission tomography is also helpful in identifying those with high risk, lipid-rich coronary plaques.
Day of admission
Studies
have shown that for ACS patients, weekend admission is associated with
higher mortality and lower utilization of invasive cardiac procedures,
and those who did undergo these interventions had higher rates of
mortality and complications than their weekday counterparts. This data
leads to the possible conclusion that access to
diagnostic/interventional procedures may be contingent upon the day of
admission, which may impact mortality. This phenomenon is described as weekend effect.
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