(F) L2: Markers for Cardiac Damage and Function (Part 2) Flashcards
Other Cardiac Markers
- A heme-containing protein (skeletal and cardiac) that binds with oxygen
- Found exclusively in muscle but absent in the circulation
- Its presence in the blood is indicative of muscle damage but not specific to the heart
- An adjunct marker in the early diagnosis of MI
- Is quickly released during muscle damage due to its low MW of 18kDa, serving as the earliest cardiac marker but is not specific
Myoglobin
Other Cardiac Markers
- Is cleared by renal filtration
- Levels are related to muscle mass and activity
- One of the protein markers to diffuse out of ischemic muscle cells
- A screening test for angina and early MI detection
- Is measured in the serum
Myoglobin
Other Cardiac Markers
Elevation: 1-4 hours
Peak: 6-9 hours
Decline: 18-24 hours
Myoglobin
Other Cardiac Markers
- An enzyme present in skeletal but not in cardiac muscle (negative marker)
- Released from damaged muscle at a fairly fixed ratio to myoglobin in cases of cardiac damage
Carbonic Anhydrase
Other Cardiac Markers
If a patient suffering from chest pains produces a (+) result for carbonic anhydrase, what is the interpretation?
The pain MAY NOT be of cardiac origin
Other Cardiac Markers
- An enzyme that catalyzes the first step in glycogenolysis
- Consists of isoenzymes from the liver, muscles, brain, myocardium, and other tissues
Glycogen Phosphorylase
Other Cardiac Markers
This GP isoenzyme is released earlier than other markers under conditions of reversible ischemia
GP-BB (brain)
Other Cardiac Markers
- Is found in all muscles but abundant in the heart
- More sensitive in the diagnosis of acute MI than TnT and myoglobin but is less specific
- Has a low MW of 15kDa and is used for fatty acid metabolism and lipid homeostasis
- An early marker of myocardial damage with same kinetics as myoglobin
Heart-type Fatty Acid-binding Protein (H-FABP)
Other Cardiac Markers
The ratio of myocardial to HFABP is (lower/higher) in the heart
Lower
Other Cardiac Markers
Elevation: 2-4 hours
Peak: 5-10 hours
Decline: 24-36 hours
Heart-type Fatty Acid-binding Protein (H-FABP)
Other Cardiac Markers
- Does not detect myocardial tissue damage as it is not released from damaged myocytes (a unique marker)
- Alters the cobalt-binding of albumin by its N-terminus domain
- A modification of this is caused by free radical formation within minutes of ischemia in the heart
- Has a reduced affinity for metal ions
- Detects ischemia prior to irreversible cell damage
Ischemia-modified Albumin (IMA)
Other Cardiac Markers
- The thick filament of the muscle contractile apparatus (heavy and light chains)
- Not specific for cardiac injuries hence not routinely used as a marker
Myosin
Other Cardiac Markers
- Includes myeloperoxidase (MPO), CRP, myeloid-related protein (MRP-8/14), and pregnancy-associated plasma protein A (PAPP-A)
- Are inferior to troponins in detecting acute MIs
- Is able to predict all-cause mortality and provide independent prognostic information apart from clinical risk factors
Novel Markers of Plaque Instability
TOF: Cardiac markers are always associated with AMIs
False (also caused by cardiac insults that relate to cardiac injury)
- This is a key feature of cardiomyopathies due to genetic issues and stress-related causes
- It comes in the form of apoptosis and/or necrosis
Cell Death
- A pathological state in which the heart fails to adequately supply the metabolic needs of the body due to a decrease in pumping function
- Not only does it come from cardiac overload but also from a complex interplay among genetic, inflammatory, and biological changes acting on cardiac myocytes, cardiac interstitium, or both
Heart Failure
This is the most common cause of heart failure
Coronary Heart Disease (CHD)
Types of Heart Failure
Indicated by pulmonary edema and decreased systemic blood supply
Left-Sided Heart Failure
Types of Heart Failure
Indicated by generalized edema
Right-Sided Heart Failure
Left or Right-sided Heart Failure?
- Most common type
- The heart loses some of its ability to pump out blood after reoxygenation
- Caused by coronary artery disease
Left-Sided
Left or Right-sided Heart Failure?
- The heart loses some of its ability to move oxygen-depleted blood to the lungs to pick up new oxygen
- Most often caused by the other kind of heart failure
- Can also occur even if the other side is apparently normal
Right-Sided
Left or Right-sided Heart Failure?
Symptoms:
1. Paroxysmal nocturnal dyspnea
2. Elevated pulmonary capillary wedge pressure
3. Pulmonary congestion with cough, cackles, wheezes, and blood-tinged sputum
4. Tachypnea
5. Restlessness
6. Tachycardia
7. Exertional dyspnea
8. Fatigue
9. Cyanosis
Left-Sided
Left or Right-sided Heart Failure?
Symptoms:
- Fatigue
- Increased peripheral venous pressure
- Ascites
- Enlarged liver and spleen
- May be secondary to chronic pulmonary problems
- Distended jugular veins
- Anorexia
- Complaints of GI distress
- Weight gain
- Dependent edema
Right-Sided
Lab Tests for Patients with Suspected Heart Failure
This can help determine if anemia or infection may be the cause of heart failure
CBC
Lab Tests for Patients with Suspected Heart Failure
This detects electrolyte imbalance which can cause fluid retention, and it may play a role in the severity of heart failure
Serum Electrolyte Levels
Lab Tests for Patients with Suspected Heart Failure
This can determine if damage to the kidneys, due to hypoperfusion, may be occurring secondary to heart failure
BUN/Creatinine
Lab Tests for Patients with Suspected Heart Failure
Increased levels in both diabetic and non-diabetic patients put them as an increased risk for heart failure
Fasting Glucose
Lab Tests for Patients with Suspected Heart Failure
- Elevated enzymes may indicate if the liver is affected due to heart failure
- It can occur secondary to the inefficiency with which the heart is able to move the venous circulation
Liver Function Tests (AST, ALT, and LD)
Lab Tests for Patients with Suspected Heart Failure
- These 2 analytes are elevated after being released in the heart secondary to the stretch induced by heart failure
- Their levels correlate closely with the severity of heart failure and can be used to differentiate cardiac causes of shortness of breath from primary lung disease
BNP and NT-proBNP Levels
Note: NT-proBNP is the precursor to BNP
B-type Natriuretic Peptide (BNP) and N-terminal pro-B-type Natriuretic Peptide (NT-proBNP)
Lab Tests for Patients with Suspected Heart Failure
This can detect ischemia, infarction, and arrhythmias as a cause for heart failure
12-lead ECG
Lab Tests for Patients with Suspected Heart Failure
- Recent studies have described a relationship between the amount of protein excreted in urine and cardiovascular risk
- This relationship may be due to the common manifestation of vascular endothelial cell dysfunction
Urinalysis
Lab Tests for Patients with Suspected Heart Failure
This includes TC, LDL, HDL, and TAG determination which are measured to determine the risk for CHD
Lipid Profile
Lab Tests for Patients with Suspected Heart Failure
This should be measured as both hyperthyroidism and hypothyroidism can be a primary cause of heart failure or can contribute to its severity
Thyroid Hormone Function Tests (TSH Levels)
Laboratory Markers for Heart Failure
- Is released in response to stress such as an increased pressure and volume load
- It consists of 17 amino acid ring structures with cystine bridges
- The main purpose of these is to increase diuresis, stimulate vasodilation, and increase excretion of sodium
- It distinguishes the cardiac and non-cardiac causes of dyspnea
- Higher levels are associated with a worse prognosis
Natriuretic Peptides
Laboratory Markers for Heart Failure
Natriuretic Peptides consist of 17 amino acid ring structures with cystine bridges consisting of what 5 members?
- ANP
- BNP
- CNP
- DNP
- Urodilatin
Laboratory Markers for Heart Failure
Natriuretic Peptides may be in the form of what? (2 answers)
- B-type Natriuretic Peptide (BNP)
- N-terminal pro-B-type Natriuretic Peptide (NT-proBNP)
Laboratory Markers for Heart Failure
- Is mainly produced in the cardiac ventricle
- Derived from a 108-aa prohormone (pro-BNP)
- It increases in response to peptide ventricular systolic and diastolic dysfunction
- Is diagnostic of congestive heart failure
B-type Natriuretic Peptide (BNP)
Laboratory Markers for Heart Failure
BNP is cleaved by this into a C-terminal fragment, active BNP, and an inactive N-terminal fragment (N-BNP or NT-proBNP)
Furin
Laboratory Markers for Heart Failure
An increased level of BNP in people with this condition indicates an increased risk of recurrent events
Acute Coronary Syndrome
Laboratory Markers for Heart Failure
- Is released by myocardial cells in response to increased volume, increased pressure, and cardiac hypertrophy
- Includes BNP and NT-proBNP
- Is elevated in patients with ventricular dysfunction
- It can predict morbidity and mortality in patients with heart failure
Pro-BNP
Laboratory Markers for Heart Failure
TOF: Higher levels of BNP or NT-proBNP are often associated with a worse prognosis
True
Laboratory Markers for Heart Failure
- There is a 2.6-fold increased risk of in-hospital mortality for heart failure patients with elevated levels of this analyte at the time of admission
- Severe chronic heart failure was also associated with a lower ejection fraction and deteriorating clinical course
Troponins
Laboratory Markers for Heart Failure
In acute heart failure patients without acute coronary syndrome (ACS), elevations in (blank) occur more often than (blank) elevations even though increases in either were related to increased mortality
- Troponin I
- Troponin T
A decrease in coronary blood flow due to coronary artery obstruction by plaques, platelets, and thrombi
Coronary Heart Disease
General results of cardiac ischemia includes what 3 conditions?
- AMI
- Angina pectoris
- CHD
Laboratory or Non-Laboratory CHD Risk Factors
- Cigarette smoking
- Hypertension
- Family history of premature CHD
- Men > 45 years old and women > 55 years old
- Obesity
- DM
- Sedentary lifestyle
Non-Laboratory Risk Factors
Laboratory or Non-Laboratory CHD Risk Factors
- Serum cholesterol
- LDL and HDL
- Hormones
- Clotting factors
- Drugs
- Toxins
- Antioxidants and oxidants
- Markers of infection/inflammation
Laboratory Risk Factors
Laboratory Risk Factors for CHD
This is the earliest identified and most important risk factor
Serum Cholesterol
Laboratory Risk Factors for CHD
This fraction serves as a primary risk factor
LDL
Laboratory Risk Factors for CHD
This is a negative risk factor
HDL
Laboratory Markers for CHD
- Found in elevated levels during inflammation and infection
- Used as an early warning test to patients at risk of CHD
- An inflammatory marker to reflect the severity of CHD and may contribute to its pathogenesis
- High levels indicate a high predisposition to develop CHD and stroke
C-Reactive Proteins (CRP)
Give the cardiovascular disease risk level for the given hs-CRP value:
< 1mg/L
Low Risk
Give the cardiovascular disease risk level for the given hs-CRP value:
1-3 mg/L
Average Risk
Give the cardiovascular disease risk level for the given hs-CRP value:
> 3mg/L
High Risk
Laboratory Markers for CHD
- There is ocurrence of atherosclerosis in patients with massive elevation of this analyte
- Measured by chromatographic techniques
- This can modify LDL which enhances its uptake by macrophages
Homocysteine (HCY)
Laboratory Markers for CHD
High levels of this marker may be caused by:
- A defect in methionine synthase
- An inborn error of metabolism
- Deficiency of vitamin cofactors for the metabolism of Vitamin B12, folate, and B6 (pyridoxine)
Homocysteine (HCY)
Homocysteine
Total Plasma Homocysteine Values:
5 to 15 µmol/L
Normal
Homocysteine
Total Plasma Homocysteine Values:
16 to 30 µmol/L
Moderate (high risk for CHD)
Homocysteine
Total Plasma Homocysteine Values:
31 to 100 µmol/L
Intermediate
Homocysteine
Total Plasma Homocysteine Values:
> 100 µmol/L
Severe (usually seen in CHD)
Homocysteine
For every 5 μmol/L (0.7 mg/L) increase in serum homocysteine concentration, the risk of ischemic heart disease increases by how many percent?
20-30%
Homocysteine
Decreasing plasma homocysteine by 3 μmol/L (0.4 mg/L) can reduce the risk of ischemic heart disease by how many percent?
16%
Homocysteine
Decreasing plasma homocysteine by 3 μmol/L (0.4 mg/L) can reduce the risk of deep vein thrombosis by how many percent?
25%
Homocysteine
Decreasing plasma homocysteine by 3 μmol/L (0.4 mg/L) can reduce the risk of stroke by how many percent?
24%
What are the 2 laboratory markers for heart failure?
- Natriuretic Peptide
- Troponins
What are the 2 laboratory markers for CHD?
- CRP
- Homocysteine
What are the 2 forms of Natriuretic Peptides?
- BNP
- Pro-BNP
Cardiac Insults Picture
What are the 3 kinds of cardiomyopathies?
- Dilated
- Hypertrophic
- Stress-Related
Cardiac Insults Picture
Wall stress is secondary to what condition?
Pulmonary embolism
Cardiac Insults Picture
Myocardial Infarction is secondary to what condition?
Ischemia
Cardiac Insults Picture
Myocarditis is caused by what microorganism?
Virus
Cardiac Insults Picture
Sepsis-related myocardial depression is caused by what harmful substance?
Bacterial toxins
Cardiac Insults Picture
What are the 2 heart traumas?
- Mechanical
- Cardioversion