14) Cardiac function Flashcards
Biochemical feature or facet that can be used to measure the progress of disease or the effects of treatment.
biomarker
Greek for gruel and refers to the massive accumulation of lipids in these vascular lesions.
athero
Was considered to be a bland lipid storage disease
Now thought to evolve from the inflammatory process
Atherosclerotic vascular disease (ASVD)
Acute coronary syndrome (ACS)
Described as a continuum of clinical signs and symptoms ranging from…
unstable angina (chest pain) to…
non-Q-wave (ECG pattern) acute myocardial infarction (AMI) and Q-wave AMI.
most common cause of ASC
atherosclerosis in coronary arteries
Locally acting autacoid polypeptides that mediate vasoconstriction by interacting with phospholipase C-linked receptors.
Released early in the inflammatory response preceding an ACS.
cytokines
Double-walled sac that encloses the heart
pericardium
Made up of cardiac muscle
Anchored to the heart’s fibrous skeleton
myocardium
Connective tissue and squamous cells make up the internal lining of the myocardium
endocardium
Deposition of tough, rigid collagen inside the vessel wall and around the atheroma
arteriosclerosis
Most common form of arteriosclerosis
Caused by the formation of multiple plaques within the coronary arteries
atherosclerosis
Results from the accumulation of atheromatous plaques within the walls of the arteries that supply the myocardium
CAD
cardiac biomarker release affected by…
- Cytosolic enzymes
- Subcellular location
- Molecular mass
- Plasma clearance
- Concentration gradients
Layering or gradation of risk factors, which are described as elements or constituents that may put someone’s health in peril
risk stratification
Many cardiac biomarkers are used for evaluating….
risk stratification
characteristics of ideal cardiac biomarkers
- Smaller markers are released faster from injured tissues.
- Soluble cytoplasmic marker is preferred to structural markers.
- Have absolute cardiac tissue specificity and should not exist in other tissues.
- Useful to differentiate between reversible (ischemic) and irreversible (necrotic) damage.
- Release from the myocardium should be complete following injury.
- Amount of marker released should be in direct proportion to the size of the injury (infarct sizing).
- Remain elevated long enough (12 to 24h) to be detected in the serum of the “late presenter.”
- For risk stratification, there should be a correlation between outcome and the presence or absence of a marker in serum or the degree of elevation of the marker above “normal.”
- Should be cleared rapidly to allow diagnosis of recurrent injury.
- Should be useful for monitoring of reperfusion and re-occlusion.
- Assays should be relatively easy and quick to perform.
Regulatory protein of the myofibril
troponin
3 troponins and their functions
- Troponin I—Binds to actin and inhibits contraction
- Troponin T—Binds tropomyosin
- Troponin C—Contains 4 Ca-binding sites & regulates contraction
Two isoforms of TnI
Several isoforms of TnT
skeletal muscle
One isoform of TnI
Several isoforms of TnT
cardiac muscle
Binds to actin and inhibits muscle contraction
cTnI
Binds tropomyosin
cTnT
Has 3 isoforms, one of which has unique cardiac specificity
cTnI
Isoform can be demonstrated in patients with muscular dystrophy, polymyositis, and end-stage renal disease.
cTnT
(cTnI/cTnT) is NOT expressed in skeletal muscle.
cTnI
what makes troponins good cardiac biomarkers?
- High level of diagnostic specificity and sensitivity.
- Possess early release kinetics after an AMI
- Remain elevated for a long interval of time
- Very low to undetectable concentrations in serum from healthy patients
- Relatively few interfering substances
Drawing blood samples periodically, usually at prescribed time intervals over the course of the patient’s admission
serial sampling
Total CK
rise
peak
return to normal
4-6 hours
24 hours
3-4 days
CK-MB
rise
peak
return to normal
4 hours
18 hours
2 days
Myoglobin
rise
peak
return to normal
1-3 hours ★ (earliest)
8-12 hours
1 day
TnT
rise
peak
return to normal
4-6 hours
10-24 hours
10 days ★ (longest)
TnI
rise
peak
return to normal
4-6 hours
10-24 hours
4 days
sources of error for cTnI
False positive
Heterophile antibodies
Rheumatoid factor
False negative
Bilirubin
Hemoglobin
Circulating cTnI autoantibodies
Interfering factor (IF)
do not affect TnT
causes of elevated troponins besides ACS
- Trauma
- HTN
- Hypotension, often with arrhythmias
- CVA
- Rhabdomyolysis (cardiac)
- Cocaine-induced rhabdomyolysis
- Post-op noncardiac surgery
- Renal failure
- DM
- Burns
- Severe asthma
- Sepsis
WHO criteria for making AMI dx and European revisions
- History of characteristic chest pain
- Diagnostic changes in the EKG
- Changes in serum enzyme levels
Revisions
1. Promote troponin to a pivotal role
2. Relegate CKMB to a secondary role
3. Eliminate the need for CK
non-cardiac CKMB elevations
- Severe skeletal muscle injury following trauma or surgery (ie crushing injury)
- Chronic muscle disease in patient with muscular dystrophy, end-stage renal disease, or polymyositis
- Healthy people who exercise and participate in physical activity such as long-distance running
- Extensive rhabdomyolysis
- Early dermatomyositis
CK index
CKMB(100)/total CK
do not use if total CK is normal
CK index >5%, <5%, and RR
> 5% —MI
<5% —crushing injury
RR —<3%
First cardiac biomarker to appear in circulation that may be used for assessment of ACS.
myoglobin
myoglobin may be pos for…
MI or crushing injury
myoglobin advantages
- High sensitivity and negative predictive value
- Useful for early detection of MI and reperfusion
myoglobin disadvantages
- Low specificity in presence of skeletal muscle injury and renal insufficiency
- Rapid clearance after necrosis
- Labor-intensive process on urine; doesn’t make very much sense to run as an early detection marker
mainly expressed in the heart ventricles, discovered in porcine brain
BNP
pathway of BNP synthesis
- Initially synthesized as preproBNP (134 amino acids)
- Cleaved into proBNP (108 aa)
- Cleaved again into NT-proBNP (76 aa) and BNP (32 aa)
part of the body’s defense against volume overload and hypertension
BNP
BNP functions
Dilate blood vessels
Increase the excretion of sodium and fluids
Reduce concentrations of neurohormones (ie. ADH) that lead to:
* Vessel constriction
* Fluid retention
* Elevated blood pressure
Elevated plasma —– indicates the presence of heart failure and provides information about its severity.
NT-proBNP
Heart is unable to pump sufficient blood to meet body’s metabolic needs and normal filling pressure.
CHF
2 types of CHF
Diastolic — heart cannot fill properly
Systolic — heart cannot contract/pump properly
s/s of CHF
Dyspnea
Increased fatigue
Edema
best biomarkers for CHF
BNP/NT-proBNP
essentially obsolete cardiac biomarker due to lack of tissue specificity
LD
found in high concentrations in the heart, kidney, and erythrocytes
LD-1
Nonspecific, acute-phase reactant. Shows up during inflammatory processes.
CRP
Measuring blood levels of hs-CRP provides better ….. than measuring any other biomarker.
risk assessment of cardiovascular disease
Produced when circulating albumin comes in contact with ischemic tissue in the heart or other organ.
Ischemia-Modified Albumin (IMA)
Albumin cobalt binding test
used to measure IMA
Cobalt is added to serum and does not bind to ischemia-modified albumin, thus leaving more free cobalt to react with the reagent dithiothreitol
Secreted by activated leukocytes
Enriched in unstable atherosclerotic lesions.
myeloperoxidase
Elevated results are seen in patients with AMI (>50 ng/mL).
myeloperoxidase
Myeloperoxidase is useful for both short- and long-term …… and may help identify …… at risk for major adverse cardiac events.
risk stratification for CVD
troponin-negative patients
This has shown to be a good indicator of cytokine storm syndrome (CSS) severity and mortality risk in COVID-19 positive patients.
IL-6
Typically measured during pregnancy to detect Down syndrome.
Pregnancy-Associated Plasma Protein-A (PAPP-A)
A zinc-binding metalloproteinase and insulin like growth factor (IGF).
Pregnancy-Associated Plasma Protein-A (PAPP-A)
Increased circulating PAPP-A is associated with ——
ACS
Found primarily in the fatty plaques that may line the walls of coronary arteries in patients with atherosclerosis
oxidized LDL
Circulating levels of —— are strongly associated with angiographically documented CAD in patients 60 years of age or younger.
Ox-LDL
Includes the recruitment of circulating macrophages into atherosclerotic lesions and stimulation of smooth muscle cell growth
Appears to function in the early stages of the inflammatory process
Placental Growth Factor (PlGF)
May serve as a strong candidate biomarker for plaque instability, myocardial ischemia, and patient prognosis in ACS
Placental Growth Factor (PlGF)
In the heart, participates in vascular remodeling, plaque instability, and ventricular remodeling after cardiac injury.
Matrix Metalloproteinase-9
Is released into the circulation when the myocardium is injured
low specificity in the presence of skeletal muscle injury and renal insufficiency
Heart-Type Fatty Acid-Binding Protein (H-FABP)
may provide a sensitive guide to the underlying pathophysiology of coronary heart disease.
FFAU
FFAU
fatty acids unbound to albumin
How do omega-3 FAs reduce risk of CVD?
- Decrease risk for arrhythmias
- Decrease risk for thrombosis
- Decrease triglycerides and remnant lipoprotein levels
- Decrease rate of growth of the atherosclerotic plaque
- Improve endothelial function
- Slightly lower blood pressure
Produced by macrophages and expressed in atherosclerotic lesions
enzyme that co-traffics with LDL in circulation
Lipoprotein-Associated Phospholipase A2 (Lp-PLA2)
Biological function is unclear.
Roles may be to:
* Respond to tissue injury and vascular lesions
* Prevent infectious pathogens from invading cells
* Promote wound healing
Lipoprotein (a)
Most important role in atherothrombosis is to inhibit clot formation at site of injury.
Lp (a)
Competes with plasminogen for binding sites thus interferes with clot lysis and increases the risk of AMI
Lp (a)
Screen for ——- if there is a(n):
* Family history of premature CVD
* Family history of hyperlipidemia
* Established CVD with normal routine lipid profile
* History of recurrent arterial stenosis
Lp (a)
Plasma ——– levels may predict cardiovascular events years in advance in a population without diagnosed CVD.
adiponectin
High blood levels are associated with reduced risk of heart attacks.
Low blood levels are found in individuals who are obese, and who are at increased risk.
adiponectin
Causes vasodilatation
Plays a role in fat metabolism and obesity
leptin
The higher the blood leptin level, the ——– the risk of developing CVD.
greater
found to have an independent protective association with unstable CAD
leptin
advantages of cardiac POC
- Rapid identification of AMI
- Decreased turn-around time for analysis
- Rapid exclusion of ACS
- Rapid stratification of cardiac patients
- Rapid identification and exclusion of CHF
