cardiac biomarkers and lipids Flashcards
Biomarkers for myocardial injury
o Myocardial necrosis = Creatine kinase (CK), CK-MB, myoglobin, troponins
o Myocardial ischemia = ischemia-modified albumin (IMA), heart-type fatty
acid-binding protein (H-FABP)
Biomarkers for hemodynamic stress
Natriuretic peptides = atrial natriuretic peptide (ANP), N-terminal proBNP,
B-type natriuretic peptide (BNP)
Biomarkers for inflammation and prognosis
C-reactive protein (CRP), sCD40L, homocysteine
cardiac biomarkers Diagnosis
Cardiac biomarkers help confirm myocardial injury/infarction
(MI)
cardiac biomarkers Risk Stratification
Biomarkers assist in determining the severity of
conditions and predicting patient outcome
cardiac biomarkers Prognosis
Certain biomarkers can predict long-term survival or
complications
cardiac biomarkers Monitoring
Biomarkers are used to track treatment response or disease
progression, particularly in heart failure and ACS
Creatine Kinase (CK, CPK) & CK-MB
* Normal
o Total CK = male 38-174 U/L, female 26-140 U/L
o Isoenzymes
CK-MM 100%
CK-MB <5%
CK-BB 0%
Creatine Kinase (CK, CPK) & CK-MB Indications
o Diagnosis of myocardial muscle injury (infarction/necrosis)
o Neurological and skeletal muscle disease
The first biomarker to rise in the setting of myocardial injury
is
CK
CK levels rise within
6 hours, peaks at 18 hours and return to
baseline in 2 to 3 days
Three Isoenzymes of CK
- CK-BB (CK1): found in the brain & lungs, rises in injuries such as
CVA and pulmonary infarction - CK-MB (CK2): cardiac-specific
- CK-MM (CK3): skeletal muscles, rises in injuries such as
myopathies, vigorous exercise, multiple IM injections, surgery,
electroconvulsive therapy
CKMB Rises in
4-6 hours of infarction, peaks 12-24 hours, returns to normal in
48-72 hours
o Helps differentiate reinfarction in setting of prior infarction
o Can be used in cases of cardiac surgery or trauma
o Can rise mildly in unstable angina and indicates an increased risk for an
occlusive event
CK Increased
alcohol, amphotericin B, ampicillin,
dexamethasone, furosemide, lithium, lidocaine, propranolol,
succinylcholine
CK
* Interfering factors
IM injections, strenuous exercise, early
pregnancy, muscle mas
Oxygen-binding muscle protein that is released rapidly following
injury to skeletal and cardiac muscle
* Normal < 90 mcg/L
* Indications = acute MI, skeletal muscle injuries or disease
* Earliest biomarker to rise after MI (within 2-3 hours)
o Used to rule out acute MI in early hours of symptoms
o Instrumental in deciding whether thrombolytic should be started
* It is less specific than troponin because it is also released from
skeletal muscle injury
o Not to be used as a standalone test for MI
myoglobin
Myoglobin
* Interfering
IM injections
Increased myoglobin
AMI, myositis, malignant hyperthermia, muscle
dystrophy, skeletal muscle ischemia, skeletal muscle trauma,
rhabdomyolysis, seizures
decreased myoglobin
polymyositis
Natriuretic Peptides
* Normal findings
o ANP 22-77 pg/mL
o BNP < 100 pg/mL
o NT-pro-BNP <300 pg/mL
o CNP: yet to be determined
natriuretic peptides Indications
identify and stratify patients with CHF
neuroendocrine peptides that oppose the activity of the
renin-angiotensin system
natriuretic peptides
- found in the cardiac atrial muscle
- Released as a result of atrial stretch, leading to vaso-relaxation, inhibition of
aldosterone secretion from the adrenal gland and renin from the kidney - Natriuresis and reduction in blood volume occurs
ANP
- found in the membrane granules of the cardiac ventricle
- Released as a result of atrial stretch, leading to vasorelaxation, inhibition of aldosterone
secretion from the adrenal gland and renin from the kidney - Natriuresis and reduction in blood volume occurs* found in the membrane granules of the cardiac ventricle
BNP
released from left ventricle in response to increased wall tension and
stretching, commonly seen in heart failure
BNP
found in the nervous system but found to be produced by endothelial cells
CNP
highly suggestive of heart failure
BNP > 400 pg/mL
cleaved into BNP and its inactive fragment
Pro-BNP
BNP
* Interfering factors
o Higher in women than men
o Higher in older patients
o Higher in patients with recent (1 month) post-cardiac surgery
o Natrecor (nesiritide) increase BNP plasma levels for days
A recombinant form of endogenous human peptide
Used to treat CHF
differentiates heart failure from other causes of dyspnea
NT-pro-BNP
Increased BNP
CHF, MI, HTN, heart transplant rejection, cor
pulmonale
Gold standard for myocardial injury
troponin
proteins found in cardiac muscle
o Highly specific and sensitive for detecting MI, especially in acute MI
o Released into bloodstream when myocardial cells are damaged
Troponins T and I
Normal troponin
o Troponin T = < 0.1ng/mL
o Troponin I = < 0.04 ng/mL
o Rise within 3-6 hours, peak 12-24 hours, can stay elevated up to 2 weeks
troponin Indications
determine cardiac ischemia, specific indicator for
cardiac muscle injury
more specific for cardiac
injury than CK-MB
Cardiac troponins
Clinical Application of Troponin
Unstable angina
* Normal: no injury occurred
* Elevated: muscle injury occurred and thrombolytic therapy may be beneficial
Detection of reperfusion associated with coronary revascularization
* A “washout” or second peak of cardiac troponin indicates reperfusion injury
Estimation of MI size
* Late (4 weeks) cardiac troponin elevations indicate degradation of contractile
apparatus
- Detection of perioperative MI
- Severity of pulmonary emboli
Elevated troponin in the setting of PE may indicate severe disease and the need
for thrombolytic therapy - Congestive heart failure
rises in renal, cardiac, brain, and
skeletal muscle injuries and hence not specific
CK-MB
An acute-phase reactant and marker of inflammation
CRP
used as a risk stratification tool
in patients with CAD
hs-CRP (high-sensitivity CRP)
o Elevated = increased risk of cardiac events, such as ACS or stroke
o Can help assess inflammatory component of atherosclerosis
o >2 mg/L is considered high risk for future event
Macromolecular complexes that transport lipids
(cholesterol, triglycerides, phospholipids) in
the blood
* Essential for transport of hydrophobic lipids
(not water-soluble)
lipoproteins
Consist of core of hydrophobic lipids
surrounded by monolayer of
phospholipids, cholesterol, and proteins
structure of lipoproteins
hydrophobic lipids such as
triglycerides and cholesteryl esters
core
form of cholesterol
that is stored in core of lipoprotein
Cholesterol ester
monolayer of phospholipids
and unesterified cholesterol
outer layer
help in
their formation, transport, and receptor
recognition
Apolipoproteins on their surface
Transport dietary triglycerides from the intestines to
peripheral tissues
Chylomicrons
Transport liver-synthesized
triglycerides to peripheral tissues
Very Low-Density Lipoproteins (VLDL)
Deliver cholesterol to cells for
membrane synthesis, hormone production, and other cellular functions
Low-Density Lipoproteins (LDL)
Collect excess cholesterol from
tissues and other lipoproteins, transporting it to the liver for excretion
(reverse cholesterol transport)
High-Density Lipoproteins (HDL)
- Largest and least dense
- Contain apoB-48, apoC-II, and apoE
chylomicrons
Found in chylomicron remnants, VLDL, and HDL
Important for the clearance of remnants by the liver
Apolipoprotein E (apoE):
Chylomicron Metabolism:
- Dietary fats (triglycerides) are absorbed in the intestine and packaged into chylomicrons
- These are transported via the lymphatic system to the bloodstream, where they deliver
triglycerides to tissues - The remnants are taken up by the liver
- Normal 7-32 mg/dL
- Secreted by the liver to transport endogenous triglycerides
- Contain apoB-100, apoC-II, and apoE
o Apolipoprotein B-100 (apoB-100):
Present in VLDL and LDL
Essential for the assembly and secretion of VLDL from the liver
Binds to the LDL receptor to mediate the uptake of LDL into cells
VLDL
VLDL Metabolism
- VLDLs are synthesized in the liver, containing triglycerides and
cholesterol - VLDL delivers triglycerides to peripheral tissues, and its remnant, IDL, is
converted to LDL
- Derived from VLDL after triglyceride loss
- Normal < 130 mg/dL (estimated by an equation)
- “Bad cholesterol” due to its role in atherosclerosis
- Contain apoB-100 and deliver cholesterol to peripheral tissues
- High levels of LDL cholesterol are linked to an increased risk of atherosclerosis
and coronary artery disease (CAD) - LDL particles deposit cholesterol in the arterial wall, leading to the formation of
plaques
LDL
LDL Metabolism:
o LDL particles are the primary carriers of cholesterol to peripheral tissues
o They are cleared from circulation by the LDL receptor on liver cells and peripheral tissues
- Smallest and most dense
- Normal: male >45 mg/dL, female >55 mg/dL
- Known as “good cholesterol” because it helps remove cholesterol from the bloodstream
and transports it to the liver
o HDL helps remove cholesterol from the walls of blood vessels, protecting against atherosclerosis - Contain apoA-I and apoC-II
o Apolipoprotein A-I (apoA-I):
Major protein in HDL
Plays a key role in cholesterol efflux from peripheral cells and reverse cholesterol
transport - Low levels of HDL are associated with an increased risk of cardiovascular disease
HDL
HDL Metabolism:
o HDLs are synthesized in the liver and intestines
o They collect cholesterol from tissues and other lipoproteins (reverse cholesterol transport)
and return it to the liver for excretion
associated with arteriosclerotic vascular disease
cholesterol
Required for the production of:
* Steroids
* Sex hormones
* Bile acids
* Cellular membranes
cholesterol
75% of cholesterol is bound to
LDL & 25% to HDL
- Familial hypercholesterolemia
- Hypothyroidism
- Uncontrolled DM
- Nephrotic syndrome
- Pregnancy
- High-cholesterol diet
- Hypertension
increased cholesterol
- Malabsorption
- Malnutrition
- Advanced cancer
- Hyperthyroidism
- Cholesterol-reducing meds
- Pernicious anemia
- Hemolytic anemia
decreased cholesterol
A lipid that is formed when the body stores excess calories as fat
* Normal <150 mg/dL
* Provides energy for the body and stored in fat cells for long-term
energy storage
* Transported by VLDL and LDL
triglycerides
Increased triglycerides
familial hypertriglyceridemia, glycogen storage disease,
hyperlipidemia, hypothyroidism, nephrotic syndrome
Elevated triglyceride levels are also a risk factor for
cardiovascular
disease, particularly in combination with low HDL and high LDL
decreased triglycerides
malabsorption, malnutrition, hyperthyroidism
The lipid profile is a routine test that
measures
- Total cholesterol
- LDL cholesterol
- HDL cholesterol
- Triglycerides
The total cholesterol/HDL ratio and
LDL/HDL ratio are also used to asses
cardiovascular risk
another marker
used to assess risk, as it reflects all
atherogenic lipoproteins (including VLDL
and IDL)
Non-HDL cholesterol
Low levels of lipoproteins, especially low HDL,
increase the risk of heart disease
hypolipidemia
Elevated levels of lipoproteins (e.g., high LDL,
high triglycerides) increase the risk of atherosclerosis and
cardiovascular disease
hyperlipidemia
Genetic disorders like familial
hypercholesterolemia (elevated LDL)
primary dyslipidemia
Caused by factors like diabetes,
obesity, hypothyroidism, and liver disease
secondary dyslipidemia
Management of Dyslipidemia Medications:
- Statins: Inhibit HMG-CoA reductase, lowering LDL cholesterol,
simvastatin/atorvastatin/etc. - Fibrates: Lower triglycerides by increasing lipoprotein lipase activity,
Gemfibrozil (Lopid) or Fenofibrate (TriCor) - Niacin: Increases HDL cholesterol
- PCSK9 inhibitors: Lower LDL by increasing LDL receptor availability, Repatha
Management of Dyslipidemia
Lifestyle Modifications
- Diet: Increase intake of unsaturated fats (e.g., olive oil, nuts), reduce saturated
fats, and avoid trans fats - Exercise: Regular physical activity to increase HDL and decrease triglycerides
- Weight Management: Reducing obesity lowers LDL and triglycerides, while
increasing HDL
What is Normal cholesterol
Answer varies based on patient/conditions
- General population normal:
o Total <200, HDL >45, LDL <130, non-HDL <130, VLDL 7-32 mg/dL,
trigs <150
Interfering Factors of Lipid Panel
- Smoking and ETOH
o Very high HDL = consider ETOHism
o ETOH can increase production of apolipoprotein A-I - If trigs > 400, will need to order a direct LDL as you can not estimate
- Binge eating
- HDL = age, sex, post-MI, hypothyroidism (increases cholesterol),
hyperthyroidism (decreases) - BB can increase trigs, decrease LDL size and decrease HDL
- Alpha blockers can decrease trigs, increase LDL size and HDL
- Dilantin can increase HDL
- Steroids increase trigs
- Estrogens increase trig
treatment by Statin Intensity
High = Atorvastatin 40+ and Rosuvastatin 20+
Moderate = Atorvastatin 10+, Rosuvastatin 5+, Simvastatin 20-40
Low = Simvastatin 10
Decreased HDL
Metabolic syndrome
Familial low HDL
Hepatocellular disease
Hypoproteinemia
HDL
o Increased
Familial hypercholesterolemia
ETOH
Excessive exercise (marathon)
LDL & VLDL
o Increased
nephrotic syndrome, glycogen storage disease, hypothyroidism,
ETOH, chronic liver disease, multiple myeloma, Cushing disease
LDL & VLDL
Decreased
familial hypoproteinemia, hyperthyroidism
