cardiac biomarkers and lipids Flashcards by Jasmin Maisuria

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)

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Biomarkers for hemodynamic stress

Natriuretic peptides = atrial natriuretic peptide (ANP), N-terminal proBNP,
B-type natriuretic peptide (BNP)

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Biomarkers for inflammation and prognosis

C-reactive protein (CRP), sCD40L, homocysteine

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cardiac biomarkers Diagnosis

Cardiac biomarkers help confirm myocardial injury/infarction
(MI)

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cardiac biomarkers Risk Stratification

Biomarkers assist in determining the severity of
conditions and predicting patient outcome

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cardiac biomarkers Prognosis

Certain biomarkers can predict long-term survival or
complications

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cardiac biomarkers Monitoring

Biomarkers are used to track treatment response or disease
progression, particularly in heart failure and ACS

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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%

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Creatine Kinase (CK, CPK) & CK-MB Indications

o Diagnosis of myocardial muscle injury (infarction/necrosis)
o Neurological and skeletal muscle disease

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The first biomarker to rise in the setting of myocardial injury
is

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CK levels rise within

6 hours, peaks at 18 hours and return to
baseline in 2 to 3 days

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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

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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

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CK Increased

alcohol, amphotericin B, ampicillin,
dexamethasone, furosemide, lithium, lidocaine, propranolol,
succinylcholine

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CK
* Interfering factors

IM injections, strenuous exercise, early
pregnancy, muscle mas

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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

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Myoglobin
* Interfering

IM injections

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Increased myoglobin

AMI, myositis, malignant hyperthermia, muscle
dystrophy, skeletal muscle ischemia, skeletal muscle trauma,
rhabdomyolysis, seizures

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decreased myoglobin

polymyositis

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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

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natriuretic peptides Indications

identify and stratify patients with CHF

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neuroendocrine peptides that oppose the activity of the
renin-angiotensin system

natriuretic peptides

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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

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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

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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