Measurements in the lab:

Triglycerides:
Chylomicrons are composed of about 90% triglycerides, and VLDL about 70%. Some triglycerides are synthesized in the liver and some are taken in through diet. The chylomicrons consist of mostly dietary triglycerides (exogenous), and VLDL are mostly synthesized in the liver (endogenous).

Cholesterol:
The lipid component in LDL is mostly cholesterol. Cholesterol is a key membrane component of all cells. It’s also a precursor building block molecule for steroid hormones and bile acids. Most cholesterol is synthesized in the liver but some is obtained from the diet (animal products). The lipid component of HDL is cholesterol and phospholipid. HDL is considered ‘good’ cholesterol because it is involved in the cholesterol removal process.

Triglycerides and HDL cholesterol are both measured in the lab, and VLDL and LDL are extrapolated. These tests require a 9-12 hour fasting period or you may see increased triglycerides from food intake.

VLDL calculation:
VLDL = Triglycerides/5

LDL calculation (Friedwald equation):
LDL = Total cholesterol – HDL –VLDL

Reference ranges for lipids:
Total cholesterol:
<200 mg/dL = desirable, 200-239 = borderline high, >240 = high

HDL cholesterol:
<40 mg/dL = low, >60 mg/dL = high

LDL cholesterol:
<100 mg/dL = optimal, 100-129 = near optimal, 130-159 = borderline high, 160-189 = high

Triglycerides:
<150 mg/dL = normal, 150-199 = borderline high, 200-499 = high, >500 = very high

Apolipoprotein markers:
Different lipoproteins carry some of the same, and some different proteins. Here is a table outlining some markers and lipid correlations.

Apolipoprotein	Lipoprotein
Apo B48	Chylomicrons
Apo B100	VLDL
Apo B100	LDL
Apo A1	HDL

Lp (a), Lipoprotein (a):
Lipoprotein (a) also known as Lp(a), is a LDL like lipoprotein with Apo A bound to Apo B100. It’s a marker for atherosclerosis and is genetically inherited. Elevated serum Lp(a) is significant because it competes with plasminogen for fibrinolytic sites which can slow down the clot removal process and contribute to atherosclerosis.

Cardiac markers:

C-reactive protein:
C-reactive protein is an acute phase reactant produced by the liver in response to injury or inflammation. It is a non-specific marker for coronary inflammation in healthy individuals and can be prognostic of coronary artery disease.

Myoglobin:
Myoglobin is a complex protein but its basic function is a secondary oxygen carrier in muscle tissue. It is similar to hemoglobin but functions more of an oxygen storage molecule in muscle tissue and is used in times of intense respiration when muscle tissue needs a lot of oxygen. Myoglobin is not normally found in the blood stream so it is a good marker for muscle injury. Myoglobin will rise within 30 minutes to 4 hours of an acute myocardial infarction (AMI), peak between 4-10 hours, and normalize within 12-24 hours; however, it’s not a specific marker for AMI because myoglobin can be increased in other muscle injuries. Myoglobin is excreted by the kidneys, so impaired renal function can cause elevations.

Creatine Kinase:
Creatine kinase, also known as creatine phosphokinase, is an enzyme involved in complex energy processes in various tissues. It has largely been replaced by troponin in terms of its clinical use. CK enzymes consist of two subunits, M for “muscle type,” and B for “brain” type. The two subunits yield three CK isoforms: CK-MB, CK-BB, and CK-MM. CK-MB was a marker that used to be used in the clinical lab because of its presence in heart tissue. The problem with this is CK-MB is also present in skeletal tissue, so it’s not specific. CK-MB in infarcted myocardium tissue is 15-24% compared to less than 2% in healthy patients; however, muscular dystrophy, end stage renal disease, polymyositis (chronic inflammation of the muscles), and extreme exercise like marathon training can also cause elevated CK-MB. CK-MB rises within 6-8 hours of AMI (slower than troponin), peaks within 24 hours, and normalizes in 48-72 hours. CK-MB can be measured using a monoclonal antibody sandwich electrochemical immunoassay.

Lactate dehydrogenase (LD):
LD is another marker no longer used in the clinical lab. LD is a transfer enzyme that catalyzes the oxidation of L-lactate to pyruvate with the mediation of NAD+ as a hydrogen acceptor. LD is found in the cytoplasm of all cells in the body. Cell concentration is 500x greater than serum concentration. Because of its wide distribution in all tissues, serum LD is raised in a lot of clinical conditions including: myocardial infarction, hemolysis, megaloblastic anemia, and disorders of the liver, kidney, lungs, and muscle.

LD is a tetramer of two subunit types, M and H. There are five isoenzymes which are no longer of clinical value but could come up on an exam:

LD1 (HHHH)
LD2 (HHHM)
LD3 (HHMM)
LD4 (HMMM)
LD5 (MMMM)

There are a few notes of importance for LD. In a normal patient, LD 1, 2, and 3 will be present with LD2 being greater than LD1. In a myocardial infarction, LD1 will be greater than LD2. LD1 moves fastest on electrophoresis, LD5 slowest. LD4 and LD5 are increased in liver and skeletal muscle disease.

Troponin:
Troponin is a major player in muscle contraction regulation. Troponin is present on all striated muscle (cardiac and skeletal) and not present on smooth muscle.

Troponin is a complex that consists of three proteins, troponin T, troponin I, and troponin C. In the body there is only one type of troponin C so it’s not clinically useful; whereas, there are three types of troponin I and troponin T. For each troponin I and T, there is a cardiac, fast twitch skeletal, and slow twitch skeletal version. Each version comes from a different gene and has unique characteristics. This is the reason troponin is superior to a marker like CK-MB, cardiac and skeletal markers can be differentiated!

Troponin I and T are very low or undetectable in serum from people without cardiac disease. The normal range is <0.01 ng/mL. When troponin is released it shows a quick spike at 4-10 hours due to the cytoplasmic fraction and can stay elevated 5-15 days due to the myofibril fraction (troponin is 97% in myofibrils and 3% in cytoplasm). Positive troponin always indicates myocardial injury but not necessarily an acute ischemic injury. Elevated but stable troponins are suggestive of a chronic process. The rise and fall of troponins is what is indicative of an acute process. Troponins can be measured using a monoclonal antibody sandwich electrochemical immunoassay.

It is important to understand the time differences of the various cardiac markers. Patients will be tested for these markers at different time intervals to elucidate what is going on. The table below outlines a few important time generalizations.

Cardiac marker	Hours to first detection	Hours to peak	Time to baseline return
Myoglobin	0.5-4	4-10	12-24 hours
CK-MB	4-10	10-24	2-3 days
Troponin I (cTnI)	4-10	10-24	5-10 days
Troponin T (cTnT)	4-10	12-48	5-15 days

Tumor markers:

Marker	Association
CA 125	Ovarian cancer
CA 19-9	Pancreatic cancer
Prostate specific antigen (PSA)	Prostate cancer
Alpha-fetoprotein (AFP)	Liver, testicular, and ovarian cancer
Carcinoembryonic antigen (CEA)	Colon cancer