Laboratory Diagnosis of Dyslipidemia


By the end of this session the reader should be able to:

  • To understand the current National Cholesterol Education Program guidelines
  • To understand risk related target goals
  • To be able to describe the various sources of lipids
  • To understand how the laboratory is used to monitor drug therapy


Chylomicron - class of lipoprotein that transports exogenous (dietary) triglycerides and cholesterol for metabolism

Dyslipidemia - disorder of lipoprotein metabolism

HDL - high density lipoprotein

IDL - intermediate density lipoprotein

LDL - low density lipoprotein

Lipid - heterogeneous group of fat and fat like substances, poorly soluble in aqueous solutions

Lipoprotein - lipid protein complex for transporting lipids in the blood

NCEP - National Cholesterol Education Program

Triglycerides - three fatty acids esterified to a glycerol backbone

VLDL - very low density lipoprotein


Lipids and lipoproteins are essential for a variety of biochemical processes and serve as hormones and energy reserves in addition to forming key elements of cell membranes. In disease states, lipids are most frequently monitored in association with atherosclerosis. Laboratory testing is essential for determining when to institute drug therapy and for monitoring disease progression. Understanding the role of the laboratory in management of dyslipidemia is essential for pharmacists as atherosclerosis and cardiac disease are the leading cause of death in developed countries.


Figure 1: Exogenous Lipoprotein Metabolism (TG, triglyceride; CE, cholesterol ester; FC, free cholesterol; PL, phospholipids; FA, fatty acids; LPL, lipoprotein lipase; B, apolipoprotein B-48; A, apoliprotein A-I; C, apoliprotein C-II; E, apoliprotein E; from Arch. Pathol. Lab. Med. 110:694-701, 1986)

Cholesterol and fatty acids are absorbed from the GI tract as chylomicrons (Figure 1). Chylomicrons are primarily triglycerides (90%) combined with cholesterol and apolipoproteins B-48 and A. In combination with HDL, apolipoprotein C, apolipoprotein E and lipoprotein lipase, a small percentage of the free fatty acids are released from the chylomicron triglyceride component. The free fatty acids are then taken up by either muscle or adipose cells. The remaining chylomicron remnant which contains 80-90% of the initial triglyceride component can then be internalized by hepatic cells. Hepatic cells synthesize triglyceride rich VLDL which is then released into circulation (Figure 2). Apolipoprotein CII activates lipoprotein lipase which releases free fatty acids to endothelial cells. The remaining VLDL remnant can either be taken back up by hepatocytes or be converted into IDL. Further metabolism results in LDL, where most of the triglyceride component of VLDL has been replaced with cholesterol. The major components of the various lipoprotein classes are shown in Table 1.

Table 1. Major Lipids and Protein Components of Lipoprotein Classes
Variable Chylomicron VLDL IDL LDL HDL
Major lipids TG TG TG, CE CE Phospholipids
Major proteins AI, B-48, CI-CIII B-100, CI-CIII, E B-100, E B100 AI, AII

From a clinical perspective, monitoring and reducing LDL is a primary goal of therapy.


Figure 2: Endogenous Lipoprotein Metabolism Pathway (IDL, intermediate-density lipoprotein; LCAT, lecithin choles- terol acyltransferase; B, apoliprotein B-100; E, apoliprotein E; from Arch. Pathol. Lab. Med. 110:694-701, 1986)

Table 2. Adult Classifications of LDL, Total and HDL Cholesterol (mg/dL)
LDL Cholesterol Total Cholesterol HDL Cholesterol
< 100 Optimal < 200 Desirable < 40 Low
100-129 Near optimal 200-239 Borderline high > 60 High
130-159 Borderline > 240 High
160-189 High
> 190 Very high


From The NCEP Guidelines [1]

  • Risk assessment-measure LDL on anyone over 20 once every 5 years
  • Clinical judgment applied to individuals should always take precedence over general management principles
  • In a meta-analysis of dietary trials, dietary lowering of serum cholesterol produces as much CHD risk reduction as did drugs, commensurate with their respective degree of cholesterol lowering
  • Since safety does not appear to be an issue for short term risk reduction in primary prevention with LDL lowering drugs, the determining factor for the lower risk cut point for drug recommendation will be cost effectiveness

Laboratory Assessment of Hyperlipidemia

  • Total cholesterol- can be measured on fasting or non-fasting specimens
  • Total cholesterol is determined from the amount of cholesterol found in HDL, LDL and VLDL
  • HDL - can be measured on fasting or non-fasting specimens
  • Triglycerides- fasting required
  • LDL - fasting required
  • LDL - if triglycerides < 400 then LDL is calculated using Friewald formula:
\begin{equation} Calculated LDL = chol - HDL - TG/5 \end{equation}
  • If triglycerides > 400 then LDL is measured directly
  • Fasting = 9-12 hours of not eating or drinking (except water)
  • Blood should be drawn with the patient sitting (5 minutes) in order to avoid hemoconcentration

Interpretation of Lipid Panels

  • Baseline lipid should be the average of two measurements, 1-4 weeks apart, before instituting drug therapy
  • Baseline measurements should also include liver enzymes (ALT or AST), CK and medical history
  • Initial follow-up should occur 6-8 weeks after drug therapy when response should be maximal


  • Cigarette smoking
  • Hypertension (BP > 140/90 mmHg or on antihypertensive medicine)
  • Low HDL cholesterol* (< 40 mg/dL)
  • Family history of heart disease
  • Age (men > 45, women > 55)

(* HDL > 60 is a negative risk factor, it removes one risk factor from the total count)

Table 3. Risk Categories and LDL Goals
Risk Category LDL Goal (mg/dL)
Very high risk < 70
CHD (or equivalents) < 100
Multiple (≥ 2) risk factors < 130
Zero to one risk factor < 160

The LDL goal is determined by risk factors. The very high risk category includes patients with a recent MI or a combination of cardiovascular disease and diabetes. Patients with established CHD (coronary heart disease) or equivalents (e.g., diabetes) have an LDL goal of < 100 mg/dL, whereas for people with fewer risk factors higher levels of LDL are considered acceptable.

Secondary Causes of Hyperlipidemia

  • Diabetes
  • Hypothyroidism
  • Obstructive liver disease
  • Chronic renal failure
  • Drugs (progestins, anabolic steroids, corticosteroids)

Secondary Prevention of CHD (Confirmed CHD Patients)

  • In patients with confirmed CHD, target LDL is < 100 mg/dL
  • Good evidence that lowering lipids is beneficial for preventing additional adverse cardiac events (myocardial infarction, death)
  • Patients with established CHD (or equivalents) should have drug therapy if LDL > 130 mg/dL as lifestyle changes unlikely to reduce LDL to < 100 mg/dL
  • In these patients, LDL lowering reduces risk of strokes
  • AMI patients should have lipids on admission or within 24 hours of presenting; if LDL is > 130, then discharge on TLC and drug therapy

Therapeutic Lifestyle Changes (TLC)

  • Reduced intakes of saturated fats and cholesterol
  • Therapeutic dietary options to enhance LDL lowering (plant stanols/sterols and increased viscous fiber)
  • Weight control
  • Increased physical activity

Metabolic Syndrome

  • Higher risk for diabetes and CHD
  • Obesity
  • Elevated triglycerides
  • Decreased HDL
  • Elevated blood pressure (> 130/85)
  • Elevated fasting plasma glucose


  • TLC for approximately 3 months; recheck labs, if not at goal then consider drug therapy
  • Drug therapy: start statin or bile acid sequestrant or nicotinic acid
Table 4. Reference Ranges and Lab Testing Frequency
Risk Level LDL Goal (mg/dL) Observed LDL (mg/dL) Repeat Lipid Labs
CHD or risk equivalent < 100 < 100 < 1 year
2+ risk factors < 130 < 130 < 2 years
0-1 risk factor < 160 130-159 < 2 years
0-1 risk factor < 160 < 130 < 5 years

The Major Classes of Drugs for Consideration are:

A) HMG CoA reductase inhibitors (statins) - lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin

  1. ↓ LDL (18-55%), ↓ Reduce TG (7-30%) ↑ HDL (5-15%)
  2. Contraindications: liver disease
  3. Adverse effects: myopathy (check creatine kinase initially), increased transaminases (rarely > 3 times upper limit of normal)

B) Bile acid sequestrants - cholestyramine, colestipol, colesevelam

  1. ↓ LDL (5-30%), No effect or ↑ TG (7-30%) ↑ HDL (3-5%)
  2. Contraindications: elevated TG (absolute > 400 mg/dL, relative > 200 mg/dL)
  3. Adverse effects: GI distress, ↓ absorption of other drugs

C) Nicotinic acid (alters lipoprotein synthesis) - crystalline, timed-release preparations, Niaspan®

  1. ↓ LDL (5-25%), ↓ TG (20-50%) ↑ HDL (15-35%)
  2. Contraindications: severe liver disease, severe gout
  3. Adverse effects: (often limit prolonged use): flushing, hyperglycemia, gout, hepatotoxicity

D) Fibric acid derivatives (peroxisome proliferator-activated receptor-alpha, PPAR-alpha agonist) - gemfibrozil, fenofibrate, clofibrate

  1. ↓ LDL (5-20%) in patients w/o hypertriglyceridemia, ↓ TG (20-50%), ↑ HDL (10-35%)
  2. Contraindications: severe hepatic or renal insufficiency
  3. Adverse effects: dyspepsia, GI distress, cholesterol gallstones, myopathy

E) Cholesterol absorption inhibitors - ezetimibe (Zetia®)

  1. ↓ LDL (17%), no change in TG or HDL
  2. Contraindications: statin contraindications apply when used in combination with a statin
  3. Adverse effects: diarrhea, upper respiratory tract infection, arthralgia


CASE 1 (Ann. Pharmacother. 37(7):1032-1035, 2003)

An 83-year-old white man with a diagnosis of acute myeloid leukemia (AML) received remission induction chemotherapy consisting of anti-CD33 antibody conjugated with a cytotoxic anti-tumor antibiotic, calicheamicin (gemtuzumab ozogamicin). His past medical history included congestive heart failure, hyperlipidemia, and hypothyroidism. He had been taking simvastatin for nearly 2 years. The patient tolerated the chemotherapy well and was discharged on his previous medications, including simvastatin 40 mg once daily, digoxin 0.25 mg once daily, and levothyroxine 0.075 mg once daily, as well as levofloxacin 500 mg once daily, acyclovir 400 mg twice daily, and fluconazole 400 mg once daily, given as prophylactic antimicrobial therapy in the setting of neutropenia. One week after discharge, the patient presented with severe generalized muscle weakness. There was no history of trauma, fever, alcohol use, seizures, or systemic inflammatory diseases. He was afebrile, and other vital signs were also normal.

Examination revealed 2 of 5 strength in all 4 extremities and decreased ankle reflexes bilaterally. Notable laboratory values included serum creatine kinase (CK) 52,716 U/L, CK MB fraction 81.5 ng/mL, serum creatinine 1.2 mg/dL (baseline 1 wk earlier 0.9 mg/dL), blood urea nitrogen 30 mg/dL (baseline 1 wk earlier 16 mg/dL), troponin I < 0.4 µg/L, calcium 8.3 mg/dL, potassium 5.1 mEq/L, alanine aminotransferase 724 U/L, aspartate aminotransferase 2367 U/L, alkaline phosphatase 187 U/L, thyroid-stimulating hormone (TSH) 37.7 µU/mL, and unbound thyroxine 0.61 ng/dL. Urinalysis showed brown urine, pH 5.0, abundant pigment casts, and a red supernatant after centrifugation.

  1. Based on the CKMB being greatly elevated (normal is < 12 mg/dL) did this patient suffer a myocardial infarction? Is the elevated CKMB consistent with the troponin result?
  2. How do you interpret the creatine kinase concentrations in this patient? If the patient is treated effectively how long will it take to normalize the CK values?
  3. Why is the serum potassium slightly elevated?
  4. How do you interpret the transaminase (ALT and AST) values for this patient?
  5. How do you interpret the thyroid function tests?
  6. How do you interpret the urinalysis data?
  7. Is this a common finding with these types of drugs?

CASE 2 (CMAJ 167(11):1261-1266, 2002)

A 41-year-old man presents for assessment of severe hypertriglyceridemia. He has previously been well. His lipid levels were checked because his serum appeared milky on screening for dyslipidemia. He has no history of abdominal pains, his medical history is unremarkable (in particular, no diabetes mellitus, hypothyroidism, obesity or pancreatitis), and he has no family history of premature coronary artery disease. He does not drink alcohol excessively and is a nonsmoker. The physician records his height (180 cm), weight (80 kg) and abdominal circumference (86 cm). Other findings on physical examination are unremarkable. The fasting lipid profile reveals a total cholesterol level of 300 (normally < 200) mg/dL, a high-density lipoprotein (HDL) cholesterol level of 9 (normally > 35) mg/dL and a triglyceride level of 2672 (normally < 200) mg/dL. The patient had previously received treatment with 2 statins, in increasing doses, without a decrease in triglycerides.

  1. How should the patient’s lipid profile be classified?
  2. What other investigations should be performed?
  3. How should the patient’s dyslipidemia be managed?

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