Chapter 3 - delete this one

OBJECTIVES

  • 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

KEY TERMS

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

BACKGROUND/SIGNIFICANCE

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.

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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.

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HYPERLIPIDEMIA

FROM THE NCEP GUIDELINES [6]

  • 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:
(1)
\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

RISK FACTORS THAT MODIFY LDL GOALS

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