High-density Information and Courses from MediaLab, Inc.

We are all aware of the clinical laboratory's role in assessing overall health and we are also aware that measuring a patient's serum lipids will provide some insight into their cardiovascular health. The traditional measurements of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides are the 'classic' cardiovascular risk markers.Laboratorians, and even the general public are now well-aware that LDL-C ('bad' cholesterol) concentrations should be low while HDL-C ('good' cholesterol) concentrations should be high. Triglycerides should be kept in check as well. Optimal levels are shown in the table below. So what is the risk if these values are not within optimal ranges?Cardiovascular risk can be simply defined as increasing the odds of having a pathology which affects blood flow and/or the heart. The most common cardiovascular pathology is atherosclerosis. Other cardiovascular pathologies whose odds increase as serum lipids and other cardiovascular markers become suboptimal are myocardial infarction (heart attack), stroke, congestive heart disease and coronary artery disease. Other diseases such as diabetes and the metabolic syndrome are also strongly associated with the classic cardiovascular risk markers LDL-C, HDL-C and triglycerides.

Lipid-carrying particles are collectively known as lipoproteins. Lipoproteins are classified according to their densities. The names of these particles, from least to most dense, are: chylomicrons, very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Most laboratorians are familiar with these particles as many, especially LDL and HDL, are routinely measured in clinical labs. In this course we will not focus on the physiology of all of these particles or the differences between them all. However it is important to understand the basic structure and function of a lipoprotein particle.

In the clinical laboratory, we routinely measure the cholesterol content of high-density lipoprotein and low-density lipoprotein particles and not the apolipoproteins on the particles or the number of particles. Proprietary detergents and reagents are used in assays for HDL-C and LDL-C to separate lipoproteins, allowing the cholesterol content of specific lipoproteins to be measured. For example, HDL-C is commonly measured using a solution of dextran sulfate and magnesium to selectively precipitate HDL from the other lipoproteins present in the sample. Once isolated, the HDL particles are 'dissolved' and the amount of cholesterol in them is determined photometrically using a color-producing enzyme reaction. LDL-C can be measured directly or can be estimated using the HDL-C, triglycerides and total cholesterol (TC) values. The Friedewald formula is often used to calculate LDL: LDL-C = TC - (HDL-C)+(Triglycerides/5). The important point to consider here is that traditional LDL-C and HDL-C measurements only tell us how much cholesterol is associated with each lipoprotein particle class. We are now learning that the number and size of the particles are important as well. The number of LDL particles appears to be more strongly predictive of cardiovascular disease than the LDL-C content, and small dense LDL are known to be more atherogenic than larger, less dense LDL particles.