Low-density Lipoprotein - Estimation of LDL Particles Via Cholesterol Content

Estimation of LDL Particles Via Cholesterol Content

Chemical measures of lipid concentration have long been the most-used clinical measurement, not because they have the best correlation with individual outcome, but because these lab methods are less expensive and more widely available.

The lipid profile does not measure LDL particles directly but instead estimates them using the Friedewald equation by subtracting the amount of cholesterol associated with other particles, such as HDL and VLDL, assuming a prolonged fasting state, etc.:

where H is HDL cholesterol, L is LDL cholesterol, C is total cholesterol, T are triglycerides, and k is 0.20 if the quantities are measured in mg/dl and 0.45 if in mmol/l.

There are limitations to this method, most notably that samples must be obtained after a 12 to 14 h fast and that LDL-C cannot be calculated if plasma triglyceride is >4.52 mmol/L (400 mg/dL). Even at triglyceride levels 2.5 to 4.5 mmol/L, this formula is considered inaccurate. If both total cholesterol and triglyceride levels are elevated then a modified formula, with quantities in mg/dl, may be used

This formula provides an approximation with fair accuracy for most people, assuming the blood was drawn after fasting for about 14 hours or longer.

However, the concentration of LDL particles, and to a lesser extent their size, has a slightly stronger correlation with individual clinical outcome than the amount of cholesterol within LDL particles, even if the LDL-C estimation is approximately correct. There is increasing evidence and recognition of the value of more targeted and accurate measurements of LDL particles. Specifically, LDL particle number (concentration), and to a lesser extent size, have shown slightly stronger correlations with atherosclerotic progression and cardiovascular events than obtained using chemical measures of the amount of cholesterol carried by the LDL particles . It is possible that the LDL cholesterol concentration can be low, yet LDL particle number high and cardiovascular events rates are high. Correspondingly, it is possible that LDL cholesterol concentration can be relatively high, yet LDL particle number low and cardiovascular events are also low. If LDL particle concentration is used to predict cardiovascular events, many other correlates of these clinical outcomes, such as diabetes mellitus, obesity and smoking, lose much of their predictive power.