Counseling patients on the role of different fats, and their association with the risk of cardiovascular disease (CVD) can be a difficult task. There are many types and subtypes of fats and, most of them play an important role for bodily functions. Furthermore, a correlation between plasma measurements of different subtypes of fats or lipoproteins and the risk for heart disease, does not have to imply a causative relationship. Cholesterol is the type of fat that most often is associated with the risk of heart disease. High blood levels of cholesterol, low density lipoprotein cholesterol (LDL-C) in particular, have been associated with increased risk. Although disputed by many, it has been proposed that cholesterol may play a causative role in CVD. Lowering blood levels of LDL-C is generally recommended to reduce the risk of CVD.
Large and small LDL particles
Triglycerides are the largest category of lipids in the human body and in our diet. About two percent of dietary lipids are phospholipids. Only a small percent of our dietary lipids are sterols. The most common animal sterol is cholesterol. To be able to travel outside cells and in the circulation, cholesterol molecules are bound to different types of proteins. The term lipoprotein describes these combinations of fats and protein.
Most people are aware that there are two types of cholesterol, depending on the types of proteins that carry the cholesterol molecules. High density lipoprotein cholesterol (HDL-C) is often termed the “good” cholesterol while LDL-C is usually termed the ”bad” cholesterol. HDL and LDL are two of five major lipoproteins that enable transport of different fat molecules, including cholesterol. The other lipoproteins are chylomicrons, IDL (intermediate density lipoprotein) and VLDL (very low density lipoprotein, mainly triglycerides).
LDL is the lipoprotein particle that is mostly involved in atherosclerosis. LDL particles exist in different sizes. On one hand there are the large, fluffy, cotton-ball like molecules, and on the other hand the small dense molecules. Many recent studies have looked into the importance of LDL-particle size. Studies show that people whose LDL particles are predominantly small and dense, have a threefold greater risk of coronary heart disease. Furthermore, the large and fluffy type of LDL may be protective. However, it is possible that the association between small LDL and heart disease reflects an increased number of LDL particles in patients with small particles. Therefore, the number of LDL particles could be more important in terms of risk than particle size in itself.
There is an inverse correlation between blood levels of triglycerides and particle size. Thus, the higher your triglycerides, the higher the number of small LDL particles. Conversely, the lower your triglycerides, the higher the number of large, fluffy LDL particles.
What is LDL-P and why is it important?
LDL-C is usually calculated using the Friedewald equation. However, this measure can underestimate LDL-C level as triglycerides increase. Direct LDL-C measurements are also available and better reveal individual issues, but are less often promoted or done due to slightly higher costs. LDL-C reflects the total content or concentration of cholesterol within LDL-C particles in mg/ml or mmol/L. Since the amount of cholesterol in each particle may vary, measuring LDL-C does not necessarily reflect the actual number of particles.
LDL-P (LDL particle number) measures the actual number of LDL particles (particle concentration, nmol/L). It appears that LDL-P may be a stronger predictor of cardiovascular events than LDL-C. Low LDL-P is a much stronger predictor of low risk than low LDL-C. In fact, about 30 – 40% of those with low LDL-C may have elevated LDL-P. Therefore you can have low LDL-C but still be at risk for CVD, particularly if your LDL-P is elevated. Discordance is when LDL-C differs from LDL-P.
Lipoproteins play an essential role for the initiation and progression of atherosclerosis. Therefore it is very important for us to understand what regulates the production and clearance of atherogenic lipoprotein particles and how these mechanisms may be influenced. LDL-C is only a measure of the cholesterol mass within LDL-particles. Thus, LDL-C only indirectly reflects the atherogenic potential of LDL particles. Apolipoprotein B (apoB) and LDL-P on the other hand reflect the number of atherogenic particles, with no mention of cholesterol mass. Therefore apoB and LDL-P are believed to be better risk predictors than LDL-C.
In a consensus statement from 2008 on lipoprotein management in patients with cardiometabolic risk, the American College of Cardiology and the American Diabetes Association recommended more prominent roles of apoB and LDL-P as target of therapy
Some patients with low LDL-C may have elevated LDL-P and the other way around. This may explain why so many patients who suffer a heart attack do not have elevated levels of LDL-C.
Reference range for LDL-P
LDL-P is measured by a so-called NMR lipid profile test. A value of less than 1.000 is considered ideal. Above 2.000 is considered very high.
- Ideal: <1000
- Moderate: 1000-1299
- Borderline High: 1300-1599
- High: >1600
How to lower LDL-P
Much has been written about how to lower LDL-C. Most doctors will recommend eating less fat and cholesterol from meat and dairy products. Statin therapy significantly lowers LDL-C. However, therapies may affect LDL-P differently. Interventions that will lower LDL-C more than LDL-P include statins, estrogen replacement therapy, some antiretrovirals, and a low-fat, high-carbohydrate diet. Interventions that lower LDL-P more than LDL-C include fibrates, niacin, pioglitazone, omega-3 fatty acids, exercise and Mediterranean, low carbohydrate diet. Although statins lower LDL-P, they may leave a significant number of patients above the LDL-P target.
Patients with high levels of triglycerides and low HDL-C are likely to have high LDL-P despite normal or low LDL-C. Such a lipid profile is typical for individuals with the metabolic syndrome. Studies indicate that these patients may benefit most from low carbohydrate diets and that carbohydrate restriction reduces LDL-P.
Dr. Thomas Dayspring MD gives a fantastic explanation of LDL particle number in CVD.