The Quebec Cardiovascular Study was the first large study demonstrating that heart attack can occur when a person’s LDL particle number is high and LDL level is low.8 This has been repeatedly confirmed in other studies, most recently in the AMORIS study, which enrolled a remarkable 175,000 participants and demonstrated the superiority of LDL particle number (measured as apoprotein B) in predicting heart attack risk.9 This measure can be thought of as actually counting the number of LDL particles in one cubic centimeter, or one milliliter of blood.
LDL particle number is among the most powerful tools we have to predict the risk of heart attack. It can be measured directly as LDL particle number by the nuclear magnetic resonance spectroscopy method or indirectly as apoprotein B, which is a more widely available method. Apoprotein B is the major protein particle of LDL, with a single protein per LDL particle. Apoprotein B thus provides a “count” of LDL particles.
How can LDL level be low when the particle number is high? Because the amount of cholesterol contained per particle can vary widely. If you have many LDL particles that contain less cholesterol in each particle, the conventionally measured LDL level will be low, but your heart disease risk will be high. Greater numbers of cholesterol-containing particles in the blood means more cholesterol deposition in plaque. The combination of low LDL level and high LDL particle number is very common, creating a situation whereby many people are mistakenly told that they are not at risk for heart attack.
High LDL particle number responds to the same treatments as high LDL level, but this method of assessment provides greater confidence in determining who to treat and how intensively to do so. Statin prescription drugs lower LDL particle number, as does the non-statin prescription drug ezetimibe, though it is less potent. Niacin (vitamin B3) lowers LDL particle number less potently than the statins, but will achieve a 10-20% reduction. In addition to prescription medicines, many nutritional strategies can lower LDL particle number.
High LDL particle number can be a source of danger even when LDL level has been reduced by treatments such as cholesterol-lowering statin drugs. This is why people who take a cholesterol-lowering medication can still suffer a heart attack. LDL particle number provides much more powerful feedback on the adequacy of treatment and is therefore a tool for further reduction of risk.10,11
LDL particles vary in size—big, medium, and small. The size difference is crucial. Small LDL particles are a far more destructive force than their larger counterparts. Like finely tuned weapons designed to wreak maximum damage, smaller particles more effectively penetrate the cellular barrier and enter arterial walls, contributing to atherosclerotic plaque. They also persist longer in the circulation, which allows more opportunity to cling like little magnets to tissues within the walls.
Once in the arterial wall, small LDL particles are more prone to oxidation, which stimulates the release of inflammatory and adhesive proteins. Small, dense LDL promotes endothelial dysfunction and enhanced production of pro-coagulants by endothelial cells. Small, dense LDL thus appears to be more atherogenic—that is, more likely to contribute to the build-up of plaque within arteries—than normal LDL.12,13
Small LDL can be an inherited predisposition that is activated by unhealthy lifestyles and weight gain. When the genetic factors are strong, it can occur in healthy people who are not overweight. It frequently causes heart disease and is found in more than half of all people who suffer heart attacks. Small LDL particles triple the likelihood of developing coronary plaque and suffering a heart attack. READ ARTICLE