This result is similar to that seen in statin-treated patients in, for example, the Treating to New Targets (TNT) trial,[47] where the LDL-HDL cholesterol interactions were explored. In TNT, for patients who attained an LDL cholesterol level <70 mg/dL on statin therapy, HDL cholesterol level was the only a predictor of future CVD events when that HDL cholesterol was <44 mg/dL. So if you lower the LDL particle concentration with a statin, HDL cholesterol only becomes important when serum levels are low, not when they are intermediate or very high.
In the MESA trial data are analyzed after adjustment for LDL particle concentration,[48] the result simulates the scenario seen clinically in statin-treated patients. Either adjusting for LDL particle concentration or treating with statins levels the playing field and the relationships between HDL cholesterol and CVD risk, as assessed by cIMT change.
Now the question becomes, what happens if instead of HDL cholesterol we control for total number of HDL particles? When we look at the HDL particle concentration, there is an inverse relationship with cIMT: the fewer the number of HDL particles, the greater the thickness of the IMT. This makes sense when we recall that individuals with low levels of HDL cholesterol have predominantly the small, cholesterol-depleted HDL particles: the result is that HDL cholesterol may not be the most accurate biomarker of risk in these patients, who often have insulin resistance disorders, for example type 2 diabetes, and metabolic syndrome.
If, however, in the small number of cholesterol-depleted HDL particles scenario, we adjust for LDL particle concentration, the relationship does not change in the same way. Rather, even after factoring in LDL particle number, future risk of CVD events, as assessed by cIMT, is more strongly associated with HDL particle concentration than with serum HDL cholesterol levels.
Thus, when we adjust the CVD risk (assessed by cIMT) associated with serum HDL cholesterol for LDL particle concentration, we again see a threshold effect, but adjust the HDL particle concentration for LDL particle concentration, and we see more of a linear relationship. As a result, this is one piece of several emerging pieces of data suggesting that HDL particle concentration is a more robust predictor of atherosclerosis and future CVD events.
J Clin Lipidol. 2011; 5(6).[47]Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007; 357:1301-1310.
[48]Mackey RH, Greenland P, Goff DC, et al. The relationship of HDL cholesterol and HDL particles to carotid atherosclerosis and incident cardiovascular events: The Multi- Ethnic Study of Atherosclerosis. Abstracts from the American Heart Association Joint Conference: Nutrition, Physical Activity and Metabolism and Metabolism and CVD Epidemiology and Prevention 2011 Scientific Sessions. 2011; 331. Abstract P410.
