non HDL , LDL and cardiovascular risk

We all know that LDL is a calculated value from triglycerides and HDL(Freidwald formula),and is not a measured value. But it still holds good in terms of predicting atherosclerosis burden. The formula becomes less accurate as triglyceride(TG) level increases, and once TG is > 400, it is inaccurate.That is the reason for treating TG first if its >500 before treating LDL.But patients do have CAD and end up with an Acute Coronary Syndrome, even after LDL levels are at target. This is what we call "residual risk".

To address this risk, there has been a good deal of studies in this aspect. In the ATP 3 NCEP guidelines, non-HDL cholesterol is the second targey after LDL cholesterol. non-HDL includes all the cholesterol particles apart from HDL, and is obtained simply by subtracting total cholesterol from HDL.It comprises of VLDL, LDL,& IDL. In a study comparing non HDL to LDL and their risk of CVD, an increase that an increase of 30 mg/dL in non–HDL-C,and LDL-C levels would result in increases in CVD risk of 19%, and 11%, respectively. Authors concluded that non-HDL is a better prdictor of CVD than LDL.

In the TNT trial(first trial to show that reducing LDL to <100 mg/dl would further reduce CV mortality), even in those who reached LDL < 70, CHD risk was still strongly influenced by low levels of HDL. 

The group of patients in whom this would apply a lot will be those with diabetes and metabolic syndrome, who typically have a high triglyceride level and a low HDL level, which would make their non HDL levels high. There is a nice small review article from Mayo Clinic Proceedings which discusses this...and also about apo-B levels(which can be expensive and may not confer more information than non HDL)

There are some other studies like ARBITER trial, niacin and statin therapy increased HDL-C levels, reduced
carotid intima media thickness,and lowered CV events compared with statin and ezetimibe therapy.And there are large trials going on to address the issue with non HDL cholesterol and CV risk. For now...based on studies so far...the non HDL cholesterol targets need to be roughly within 30mg/dl more than the LDL targets. adding Niacin to a statin ..to bring up the HDL..and in this way reduce the non HDL cholesterol is an acceptable option for now.