Concerns about the Use of Non-high-density Lipoprotein Cholesterol as a Lipid Predictor

Introduction: Non-high-density lipoprotein (non-HDL) cholesterol is the sum of low-density lipoprotein (LDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol, and is usually approximated by the total cholesterol minus HDL-cholesterol. The National Lipid Association (NLA) has advocated the use of non-HDL cholesterol as its favoured lipid predictor. Cut-off points are based on LDL cholesterol values, with a lower end at 100 mg/dL (2.50 mmol/L) and a higher end at 190 mg/dL (4.75 mmol/L), adding 30 mg/dL (0.75 mmol/L) to keep triglyceride (TG) levels <150 mg/dL (1.70 mmol/L). Objectives: The author will demonstrate that the use of non-HDL cholesterol has not been fully considered. Methods: The author will examine a general population lipid database to demonstrate the frequency of distribution of non-HDL cholesterol in the part of the population that was known to have developed a form of atherothrombotic disease (ATD) and in the part that was not known to have done so. The effect of stratifying each non-HDL cholesterol quintile in terms of another lipid predictor that does not involve VLDL-cholesterol or TG will be demonstrated. The other risk predictor is the cholesterol retention fraction (CRF) defined as (LDL-HDL)/LDL. Findings: All non-HDL cholesterol quintiles above the lowest quintile had higher frequencies in the ATD population than in the non-ATD population. The highest two quintiles had frequencies in the ATD population that are 2.5-times as high as those in the non-ATD population, whereas in the middle two quintiles, the frequency in the ATD population was minimally higher than in the non-ATD population. In the lowest quintile, the frequency is much higher in the non-ATD population than in the ATD population. At any non-HDL cholesterol quintile, the average age of ATD onset depends on cigarette smoking (not discussed here) and the CRF. Higher CRF levels equate to an earlier average age of ATD onset and lower levels of CRF equate to a later onset. A 75-year-old male who was a hypertensive diabetic and a former smoker was not on statins because of low lipid levels, had clean arteries on angiography, whereas a 45-year-old normotensive, non-smoking patient with severe dyslipidaemia (obtained at first encounter) had a massive stroke due to carotid stenosis. Both had non-HDL cholesterol levels in the intermediate ATD risk quintiles. Conclusions: Non-HDL cholesterol is not the optimal predictor of the population at risk of atherothrombotic disease and its use should be reconsidered.