LDL Cholesterol as a Predictor of Mortality, and Beyond

The 'necessity' of a fasting lipid panel for assessment of atherosclerotic cardiovascular disease (ASCVD) risk has been assumed now for decades. The rationale for this position has been the estimation of levels of low density lipoprotein cholesterol (LDL-C), a major risk factor for ASCVD, by correcting for non-fasting changes in plasma triglycerides using the so-called Friedewald equation developed during the 1960s at the then National Heart Institute1. Because LDL-C determination by ultracentrifugation is time consuming and expensive and direct LDL-C measurements have proven no more accurate than the Friedewald equation, the calculation of LDL-C has remained more than adequate, and was recently endorsed by the 2013 ACC/AHA Risk Assessment Work Group2 and utilized in the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease Risk in Adults3. The equation estimates LDL-C after measuring total cholesterol, high density cholesterol (HDL-C) and triglycerides (TG), and then subtracting from the total cholesterol concentration the HDL-C plus very low density lipoprotein cholesterol (VLDL-C) which is estimated by TG/5. This formula is not used when plasma TG >400 mg/dL because in this metabolic setting VLDL particles contain relatively less cholesterol and VLDL-C contribution is therefore overestimated and the calculated LDL-C is falsely low.