Perspectives on the Changing Landscape of Measuring Cardiovascular Risk Related to LDL

The clinical laboratory plays a critical role in the assessment of atherosclerotic cardiovascular disease (ASCVD)9 risk. Since the 1970s, this laboratory assessment has been primarily through tests in the lipid panel, which included cholesterol, triglycerides (TG), and HDL cholesterol (HDL-C) based on fasting serum or plasma specimens. Until the advent of direct LDL cholesterol (LDL-C) tests approximately 20 years ago, LDL-C was almost exclusively estimated by the Friedewald equation (valid when TG <400 mg/dL or <4.5 mmol/L), and to date the vast majority of LDL-C is still calculated. This testing paradigm has undergone substantial changes over the past decade, with the emergence of new research and guidelines recommending alternate approaches for the laboratory assessment of ASCVD risk. As early as 2009, various clinical laboratory associations started recommending the use of a nonfasting specimen for routine lipid panels as a result of several studies supporting its use in cardiovascular risk assessment. In 2013, Martin and coworkers reported a new equation for estimating LDL-C that was more accurate than the Friedewald equation when compared to ultracentrifugation method (also known as β quantification). This new equation was reported to overcome the poor performance of the Friedewald equation at TG >150 mg/dL (>1.7 mmol/L) and at low concentrations of LDL-C (<70 mg/dL or <1.8 mmol/L), which may now be more common and clinically relevant owing to the use of more effective lipid-lowering therapy. Not all studies, however, have shown a significant difference between the old and new LDL-C equations when compared to preparative ultracentrifugation, the gold standard method for measuring LDL-C. Nevertheless, many clinical laboratories and at least one major provider of diagnostic testing services in the US switched to the new equation in 2017. In 2018, the American College of Cardiology and the American Heart Association (ACC/AHA) published new guidelines on the …