Non–High-Density Lipoprotein Cholesterol and Guidelines for Cholesterol Lowering in Recent History

Stanley S. Levinson, PhD


Lab Med. 2020;51(1):14-23. 

In This Article

Abstract and Introduction


Background: The National Cholesterol Education Program (NCEP) released guidelines for treating cholesterol in 1988, 1994, and 2002. After a hiatus, the guidelines were released again in 2013, 2016, 2017, and 2018.

Methods: In this article, I review these guidelines, factors that affected their release, how they evolved, and why recommended treatment targets are reasonable. Also, to aid reader understanding, I briefly discuss biochemical mechanisms and the pathophysiology of beta-lipoproteins, focusing on the importance on non–high-density cholesterol (non-HDLC) in assessing risk and as a target for treatment. The concepts discussed are important to laboratory clinicians because those workers inscribe target values on the reports and may consult with medical staff members.

Conclusions: The newest recommendations, released in 2018, are an extension of the 2017 guidelines that defined non-HDLC as equivalent to low-density lipoprotein cholesterol (LDLC). For the reasons discussed herein, non-HDLC has advantages over LDLC. Laboratories reporting cholesterol results should include non-HDLC values and cutoffs in their reports.


In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) released new guidelines from an expert group[1] that recommended that therapy for lowering low-density lipoprotein cholesterol (LDLC) be focused on the intensity of drug treatment, rather than on a targeted concentration (target value), as previous expert groups had recommended. In 2016, an ACC Expert Consensus Committee[2] released new guidelines that restored target values and introduced non–high-density lipoprotein cholesterol (non-HDLC) as an equivalent target to LDLC in patients with diabetes mellitus and those with elevated triglycerides. In 2017, the American College of Cardiology Task Force on Expert Consensus Committee released still-newer guidelines on the role of nonstatin therapies for preventing coronary disease.[3] These guidelines, which were an update of the 2016 ACC guidelines,[2] extended the use of non-HLDC as a target for all risk groups.

In this review, I discuss briefly how these recommendations evolved, how treatment targets reasonably meet the needs for reducing coronary disease, the biochemical mechanisms that support the recommendations, and why the specific target values selected are reasonable. To help readers understand dyslipidemias treatments, I also briefly discuss the pathophysiology of beta-lipoproteins, the relationship of those lipoproteins to atherosclerotic disease, the biochemical sites at which treatments act, and the growing importance of non-HDLC as a marker and target. These concepts are important to laboratory clinicians because those workers inscribe target values on the reports and may have to consult with medical staff members regarding the rationale for and use of these values.