Concordance of LDL-cholesterol levels between the Friedewald, Martin/Hopkins, and Sampson equations in patients with atherosclerotic cardiovascular disease

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Publication Date


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AHA Scientific Sessions 2021, November 13-15, 2021, Boston, MA and Virtual


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Introduction: Accurate estimation of low-density lipoprotein cholesterol (LDL-C) is important for cardiovascular risk assessment and guiding cholesterol-lowering therapy. Different methods currently exist to estimate LDL-C. There is limited data in patients with atherosclerotic cardiovascular disease (ASCVD) in prior studies.

Objectives: To assess concordance of estimated LDL-C using the Friedewald, Martin/Hopkins, and Sampson equations.

Methods: We performed a retrospective analysis of electronic health record data from a large multistate healthcare system. Patients with ASCVD and triglycerides (TG) <400 mg/dL between October 1, 2015 and June 30, 2019 were included. LDL-C was estimated using the Friedewald equation (with a fixed TG to very LDL-C [VLDL-C] ratio of 5:1), Martin/Hopkins equation (with a flexible ratio), and Sampson equation (with estimation of VLDL-C by multiple least squares regression). Pairwise comparisons were performed, with patients categorized as concordant if the LDL-C was <70 mg/dL using both equations and discordant if the LDL-C was <70 mg/dL for the reference equation and ≥70 mg/dL for the comparator.

Results: The study included 146,106 patients with ASCVD (median age 68 years, 56% male, and 91% White). Discordance rates were 15% for the Friedewald vs Martin/Hopkins comparison, 9% for the Friedewald vs Sampson comparison, and 7% for the Sampson vs Martin/Hopkins comparison. Estimated LDL-C was lower for the Friedewald and Sampson equations compared to the Martin/Hopkins equation. Discordance was more pronounced at lower LDL-C cut points and in those with TG ≥150 mg/dL.

Conclusions: Important differences in estimated LDL-C exist between the three equations, particularly among those with TG ≥150 mg/dL. These results in ASCVD patients, synthesized with prior evidence, raise concern that reliance upon the Friedewald and Sampson equations may result in underestimation and thus, undertreatment of LDL-C in those at increased risk.

Clinical Institute

Cardiovascular (Heart)