A Modified Sampson–NIH Equation with Improved Accuracy for Estimating Low Levels of Low-Density Lipoprotein-Cholesterol

BACKGROUND: Cardiovascular guidelines have long recommended low-density lipoprotein-cholesterol (LDL-C) as the primary target for lipid-lowering therapy. Recent guidelines have emphasized the importance of achieving low LDL-C levels; hence, the accurate measurement of low LDL-C is increasingly clinically relevant. METHODS: Using lipid panel test results from the Mayo Clinic (n = 24 590) and the FOURIER clinical trial of evolocumab (n = 9605), the following modified Sampson equation was developed by least-squares regression to match LDL-C (mg/dL) by the β-quantification reference method, by combining terms into non High Density Lipoprotein Cholesterol (nonHDLC = Total Cholesterol - High Density Lipoprotein Cholesterol) and forcing the coefficient to be one. RESULTS: The modified Sampson equation demonstrated significant improvement in its concordance to the reference method compared to other equations (the Lin Concordance Correlation Coefficient 0.992, P < 0.001). By overall kappa analysis, it showed the best agreement to the reference method at the 55 mg/dL cutpoint (1.4 mmol/L, 0.98 [P < 0.001], Sampson-NIH: 0.96, Martin-Hopkins: 0.96, Friedewald: 0.94) and the 70 mg/dL cutpoint (1.8 mmol/L, 0.97 [P < 0.001], Sampson-NIH: 0.94, Martin-Hopkins: 0.95, Friedewald: 0.92). The false classification rate of the modified Sampson equation was also significantly lower compared to the other equations at 55 mg/dL (15%, [P < 0.001], Sampson-NIH: 29%, Martin-Hopkins: 28%, Friedewald: 37%) and 70 mg/dL (18%, [P < 0.001]; Sampson-NIH: 30%, Martin-Hopkins: 28.%, Friedewald: 34%). The new equation increases the percentage of correctly classified patients with low LDL-C by approximately 10% to 20% over the other equations based on its net reclassification index. CONCLUSIONS: The modified Sampson equation shows improved accuracy compared to other equations for low LDL-C. It more accurately identifies high-risk patients, who are not at their LDL-C goals and could benefit from more intensive lipid-lowering therapy.