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A Modified Sampson-NIH Equation with Improved Accuracy for Estimating Low Levels of Low-Density
Maureen Sampson1, Rafael Zubiran2, Anna Wolska2
1Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States.
Insights
A new modified Sampson equation accurately measures low-density lipoprotein-cholesterol (LDL-C) levels, improving identification of high-risk cardiovascular patients. This enhanced accuracy helps tailor lipid-lowering therapy for better patient outcomes.
Area of Science:
- Cardiovascular Medicine
- Clinical Chemistry
- Biostatistics
Background:
- Cardiovascular guidelines prioritize low-density lipoprotein-cholesterol (LDL-C) for lipid-lowering therapy.
- Accurate measurement of low LDL-C is critical for effective cardiovascular risk management.
Purpose of the Study:
- To develop and validate a modified Sampson equation for precise LDL-C measurement.
- To improve the accuracy of calculating low LDL-C compared to existing equations.
Main Methods:
- Developed a modified Sampson equation using least-squares regression on Mayo Clinic and FOURIER trial data.
- Validated the equation against the β-quantification reference method for LDL-C.
Main Results:
- The modified Sampson equation showed superior concordance (CCC 0.992) and agreement (kappa 0.98 at 55 mg/dL) to the reference method.
- It significantly reduced the false classification rate for low LDL-C at 55 mg/dL (15%) and 70 mg/dL (18%).
- The equation improved correct classification of patients with low LDL-C by 10-20% via net reclassification index.
Conclusions:
- The modified Sampson equation offers improved accuracy for calculating low LDL-C.
- It enhances the identification of high-risk patients not meeting LDL-C goals.
- This improved accuracy supports more intensive and effective lipid-lowering treatment strategies.
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.
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