A-208 An Improved Formula for Predicting Low LDL-C Based on an Enhanced Sampson-NIH Equation

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is used to assess atherosclerotic cardiovascular disease (ASCVD) risk and to manage lipid-lowering therapy. Proprotein convertase subtilisin/kexin (type 9) serine protease (PCSK9) inhibitors decrease LDL-C by up to 70% when used in conjunction with statins. Due to cost, insurance companies restrict their use. To be eligible for PCSK9 therapy, a patient must have pre-existing ASCVD and LDL-C > 70 mg/dL, while on a maximally tolerated dose of statins. Most clinical laboratories calculate LDL-C by the Friedewald Equation (FWLDL-C), which utilizes results from the standard lipid panel (total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C)). However, this often leads to an underestimation of LDL-C, especially when TG concentrations are elevated. More accurate equations have recently been developed, such as the Martin (MLDL-C), Sampson-NIH (SLDL-C) and extended Martin (ext-MLDL-C) equations. Using LDL-C determined by the beta-quantification reference method (BQ), we developed the following enhanced version of the Sampson-NIH Equation (eSLDL-C), which includes apoB as an independent variable: eSLDL-C = TC/1.15-(HDL-C)/1.25-TG/6.98-(TG × NonHDL-C)/1115 + TG2/8903.23 + (TG × ApoB)/1237 + ApoB/4.54–4.73 Methods Results for clinically ordered ApoB, BQ, and lipid panels were used. To test the accuracy of the various equations, we compared BQLDL-C to FWLDL-C, MLDL-C, extMLDL-C, SLDL-C and eSLDL-C by regression analysis (N = 12 101, TG < 800). Accuracy of each equation was compared to the BQ reference method for classifying patients (LDL-C ≤ 150, n = 9374) as either being below or above the 70 mg/dL treatment decision threshold for PCSK9 therapy. Results The eSLDL-C equation performed substantially better than the other equations for estimating low LDL-C (BQLDL-C ≤ 100 mg/dL, TG 5–800 mg/dL, n = 4115), with a mean absolute difference (MAD) of 3.80 mg/dL (compared to SLDL-C: 6.05; FWLDL-C: 8.71; MLDL-C: 6.43; extMLDL-C: 6.39). It also had the best overall normalized Matthew’s Correlation Coefficient (nMCC) for the best balance of sensitivity and specificity for identifying patients that are above the 70 mg/dL treatment threshold (eSLDL-C-94.7% (92.2% spec, 98.5% sen), SLDL-C-90.7% (94.8% spec, 95.5% sen), FWLDL-C-88.2% (98.0% spec, 92.7% sen), MLDL-C-90.3% (88.9% spec, 96.5% sen), and extMLDL-C-90.1% (88.4% spec, 96.5% sen)). In our dataset with 1125 subjects being belo