Accuracy of Small Dense Low-density Lipoprotein-cholesterol Concentration Estimated via Sampson’s Equation in Healthy Subjects and Patients with Diabetes

Abstract

Aim: Sampson et al. proposed a method to calculate small dense low-density lipoprotein-cholesterol (sdLDL-C) concentrations using common lipid measurements, but its accuracy remains unresolved. We examined the difference between Sampson's equation and direct measurement in patients with diabetes. Methods: sdLDL-C was measured directly by our established homogeneous assay and estimated by Sampson's equation in patients with diabetes (n=1542) and healthy control subjects (n=673). Large-buoyant (lb)LDL-C was estimated using triglycerides and LDL-C, and sdLDL-C was obtained by subtracting lbLDL-C from LDL-C. The effect of fasting/nonfasting state or lipid-lowering drug therapy on sdLDL-C values was also examined in 30 and 43 patients with diabetes, respectively. Results:The coefficient of determination (R 2 ) between calculated sdLDL-C and direct measurement was 0.73 and 0.61 for healthy controls and patients with diabetes, respectively. The R 2 between calculated sdLDL-C and nonHDL-C or apolipoprotein B was 0.64 and 0.65, respectively. Calculated sdLDL-C was 4-5 mg/dl or 17%-18% higher than the direct measurement. The lower the plasma lipids, especially sdLDL-C, the greater the dissociation between the two methods. Sampson sdLDL-C was also found to give a positive bias when calculated for the nonfasting samples. Statins and pemafibrate significantly reduced sdLDL-C, but their therapeutic effect was underestimated by 5 mg/dl (24%) via Sampson's equation. Conclusions:The correlation between Sampson's equation and direct measurements of sdLDL-C was reduced in patients with diabetes. Furthermore, the correlations with nonHDL-C and apolipoprotein B were even higher than those with direct sdLDL-C. The accuracy of Sampson's equation decreased with lower sdLDL-C concentrations and was also influenced by diet.

Validation of Estimated Small Dense Low-Density Lipoprotein Cholesterol Concentration in a Japanese General Population

“…However, correlations of estimated sdLDL-C with other lipid parameters including TG, non-HDL-C and ApoB were not investigated. Another study using 2,215 Japanese subjects showed that there was a stronger correlation between estimated and measured levels of sdLDL-C in 673 healthy subjects (R 2 =0.736) than in 1,542 patients with diabetes mellitus (R 2 =0.614) 15) . The correlations of measured sdLDL-C or estimated sdLDL-C with non-HDL-C and TG were weaker in patients with diabetes mellitus than in healthy subjects in that study 15) .…”

“…Another study using 2,215 Japanese subjects showed that there was a stronger correlation between estimated and measured levels of sdLDL-C in 673 healthy subjects (R 2 =0.736) than in 1,542 patients with diabetes mellitus (R 2 =0.614) 15) . The correlations of measured sdLDL-C or estimated sdLDL-C with non-HDL-C and TG were weaker in patients with diabetes mellitus than in healthy subjects in that study 15) . Furthermore, calculated levels of sdLDL-C by Sampson's equation were underestimated by anti-dyslipidemic drugs including statins and pemafibrate in the previous study 15) .…”

“…To the best of our knowledge, there has been only one report regarding the validation of estimated sdLDL-C calculated by Sampson's equation, and it was shown that there was a weaker correlation between measured and estimated sdLDL-C levels in elderly patients with diabetes mellitus (n=1,542, mean age: 65 years) (R 2 =0.614) than in relatively young healthy subjects (n=673, mean age: 39 years) (R 2 =0.736) 15) . Therefore, the validation and exploration of estimated sdLDL-C level have not been fully investigated, and a more accurate estimation of sdLDL-C is necessary.…”

“…To the best of our knowledge, there were two previous studies that focused on the association between levels of measured and estimated sdLDL-C 12,15) . Using a large number of US subjects (n=20,171), Sampson et al proposed a formula for calculating sdLDL-C and showed that the estimated sdLDL-C level was highly correlated with measured sdLDL-C level (R 2 =0.745) 12) .…”

The Oxidized Lipoproteins In Vivo: Its Diversity and Behavior in the Human Circulation

“…However, a commercially available, less labor-intensive application, the Lipoprint ® LDL system, is often used in clinical settings [ 26 ]. Increased sdLDL levels have been observed in patients with diabetes mellitus and coronary heart disease (CHD), and it is potentially a clinical marker for these diseased conditions [ 27 , 28 ].…”