Background: Increased small dense low-density lipoprotein-cholesterol (sdLDL-C) is a risk factor for atherosclerotic cardiovascular disease (ASCVD) but typically requires advanced lipid testing. We describe two new equations, first one for calculating large buoyant LDL-C (lbLDL-C), based only upon results from the standard lipid panel, and the second one for sdLDL-C.
Methods: Equations for sdLDL-C and lbLDL-C were generated with least-squares regression analysis using the direct Denka sdLDL-C assay as reference (n = 20 171). sdLDL-C was assessed as a risk-enhancer test in the National Heart and Nutrition Examination Survey (NHANES), and for its association with ASCVD in the Multi-Ethnic Study of Atherosclerosis (MESA).
Results: The newly derived equations depend on two terms, namely LDL-C as determined by the Sampson equation, and an interaction term between LDL-C and the natural log of triglycerides (TG). The lbLDL-C equation (lbLDLC=1.43 × LDLC-0.14 ×(ln(TG)× LDLC)- 8.99) was more accurate (R2 = 0.933, slope = 0.94) than the sdLDL-C equation (sdLDLC=LDLC- lbLDLC; R2 = 0.745, slope = 0.73). Using the 80th percentile (46 mg/dL) as a cut-point, sdLDL-C identified in NHANES additional high-risk patients not identified by other risk-enhancer tests based on TG, LDL-C, apolipoprotein B, and nonHDL-C. By univariate survival-curve analysis, estimated sdLDL-C was superior to other risk-enhancer tests in predicting ASCVD events in MESA. After multivariate adjustment for other known ASCVD risk factors, estimated sdLDL-C had the strongest association with ASCVD compared to other lipid parameters, including measured sdLDL-C.
Conclusions: Estimated sdLDL-C could potentially be calculated on all patients tested with a standard lipid panel to improve ASCVD risk stratification.
Published by Oxford University Press on behalf of the American Association for Clinical Chemistry 2021. This work is written by US Government employees and is in the public domain in the US.