One-third of patients in the study sample were randomly assigned to a validation data set. Patients were grouped by those fulfilling the Friedewald equation criterion of triglycerides lower than 400 mg/dL (to convert to millimoles per liter, multiply by 0.0113) and those with triglycerides of 400 or higher.
Friedewald LDL-C (LDL-CF) was estimated as (non–HDL-C) – (triglycerides/5) in mg/dL.1 (link) Novel LDL-C (LDL-CN) estimates were derived as (non–HDL-C) – (triglycerides/adjustable factor mg/dL), where the adjustable factor was determined as the strata-specific median TG:VLDL-C ratio. Numerical subscripts (eg, LDL-C180 for 180-cell stratification) were used to identify variants of LDL-CN. Alternative LDL-C estimates were also calculated based on previously proposed formulas.2 (link),18 (link)–23 (link) The reference standard direct LDL-C (LDL-CD) was subtracted from each LDL-C estimate to determine the absolute difference in their values in milligrams per deciliter.
Direct and estimated LDL-C values were classified according to clinical practice guidelines in the United States (<70, 70–99, 100–129, 130–159, 160–189, and ≥190 mg/dL; to convert to millimole per liter, multiply by 0.0259) and Europe (<70, 70–99, 100–154, 155–189, and ≥190 mg/dL).3 (link)–5 (link),7 (link),8 (link) Concordance in classification between LDL-C estimates and LDL-CD was examined in the whole study population and subgroups. The initial classification was defined by the estimated parameter because this is the parameter routinely available in clinical practice. Odds ratios (ORs) for discordance in subgroups were calculated using logistic regression. Based on prior literature,24 (link)–30 (link) definitions of Fredrickson-Levy phenotypes are provided in eTable 4 in the Supplement.
Statistical analyses were performed in Stata (StataCorp), version 11.0, and logarithmically scaled pseudocolor encoded data density plots were generated in R (http://r-project.org), version 2.14.1. We considered a 2-tailed P of less than .05 statistically significant.