Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications.

OBJECTIVES: The aim of this study was to compare Friedewald-estimated and directly measured low-density lipoprotein cholesterol (LDL-C) values. BACKGROUND: LDL-C is routinely estimated by the Friedewald equation to guide treatment; however, compatibility with direct measurement has received relatively little scrutiny, especially at levels <70 mg/dl now targeted in high-risk patients. METHODS: We examined 1,340,614 U.S. adults who underwent lipid profiling by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011. Following standard practice, Friedewald LDL-C was not estimated if triglyceride levels were ≥ 400 mg/dl (n = 30,174), yielding 1,310,440 total patients and 191,333 patients with Friedewald LDL-C <70 mg/dl. RESULTS: Patients were 59 ± 15 years of age and 52% were women. Lipid distributions closely matched those in the National Health and Nutrition Examination Survey. A greater difference in the Friedewald-estimated versus directly measured LDL-C occurred at lower LDL-C and higher triglyceride levels. If the Friedewald-estimated LDL-C was <70 mg/dl, the median directly measured LDL-C was 9.0 mg/dl higher (5th to 95th percentiles, 1.8 to 15.4 mg/dl) when triglyceride levels were 150 to 199 mg/dl and 18.4 mg/dl higher (5th to 95th percentiles, 6.6 to 36.0 mg/dl) when triglyceride levels were 200 to 399 mg/dl. Of patients with a Friedewald-estimated LDL-C <70 mg/dl, 23% had a directly measured LDL-C ≥ 70 mg/dl (39% if triglyceride levels were concurrently 150 to 199 mg/dl; 59% if triglyceride levels were concurrently 200 to 399 mg/dl). CONCLUSIONS: The Friedewald equation tends to underestimate LDL-C most when accuracy is most crucial. Especially if triglyceride levels are ≥ 150 mg/dl, Friedewald estimation commonly classifies LDL-C as <70 mg/dl despite directly measured levels ≥ 70 mg/dl, and therefore additional evaluation is warranted in high-risk patients.

Indicators of the atherogenic lipoprotein phenotype measured with density gradient ultracentrifugation predict changes in carotid intima-media thickness in men and women.

OBJECTIVE: Progression of carotid intima-media thickness (CIMT) is a surrogate indicator for the early stages of atherosclerosis. METHODS: The study investigated relationships between baseline lipoprotein cholesterol, triglyceride (TG), and apolipoprotein (Apo) B levels assessed with density gradient ultracentrifugation (DGU) and progression of posterior wall common CIMT in men (45-75 years of age) and women (55-74 years of age) in the control arm of a clinical trial. Participants had baseline posterior wall CIMT 0.7-2.0 mm, without significant stenosis. CIMT was assessed using B-mode ultrasound at baseline, and 12 and ~18 months. A DGU cholesterol panel that assessed the major lipoprotein classes and subclasses, plus triglycerides, lipoprotein (a) cholesterol, low-density lipoprotein (LDL) peak time (inversely related to LDL particle density), and Apo B were performed on fasting baseline samples. Apo B was also measured using an enzyme linked immunosorbent assay. RESULTS: Baseline CIMT was inversely associated (P < 0.001) with CIMT progression. After adjustment for baseline CIMT, significant predictors of posterior wall CIMT progression in linear regression analyses included LDL peak time (inverse, P = 0.045), total high-density lipoprotein cholesterol (HDL-C) (inverse, P = 0.001), HDL(2)-C (inverse, P = 0.005), HDL(3)-C (inverse, P = 0.003), very low-density lipoprotein (VLDL)-C (P = 0.037), and VLDL(1+2)-C (P = 0.016). CONCLUSION: These data indicate that DGU-derived indicators of the "atherogenic lipoprotein phenotype," including increased TG-rich lipoprotein cholesterol, lower HDL-C and HDL-C subfractions, and a greater proportion of LDL-C carried by more dense LDL particles, are associated with CIMT progression in men and women at moderate risk for coronary heart disease.