Fasting vs Non-Fasting and Low-Density Lipoprotein-Cholesterol Accuracy
Background—Recent recommendations favoring non-fasting lipid assessment may impact low-density lipoprotein-cholesterol (LDL-C) estimation. The novel method of LDL-C estimation (LDL-CN) uses a flexible approach to derive patient-specific triglyceride (TG) to very low-density lipoprotein-cholesterol ratios. This adaptability may confer an accuracy advantage in non-fasting patients over the fixed approach of the classical Friedewald method (LDL-CF).
Methods—We used a US cross-sectional sample of 1,545,634 patients (959,153 fasting ≥10-12 hours; 586,481 non-fasting) from the second harvest of the Very Large Database of Lipids study to assess for the first time the impact of fasting status on novel LDL-C accuracy. Rapid ultracentrifugation was used to directly measure LDL cholesterol content (LDL-CD). Accuracy was defined as the percentage of LDL-CD falling within an estimated LDL-C (LDL-CN or LDL-CF) category by clinical cutpoints. For low estimated LDL-C (<70 mg/dL), we evaluated accuracy by TG levels. The magnitude of absolute and percent differences between LDL-CD and estimated LDL-C (LDL-CN or LDL-CF) was stratified by LDL-C and TG categories.
Results—In both fasting and non-fasting samples, accuracy was higher with the novel method across all clinical LDL-C categories (range: 87-94%) compared to Friedewald estimation (range: 71-93%) (p≤0.001). With LDL-C <70 mg/dL, non-fasting LDL-CN accuracy (92%) was superior to LDL-CF (71%) (p<0.001). In this LDL-C range, 19% of fasting and 30% of non-fasting patients had differences ≥10 mg/dL between LDL-CF and LDL-CD, whereas only 2% and 3% of patients respectively had similar differences with novel estimation. Accuracy of LDL-C <70 mg/dL further decreased as TG increased, particularly for Friedewald estimation (range: 37-96%) versus the novel method (range: 82-94%). With TG 200-399 mg/dL in non-fasting patients, LDL-CN <70 mg/dL accuracy (82%) was superior to LDL-CF (37%) (p<0.001). In this TG range, 73% of fasting and 81% of non-fasting patients had ≥10 mg/dL differences between LDL-CF and LDL-CD, compared to 25% and 20% of patients respectively with LDL-CN.
Conclusions—Novel adaptable LDL-C estimation performs better in non-fasting samples than the fixed Friedewald estimation, with a particular accuracy advantage in settings of low LDL-C and high TG. In addition to stimulating further study, these results may have immediate relevance to guideline committees, laboratory leadership, clinicians and patients.
Clinical Trial Registration—URL: clinicaltrials.gov Unique Identifier: NCT01698489
- Received July 23, 2017.
- Revision received September 7, 2017.
- Accepted September 25, 2017.