Comparison of LDL cholesterol concentrations by Friedewald calculation and direct measurement in relation to cardiovascular events in 27,331 women

Abstract

Background: National Cholesterol Education Program (NCEP) guidelines recommend development of direct assays for LDL cholesterol (LDL-C) measurement, but it is unclear how these assays compare with Friedewald calculation in predicting cardiovascular disease (CVD).

Methods: In a study of 27 331 healthy women with triglycerides <or=4.52 mmol/L (<or=400 mg/dL), baseline fasting Friedewald LDL-C was compared with fasting and nonfasting direct homogenous measurement for incident CVD during an 11-year period.

Results: Fasting LDL-C measurements obtained by the 2 methods were highly correlated (r = 0.976, P < 0.001). Compared with fasting Friedewald LDL-C, mean fasting direct LDL-C was 0.15 mmol/L (5.6 mg/dL) lower and nonfasting direct LDL-C 0.30 mmol/L (11.5 mg/dL) lower, both P < 0.0001. The adjusted hazard ratio per 1-SD increment was 1.23 [95% CI 1.15-1.32; 1-SD 0.88 mmol/L (34.1 mg/dL)] for fasting direct LDL-C and 1.22 [95% CI 1.14-1.30; 1-SD 0.90 mmol/L (34.9 mg/dL)] for fasting Friedewald. Nonfasting LDL-C was not associated with CVD by either method. Fasting LDL-C measurements fell into the same NCEP risk category with either method for 79.3% of participants, whereas they differed by 1 NCEP category for 20.7% of participants, with most classified into a lower-risk category by direct LDL-C.

Conclusions: The association of LDL-C with CVD by the 2 methods was nearly identical in fasting samples. However, the lower direct LDL-C concentrations may misclassify many individuals into a lower NCEP category. Moreover, the lack of association of nonfasting direct LDL-C with CVD raises questions regarding the clinical utility of a direct assay for LDL-C in nonfasting blood samples.

Trial registration: ClinicalTrials.gov NCT00000479.

Figure 1

Scatterplot showing the correlation of Friedewald fasting and direct fasting LDL-C values, Pearson correlation coefficient 0.976, P<0.001 (left); and Bland-Altman plot showing the difference between direct fasting and Friedewald fasting values vs the mean of the two (right). The mean difference (direct minus Friedewald) was − 5.64 (95% CI − 5.75, − 5.53).

Figure 1

Scatterplot showing the correlation of Friedewald fasting and direct fasting LDL-C values, Pearson correlation coefficient 0.976, P<0.001 (left); and Bland-Altman plot showing the difference between direct fasting and Friedewald fasting values vs the mean of the two (right). The mean difference (direct minus Friedewald) was − 5.64 (95% CI − 5.75, − 5.53).

Figure 2

Boxplots showing the 2.5, 25, 50, 75, and 97.5% cumulative percentile values and extreme values, according to time since last meal, for direct nonfasting LDL-C (left) and direct fasting LDL-C (right).

Figure 2

Boxplots showing the 2.5, 25, 50, 75, and 97.5% cumulative percentile values and extreme values, according to time since last meal, for direct nonfasting LDL-C (left) and direct fasting LDL-C (right).