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Clin Chem. 2009 May;55(5):888-94. doi: 10.1373/clinchem.2008.117929.

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

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Division of Preventive Medicine, Donald W Reynolds Center for Cardiovascular Research, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.



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).


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.


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.


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.


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