Abstract

Aims: To compare low-density lipoprotein cholesterol (LDL-C) values calculated by the Friedewald equation with direct LDL-C in patient samples and assess the possible impact on re-classification of LDL-C target values for primary prevention or high cardiovascular disease (CVD) risk (<2.5 mmol/L) and secondary prevention or very high CVD risk (<1.8 mmol/L). LDL-C is an important CVD risk factor. Over the last decade, there has been a change in laboratory methodology from indirectly calculated LDL-C with the Friedewald equation to direct LDL-C measurements (dLDL-C).Methods: Reported results for plasma triglycerides, total cholesterol, high-density lipoprotein-cholesterol, and dLDL-C from 34,981 samples analyzed in year 2014 were extracted from the laboratory information system, Uppsala University Hospital, Uppsala, Sweden.Results: dLDL-C was approximately 10% lower than the corresponding LDL-C results calculated by the Friedewald equation in both men and women. In subjects with triglyceride concentrations above 4 mmol/L (n = 1250) the same discordant pattern was seen as for the entire study population. Altogether 5469 out of 18,051 men (30.3%) and 4604 out of 16,928 women (27.2%) were down-classified at least one CVD risk category. A very small number of subject was up-classified, in total 37 out of 18,051 men (0.2%) and 28 out of 16,928 women (0.2%).Conclusions: The two LDL-C methods had a high concordance, but the direct LDL-C measurement consistently gave approx. 10% lower values, and this caused one-third of subjects to be re-classified as having a lower cardiovascular disease risk in relation to recommended LDL-C target values and decision limits.

Highlights

  • Low-density lipoprotein cholesterol (LDL-C) is an established cardiovascular risk factor often used as a surrogate marker for cardiovascular outcomes in randomized clinical trials [1]

  • The laboratory participates in the Swedish external quality assurance programs for triglycerides, total cholesterol, HDLcholesterol, and LDL-cholesterol provided by Equalis (Uppsala, Sweden)

  • In this study of unselected and consecutively analyzed lipid profiles, direct measurement of LDL-C (dLDL-C) consistently showed approximately 10% lower values than LDL-C calculated using the Friedewald equation over the entire range of direct LDL-C studied

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Summary

Introduction

Low-density lipoprotein cholesterol (LDL-C) is an established cardiovascular risk factor often used as a surrogate marker for cardiovascular outcomes in randomized clinical trials [1]. Current cardiovascular disease (CVD) prevention guidelines are based on an overall cardiovascular risk assessment including LDL-C values, and these guidelines are a trigger for intensity of treatment with lipid-modifying therapy (LMT). For more than 25 years laboratories have reported LDL-C calculated from total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglyceride concentrations using the Friedewald equation [3]. There was a shift towards direct HDL-C methods instead of precipitation methods, and, secondly, there has been a change from calculated LDL-C to direct measurement of LDL-C (dLDL-C) [4]. There is a paucity of knowledge on the concordance between direct and calculated LDL-C measurements

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