Treatment target re-classification of subjects comparing estimation of low-density lipoprotein cholesterol by the Friedewald equation and direct measurement of LDL-cholesterol

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.

Keywords:

• Direct LDL-C measurement
• Friedewald equation
• LDL-cholesterol
• primary prevention
• re-classification
• secondary prevention

Additional information

Funding

This study was supported by grants from the Swedish government under the agreement for medical education and research (ALF-medel).

Notes on contributors

Anders Larsson

Professor Anders Larsson, MD, PhD, Senior consultant clinical chemistry, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Emil Hagström

Associate Professor Emil Hagström, MD, PhD, Senior consultant cardiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden and Uppsala Clinical Research Centre, Uppsala, Sweden.

Lennart Nilsson

Professor Lennart Nilsson, MD, PhD, Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden.

Maria K. Svensson

Professor Maria K. Svensson, MD, PhD, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.