Longitudinal study of circulating oxidized LDL and HDL and fatty liver: the Cardiovascular Risk in Young Finns Study

Abstract

Oxidative reactions are thought to play a role in the inflammatory condition called fatty liver. It is unclear whether oxidized lipoprotein lipids or proteins are associated with future fatty liver. In the Cardiovascular Risk in Young Finns Study, we determined the circulating levels of LDL and HDL oxidized lipids and studied their associations with fatty liver assessed by ultrasonography. There were 1286 middle-aged subjects with normal liver and 288 subjects with fatty liver. Analysis of oxidized lipids consisted of conjugated dienes in isolated HDL (oxHDLlipids) and LDL (oxLDLlipids). Oxidized LDL was also measured with a method based on antibodies against oxidized apolipoprotein B (oxLDLprot). After adjustment for age, sex, leisure-time physical activity, body mass index, alcohol intake, smoking, serum LDL and HDL cholesterol as well as particle concentrations, participants with elevated oxLDLlipids (odds ratio for 1-SD change in oxLDLlipids = 1.27, p = 0.011) had an increased risk for fatty liver. Similarly, a high oxidation score (oxLDLlipids + oxLDLprot) was directly associated with fatty liver (odds ratio=1.34, p = 0.012). The strongest direct association was seen with a high oxLDLlipids/oxHDLlipids ratio (odds ratio=1.49, p = 0.001). These data suggest that oxidized lipoprotein lipids are linked with the risk of fatty liver in middle-aged adults.

Keywords:

• Conjugated dienes
• lipoprotein oxidation
• oxidative stress
• population study
• steatosis

Acknowledgements

The authors thank Irina Lisinen and Ville Aalto for data management.

Declaration of interest

P. S., A. J. K., and M. A. K. are shareholders of Brainshake Ltd. (www.brainshake.fi), a startup company offering NMR-based metabolite profiling. Other authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

 The Young Finns Study has been financially supported by the Academy of Finland: Grants 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117797 (Gendi), and 41071 (Skidi), the Social Insurance Institution of Finland, Kuopio, Tampere, and Turku University Hospital Medical Funds, Juho Vainio Foundation, Paavo Nurmi Foundation, Finnish Foundation of Cardiovascular Research and Finnish Cultural Foundation, Tampere Tuberculosis Foundation, Emil Aaltonen Foundation and Yrjö Jahnsson foundation. Applications of the quantitative serum NMR methodology have been supported by the Sigrid Juselius Foundation, the Novo Nordisk Foundation, the Finnish Diabetes Research Foundation, and the strategic and infrastructural research funding from the University of Oulu, Finland, as well as by the British Heart Foundation, the Wellcome Trust, and the Medical Research Council, UK.