Plasma legumain in familial hypercholesterolemia: associations with statin use and cardiovascular risk markers

Abstract

Legumain is known to be regulated in atherosclerotic disease and may have both pro- and anti-atherogenic properties. The study aimed to explore legumain in individuals with familial hypercholesterolemia (FH), a population with increased cardiovascular risk. Plasma legumain was measured in 251 subjects with mostly genetically verified FH, of which 166 were adults (≥18 years) and 85 were children and young adults (<18 years) and compared to 96 normolipidemic healthy controls. Plasma legumain was significantly increased in the total FH population compared to controls (median 4.9 versus 3.3 pg/mL, respectively, p < 0.001), whereof adult subjects with FH using statins had higher levels compared to non-statin users (5.7 versus 3.9 pg/mL, respectively, p < 0.001). Children and young adults with FH (p = 0.67) did not have plasma legumain different from controls at the same age. Further, in FH subjects, legumain showed a positive association with apoB, and markers of inflammation and platelet activation (i.e. fibrinogen, NAP2 and RANTES). In the current study, we show that legumain is increased in adult subjects with FH using statins, whereas there was no difference in legumain among children and young adults with FH compared to controls. Legumain was further associated with cardiovascular risk markers in the FH population. However the role of legumain in regulation of cardiovascular risk in these individuals is still to be determined.

Keywords:

• Familial hypercholesterolemia
• legumain
• statins
• inflammation
• cardiovascular disease

Acknowledgements

The authors would like to acknowledge Ellen Lund Sagen, Navida Akther Sheikh and Annika Michelsen for technical assistance.

Authors’ contributions

IG, IN, JJC, BH, KBH contributed to the conception and design of the study; JJC, LKLØ, TU analyzed the data; IG, IN, JJC, BH, KBH contributed in writing and revising the manuscript. All authors interpreted and discussed the data; read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s). Dr. Bogsrud has received research grants and/or personal fees from Amgen and Sanofi, none of which are related to the content of this manuscript. Dr. Retterstøl has received research grants and/or personal fees from Akcea, Amgen, Mills, Sanofi, and Sunnovion, none of which are related to the content of this manuscript. Dr. Holven has received research grants and/or personal fees from Mills, Amgen and Sanofi, none of which are related to the content of this manuscript.

Additional information

Funding

This work was supported by the Norwegian Health Authority South-East [grant numbers 2018084 and 2019067 to B.H., and 2020047 to I.G.], the University of Oslo, Oslo; the Norwegian National Advisory Unit on FH, Oslo University Hospital, Oslo, Norway; the Throne-Holst Foundation for Nutrition Research, Oslo, Norway.