Sex-specific predictors of PCSK9 levels in a European population: the IMPROVE study

Ferri, N. et al. (2020) Sex-specific predictors of PCSK9 levels in a European population: the IMPROVE study. Atherosclerosis, 309, pp. 39-46. (doi: 10.1016/j.atherosclerosis.2020.07.014) (PMID:32862087)

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Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of low-density lipoprotein cholesterol plasma levels and circulating PCSK9, which differs between genders. PCSK9 represents a valid pharmacological target for preventing cardiovascular (CV) events. We aimed to investigate sex-related associations between PCSK9 plasma levels and biochemical and anthropomorphic factors, and familial and personal morbidities, in a large European cohort (n=3,673) of men (47.9%) and women (52.1%). Methods: Individuals (aged 54 to 79 years) free of CV diseases were enrolled in 7 centers of five European countries: Finland, France, Italy, the Netherlands, and Sweden. PCSK9 plasma levels were measured by ELISA. Results: PCSK9 was higher in women than in men. Multiple linear regression analysis showed that latitude, sex, and treatments with statins and fibrates were the strongest predictors of PCSK9 in the whole group. These variables, together with triglycerides and high-density lipoprotein cholesterol, were also associated with PCSK9 in men or women. Mean corpuscular hemoglobin concentration and pack-years were PCSK9 independent predictors in women, whereas hypercholesterolemia and physical activity were independent predictors in men. The associations between PCSK9 and latitude, uric acid, diabetes, hypercholesterolemia and physical activity were significantly different in men and women (pinteraction <0.05 for all). Conclusions: Besides confirming the association with lipids in the whole group, our study revealed previously unknown differences in PCSK9 predictors in men and women. These might be taken into account when defining individual risk for CV events and/or for refining PCSK9 lowering treatments.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Strawbridge, Dr Rona
Authors: Ferri, N., Ruscica, M., Coggi, D., Bonomi, A., Amato, M., Frigerio, B., Sansaro, D., Ravani, A., Veglia, F., Capra, N., Lupo, M. G., Macchi, C., Castelnuovo, S., Savonen, K., Silveira, A., Kurl, S., Giral, P., Pirro, M., Strawbridge, R. J., Tremoli, E., Gigante, B., Colombo, G. I., and Baldassarre, D.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
Journal Name:Atherosclerosis
ISSN (Online):1879-1484
Published Online:30 July 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Atherosclerosis 309: 39-46
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
302131Understanding the excess risk of cardiometabolic disease in individuals with serious mental illnessJill PellMedical Research Council (MRC)MR/S003061/1HW - Public Health