Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of low-density lipoprotein cholesterol plasma levels. Circulating PCSK9, which differs between genders, 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 = 3673) of men (47.9%) and women (52.1%). Methods: Individuals (aged 54–79 years) free of CV diseases were enrolled in seven 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.

Sex-specific predictors of PCSK9 levels in a European population : the IMPROVE study / N. Ferri, M. Ruscica, D. Coggi, A. Bonomi, M. Amato, B. Frigerio, D. Sansaro, A. Ravani, F. Veglia, N. Capra, M.G. Lupo, C. Macchi, S. Castelnuovo, K. Savonen, A. Silveira, S. Kurl, P. Giral, M. Pirro, R.J. Strawbridge, B. Gigante, A.J. Smit, E. Tremoli, G.I. Colombo, D. Baldassarre. - In: ATHEROSCLEROSIS. - ISSN 0021-9150. - 309(2020 Sep 01), pp. 39-46.

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

N. Ferri
Primo
Writing – Original Draft Preparation
;
M. Ruscica
Secondo
Writing – Original Draft Preparation
;
D. Coggi;F. Veglia
Formal Analysis
;
C. Macchi;E. Tremoli
Funding Acquisition
;
D. Baldassarre
Ultimo
Supervision
2020

Abstract

Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of low-density lipoprotein cholesterol plasma levels. Circulating PCSK9, which differs between genders, 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 = 3673) of men (47.9%) and women (52.1%). Methods: Individuals (aged 54–79 years) free of CV diseases were enrolled in seven 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.
Atherosclerosis; Cardiovascular risk factors; PCSK9 predictors; Sex differences
Settore BIO/14 - Farmacologia
1-set-2020
Article (author)
File in questo prodotto:
File Dimensione Formato  
0112 Ferri Sex-specific predictors of PCSK9.pdf

accesso aperto

Descrizione: Articolo principale
Tipologia: Publisher's version/PDF
Dimensione 2.92 MB
Formato Adobe PDF
2.92 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/761334
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 27
  • ???jsp.display-item.citation.isi??? 25
social impact