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

IMPROVE Study Group, Nicola Ferri, Massimiliano Ruscica, Daniela Coggi, Alice Bonomi, Mauro Amato, Beatrice Frigerio, Daniela Sansaro, Alessio Ravani, Fabrizio Veglia, Nicolo Capra, Maria G. Lupo, Chiara Macchi, Samuela Castelnuovo, Kai Savonen, Angela Silveira, Sudhir Kurl, Philippe Giral, Matteo Pirro, Rona J. StrawbridgeBruna Gigante, Andries J. Smit, Elena Tremoli, Gualtiero Colombo, Damiano Baldassarre*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Scopus)
110 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)39-46
Number of pages8
JournalAtherosclerosis
Volume309
DOIs
Publication statusPublished - Sept-2020

Keywords

  • Atherosclerosis
  • Cardiovascular risk factors
  • Sex differences
  • PCSK9 predictors
  • SUBTILISIN/KEXIN TYPE 9
  • INTIMA-MEDIA THICKNESS
  • CARDIOVASCULAR-DISEASE
  • CIRCULATING PCSK9
  • PLASMA PCSK9
  • RISK
  • ATHEROSCLEROSIS
  • DETERMINANTS
  • ASSOCIATION
  • MECHANISMS

Fingerprint

Dive into the research topics of 'Sex-specific predictors of PCSK9 levels in a European population: The IMPROVE study'. Together they form a unique fingerprint.

Cite this