Nicola Ferri1, Massimiliano Ruscica2, Daniela Coggi2, Alice Bonomi3, Mauro Amato3, Beatrice Frigerio3, Daniela Sansaro3, Alessio Ravani3, Fabrizio Veglia3, Nicolò Capra3, Maria G Lupo1, Chiara Macchi2, Samuela Castelnuovo4, Kai Savonen5, Angela Silveira6, Sudhir Kurl7, Philippe Giral8, Matteo Pirro9, Rona J Strawbridge10, Bruna Gigante11, Andries J Smit12, Elena Tremoli3, Gualtiero I Colombo3, Damiano Baldassarre13. 1. Dipartimento di Scienze Del Farmaco, Università Degli Studi di Padova, Padova, Italy. 2. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università Degli Studi di Milano, Milan, Italy. 3. Centro Cardiologico Monzino, IRCCS, Milan, Italy. 4. Centro Dislipidemie E. Grossi Paoletti, Ospedale Ca' Granda di Niguarda, Milan, Italy. 5. Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland. 6. Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. 7. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Finland. 8. Assistance Publique - Hopitaux de Paris, Service Endocrinologie-Metabolisme, Groupe Hôpitalier Pitie-Salpetriere, Unités de Prévention Cardiovasculaire, Paris, France. 9. Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. 10. Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom; Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Health Data Research, UK. 11. Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. 12. Department of Medicine, University Medical Center Groningen, Groningen & Isala Clinics Zwolle, Department of Medicine, the Netherlands. 13. Centro Cardiologico Monzino, IRCCS, Milan, Italy; Department of Medical Biotechnology and Translational Medicine, Università Degli Studi di Milano, Milan, Italy. Electronic address: damiano.baldassarre@unimi.it.
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.
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.
Authors: Dániel Kucsera; Viktória E Tóth; Dorottya Gergő; Imre Vörös; Zsófia Onódi; Anikó Görbe; Péter Ferdinandy; Zoltán V Varga Journal: Front Physiol Date: 2021-02-22 Impact factor: 4.566