TY - JOUR
T1 - Sex-specific predictors of PCSK9 levels in a European population
T2 - The IMPROVE study
AU - IMPROVE Study Group
AU - Ferri, Nicola
AU - Ruscica, Massimiliano
AU - Coggi, Daniela
AU - Bonomi, Alice
AU - Amato, Mauro
AU - Frigerio, Beatrice
AU - Sansaro, Daniela
AU - Ravani, Alessio
AU - Veglia, Fabrizio
AU - Capra, Nicolo
AU - Lupo, Maria G.
AU - Macchi, Chiara
AU - Castelnuovo, Samuela
AU - Savonen, Kai
AU - Silveira, Angela
AU - Kurl, Sudhir
AU - Giral, Philippe
AU - Pirro, Matteo
AU - Strawbridge, Rona J.
AU - Gigante, Bruna
AU - Smit, Andries J.
AU - Tremoli, Elena
AU - Colombo, Gualtiero
AU - Baldassarre, Damiano
AU - Mulder, Douwe Johannes
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Cardiovascular risk factors
KW - Sex differences
KW - PCSK9 predictors
KW - SUBTILISIN/KEXIN TYPE 9
KW - INTIMA-MEDIA THICKNESS
KW - CARDIOVASCULAR-DISEASE
KW - CIRCULATING PCSK9
KW - PLASMA PCSK9
KW - RISK
KW - ATHEROSCLEROSIS
KW - DETERMINANTS
KW - ASSOCIATION
KW - MECHANISMS
U2 - 10.1016/j.atherosclerosis.2020.07.014
DO - 10.1016/j.atherosclerosis.2020.07.014
M3 - Article
SN - 0021-9150
VL - 309
SP - 39
EP - 46
JO - Atherosclerosis
JF - Atherosclerosis
ER -