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

被引：37

作者：

Ferri, Nicola ^{[1
]}

Ruscica, Massimiliano ^{[2
]}

Coggi, Daniela ^{[2
]}

Bonomi, Alice ^{[3
]}

Amato, Mauro ^{[3
]}

Frigerio, Beatrice ^{[3
]}

Sansaro, Daniela ^{[3
]}

Ravani, Alessio ^{[3
]}

Veglia, Fabrizio ^{[3
]}

Capra, Nicolo ^{[3
]}

Lupo, Maria G. ^{[1
]}

Macchi, Chiara ^{[2
]}

Castelnuovo, Samuela ^{[4
]}

Savonen, Kai ^{[5
]}

Silveira, Angela ^{[6
]}

Kurl, Sudhir ^{[7
]}

Giral, Philippe ^{[8
]}

Pirro, Matteo ^{[9
]}

Strawbridge, Rona J. ^{[10
,11
,12
]}

Gigante, Bruna ^{[11
]}

Smit, Andries J. ^{[13
]}

Tremoli, Elena ^{[3
]}

Colombo, Gualtiero, I ^{[3
]}

Baldassarre, Damiano ^{[3
,14
]}

机构：

[1] Univ Padua, Dipartimento Sci Farmaco, Padua, Italy

[2] Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy

[3] IRCCS, Ctr Cardiol Monzino, Milan, Italy

[4] Osped Ca Granda Milano, Ctr Dislipidemie E Grossi Paoletti, Milan, Italy

[5] Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland

[6] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden

[7] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, Kuopio, Finland

[8] Grp Hop Pitie Salpetriere, AP HP, Serv Endocrinol Metab, Unites Prevent Cardiovasc, Paris, France

[9] Univ Perugia, Dept Clin & Expt Med, Internal Med Angiol & Arteriosclerosis Dis, Perugia, Italy

[10] Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland

[11] Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden

[12] Hlth Data Res, London, England

[13] Groningen & Isala Clin Zwolle, Dept Med, Univ Med Ctr Groningen, Zwolle, Netherlands

[14] Univ Milan, Dept Med Biotechnol & Translat Med, Via Vanvitelli 32, I-20129 Milan, Italy

来源：

ATHEROSCLEROSIS | 2020年 / 309卷

基金：

英国医学研究理事会;

关键词：

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;

D O I：

10.1016/j.atherosclerosis.2020.07.014

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：39 / 46

页数：8

共 51 条

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