Dipartimento di Scienze Del Farmaco, Università Degli Studi di Padova, Padova, Italy.
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università Degli Studi di Milano, Milan, Italy.
Atherosclerosis. 2020 Sep;309:39-46. doi: 10.1016/j.atherosclerosis.2020.07.014. Epub 2020 Jul 30.
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%).
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.
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 (p <0.05 for all).
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.
前蛋白转化酶枯草溶菌素 9（PCSK9）是调节低密度脂蛋白胆固醇（LDL-C）水平的关键调控因子之一。循环中的 PCSK9 在性别之间存在差异，是预防心血管（CV）事件的有效药物靶点。我们旨在研究男女之间 PCSK9 血浆水平与生化和人体测量因素以及家族和个人疾病之间的相关性，该研究纳入了来自七个中心的 3673 名男性（47.9%）和女性（52.1%）的大型欧洲队列。
纳入无 CV 疾病的个体（年龄 54-79 岁），这些个体来自五个欧洲国家的七个中心：芬兰、法国、意大利、荷兰和瑞典。通过 ELISA 法测定 PCSK9 血浆水平。
女性的 PCSK9 水平高于男性。多元线性回归分析显示，纬度、性别以及他汀类药物和贝特类药物的治疗是整个研究群体中 PCSK9 的最强预测因子。这些变量与甘油三酯和高密度脂蛋白胆固醇一起，也是男性或女性中 PCSK9 的相关因素。红细胞平均血红蛋白浓度和吸烟包年是女性 PCSK9 的独立预测因子，而高胆固醇血症和体力活动是男性 PCSK9 的独立预测因子。在男性和女性中，PCSK9 与纬度、尿酸、糖尿病、高胆固醇血症和体力活动之间的关联存在显著差异（p<0.05 ）。
除了在整个研究群体中证实了与血脂的相关性外，本研究还揭示了男女之间 PCSK9 预测因子的未知差异。在确定个体发生 CV 事件的风险或制定 PCSK9 降低治疗方案时，可能需要考虑这些差异。
