Liberati Viola, Guidotti Giulia, Sorrentino Andrea, Slanzi Margherita, Lotti Elena, Crudele Felice, Rogolino Angela, Alfano Francesco, Giusti Betti, Gori Anna Maria, Berteotti Martina, Marcucci Rossella
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
Atherothrombotic Diseases, "Careggi" University Hospital, 50134 Florence, Italy.
J Clin Med. 2025 Jun 24;14(13):4469. doi: 10.3390/jcm14134469.
Atherosclerotic cardiovascular disease (ASCVD) is often perceived as a male-dominant condition, yet recent European data show that more women live with and die from it. Gender disparities have been reported in the management of dyslipidemia, with women less likely to receive high-intensity lipid-lowering therapy and to reach low-density lipoprotein cholesterol (LDL-C) goals. This study aimed to assess sex-specific differences in response to and tolerance of PCSK9-targeted therapies-monoclonal antibodies (evolocumab, alirocumab) and small interfering RNA (inclisiran)-as well as LDL-C goal attainment according to current ESC guidelines. We conducted a prospective registry of patients initiating PCSK9-targeted therapy at a specialized lipid center between April 2018 and June 2024. Baseline lipid profiles were recorded and monitored over follow-up. Of the 341 patients, 122 (35.8%) were women and 219 (64.2%) were men, with a mean age of 66.4 ± 12.6 years for the women and 63.9 ± 11.8 years for the men. The women more frequently had heterozygous familial hypercholesterolemia (HeFH) (61.5% vs. 38.4%, < 0.001) and a lower prevalence of previous cardiovascular events compared to the men (62.3% vs. 84.5%, < 0.001). A higher proportion of the women were classified as high cardiovascular risk compared to the men (37.7% vs. 15.5%, < 0.001). Risk categories were assigned according to ESC guidelines, with LDL-C targets of <70 mg/dL for high-risk patients and <55 mg/dL for very high risk patients, along with a ≥50% LDL-C reduction for both categories. In the very high risk group, fewer women achieved LDL-C targets at the first two follow-up visits (first follow-up: 50.0% vs. 76.6%, = 0.008; second follow-up: 55.3% vs. 68.1%, = 0.049). Although treatment prescription and tolerance were similar between sexes, women showed smaller LDL-C reductions at the first follow-up (51.7 ± 23.9% vs. 57.3 ± 24.9%, = 0.044). PCSK9-targeted therapies were effective in both sexes at third follow-up, although women showed a tendency toward a delayed response and lower target attainment, indicating the potential need for more personalized management strategies.
动脉粥样硬化性心血管疾病（ASCVD）通常被认为是一种以男性为主的疾病，但最近的欧洲数据显示，患有该疾病并死于该病的女性更多。血脂异常管理方面存在性别差异，女性接受高强度降脂治疗并达到低密度脂蛋白胆固醇（LDL-C）目标的可能性较小。本研究旨在评估针对PCSK9的疗法（单克隆抗体（依洛尤单抗、阿利西尤单抗）和小干扰RNA（inclisiran））的反应和耐受性的性别差异，以及根据当前欧洲心脏病学会（ESC）指南实现LDL-C目标的情况。我们对2018年4月至2024年6月期间在一家专业脂质中心开始接受PCSK9靶向治疗的患者进行了一项前瞻性登记。记录基线血脂水平并在随访期间进行监测。在341例患者中，122例（35.8%）为女性，219例（64.2%）为男性，女性的平均年龄为66.4±12.6岁，男性为63.9±11.8岁。与男性相比，女性更常患有杂合子家族性高胆固醇血症（HeFH）（61.5%对38.4%，P<0.001），既往心血管事件的患病率较低（62.3%对84.5%，P<0.001）。与男性相比，女性中被归类为高心血管风险的比例更高（37.7%对15.5%，P<0.001）。根据ESC指南分配风险类别，高危患者的LDL-C目标为<70mg/dL，极高危患者为<55mg/dL，两类患者的LDL-C均降低≥50%。在极高危组中，在前两次随访中达到LDL-C目标的女性较少（第一次随访：50.0%对76.6%，P=0.008；第二次随访：55.3%对68.1%，P=0.049）。尽管两性之间的治疗处方和耐受性相似，但女性在第一次随访时LDL-C降低幅度较小（51.7±23.9%对57.3±24.9%，P=0.044）。在第三次随访时，针对PCSK9的疗法对两性均有效，尽管女性显示出反应延迟和目标达成率较低的趋势，这表明可能需要更个性化的管理策略。
