Abstract：
OBJECTIVE: Familial hypercholesterolaemia (FH) is a highly prevalent monogenic disorder characterized by elevated LDL cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Sex disparities in diagnosis, lipid-lowering therapy, and achieved lipid levels have emerged worldwide, resulting in barriers to care in FH. A systematic review was performed to investigate sex-related disparities in treatment, response, and lipid target achievement in FH (PROSPERO, CRD42022353297).
METHODS: MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases were searched from inception to 26 April 2023. Records were eligible if they described sex differences in the treatment of adults with FH.
RESULTS: Of 4432 publications reviewed, 133 met our eligibility criteria. In 16 interventional clinical trials (eight randomized and eight non-randomized; 1840 participants, 49.4% females), there were no differences between males and females in response to fixed doses of lipid-lowering therapy, suggesting that sex was not a determinant of response. Meta-analysis of 25 real-world observational studies (129 441 participants, 53.4% females) found that females were less likely to be on lipid-lowering therapy compared with males (odds ratio .74, 95% confidence interval .66-.85). Importantly, females were less likely to reach an LDL-C < 2.5 mmol/L (odds ratio .85, 95% confidence interval .74-.97). Similarly, treated LDL-C levels were higher in females. Despite this, male sex was associated with a two-fold greater relative risk of major adverse cardiovascular events including myocardial infarction, atherosclerotic cardiovascular disease, and cardiovascular mortality.
CONCLUSIONS: Females with FH were less likely to be treated intensively and to reach guideline-recommended LDL-C targets. This sex bias represents a surmountable barrier to clinical care.
METHODS: MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases were searched from inception to 26 April 2023. Records were eligible if they described sex differences in the treatment of adults with FH.
RESULTS: Of 4432 publications reviewed, 133 met our eligibility criteria. In 16 interventional clinical trials (eight randomized and eight non-randomized; 1840 participants, 49.4% females), there were no differences between males and females in response to fixed doses of lipid-lowering therapy, suggesting that sex was not a determinant of response. Meta-analysis of 25 real-world observational studies (129 441 participants, 53.4% females) found that females were less likely to be on lipid-lowering therapy compared with males (odds ratio .74, 95% confidence interval .66-.85). Importantly, females were less likely to reach an LDL-C < 2.5 mmol/L (odds ratio .85, 95% confidence interval .74-.97). Similarly, treated LDL-C levels were higher in females. Despite this, male sex was associated with a two-fold greater relative risk of major adverse cardiovascular events including myocardial infarction, atherosclerotic cardiovascular disease, and cardiovascular mortality.
CONCLUSIONS: Females with FH were less likely to be treated intensively and to reach guideline-recommended LDL-C targets. This sex bias represents a surmountable barrier to clinical care.
摘要：
目的：家族性高胆固醇血症（FH）是一种高度流行的单基因疾病，其特征是LDL胆固醇（LDL-C）水平升高和过早的动脉粥样硬化性心血管疾病。诊断中的性别差异，降脂治疗,并达到脂质水平已经在世界范围内出现，导致FH的护理障碍。进行了系统评价以调查与性别相关的治疗差异，回应,和FH中的脂质目标实现(PROSPERO，CRD4202253297).
方法：MEDLINE，Embase,科克伦图书馆,PubMed,Scopus,PsycInfo,和灰色文献数据库从开始到2023年4月26日进行了检索。如果他们描述了FH成人治疗中的性别差异，则记录合格。
结果：在所审查的4432份出版物中，133符合我们的资格标准。在16项介入临床试验中(8项随机和8项非随机；1840名参与者，49.4%女性)，男性和女性对固定剂量降脂治疗的反应没有差异，表明性别不是反应的决定因素。25项真实世界观察性研究的荟萃分析(129441名参与者，53.4％的女性）发现，与男性相比，女性不太可能接受降脂治疗（比值比.74，95％置信区间.66-.85）。重要的是,女性不太可能达到LDL-C<2.5mmol/L（比值比.85，95％置信区间.74-.97）。同样，女性接受治疗的LDL-C水平较高。尽管如此,男性与包括心肌梗死在内的主要不良心血管事件的相对风险高2倍,动脉粥样硬化性心血管疾病，和心血管死亡率。
结论：女性FH患者接受强化治疗和达到指南推荐的LDL-C目标的可能性较小。这种性别偏见代表了临床护理的可克服障碍。
方法：MEDLINE，Embase,科克伦图书馆,PubMed,Scopus,PsycInfo,和灰色文献数据库从开始到2023年4月26日进行了检索。如果他们描述了FH成人治疗中的性别差异，则记录合格。
结果：在所审查的4432份出版物中，133符合我们的资格标准。在16项介入临床试验中(8项随机和8项非随机；1840名参与者，49.4%女性)，男性和女性对固定剂量降脂治疗的反应没有差异，表明性别不是反应的决定因素。25项真实世界观察性研究的荟萃分析(129441名参与者，53.4％的女性）发现，与男性相比，女性不太可能接受降脂治疗（比值比.74，95％置信区间.66-.85）。重要的是,女性不太可能达到LDL-C<2.5mmol/L（比值比.85，95％置信区间.74-.97）。同样，女性接受治疗的LDL-C水平较高。尽管如此,男性与包括心肌梗死在内的主要不良心血管事件的相对风险高2倍,动脉粥样硬化性心血管疾病，和心血管死亡率。
结论：女性FH患者接受强化治疗和达到指南推荐的LDL-C目标的可能性较小。这种性别偏见代表了临床护理的可克服障碍。
