Sex as a Biological Variable in Atherosclerosis
Sex as a Biological Variable in Atherosclerosis
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DOI：
10.1161/circresaha.120.315930
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发表时间：
2020-04-24
影响因子：
20.1
通讯作者：
Jaffe，Iris Z.
中科院分区：
文献类型：
--
作者：
Man，Joshua J.;Beckman，Joshua A.;Jaffe，Iris Z.
动脉粥样硬化是一种慢性炎症性血管疾病，是心脏病发作和缺血性中风的主要原因。尽管动脉粥样硬化的发病率和并发症的性别二态性是众所周知的，但在临床和临床前文献中，严格阐述性别作为动脉粥样硬化生物学变量的潜在机制的数据相对有限。在多项组织学和影像学研究中，男性的总斑块负荷和炎症标志物似乎高于女性，并且可以预测心血管事件。然而，虽然年轻女性相对免受心血管疾病的影响，但到70岁时，女性心肌梗死的发病率最终超过男性，这表明性别和年龄之间存在相互作用。大多数在动物动脉粥样硬化模型中进行的临床前研究并没有对两种性别进行研究，即使在这些研究中，将性别作为自变量进行的有效的直接统计比较仍然很少。本文回顾了现有的数据。总的来说，雄性动物似乎比雌性动物有更多的发炎但更小的斑块。斑块炎症通常被用作动物斑块脆弱性的替代终点。现有数据支持这样的观点，即斑块炎症可能与评估性别特异性机制更相关，而不是斑块大小，因为这些发现与缺血事件和死亡率的性别差异相关，因此可能更能反映人类状况。总的来说，相对于探索动脉粥样硬化机制的大量文献，直接比较两性之间斑块炎症的临床前研究数量极其有限。在动脉粥样硬化的机理研究中，如果没有包括两性和年龄，就失去了发现潜在的性别特异性机制的机会。了解驱动性作为动脉粥样硬化疾病生物学变量的机制对于未来的精准医学策略至关重要，以减轻全球男性和女性死亡的主要原因。
Atherosclerosis is a chronic inflammatory vascular disease and the predominant cause of heart attack and ischemic stroke. Despite the well-known sexual dimorphism in the incidence and complications of atherosclerosis, there are relatively limited data in the clinical and preclinical literature to rigorously address mechanisms underlying sex as a biological variable in atherosclerosis. In multiple histological and imaging studies, overall plaque burden and markers of inflammation appear to be greater in men than women and are predictive of cardiovascular events. However, while younger women are relatively protected from cardiovascular disease, by the seventh decade, the incidence of myocardial infarction in women ultimately surpasses that of men, suggesting an interaction between sex and age. Most preclinical studies in animal atherosclerosis models do not examine both sexes, and even in those that do, well-powered direct statistical comparisons for sex as an independent variable remain rare. This article reviews the available data. Overall, male animals appear to have more inflamed yet smaller plaques compared to female animals. Plaque inflammation is often used as a surrogate end point for plaque vulnerability in animals. The available data support the notion that rather than plaque size, plaque inflammation may be more relevant in assessing sex-specific mechanisms since the findings correlate with the sex difference in ischemic events and mortality and thus may be more reflective of the human condition. Overall, the number of preclinical studies directly comparing plaque inflammation between the sexes is extremely limited relative to the vast literature exploring atherosclerosis mechanisms. Failure to include both sexes and to address age in mechanistic atherosclerosis studies are missed opportunities to uncover underlying sex-specific mechanisms. Understanding the mechanisms driving sex as a biological variable in atherosclerotic disease is critical to future precision medicine strategies to mitigate what is still the leading cause of death of men and women worldwide.