Autoimmune diseases are associated with a dramatically increased risk of atherosclerotic cardiovascular disease and its clinical manifestations. The increased risk is consistent with the notion that atherogenesis is modulated by both protective and disease-promoting immune mechanisms. Notably, traditional cardiovascular risk factors such as dyslipidaemia and hypertension alone do not explain the increased risk of cardiovascular disease associated with autoimmune diseases. Several mechanisms have been implicated in mediating the autoimmunity-associated cardiovascular risk, either directly or by modulating the effect of other risk factors in a complex interplay. Aberrant leukocyte function and pro-inflammatory cytokines are central to both disease entities, resulting in vascular dysfunction, impaired resolution of inflammation and promotion of chronic inflammation. Similarly, loss of tolerance to self-antigens and the generation of autoantibodies are key features of autoimmunity but are also implicated in the maladaptive inflammatory response during atherosclerotic cardiovascular disease. Therefore, immunomodulatory therapies are potential efficacious interventions to directly reduce the risk of cardiovascular disease, and biomarkers of autoimmune disease activity could be relevant tools to stratify patients with autoimmunity according to their cardiovascular risk. In this Review, we discuss the pathophysiological aspects of the increased cardiovascular risk associated with autoimmunity and highlight the many open questions that need to be answered to develop novel therapies that specifically address this unmet clinical need.

自身免疫性疾病与动脉粥样硬化性心血管疾病及其临床表现的风险急剧增加有关。风险增加与动脉粥样硬化生成受保护和促进疾病的免疫机制调节的观点一致。值得注意的是，传统的心血管危险因素（如血脂异常和高血压）并不能单独解释与自身免疫性疾病相关的心血管疾病风险增加。几种机制与介导自身免疫相关的心血管风险有关，无论是直接介导还是通过在复杂相互作用中调节其他风险因素的影响。异常的白细胞功能和促炎细胞因子是这两种疾病的核心，导致血管功能障碍、炎症消退受损和慢性炎症的促进。同样，对自身抗原的耐受性丧失和自身抗体的产生是自身免疫的关键特征，但也与动脉粥样硬化性心血管疾病期间适应不良的炎症反应有关。因此，免疫调节疗法是直接降低心血管疾病风险的潜在有效干预措施，自身免疫性疾病活动的生物标志物可能是根据自身免疫患者心血管风险对自身免疫患者进行分层的相关工具。在本综述中，我们讨论了与自身免疫相关的心血管风险增加的病理生理学方面，并强调了许多需要回答的开放性问题，以开发专门解决这一未满足临床需求的新疗法。