Sunil Bhuvana, Ashraf Ambika P
Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Mary Bridge Children's Hospital, Tacoma, WA, USA.
Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, University of Alabama at Birmingham, 1600 4th Ave S CPP, Suite M30, Birmingham, AL, 35233, USA.
Curr Atheroscler Rep. 2022 Apr;24(4):265-275. doi: 10.1007/s11883-022-01000-2. Epub 2022 Feb 2.
Hypertriglyceridemia (HTG) is widely prevalent in youth. There is an unmet need for effective medications in the management of HTG in youth. The purpose of this review is to summarize the approach to HTG in acute and chronic settings, and highlight emerging therapies targeted at specific genes, proteins, and enzymes to selectively alter triglyceride (TG) metabolism.
Genetic and lifestyle factors play a significant role in the pathophysiology of HTG. Severe elevation of TG poses a risk of acute pancreatitis, while mild-to-moderate HTG increases the risk for premature atherosclerotic cardiovascular disease (ASCVD) and, increasingly, has been linked with non-alcoholic fatty liver disease. Although a variety of therapeutic agents are in development, strict adherence to a heart healthy lifestyle, including dietary changes, remain the cornerstone of management for youth with HTG. In addition to lifestyle changes, pharmacological interventions, including fibrates, omega 3 fatty acids, and statins may be considered for management of moderate-to-severe HTG. In view of its association with premature cardiovascular disease (CVD), non-high-density-lipoprotein-C (non-HDL-C) is an important target for therapy in children with moderate HTG. Management of HTG is dependent on its etiology, concomitant symptoms, and degree of TG elevation. The last two decades have seen remarkable changes in drug development, specifically those that act through the lipoprotein lipase complex, including new targeted treatments such as inhibitors of apolipoprotein C3 and angiopoietin-like protein 3.
高甘油三酯血症(HTG)在青少年中广泛流行。在青少年HTG的管理方面,对有效药物存在未满足的需求。本综述的目的是总结急性和慢性情况下HTG的治疗方法,并强调针对特定基因、蛋白质和酶以选择性改变甘油三酯(TG)代谢的新兴疗法。
遗传和生活方式因素在HTG的病理生理学中起重要作用。TG的严重升高会引发急性胰腺炎的风险,而轻度至中度HTG会增加过早发生动脉粥样硬化性心血管疾病(ASCVD)的风险,并且越来越多地与非酒精性脂肪肝病相关。尽管有多种治疗药物正在研发中,但严格坚持有益心脏健康的生活方式,包括饮食改变,仍然是青少年HTG管理的基石。除了生活方式改变外,对于中度至重度HTG的管理,可考虑药物干预,包括贝特类药物、ω-3脂肪酸和他汀类药物。鉴于其与过早心血管疾病(CVD)的关联,非高密度脂蛋白胆固醇(non-HDL-C)是中度HTG儿童治疗的重要靶点。HTG的管理取决于其病因、伴随症状和TG升高的程度。在过去二十年中,药物研发发生了显著变化,特别是那些通过脂蛋白脂肪酶复合物起作用的药物,包括新的靶向治疗药物,如载脂蛋白C3抑制剂和血管生成素样蛋白3抑制剂。