Department of Medicine; Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5C1.
Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5B7.
Endocr Rev. 2022 Jul 13;43(4):611-653. doi: 10.1210/endrev/bnab037.
Lipid disorders involving derangements in serum cholesterol, triglycerides, or both are commonly encountered in clinical practice and often have implications for cardiovascular risk and overall health. Recent advances in knowledge, recommendations, and treatment options have necessitated an updated approach to these disorders. Older classification schemes have outlived their usefulness, yielding to an approach based on the primary lipid disturbance identified on a routine lipid panel as a practical starting point. Although monogenic dyslipidemias exist and are important to identify, most individuals with lipid disorders have polygenic predisposition, often in the context of secondary factors such as obesity and type 2 diabetes. With regard to cardiovascular disease, elevated low-density lipoprotein cholesterol is essentially causal, and clinical practice guidelines worldwide have recommended treatment thresholds and targets for this variable. Furthermore, recent studies have established elevated triglycerides as a cardiovascular risk factor, whereas depressed high-density lipoprotein cholesterol now appears less contributory than was previously believed. An updated approach to diagnosis and risk assessment may include measurement of secondary lipid variables such as apolipoprotein B and lipoprotein(a), together with selective use of genetic testing to diagnose rare monogenic dyslipidemias such as familial hypercholesterolemia or familial chylomicronemia syndrome. The ongoing development of new agents-especially antisense RNA and monoclonal antibodies-targeting dyslipidemias will provide additional management options, which in turn motivates discussion on how best to incorporate them into current treatment algorithms.
涉及血清胆固醇、甘油三酯或两者异常的脂质代谢紊乱在临床实践中很常见,通常与心血管风险和整体健康有关。最近在知识、建议和治疗选择方面的进展,需要对这些疾病采取更新的方法。较旧的分类方案已经过时,取而代之的是基于常规脂质谱上确定的主要脂质异常的方法,这是一种实用的起点。尽管存在单基因脂质代谢紊乱,并且识别这些紊乱很重要,但大多数脂质代谢紊乱患者都具有多基因易感性,通常在肥胖和 2 型糖尿病等继发性因素的背景下。就心血管疾病而言,升高的低密度脂蛋白胆固醇基本上是因果关系,全球临床实践指南已为该变量推荐了治疗阈值和目标。此外,最近的研究已确定升高的甘油三酯是心血管风险因素,而先前认为降低的高密度脂蛋白胆固醇的贡献较小。诊断和风险评估的更新方法可能包括测量载脂蛋白 B 和脂蛋白(a)等次要脂质变量,以及选择性使用基因检测来诊断罕见的单基因脂质代谢紊乱,如家族性高胆固醇血症或家族性乳糜微粒血症综合征。针对脂质代谢紊乱的新型药物——特别是反义 RNA 和单克隆抗体的不断发展,将提供更多的治疗选择,这反过来又促使人们讨论如何将它们最好地纳入当前的治疗算法中。