Saadatagah Seyedmohammad, Larouche Miriam, Naderian Mohammadreza, Nambi Vijay, Brisson Diane, Kullo Iftikhar J, Duell P Barton, Michos Erin D, Shapiro Michael D, Watts Gerald F, Gaudet Daniel, Ballantyne Christie M
Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Center for Translational Research on Inflammatory Diseases, Baylor College of Medicine, Houston, TX, USA.
Am J Prev Cardiol. 2025 Mar 28;22:100978. doi: 10.1016/j.ajpc.2025.100978. eCollection 2025 Jun.
Extreme hypertriglyceridemia, defined as triglyceride (TG) levels ≥1000 mg/dL, is almost always indicative of chylomicronemia. The current diagnostic approach categorizes individuals with chylomicronemia into familial chylomicronemia syndrome (FCS; prevalence 1-10 per million), caused by the biallelic combination of pathogenic variants that impair the lipolytic action of lipoprotein lipase (LPL), or multifactorial chylomicronemia syndrome (MCS, 1 in 500). A pragmatic framework should emphasize the severity of the phenotype and the risk of complications. Therefore, we endorse the term "persistent chylomicronemia" defined as TG ≥1000 mg/dL in more than half of the measurements to encompass patients with the highest risk for pancreatitis, regardless of their genetic predisposition. We suggest classification of PC into four subtypes: 1) genetic FCS, 2) clinical FCS, 3) PC with "alarm" features, and 4) PC without alarm features. Although patients with FCS most likely have PC, the vast majority with PC do not have genetic FCS. Proposed alarm features are: (a) history of recurrent TG-induced acute pancreatitis, (b) recurrent hospitalizations for severe abdominal pain without another identified cause, (c) childhood pancreatitis, (d) family history of TG-induced pancreatitis, and/or (e) post-heparin LPL activity <20 % of normal value. Alarm features constitute the strongest risk factors for future acute pancreatitis risk. Patients with PC and alarm features have very high risk of pancreatitis, comparable to that in patients with FCS. Effective, innovative treatments for PC, like apoC-III inhibitors, have been developed. Combined with lifestyle modifications, these agents markedly lower TG levels and risk of pancreatitis in the very-high-risk groups, irrespective of the monogenic etiology. Pragmatic definitions, education, and focus on patients with PC specifically those with alarm features could help mitigate the risk of acute pancreatitis and other complications.
极高甘油三酯血症定义为甘油三酯（TG）水平≥1000mg/dL，几乎总是提示乳糜微粒血症。目前的诊断方法将乳糜微粒血症患者分为家族性乳糜微粒血症综合征（FCS；患病率为百万分之一至十万分之一），其由损害脂蛋白脂肪酶（LPL）脂解作用的致病变异的双等位基因组合引起，或多因素乳糜微粒血症综合征（MCS，500人中1例）。一个实用的框架应强调表型的严重程度和并发症风险。因此，我们支持“持续性乳糜微粒血症”这一术语，定义为在超过半数的测量中TG≥1000mg/dL，以涵盖胰腺炎风险最高的患者，无论其遗传易感性如何。我们建议将持续性乳糜微粒血症分为四种亚型：1）遗传性FCS，2）临床FCS，3）具有“警示”特征的持续性乳糜微粒血症，4）无警示特征的持续性乳糜微粒血症。虽然FCS患者很可能患有持续性乳糜微粒血症，但绝大多数持续性乳糜微粒血症患者并非遗传性FCS。提出的警示特征包括：（a）复发性TG诱导的急性胰腺炎病史，（b）因严重腹痛反复住院且无其他明确病因，（c）儿童期胰腺炎，（d）TG诱导的胰腺炎家族史，和/或（e）肝素后LPL活性<正常价值的20%。警示特征是未来急性胰腺炎风险的最强危险因素。具有警示特征的持续性乳糜微粒血症患者胰腺炎风险非常高，与FCS患者相当。已经开发出针对持续性乳糜微粒血症的有效、创新治疗方法，如载脂蛋白C-III抑制剂。与生活方式改变相结合，这些药物可显著降低极高风险组的TG水平和胰腺炎风险，无论其单基因病因如何。实用的定义、教育以及关注持续性乳糜微粒血症患者，特别是那些具有警示特征的患者，有助于降低急性胰腺炎和其他并发症的风险。
