Silvain Johanne, Materne Clément, Zeitouni Michel, Procopi Niki, Guedeney Paul, Brugier Delphine, Galier Sophie, Lhomme Marie, Ponnaiah Maharajah, Guillas Isabelle, Kc Pukar, Dahik Veronica D, Frisdal Eric, Vicaut Eric, Lesnik Philippe, Rahoual Ghilas, Le Goff Wilfried, Montalescot Gilles, Kerneis Mathieu, Guerin Maryse
ACTION Study Group, Institut de Cardiologie Hôpital Pitié-Salpêtrière (AP-HP), F-75013 Paris, France.
Sorbonne University, INSERM Unité de recherche sur les maladies cardiovasculaires, le métabolisme et la nutrition, UMR_S1166-ICAN F-75013 Paris, France.
Eur J Prev Cardiol. 2024 Nov 7. doi: 10.1093/eurjpc/zwae356.
Low cholesterol efflux capacity and elevated levels of Interleukin-1ß (IL-1ß) are both associated with residual cardiovascular risk in patients with acute myocardial infarction (MI) and may be used as new biomarkers to identify patients at higher cardiovascular risk.
We evaluated potential synergetic effect of cholesterol efflux capacity and IL-1ß on recurrent major adverse cardiovascular events (MACE) at one-year in 2012 patients with acute ST- segment elevation MI who underwent primary percutaneous coronary intervention. In addition, we evaluated the contribution to residual risk of HDL biological functions from 20 patients of the two extreme subgroups, focusing on cholesterol efflux capacity and anti-inflammatory properties.
Patients with MACE during the first year after the MI had significantly lower serum cholesterol efflux capacity as compared to those without recurrent events and higher level of IL-1ß, both associations were confirmed after multivariate analysis. We found an inverse relationship between CEC and circulating levels of the inflammatory markers IL-1ß, defining a very high risk (Low CEC/High IL-1ß) and a low risk (High CEC/Low IL-1ß) group of patients. Patients combining Low CEC/High IL-1ß exhibited the highest risk of recurrent MACE at one year showing an additive prognostic value of these biomarkers, regardless of all the other clinical or biological factors. In this very high-risk subgroup, patients exhibited reduced HDL-efflux capacity and defective ABCA1 and SR-BI with enhanced pro-inflammatory activity as a potential explanation for our clinical findings.
Impaired cholesterol efflux capacity and elevated IL-1β synergistically increase the residual cardiovascular risk in MI patients, which could be explained by reduced HDL-efflux capacity and enhanced HDL pro-inflammatory activity.
低胆固醇流出能力和白细胞介素-1β（IL-1β）水平升高均与急性心肌梗死（MI）患者的残余心血管风险相关，可作为识别心血管风险较高患者的新生物标志物。
我们评估了2012例接受直接经皮冠状动脉介入治疗的急性ST段抬高型MI患者中，胆固醇流出能力和IL-1β对1年内复发性主要不良心血管事件（MACE）的潜在协同作用。此外，我们评估了两个极端亚组中20例患者的高密度脂蛋白（HDL）生物学功能对残余风险的贡献，重点关注胆固醇流出能力和抗炎特性。
与无复发事件的患者相比，MI后第一年发生MACE的患者血清胆固醇流出能力显著降低，IL-1β水平更高，多变量分析后这两种关联均得到证实。我们发现胆固醇流出能力（CEC）与炎症标志物IL-1β的循环水平呈负相关，确定了一组高风险（低CEC/高IL-1β）和低风险（高CEC/低IL-1β）患者。合并低CEC/高IL-1β的患者在1年内复发性MACE的风险最高，表明这些生物标志物具有附加预后价值，无论所有其他临床或生物学因素如何。在这个高风险亚组中，患者表现出HDL流出能力降低、ABCA1和SR-BI缺陷以及促炎活性增强，这可能是我们临床发现的潜在解释。
胆固醇流出能力受损和IL-1β升高协同增加MI患者的残余心血管风险，这可以通过HDL流出能力降低和HDL促炎活性增强来解释。
