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低 LCAT 活性与 CKD 患者的急性失代偿性心力衰竭和死亡率相关。

Low LCAT activity is linked to acute decompensated heart failure and mortality in patients with CKD.

机构信息

Division of Pharmacology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria.

Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.

出版信息

J Lipid Res. 2024 Sep;65(9):100624. doi: 10.1016/j.jlr.2024.100624. Epub 2024 Aug 20.

Abstract

Chronic kidney disease (CKD) is often associated with decreased activity of lecithin-cholesterol acyltransferase (LCAT), an enzyme essential for HDL maturation. This reduction in LCAT activity may potentially contribute to an increased risk of cardiovascular mortality in patients with CKD. The objective of this study was to investigate the association between LCAT activity in patients with CKD and the risk of adverse outcomes. We measured serum LCAT activity and characterized lipoprotein profiles using nuclear magnetic resonance spectroscopy in 453 non-dialysis CKD patients from the CARE FOR HOMe study. LCAT activity correlated directly with smaller HDL particle size, a type of HDL potentially linked to greater cardiovascular protection. Over a mean follow-up of 5.0 ± 2.2 years, baseline LCAT activity was inversely associated with risk of death (standardized HR 0.62, 95% CI 0.50-0.76; P < 0.001) and acute decompensated heart failure (ADHF) (standardized HR 0.67, 95% CI 0.52-0.85; P = 0.001). These associations remained significant even after adjusting for other risk factors. Interestingly, LCAT activity was not associated with the incidence of atherosclerotic cardiovascular events or kidney function decline during the follow-up. To conclude, our findings demonstrate that low LCAT activity is independently associated with all-cause mortality and ADHF in patients with CKD, and is directly linked to smaller, potentially more protective HDL subclasses.

摘要

慢性肾脏病(CKD)常伴有卵磷脂胆固醇酰基转移酶(LCAT)活性降低,LCAT 是高密度脂蛋白(HDL)成熟所必需的酶。LCAT 活性的这种降低可能会增加 CKD 患者心血管死亡率的风险。本研究旨在探讨 CKD 患者 LCAT 活性与不良结局风险之间的关系。我们在 CARE FOR HOMe 研究中的 453 名非透析 CKD 患者中测量了血清 LCAT 活性,并使用核磁共振光谱法对脂蛋白谱进行了特征描述。LCAT 活性与较小的 HDL 颗粒大小直接相关,HDL 的这种类型可能与更大的心血管保护作用有关。在平均 5.0±2.2 年的随访期间,基线 LCAT 活性与死亡风险呈负相关(标准化 HR 0.62,95%CI 0.50-0.76;P<0.001)和急性失代偿性心力衰竭(ADHF)(标准化 HR 0.67,95%CI 0.52-0.85;P=0.001)。即使在调整了其他危险因素后,这些关联仍然显著。有趣的是,LCAT 活性与随访期间动脉粥样硬化性心血管事件或肾功能下降的发生率无关。总之,我们的研究结果表明,低 LCAT 活性与 CKD 患者的全因死亡率和 ADHF 独立相关,并且与较小的、可能更具保护作用的 HDL 亚类直接相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f92/11416249/27029268fefd/ga1.jpg

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