Lipoprotein(a) screening for cardiac allograft vasculopathy among heart transplant recipients

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of clinical lipidology Pub Date : 2025-05-01 DOI:10.1016/j.jacl.2025.04.032

Deepasree Bangaru-Raju MD, Dhivyashree Bangaru-Raju MD, Vi Nguyen PharmD, Shamim Khosrowjerdi BS, Sotirios Tsimikas MD, Jose Benjamin Cruz Rodriguez MD, Antoinette Birs MD, Andrew Kao MD

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Abstract

Background/Synopsis

Lipoprotein(a) [Lp(a)] is a well-established inheritable risk factor of atherosclerotic cardiovascular disease (ASCVD) for which the National Lipid Association (NLA) recommends Lp(a) screening once in all adults. Heart transplant (HTx) recipients develop both cardiac allograft vasculopathy (CAV) hallmarked by a chronic but progressive coronary intimal thickening as well as atherosclerosis. While traditional ASCVD risk factors such as hypertension, diabetes, hyperlipidemia are stringently optimized among transplant recipients, the impact of Lp(a) on CAV development remains unknown.

Objective/Purpose

Elevated Lp(a), defined as level > 50mg/dL, has been shown to confer development of ASCVD. The complex pathophysiology of early CAV is a result of both donor and recipients baseline risk factors, and post-transplant factors. This study aims to investigate the association of Lp(a) and early CAV development in HTx recipients.

Methods

A single-center, retrospective study analyzed 88 HTx recipients between 2015 to 2024 with measured Lp(a) and at least one post-HTx coronary angiogram with highly sensitive intravascular ultrasound (IVUS). The primary endpoint was CAV quantified by maximal intimal thickness (MIT) of 1mm and 1.5mm. Cox proportional hazard models were used to evaluate the association of elevated Lp(a) with MIT. The model was adjusted for key covariates: treated cytomegalovirus, rejection, LDL-cholesterol, high intensity statin use, donor ischemic time, BMI, and sex.

Results

A total of 24 (27.3%) of HTx recipients had an elevated Lp(a) > 50 mg/dL; median Lp(a) was 17.5 [7.0, 34.0] and 91.5 [68.8, 128.5] mg/dL, respectively. Median follow-up time post HTx was 2.12 years [1.17, 4.04]. Baseline lipid profile and characteristics were similar between groups, Table 1. In univariate analysis, Lp(a) > 50 mg/dL was not associated with MIT 1.5mm development (HR 1.9, 95% CI 0.49-7.60, p = 0.35), nor in multivariate analysis, (HR 2.36, 95% CI 0.45-12.4, p = 0.30; overall model p = 0.03). LDL-C > 100 mg/dL was highly correlated with CAV outcomes (HR 4.7, p = 0.02).

Conclusions

Elevated Lp(a) was not associated with an increased risk for the early development of CAV as determined by IVUS. As elevated Lp(a) has been associated with increased long-term risk of angiographic disease, additional study is required to understand how cumulative exposure to elevated Lp(a) may contribute to this process. The complex relationship between Lp(a), the immune response to HTx, and CAV warrants further investigation.

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心脏移植受者血管病变的脂蛋白(a)筛查

背景/简介脂蛋白(a) [Lp(a)]是一种公认的动脉粥样硬化性心血管疾病（ASCVD）的遗传危险因素，美国国家脂质协会（NLA）建议在所有成年人中进行一次脂蛋白(a)筛查。心脏移植（HTx）受者会发生以慢性进行性冠状动脉内膜增厚和动脉粥样硬化为特征的同种异体心脏移植血管病变（CAV）。虽然传统的ASCVD危险因素如高血压、糖尿病、高脂血症在移植受者中得到了严格的优化，但Lp(a)对CAV发展的影响尚不清楚。目的/目的Lp(a)升高，定义为水平>；50mg/dL已被证明会导致ASCVD的发展。早期CAV复杂的病理生理是供体和受体基线危险因素以及移植后因素共同作用的结果。本研究旨在探讨Lp(a)与HTx受体早期CAV发展的关系。方法一项单中心回顾性研究分析了2015年至2024年间88例HTx患者的Lp(a)测量和至少一次HTx术后高灵敏度血管内超声（IVUS）冠状动脉造影。主要终点是CAV量化的最大内膜厚度（MIT）为1mm和1.5mm。Cox比例风险模型用于评估Lp(a)升高与MIT的关系。该模型针对关键协变量进行了调整：接受治疗的巨细胞病毒、排斥反应、低密度脂蛋白胆固醇、高强度他汀类药物使用、供体缺血时间、BMI和性别。结果HTx受体患者Lp(a) >升高24例（27.3%）；50毫克/分升;中位Lp(a)分别为17.5[7.0,34.0]和91.5 [68.8,128.5]mg/dL。HTx术后中位随访时间为2.12年[1.17,4.04]。各组间基线脂质谱和特征相似，见表1。单变量分析中，Lp(a) >；50 mg/dL与MIT 1.5mm发展无关（HR 1.9, 95% CI 0.49-7.60, p = 0.35），在多变量分析中也无关(HR 2.36, 95% CI 0.45-12.4, p = 0.30；整体模型p = 0.03)。低密度比;100 mg/dL与CAV预后高度相关（HR 4.7, p = 0.02）。结论经IVUS检测，Lp(a)升高与CAV早期发展风险增加无关。由于Lp(a)升高与血管造影疾病的长期风险增加有关，需要进一步的研究来了解累积暴露于升高的Lp(a)是如何促成这一过程的。Lp(a)、HTx免疫应答和CAV之间的复杂关系值得进一步研究。

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来源期刊

Journal of clinical lipidology 医学-药学

CiteScore

7.00

自引率

6.80%

发文量

209

审稿时长

49 days

期刊介绍： Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner. Sections of Journal of clinical lipidology will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.