Wallace Ryan L, Ogunmoroti Oluseye, Zhao Di, Vaidya Dhananjay, Heravi Amir, Guallar Eliseo, Ndumele Chiadi E, Lima Joao A C, Ouyang Pamela, Budoff Matthew J, Allison Matthew, Thomas Isac, Fashanu Oluwaseun E, Hoogeveen Ron, Post Wendy S, Michos Erin D
Department of Cardiology, MedStar Washington Hospital Center, Washington, DC, USA.
Division of Cardiology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Atheroscler Plus. 2022 Dec 21;51:13-21. doi: 10.1016/j.athplu.2022.12.002. eCollection 2023 Mar.
Urinary isoprostanes are markers of systemic oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC), thoracic aortic calcium (TAC) and carotid plaque are measure subclinical atherosclerosis and prognosticate ASCVD risk. We examined the associations between urinary isoprostane levels and measures of plaque prevalence, burden, incidence and progression across three vascular beds in a cohort from the Multi-Ethnic Study of Atherosclerosis.
Urinary levels of 8-isoprostane and 2,3-dinor-8-F-isoprostane were measured in 1089 participants (mean ± SD 62 ± 8 years, 48% women) at baseline. Participants underwent computed tomography for CAC and TAC, and duplex ultrasound for carotid plaque. TAC and CAC were reassessed at 2.4 and 10 years, respectively. Regression models were adjusted for CVD risk factors.
In adjusted models, there were no significant associations between isoprostane levels with CAC prevalence or progression. Highest versus lowest tertile of 8-isoprostane was associated with 28% lower prevalence of descending TAC at baseline [prevalence ratio (PR) 0.72 95% CI (0.56, 0.94)], while 1-SD higher 2,3-dinor-8-F-isoprostane was associated with 96% higher incident ascending TAC at follow-up [Relative Risk 1.96 (1.24, 3.09)]. Highest versus lowest tertile of isoprostane measures were associated with 22% higher prevalence of carotid plaque [(PR 1.22 (1.04, 1.45)] and 14% difference [3,26] in greater extent of carotid plaque at baseline.
Higher urinary isoprostanes were inconsistently associated with some measures of subclinical atherosclerosis by imaging. This suggests a limited role of urinary isoprostane levels as a prognostic marker for the development of ASCVD.
The MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.
尿中异前列腺素是全身氧化应激的标志物，氧化应激与动脉粥样硬化性心血管疾病（ASCVD）的发病机制有关。冠状动脉钙化（CAC）、胸主动脉钙化（TAC）和颈动脉斑块是亚临床动脉粥样硬化的测量指标，并可预测ASCVD风险。我们在动脉粥样硬化多族裔研究队列中，研究了尿中异前列腺素水平与三个血管床斑块患病率、负荷、发病率和进展情况测量指标之间的关联。
在1089名参与者（平均±标准差62±8岁，48%为女性）基线时测量尿中8-异前列腺素和2,3-二硝基-8-F-异前列腺素水平。参与者接受了CAC和TAC的计算机断层扫描以及颈动脉斑块的双功超声检查。分别在2.4年和10年时重新评估TAC和CAC。回归模型针对心血管疾病风险因素进行了调整。
在调整后的模型中，异前列腺素水平与CAC患病率或进展之间无显著关联。8-异前列腺素最高三分位数与最低三分位数相比，基线时降主动脉TAC患病率低28%[患病率比（PR）0.72，95%置信区间（CI）（0.56，0.94）]，而2,3-二硝基-8-F-异前列腺素每升高1个标准差，随访时升主动脉TAC发病率高96%[相对风险1.96（1.24，3.09）]。异前列腺素测量指标最高三分位数与最低三分位数相比，颈动脉斑块患病率高22%[PR 1.22（1.04，1.45）]，且基线时颈动脉斑块范围差异为14%[3,26]。
尿中异前列腺素水平升高与通过影像学测量的某些亚临床动脉粥样硬化指标之间的关联并不一致。这表明尿中异前列腺素水平作为ASCVD发生的预后标志物作用有限。
MESA队列设计在clinicaltrials.gov上注册如下：https://clinicaltrials.gov/ct2/show/NCT00005487。
