Associations of urinary isoprostanes with measures of subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)

Ryan L Wallace; Oluseye Ogunmoroti; Di Zhao; Dhananjay Vaidya; Amir Heravi; Eliseo Guallar; Chiadi E Ndumele; Joao A C Lima; Pamela Ouyang; Matthew J Budoff; Matthew Allison; Isac Thomas; Oluwaseun E Fashanu; Ron Hoogeveen; Wendy S Post; Erin D Michos

doi:10.1016/j.athplu.2022.12.002

Associations of urinary isoprostanes with measures of subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)

Atheroscler Plus. 2022 Dec 21:51:13-21. doi: 10.1016/j.athplu.2022.12.002. eCollection 2023 Mar.

Authors

Ryan L Wallace¹, Oluseye Ogunmoroti², Di Zhao³, Dhananjay Vaidya^{3

4}, Amir Heravi⁴, Eliseo Guallar³, Chiadi E Ndumele^{2

3}, Joao A C Lima², Pamela Ouyang², Matthew J Budoff⁵, Matthew Allison⁶, Isac Thomas⁶, Oluwaseun E Fashanu⁷, Ron Hoogeveen⁸, Wendy S Post², Erin D Michos^{2

3}

Affiliations

¹ Department of Cardiology, MedStar Washington Hospital Center, Washington, DC, USA.
² Division of Cardiology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
³ Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
⁴ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Lundquist Institute, Division of Cardiology, University of California Los Angeles, Los Angeles, CA, USA.
⁶ Division of Preventive Medicine, Department of Family Medicine, University of California San Diego, San Diego, CA, USA.
⁷ Sands Constellation Heart Institute, Rochester Regional Health, Rochester, NY, USA.
⁸ Department of Medicine, Baylor College of Medicine, Houston, TX, USA.

Abstract

Background: 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.

Methods: Urinary levels of 8-isoprostane and 2,3-dinor-8-F₂-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.

Results: 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-F₂-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.

Conclusions: 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.

Trial registration: The MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.

Associated data

ClinicalTrials.gov/NCT00005487