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

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          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-F 2-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-F 2-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.

          Highlights

          • •

            Urinary isoprostane levels can be measured to help quantify oxidative stress.

          • •

            Oxidative stress has been implicated in the pathogenesis of atherosclerosis.

          • •

            We studied the relationship between urinary isoprostanes and ASCVD.

          • •

            We found inconsistent relationships between urinary isoprostanes and ASCVD.

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          Most cited references42

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          Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association

          Connie Tsao, Aaron Aday, Zaid I Almarzooq … (2022)
          Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). Methods: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2022 Statistical Update is the product of a full year’s worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year’s edition includes data on the monitoring and benefits of cardiovascular health in the population and an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, and the global burden of cardiovascular disease and healthy life expectancy. Results: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. Conclusions: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
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            Multi-ethnic study of atherosclerosis: objectives and design.

            D E Bild (2002)
            The Multi-Ethnic Study of Atherosclerosis was initiated in July 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease (CVD) in a population-based sample of 6,500 men and women aged 45-84 years. The cohort will be selected from six US field centers. Approximately 38% of the cohort will be White, 28% African-American, 23% Hispanic, and 11% Asian (of Chinese descent). Baseline measurements will include measurement of coronary calcium using computed tomography; measurement of ventricular mass and function using cardiac magnetic resonance imaging; measurement of flow-mediated brachial artery endothelial vasodilation, carotid intimal-medial wall thickness, and distensibility of the carotid arteries using ultrasonography; measurement of peripheral vascular disease using ankle and brachial blood pressures; electrocardiography; and assessments of microalbuminuria, standard CVD risk factors, sociodemographic factors, life habits, and psychosocial factors. Blood samples will be assayed for putative biochemical risk factors and stored for use in nested case-control studies. DNA will be extracted and lymphocytes will be immortalized for genetic studies. Measurement of selected subclinical disease indicators and risk factors will be repeated for the study of progression over 7 years. Participants will be followed through 2008 for identification and characterization of CVD events, including acute myocardial infarction and other coronary heart disease, stroke, peripheral vascular disease, and congestive heart failure; therapeutic interventions for CVD; and mortality.
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              Roles of Vascular Oxidative Stress and Nitric Oxide in the Pathogenesis of Atherosclerosis.

              Ulrich Förstermann, Ning Xia, Huige Li (2017)
              Major reactive oxygen species (ROS)-producing systems in vascular wall include NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase, xanthine oxidase, the mitochondrial electron transport chain, and uncoupled endothelial nitric oxide (NO) synthase. ROS at moderate concentrations have important signaling roles under physiological conditions. Excessive or sustained ROS production, however, when exceeding the available antioxidant defense systems, leads to oxidative stress. Animal studies have provided compelling evidence demonstrating the roles of vascular oxidative stress and NO in atherosclerosis. All established cardiovascular risk factors such as hypercholesterolemia, hypertension, diabetes mellitus, and smoking enhance ROS generation and decrease endothelial NO production. Key molecular events in atherogenesis such as oxidative modification of lipoproteins and phospholipids, endothelial cell activation, and macrophage infiltration/activation are facilitated by vascular oxidative stress and inhibited by endothelial NO. Atherosclerosis develops preferentially in vascular regions with disturbed blood flow (arches, branches, and bifurcations). The fact that these sites are associated with enhanced oxidative stress and reduced endothelial NO production is a further indication for the roles of ROS and NO in atherosclerosis. Therefore, prevention of vascular oxidative stress and improvement of endothelial NO production represent reasonable therapeutic strategies in addition to the treatment of established risk factors (hypercholesterolemia, hypertension, and diabetes mellitus).
              Article 0 comments Cited 348 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Erin D. Michos: @ErinMichos
                Journal
                Journal ID (nlm-ta): Atheroscler Plus
                Journal ID (iso-abbrev): Atheroscler Plus
                Title: Atherosclerosis Plus
                Publisher: Elsevier
                ISSN (Print): 2667-0909
                ISSN (Electronic): 2667-0895
                Publication date PMC-release: 21 December 2022
                Publication date Collection: March 2023
                Publication date (Electronic): 21 December 2022
                Volume: 51
                Pages: 13-21
                Affiliations
                [a ]Department of Cardiology, MedStar Washington Hospital Center, Washington, DC, USA
                [b ]Division of Cardiology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA
                [c ]Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
                [d ]Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
                [e ]Lundquist Institute, Division of Cardiology, University of California Los Angeles, Los Angeles, CA, USA
                [f ]Division of Preventive Medicine, Department of Family Medicine, University of California San Diego, San Diego, CA, USA
                [g ]Sands Constellation Heart Institute, Rochester Regional Health, Rochester, NY, USA
                [h ]Department of Medicine, Baylor College of Medicine, Houston, TX, USA
                Author notes
                [∗ ]Corresponding author. Division of Cardiology Johns Hopkins University School of Medicine, USA. edonnell@ 123456jhmi.edu @ErinMichos
                Article
                Publisher Item ID: S2667-0895(22)00060-8
                DOI: 10.1016/j.athplu.2022.12.002
                PMC ID: 10037087
                SO-VID: b47901e2-8a39-4f57-b815-1371a047de1e
                Copyright © © 2022 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 29 August 2022
                Date revision received : 23 November 2022
                Date accepted : 16 December 2022
                Categories
                Subject: Full Length Article

                Data availability:

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