An increasing body of evidence identifies pollutant exposure as a risk factor for cardiovascular disease (CVD), while CVD incidence is rising steadily with the aging population. Although numerous experimental studies are now available, the mechanisms through which lifetime exposure to environmental pollutants can result in CVD are not fully understood. To comprehensively describe and understand the pathways through which pollutant exposure leads to cardiotoxicity, a systematic mapping review of the available toxicological evidence is needed. This protocol outlines a step-by-step framework for conducting this review. Using the National Toxicology Program (NTP) Health Assessment and Translation (HAT) approach for conducting toxicological systematic reviews, we selected 362 out of 8110 in vitro (17%), in vivo (67%), and combined (15%) studies for 129 potential cardiotoxic environmental pollutants, including heavy metals (29%), air pollutants (16%), pesticides (27%), and other chemicals (28%). The internal validity of included studies is being assessed with HAT and SYRCLE risk of bias tools. Tabular templates are being used to extract key study elements regarding study setup, methodology, techniques, and (qualitative and quantitative) outcomes. Subsequent synthesis will consist of an explorative meta-analysis of possible pollutant-related cardiotoxicity. Evidence maps and interactive knowledge graphs will illustrate evidence streams, cardiotoxic effects, and associated quality of evidence, helping researchers and regulators to efficiently identify pollutants of interest. The evidence will be integrated in novel adverse outcome pathways to facilitate regulatory acceptance of non-animal methods for cardiotoxicity testing. The current article describes the progress of the steps made in the systematic mapping review process.
Keywords: environmental chemicals; evidence-based toxicology; heart failure; meta-analysis; new approach methodologies (NAMs).
Heart disease is a leading global cause of death. Recent research indicates that certain environmental chemicals can worsen heart problems. We are conducting a rigorous review of scientific studies to understand how these chemicals affect the heart, i.e. cause cardiotoxicity. This will inform policymakers and promote non-animal testing methods for cardiotoxicity by providing a clear overview of the evidence. We have reviewed over 8,000 articles and focused on 362 studies on 129 chemicals, including heavy metals, air pollutants, and pesticides, and their effects on the heart. The current manuscript describes the methods used and the different steps in this process. The outcome of our systematic review will be a comprehensive database that will aid the development of alternative testing methods for cardiotoxicity.