Protocol for a Systematic Review and Meta-Analysis of Observational Studies on the Association of Exposure to Toxic Environmental Pollutants and Left Ventricular Dysfunction.

The association between environmental exposure to toxic substances and cardiovascular diseases (CVDs) in humans is widely recognized. However, the analysis of underlying pathophysiological mechanisms is essential to target meaningful endpoints of cardiotoxicity and allow a close-to-real life understanding of the role of chronic and acute exposure to multiple toxicants. The aim of this study is to outline the process for a systematic review of the literature that investigates the relationship between environmental pollution and left ventricular dysfunction. This systematic review and meta-analysis protocol will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) statement. PubMed, Embase, and Web of Science databases will be searched without applying search filters. Two independent reviewers will screen all titles and abstracts and identify the articles to be included in the synthesis. The risk of bias (RoB) will be assessed using an instrument developed for non-randomized (i.e., observational) studies (NRS) of environmental exposures. The results of cohort, case-control, cross-sectional, time-series, and case-crossover studies will be extracted and presented in tables considering different population subgroups and length of exposure. This protocol will be expected to provide a sound basis for selecting toxic chemicals and pollutants to contribute with the epidemiological evidence to the in vitro testing protocol within the EU-funded ALTERNATIVE Project.