Effects of controlled, acute exposure to air pollutants on heart rate variability in humans: a meta-regression and methodological recommendations

The consequences of air pollution on cardiovascular disease (CVD) are heavily supported. One proposed mechanism that underpins the development of many CVD-related pathologies is autonomic imbalance, which can be measured through the high frequency (HF) component of heart rate variability (HRV). Despite evidence suggesting that air pollution reduces HRV, findings remain inconsistent across varying exposure durations and study designs. This meta-regression addressed the question: Is there a dose-response relationship between controlled pollutant exposure duration (in hours), compared to filtered air, and autonomic imbalance (HF component of HRV) in adult humans? We searched PubMed, Scopus, and Embase for cross-over or randomized controlled trials involving adults exposed to both a filtered air and air pollutant condition in controlled environments. These studies needed to report HF before and after exposure. Quality, bias, and certainty of evidence were assessed using the Critical Appraisal Skills Programme checklist, the Cochrane risk-of-bias 2 tool, and the Grading of Recommendations Assessment, Development and Evaluation framework, respectively. We used a restricted cubic spline (RCS) model to estimate the standardized mean difference (SMD) of exposure duration (in hours) on the HF component of HRV. This meta-regression included u=27 studies, from which we extracted k=55 effect sizes, representing n=747 participants. The RCS modelling indicated that study-level exposure duration was negatively associated with HRV, with studies using longer exposure protocols reporting a minor pooled decrease in HRV relative to filtered air controls (SMD=-0.221 [-0.365, -0.077], p=0.003). Only study bias significantly moderated the effect of exposure hour on HRV (p=0.084). These findings suggest a duration-dependent association at the study level, with greater pooled decreases in HRV (HF) observed in studies employing exposure protocols beyond 3 hours. This work also assessed critical study design considerations including exposure duration, pollutant types, disease states, publication quality/bias, and exercise protocols to provide methodological suggestions. These recommendations are essential for reducing variation in future cross-over studies and refining CVD-related air quality policies. This meta-regression was registered with PROSPERO (CRD42023470139) and was supported in part by the National Institute of Environmental Health Sciences of the National Institutes of Health [T32ES011564; R01ES029846; P42ES023716].