Evidence linking quaternary ammonium compounds (QACs) to cardiac function changes remains limited, particularly at the population level, and mechanistic insights are largely unexplored. To address this critical knowledge gap, we conducted a five-month longitudinal panel study that integrated epidemiological assessments with mechanistic multiomics analyses, involving 76 healthy elderly participants in Jinan, Shandong Province, China. Across five repeated measurement visits, participants underwent structured, face-to-face questionnaires, standardized physical examinations, and systematic biosample collection. Data on demographic characteristics, urinary QAC concentrations, and electrocardiogram (ECG) parameters were comprehensively gathered. Correlations between 9 QACs and 5 ECG parameters were assessed using a linear mixed-effects model (LMM), while interaction and stratified analyses examined body fat-related modulation of QAC-induced ECG disturbances. To elucidate the underlying biomolecular perturbations, multiomics analyses were further performed. Our results revealed that benzyltrimethylammonium bromide (BTMAC), dimethyldioctylammonium bromide (C8-DDAC), and diallyldimethylammonium chloride (DAD) were significantly associated with ECG alterations, suggesting potential cardiotoxicity in human populations. Specifically, both BTMAC and DAD were associated with prolonged QRS time, whereas C8-DDAC was related to increased QT interval, QTc interval, and RV5/SV1 amplitude, as well as a reduced QRS time. Interestingly, higher body fat content attenuated the adverse cardiac effects induced by QAC exposures, indicating a possible protective buffering mechanism. Moreover, the causal inference test (CIT) and ingenuity pathway analysis (IPA) collectively indicated that QAC-induced cardiac electrophysiological dysfunction may be associated with certain critical signaling pathways, particularly those involving tumor protein p53 (TP53), nucleosome assembly protein 1 like 1 (NAP1L1), dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and peroxisome proliferator activated receptor alpha (PPARα) signaling. Taken together, this study provides the first population-based evidence of QAC-associated cardiotoxicity and proposes the underlying biomolecular alternations. These insights offer a scientific foundation for developing targeted strategies to prevent and mitigate environmentally induced cardiovascular risks in susceptible populations.
Guo et al. (Tue,) studied this question.