Abstract Body (Do not enter title and authors here): Background: Trihalomethanes, by-products of drinking water disinfection and quality improvement, have been heavily studied as potential carcinogens. Efforts by the Environmental Protection Agency have set exposure limits to trihalomethanes, but with unclear impacts on population health. Importantly, there are very few studies examining associations between water trihalomethane content (THMC) and non-cancer risks, such as cardiac risk.

Purpose: Our aim was to assess the relationship between THMC and cardiac mortality in a U.S. population.

Approach: We used publicly available data from the National Health and Nutrition Examination Survey (NHANES) between 1999-2010. Adult participants without prior atherosclerotic cardiovascular disease were included in the study. Water THMC was normalized using World Health Organization guidelines. THMC values greater than 1.0 were excluded, as this suggests contamination. THMC exposure was stratified by tertile. Cardiac (ICD-10: I019-I043) and other mortality events were collected through December 2019. Hazard ratios (HR) for cardiac mortality were derived from Cox proportional hazards regression. Model 1 adjusted for age, sex, race/ethnicity and poverty-income ratio, and model 2 further adjusted for body-mass index, hypertension, diabetes mellitus, and use of relevant medications. Sensitivity models adjusted for the competing risks of non-cardiac mortality. Results are presented with standard deviations or 95% confidence intervals (95%CI).

Results: A total of 8289 participants (43.0±14.7 years, 51.5% female, 69.8% Caucasian) were included in the study. Cardiovascular risk factors were not different between THMC groups except for older age in the low THMC group (p=0.023) and a lower estimated glomerular filtration rate (p=0.003). THMC exposures in the first (HR 1.63, 95%CI: 1.03-2.59, p=0.039) and second tertiles (HR 1.70, 95%CI: 1.13-2.55, p=0.011) were associated with greater risk of cardiac mortality. Similar results were observed after accounting for competing risks of non-cardiac mortality. Associations retained significance after model 2 adjustments (all p<0.05). THMC exposure was not associated with cancer mortality (p>0.17).

Conclusions: Our findings suggest that sanitization by-products (THMC) show an inverse relationship wtih risk of cardiac-specific mortality. This unexpected result may be informative for public health policies managing water treatment to balance cardiovascular and cancer-associated risks.