Blood Levels of Organochlorine Contaminants Mixtures and Cardiovascular Disease

Abstract

ImportanceCardiovascular toxic effects derived from high exposures to individual organochlorine compounds are well documented. However, there is no evidence on low but continuous exposure to combined organochlorine compounds in the general population.ObjectiveTo evaluate the association of combined exposure to several organochlorine compounds, including organochlorine pesticides and polychlorinated biphenyls, with incident cardiovascular disease (CVD) in the general population.Design, Setting, and ParticipantsThis prospective nested case–control study included data from 2 cohorts: the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-Year-Olds (60YO), with matched case-control pairs based on age, sex, and sample date. Baseline blood sampling occurred from November 2003 to September 2009 (SMC-C) and from August 1997 to March 1999 (60YO), with follow-up through December 2017 (SMC-C) and December 2014 (60YO). Participants with myocardial infarction or ischemic stroke were matched with controls for composite CVD evaluation. Data were analyzed from September 2020 to May 2023.ExposuresA total of 25 organochlorine compounds were measured in blood at baseline by gas chromatography–triple quadrupole mass spectrometry. For 7 compounds, more than 75% of the samples were lower than the limit of detection and not included.Main Outcomes and MeasuresIncident cases of primary myocardial infarction and ischemic stroke were ascertained via linkage to the National Patient Register (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I21 and I63). The quantile-based g-computation method was used to estimate the association between the combined exposure to several organochlorine compounds and composite CVD.ResultsOf 1528 included participants, 1024 (67.0%) were female, and the mean (SD) age was 72 (7.0) years in the SMC-C and 61 (0.1) years in the 60YO. The odds ratio of composite CVD was 1.71 (95% CI, 1.11-2.64) per 1-quartile increment of total organochlorine compounds mixture. Organochlorinated pesticides were the largest contributors, and β-hexachlorocyclohexane and transnonachlor had the highest impact. Most of the outcome was not explained by disturbances in the main cardiometabolic risk factors, ie, high body mass index, hypertension, lipid alteration, or diabetes.Conclusions and RelevanceIn this prospective nested case-control study, participants with higher exposures to organochlorines had an increased probability of experiencing a cardiovascular event, the major cause of death worldwide. Measures may be required to reduce these exposures.

OMICs Signatures Linking Persistent Organic Pollutants to Cardiovascular Disease in the Swedish Mammography Cohort

“…These findings are in line with several other studies showing, on the one hand, null or inverse associations − for PFAS exposure, and on the other hand, positive associations of OC exposures with both, CVD risk factors (i.e., obesity, diabetes, and lipid abnormalities) and stroke and MI outcomes. , Although there are also studies showing associations of PFAS with increased CVD risk, − these findings are consistent with our previous work in the same study population but without the inclusion of omics, showing a tendency of inverse associations between PFAS exposures and MI and associations between OC exposures with increased risk of MI and stroke . Herein, we further elaborate on the mechanisms underlying these observed associations.…”

“… 44 , 45 Although there are also studies showing associations of PFAS with increased CVD risk, 46 − 48 these findings are consistent with our previous work in the same study population but without the inclusion of omics, showing a tendency of inverse associations between PFAS exposures and MI 19 and associations between OC exposures with increased risk of MI and stroke. 18 Herein, we further elaborate on the mechanisms underlying these observed associations. In agreement with opposite associations with CVD risk for PFAS (decreased risk) and OC (increased risk), our results showed unique omics features in the OC and the PFAS component models, which may indicate differences in mode of action.…”

“…Study population characteristics by the case-control status for each outcome as well as for the total study population are summarized in Table . More detailed information regarding study population characteristics or exposures to individual POP compounds has already been described. , The loadings of each of the two POP components (obtained from a PCA as mentioned above) referred to as the OC and PFAS components, respectively, are described in Supporting Table 3; prominent exposures (loading >0.8) included oxychlordane, transnonachlor, PCB 153, PCB 156, PCB 170, PCB 180, PCB 183, and PCB 187 in the OC component and PFDA, PFNA, and PFUnDA in the PFAS component.…”

“…For PFAS, so far there is only consistent evidence for associations with elevated cholesterol, , and although there are studies showing associations with atherosclerosis, studies on CVD have not been able to demonstrate associations with increased risk . Our previous studies based on the same study population showed associations of OCs with increased CVD risk, and while PFAS associated with elevated cholesterol, they also inversely associated with triglycerides and there was a tendency for inverse associations with CVD risk . Although knowledge of molecular mechanisms is imperative for establishing causality, the exact mechanisms remain unknown.…”