Occupational Pesticide Exposure Linked to CVD

Stephanie Edwards

December 05, 2019

High levels of exposure to pesticides are positively associated with cardiovascular disease (CVD) incidence, research based on the Kuakini Honolulu Heart Program (HPP) suggests.

The longest longitudinal study of occupational pesticide exposure among more than 7500 Japanese-American men showed a significant association between incident CVD and pesticide exposure after 10 years of follow-up.

"The findings of this research provide insight into the harmful effects of pesticides on the cardiovascular system and confirm a positive association between high levels of pesticide exposure and CVD incidence," Zara K. Berg, PhD, Department of Complementary and Integrative Medicine, University of Hawaii at Manoa, Honolulu, and colleagues conclude.

The study was published in the October 1 issue of the Journal of the American Heart Association.

Nieca Goldberg, MD, NYU Center for Women's Health, New York City, who was not involved in the research, said "it raises an important question about something that is potentially an environmental hazard, like pesticides, and its link to cardiovascular disease."

Goldberg told theheart.org | Medscape Cardiology that "cardiovascular risk factors like high blood pressure, high cholesterol, and diabetes have been really tested and researched as the major risk factors for heart disease," but added, "I think studies like this are important because sometimes heart disease cannot be explained by the risk factors, the major risk factors," and so "people are continuing to look at other things that may in fact raise risk for heart disease."

Significant Trends

Significant Trends

Multiple studies using the Kuakini HPP have investigated the connection of various outcomes with occupational pesticide exposure, including mortality, cancer, and Parkinson disease, but have not yet evaluated the association between CVD incidence and occupational pesticide exposure, the authors write.

"Most previous studies examining occupational chemical exposure and cerebrovascular accident (CVA), coronary heart disease (CHD), and CVD have looked at CVD mortality only," they note.

Using data on this cohort of 7557 Japanese-American men between the ages of 45 and 68 years free from CVD at baseline from the Kuakini HPP, researchers used the Occupational Safety Health Administration exposure scale to assess the intensity level and length of exposure to pesticides for each occupation reported in the program. From this, four categories were defined: no exposure, low exposure, medium exposure, and high exposure.

Longitudinal follow-up, with data accessible for a 34-year span, was based on a hospital surveillance system, review of death records, periodic examinations, and an autopsy study to review incident cases of CHD, CVA, and CVD.

Covariate risk factors were measured at different phases of the study. These included age (years), systolic blood pressure (SBP), diastolic blood pressure (DBP), smoking, total cholesterol (mg/dL), triglycerides (mg/dL), physical activity, alcohol intake (oz/mo), glucose (mg/dL), body mass index (BMI), and education (high-school graduate). Education level, smoking, and alcohol consumption were self-reported.

The authors found those who developed incident CVD were significantly older, had higher levels of BMI, SBP, DBP, total cholesterol, triglycerides, nonfasting glucose, and smoking, and had significantly lower alcohol consumption. No associations with physical activity or education were found.

Pesticide exposure in the first 10 years of follow-up was significantly associated with CVD incidence, however, no significant association was found in follow-up periods >10 years, up to 34 years post exposure. The authors speculate that "other risk factors associated with aging may mask the effects of toxic pesticide exposure later in life."

Conversely, the authors found a nonsignificant trend between low to moderate levels of pesticide exposure and less CVD, suggesting that low to moderate levels of pesticide exposure may have a protective effect.

Incident CVD Risk by Pesticide Exposure for First 10-Year Follow-up
Models Low to Moderate Exposure, (Hazard Ratio 95% CI) Value High Exposure, Hazard Ratio (95% CI) P Value
Unadjusted 0.57 (0.24–1.37) .209 1.46 (1.10–1.95) .009
Adjusted for age 0.54 (0.22–1.30) .166 1.27 (0.95–1.69) .108
Adjusted for age and all risk factors 0.49 (0.20–1.19) .116 1.42 (1.05–1.92) .021

The authors note that the apparent protective effect with low to moderate pesticide exposure could potentially be due to the hormesis principle, "which argues that low-dose exposures to some toxic agents may be protective in some individuals, and may stimulate homeostasis of the organism," they write. "It is thought that low-dose exposure at nontoxic levels causes stimulation of protective enzymes, which provide enhanced protection against occasional exposure to higher, more toxic levels."

Some limitations were addressed by the authors. First, the specific pesticide exposure was unknown; however, the Hawaii Department of Agriculture in 1969 listed "organophosphates, organochlorines, insecticides, and herbicides as being commonly used in agricultural work at that time."

Another limitation is that the sample size of the moderate pesticide exposure group and the low pesticide exposure group was small, and therefore they were combined. Most participants fell within the no exposure group. Although the researchers were able to adjust for major CVD risk factors, they were not able to adjust for all risk factors. Last, the study population consisted only of men of Japanese ancestry, limiting the generalizability of the group.

Still, they conclude, "these data could be helpful in identifying groups of subjects, such as those involved in agriculture and the manufacturing of pesticides, who may be at higher risk of developing CVD. In addition, they highlight the importance of measures adopted by the National Institute of Occupational Safety and Health, such as protective gear to limit occupational exposure to pesticides, to reduce the increased risk of developing CVD and other diseases associated with pesticide exposure."

The authors suggest that future studies on the effects of pesticide exposure and its relation to genetic polymorphisms on the PON1, -2, and -3 genes, as well as gene-environment interactions, may help in beginning to understand the development of oxidative stress due to pesticide exposure.

Previous studies noted in the publication have shown that pesticides like polychlorinated biphenyls (PCB) decrease this gene activity, which is responsible for reducing oxidative stress, lipid metabolism, and production of HDL.

They also note that previous studies have found that tetrachlorodibenzo-p-dioxin (TCBB) was still found 20 years after exposure and was responsible for liver problems and, ultimately, cardiovascular morbidity.

The study was supported by the National Institutes of Health, the National Heart, Lung, and Blood Institute; a National Institute of Neurological Disorders and Stroke; and the National Institute for Occupational Safety and Health. The authors report no relevant disclosures.

J Am Heart Assoc. 2019;8:e012569. Full text

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