Clinical Review

Association of Dioxin and Dioxin-like Congeners With Hypertension

Although 7 of 8 studies found moderate evidence of an association with hypertension in patients with at least 1 chemical congener, these studies cannot prove a causal relationship.

Fed Pract. 2018 May;35(5):20-26

Author(s):

References

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11. Yi SW, Ohrr H, Hong JS, Yi JJ. Agent Orange exposure and prevalence of self-reported diseases in Korean Vietnam veterans. J Prev Med Public Health. 2013;46(5):213-225.

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Persistent organic pollutants (POPs), endocrine-disrupting, lipophilic chemicals that concentrate in adipose tissue, increasingly are being studied for a wide range of health effects.¹ Persistent organic pollutants include bisphenol A, phthalates, dioxins, hexachlorobenzene, dichlorodiphenyltrichloroethane (DDT), polybrominated diphenyl ethers, and polychlorinated biphenyls (PCBs). Chlorinated dibenzo-p-dioxins are known as polychlorinated dibenzodioxins (PCDDs), or simply dioxins. Categorization of this group of chemicals is based on the structural chlorinated constituents. Of the 75 congener molecules, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic, and this dioxin, given its more serious health implications, has been studied the most.^1,2

Because it was a contaminant in the herbicide Agent Orange, the main defoliant used by the US military in southern Vietnam during the Vietnam War, TCDD is of primary interest. Agent Orange consists of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in equal parts. Like other dioxins, TCDD is lipophilic and retained in adipose tissue.^1,3 Contemporaneous sources include occupational and residential exposure from pulp and paper mills, metallurgy, incinerators, industrial waste, fossil fuel combustion, and industrial accidents and poisonings.^1-4

Another main class of POPs, polychlorinated benzenes, includes 209 synthetic PCB congener chemicals, a subset of which is referred to as dioxin-like PCBs.¹ Organochlorine (OC) pesticides and PCBs were once manufactured as lubricants and coolants for electronics but are now banned; nevertheless, they remain concentrated in fish and mammals and persist in the food chain.^3,5,6 These chemicals of interest (COIs) are graded for toxicity based on toxic equivalency factors relative to TCDDs in a 2005 World Health Organization assessment.³

Polychlorinated dibenzofurans (PCDFs), TCDD, PCBs, PCDDs, and other environmental toxins are being studied as possible contributing factors in the development of hypertension. The authors review the results of several recent studies on COI exposure and hypertension.

In 2017, the American College of Cardiology and the American Heart Association lowered the threshold for hypertension to systolic blood pressure (SBP) > 130 mm Hg and diastolic blood pressure (DBP) > 80 mm Hg.⁷ This new guideline would categorize 46% of the US population as having hypertension, compared with 32% under the former cutoff of 140/90 mm Hg.⁷ Modifiable factors (eg, diet, body mass index [BMI], smoking, alcohol, physical activity) and nonmodifiable factors (eg, age, family history, sex, race/ethnicity) have a role in the pathophysiology of hypertension. Between 90% and 95% of hypertension is considered primary. Hypertension increases the risk of developing ischemic heart disease, atherosclerosis, aortic dissection, small blood vessel disease, congestive heart failure, and renal failure, and thus results in considerable morbidity and mortality each year.⁸

Contaminant Exposure and Hypertension Risk

Vietnam-Era Army Chemical Corps

The US Army Chemical Corps (ACC) Vietnam-Era Veterans Health Study (2012-2013) recorded the long-term health burdens imposed by Agent Orange exposure and Vietnam War service.^9,10 This cross-sectional study reexamined a subset of 5,609 Vietnam-era ACC veterans for an association of self-reported, physician-diagnosed hypertension (≥ 140/90 mm Hg) and herbicide spraying history confirmed with serum TCDD levels. The 22 Army units that made up the ACC were in charge of spreading Agent Orange and other defoliants on opposition camps between 1965 and 1973. The herbicide was dispersed aerially and on the ground. The ACC was also responsible for dispensing napalm, tear gas, and other chemicals.

A previous phone survey found an association of self-reported hypertension and herbicide spraying in ACC veterans with associated Vietnam service and herbicide spraying history, verified with serum TCDD levels (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.00-1.58).⁹ Median age of ACC veterans with Vietnam War service at the time of the survey was 53 years.

The 2012-2013 study assessed respondents with a record of their serum TCDD measurements from the time of the survey.¹⁰ Most of the respondents were aged in their 60s. The stated purpose of the health study was to examine the association of Vietnam veterans’ occupational herbicide exposure and hypertension risk, rather than isolate a certain responsible chemical, though serum TCDD levels were used to confirm spraying history. After adjustments for age, tobacco use, alcohol use, race, and BMI but not salt intake, family history of hypertension, psychiatric health, or diabetes mellitus (DM) comorbidity, the OR of self-reported, physician-diagnosed hypertension was 1.74 (95% CI, 1.44-2.11) for sprayers and 1.26 (95% CI, 1.05-1.53) for Vietnam veterans.¹⁰

Vietnam War Veterans From Korea

Soldiers of the Republic of Korea (ROK) who fought in the Vietnam War also were exposed to Agent Orange and other defoliants and herbicides. In 2013, Yi and colleagues contacted 187,897 ROK Vietnam veterans to analyze their Agent Orange exposure and self-reported diseases decades after the war.¹¹ By mail, the researchers administered a questionnaire of perceived Agent Orange exposure (eg, spraying, handling spray equipment, having contact with COIs). The Korean veterans were classified by military assignment and by their proximity to areas sprayed with Agent Orange, according to the military records of 3 US combat units: Capital Division, 9th Division, and Marine Second Brigade. The ROK veterans in those units presumably would have similar levels of Agent Orange exposure.