Clinical Context

Global prevalence of hypertension is more than 1 billion. It is a leading risk factor for cardiovascular disease (CVD) and cause of death and disability-adjusted life-years globally. Studies of associations between PFAS exposure and incident hypertension have yielded conflicting results.

During menopausal transition, hormone levels fluctuate and risk for hypertension and CVD increases. The present study tested the hypothesis that higher serum PFAS concentrations would be linked to higher risks for incident hypertension among middle-aged women.

Study Synopsis and Perspective

Exposure to per- and polyfluoroalkyl substances (PFAS), a class of widely used synthetic chemicals dubbed "forever chemicals," may be a modifiable risk factor for the development of hypertension.

In a large, prospective study, researchers found an association between higher blood levels of PFAS and increased risk for hypertension in middle-aged women. Women in the highest tertile of overall PFAS concentrations had a 71% increased risk of developing hypertension.

"Our findings suggest that long-term cumulative exposure, even before midlife, may increase the risk of high blood pressure, and therefore, the benefit of reducing the population exposure to PFAS and potential prevention of high blood pressure and other health conditions would be enormous," Sung Kyun Park, ScD, MPH, from the University of Michigan School of Public Health, Ann Arbor, told theheart.org | Medscape Cardiology.

The study was published online June 13 in Hypertension.^[1]

"PFAS are forever chemicals as well as everywhere chemicals," Dr Park noted.

Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and drinking water. They have been detected in the blood of most people and have been linked to a variety of health concerns.

"A few studies showed an association between PFAS and hypertension, but those were cross-sectional and examined prevalence of hypertension. It was unclear whether PFAS are associated with the development (incidence) of hypertension," Dr Park explained.

For their study, the researchers examined the association between serum concentrations of PFAS and risks for incident hypertension in 1058 initially normotensive women participating in the Study of Women's Health Across the Nation-Multi-Pollutant Study (SWAN-MPS). The women were followed-up annually between 1999 and 2017.

During 11,722 person-years of follow-up, 470 of the women developed hypertension, at a rate of 40.1 cases per 1000 person-years. Hypertension was defined as blood pressure of at least 140 mm Hg systolic or at least 90 mm Hg diastolic or receiving antihypertensive treatment.

Women in the highest tertile of baseline serum concentration of perfluorooctane sulfonate (PFOS) had a 42% higher risk of developing hypertension compared with their peers in the lowest tertile (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [CI], 1.19-1.68; P trend<0.0001).

Similar results were found for perfluorooctanoate (PFOA) and 2-N-ethyl-perfluorooctane sulfonamido acetate (EtFOSAA), with 47% (aHR, 1.47; 95% CI, 1.24-1.75; P trend<0.0001) and 42% (aHR, 1.42; 95% CI, 1.19-1.70; P trend=0.0003) higher risks for incident hypertension, respectively, comparing the highest with the lowest tertiles.

The risks persisted after adjusting for various factors, including race, study site, education, financial strain, smoking status, alcohol use, total calorie intake, and menopausal status.

In the PFAS "mixture" analysis, women in the highest tertile of overall PFAS concentrations were 71% more likely to develop hypertension during follow-up compared with women in the lowest tertile (aHR, 1.71; 95% CI, 1.15-2.54; P trend=.008).

"These findings suggest that PFAS might be an underappreciated contributing factor to women's cardiovascular disease [CVD] risk," the researchers write.

They caution that the study only included middle-aged women and that it is unclear whether the findings hold for middle-aged men.

"This is an important question, but the answer is that we do not know," Dr Park told theheart.org | Medscape Cardiology.

"Women become more susceptible to metabolic changes and hypertension risk during the menopausal transition. Our findings suggest that PFAS may play a role in the development of hypertension in women during this critical life stage," Dr Park said.

The researchers say that more research is needed to confirm and expand the findings and to find ways to reduce PFAS exposure.

"If confirmed in future studies, these findings suggest that understanding human exposure to PFAS and developing effective strategies to reduce PFAS exposure may help prevent the development of hypertension and thereby reduce the global burden of CVD," the researchers write.

This is an "interesting" study and shows that "the more we learn about PFAS, the worse it seems to get," Ankur Shah, MD, from the Division of Kidney Disease and Hypertension, Warren Alpert Medical School of Brown University, Providence, Rhode Island, told theheart.org | Medscape Cardiology.

"This multisite, multiracial, and multiethnic, community-based longitudinal study establishes an association between PFAS and hypertension," said Dr Shah, who was not involved in the study.

"This adds to a growing literature base of associations of PFAS with illnesses, including malignancy, thyroid disorders, diabetes, ulcerative colitis, hyperlipidemia, and pregnancy-induced hypertension," he noted.

Dr Shah also noted that the authors adjusted for race and ethnicity, study site, education, financial strain, smoking status, environmental tobacco smoke, alcohol consumption, total calorie intake, and menopausal status "and still found a strong association."

"Still to be determined are both whether PFAS are the causative agent or if there is an unmeasured/unadjusted-for entity which has resulted in both increased PFAS exposure and hypertension, as well as if PFAS are causative, if reduction in PFAS exposure would be result in blood pressure reduction," Dr Shah added.

The study had no sources of funding. Dr Park and Dr Shah have disclosed no relevant financial relationships.

Hypertension. Published online June 13, 2022.^[1]

Clinical Implications

• PFAS had positive associations with incident hypertension, even after adjustment for multiple variables, suggesting that PFAS might be an underappreciated contributor to women's CVD risk.
• As PFAS are ubiquitous in most humans and the environment, the findings create significant public health concern.
• Implications for the Health Care Team: The heathcare team should be aware that PFAS are potentially modifiable risk factors for hypertension and CVD.

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