Endocrine-Disrupting Chemical Exposures in Pregnancy: a Sensitive Window for Later-Life Cardiometabolic Health in Women

Abstract Purpose of Review Pregnancy can be seen as a “stress test” with complications predicting later-life cardiovascular disease risk. Here, we review the growing epidemiological literature evaluating environmental endocrine-disrupting chemical (EDC) exposure in pregnancy in relation to two important cardiovascular disease risk factors, hypertensive disorders of pregnancy and maternal obesity. Recent Findings Overall, evidence of EDC-maternal cardiometabolic associations was mixed. The most consistent associations were observed for phenols and maternal obesity, as well as for perfluoroalkyl substances (PFASs) with hypertensive disorders. Research on polybrominated flame retardants and maternal cardiometabolic outcomes is limited, but suggestive. Summary Although numerous studies evaluated pregnancy outcomes, few evaluated the postpartum period or assessed chemical mixtures. Overall, there is a need to better understand whether pregnancy exposure to these chemicals could contribute to adverse cardiometabolic health outcomes in women, particularly given that cardiovascular disease is the leading cause of death in women.

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Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.573727 ◽

2020 ◽

Vol 8 ◽

Author(s):

Almudena Veiga-Lopez ◽

Visalakshi Sethuraman ◽

Nastassia Navasiolava ◽

Barbara Makela ◽

Isoken Olomu ◽

...

Keyword(s):

Cardiovascular Disease ◽

Alkaline Phosphatase ◽

Phosphatase Activity ◽

Vascular Calcification ◽

Alkaline Phosphatase Activity ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Inorganic Pyrophosphate ◽

Ectopic Mineralization ◽

In Pregnancy

Epidemiological studies indicate that elevated alkaline phosphatase activity is associated with increased cardiovascular disease risk. Other epidemiological data demonstrate that mothers giving multiple childbirths (multipara) are also at increased risk of developing late-onset cardiovascular disease. We hypothesized that these two associations stem from a common cause, the insufficient plasma level of the ectopic mineralization inhibitor inorganic pyrophosphate, which is a substrate of alkaline phosphatase. As alkaline phosphatase activity is elevated in pregnancy, we hypothesized that pyrophosphate concentrations decrease gestationally, potentially leading to increased maternal vascular calcification and cardiovascular disease risk in multipara. We investigated plasma pyrophosphate kinetics pre- and postpartum in sheep and at term in humans and demonstrated its shortage in pregnancy, mirroring alkaline phosphatase activity. Next, we tested whether multiparity is associated with increased vascular calcification in pseudoxanthoma elasticum patients, characterized by low intrinsic plasma pyrophosphate levels. We demonstrated that these patients had increased vascular calcification when they give birth multiple times. We propose that transient shortages of pyrophosphate during repeated pregnancies might contribute to vascular calcification and multiparity-associated cardiovascular disease risk threatening hundreds of millions of healthy women worldwide. Future trials are needed to assess if gestational pyrophosphate supplementation might be a suitable prophylactic treatment to mitigate maternal cardiovascular disease risk in multiparous women.

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Childhood Socioeconomic Status and Cardiometabolic Health: A Test of the John Henryism Hypothesis in African American Elders

The Journals of Gerontology Series A ◽

10.1093/gerona/glab280 ◽

2021 ◽

Author(s):

Samuele Zilioli ◽

Jennifer M Gómez ◽

Yanping Jiang ◽

Jacqueline Rodriguez-Stanley

Keyword(s):

Cardiovascular Disease ◽

Socioeconomic Status ◽

African American ◽

Systemic Inflammation ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Outcome Variable ◽

Cardiometabolic Health ◽

John Henryism ◽

Increased Risk

Abstract Background John Henryism (JH) is a form of active high-effort coping. Low socioeconomic status (SES) African Americans adopting JH to deal with structural racism and other chronic stressors might be more likely to display cardiovascular disease risk factors. Previous tests of this hypothesis have mostly focused on the moderating role of current SES and hypertension as the outcome variable. Further, most of the previous work has been conducted among young and middle-aged adults. The present study aimed at extending work on the JH hypothesis by testing the combined effect of JH and childhood SES on metabolic syndrome and systemic inflammation among African American elders. Methods One-hundred and seventy urban African American older adults (Mage = 67.64 years, 75.9% female) were recruited. Participants completed questionnaires assessing JH, childhood SES, and other variables used as covariates (i.e., demographic information, chronic conditions, medication use, and health behaviors). Blood pressure, waist circumference, and blood were also collected. Triglycerides, HDL cholesterol, hemoglobin A1C, and C-Reactive Protein levels were measured from the blood samples. Results JH was positively associated with MetS symptoms among participants reporting low childhood SES levels, but not among those reporting high childhood SES levels. The same pattern did not emerge when we considered current SES. Similar patterns of results did not emerge as far as systemic inflammation was concerned. Conclusions Our findings highlight the importance of considering the joint impact of objective conditions early in life and individual psychological proclivities in explaining increased risk for cardiovascular disease risk in this population.

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Nutrition transition in 2 lowland Bolivian subsistence populations

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy250 ◽

2018 ◽

Vol 108 (6) ◽

pp. 1183-1195 ◽

Cited By ~ 19

Author(s):

Thomas S Kraft ◽

Jonathan Stieglitz ◽

Benjamin C Trumble ◽

Melanie Martin ◽

Hillard Kaplan ◽

...

Keyword(s):

Cardiovascular Disease ◽

Dietary Diversity ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Nutrition Transition ◽

High Energy ◽

Dietary Factors ◽

Cardiometabolic Health ◽

Low Fat ◽

Complex Carbohydrates

ABSTRACT Background Traditional diets are often credited for the robust cardiometabolic health of subsistence populations. Yet, rural subsistence populations are undergoing nutrition transitions that have been linked to the increase in chronic noncommunicable diseases. Few studies have presented detailed dietary estimates in transitioning populations. Objectives We aimed to 1) characterize and compare dietary profiles of 2 neighboring subsistence populations in Bolivia who vary in market integration and 2) identify dietary factors contributing to low cardiovascular disease risk. Design We used a mixed longitudinal design to estimate nutrient intake via 24-h recall and dietary questionnaires among 1299 Tsimane (aged 30–91 y) and 229 Moseten (aged 30–84 y) men and women. We constructed population-level estimates of energy intake, dietary diversity, and nutrient shortfalls and analyzed dietary changes over time and space using multilevel models. Last, we compared Tsimane and Moseten dietary profiles with those of Americans (NHANES). Results The Tsimane diet was characterized by high energy (2422–2736 kcal/d), carbohydrate (376–423 g/d), and protein (119–139 g/d) intakes; low fat intake (40–46 g/d); and low dietary diversity relative to the average US diet. Most calories (64%) were derived from complex carbohydrates. Total energy and carbohydrate intake increased significantly during the 5-y study, particularly in villages near market towns. Tsimane consumption of food additives (lard, oil, sugar, salt) increased significantly [sugar (15.8 g ⋅ person−1 ⋅ d−1) and oil (4.9 mL ⋅ person−1 ⋅ d−1)] between 2010 and 2015. The more-acculturated Moseten consumed substantially more sugar (by 343%) and oil (by 535%) than the Tsimane. Conclusions A high-energy diet rich in complex carbohydrates is associated with low cardiovascular disease risk when coupled with a physically active lifestyle. A transition away from a high-fiber and low-fat, low-salt, and low-processed-sugar diet is a salient health risk for transitioning populations. Evidence of a nutrition transition in Bolivia parallels trends of increasing body fat and body mass index, which suggests that a low prevalence of cardiovascular disease may not persist.

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Hypertensive Disorders of Pregnancy and Maternal Cardiovascular Disease Risk Factor Development

Annals of Internal Medicine ◽

10.7326/m17-2740 ◽

2018 ◽

Vol 169 (4) ◽

pp. 224 ◽

Cited By ~ 47

Author(s):

Jennifer J. Stuart ◽

Lauren J. Tanz ◽

Stacey A. Missmer ◽

Eric B. Rimm ◽

Donna Spiegelman ◽

...

Keyword(s):

Cardiovascular Disease ◽

Risk Factor ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Cardiovascular Disease Risk Factor ◽

Hypertensive Disorders Of Pregnancy ◽

Disease Risk Factor ◽

Hypertensive Disorders

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Maternal obesity causes fetal cardiac hypertrophy and alters adult offspring myocardial metabolism in mice

10.1101/2021.09.15.460457 ◽

2021 ◽

Author(s):

Owen R Vaughan ◽

Fredrick Rosario ◽

Jeannie Chan ◽

Laura A Cox ◽

Veronique Ferchaud-Roucher ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cardiac Dysfunction ◽

Maternal Obesity ◽

Myocardial Metabolism ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Adult Offspring ◽

Palmitoyl Carnitine ◽

18F Fluorodeoxyglucose ◽

Pparg Expression

Obesity in pregnant women causes fetal cardiac dysfunction and increases offspring cardiovascular disease risk but its effect on myocardial metabolism is unknown. We hypothesised that maternal obesity alters fetal cardiac expression of metabolism-related genes and shifts offspring myocardial substrate preference from glucose towards lipids. Female mice were fed control or obesogenic diets before and during pregnancy. Fetal hearts were studied in late gestation (embryonic day, E18.5; term≈E21) and offspring were studied at 3, 6, 9 or 24 months postnatally. Maternal obesity increased heart weight and peroxisome proliferator activated receptor γ (Pparg) expression in female and male fetuses and caused left ventricular diastolic dysfunction in the adult offspring. Cardiac dysfunction progressively worsened with age in female, not male, offspring of obese dams, compared to age-matched controls. In 6-month-old offspring, exposure to maternal obesity increased cardiac palmitoyl carnitine-supported mitochondrial respiration in males and reduced myocardial 18F-fluorodeoxyglucose uptake in females. Cardiac Pparg expression remained higher in adult offspring of obese than control dams and correlated with contractile and metabolic function. Maternal obesity did not affect cardiac palmitoyl carnitine respiration in females or 18F-fluorodeoxyglucose uptake in males, or alter cardiac 3H-oleic acid uptake, pyruvate respiration, lipid content or fatty acid/glucose transporter abundance in offspring of either sex. The results support our hypothesis and show that maternal obesity affects offspring cardiac metabolism in a sex-dependent manner. Persistent upregulation of Pparg expression in response to overnutrition in utero may mechanistically underpin programmed cardiac impairments and contribute to cardiovascular disease risk in children of women with obesity.

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Long-Term Cardiovascular Disease Risk in Women After Hypertensive Disorders of Pregnancy: Recent Advances in Hypertension

Hypertension ◽

10.1161/hypertensionaha.121.16506 ◽

2021 ◽

Author(s):

Kavia Khosla ◽

Sarah Heimberger ◽

Kristin M. Nieman ◽

Avery Tung ◽

Sajid Shahul ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Risk Reduction ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Hypertensive Disorders Of Pregnancy ◽

Cardiovascular Risk Reduction ◽

Hypertensive Disorders ◽

History Of

Patients with a history of hypertensive disorders of pregnancy (HDP) suffer higher rates of long-term cardiovascular events including heart failure, coronary artery disease, and stroke. Cardiovascular changes during pregnancy can act as a natural stress test, subsequently unmasking latent cardiovascular disease in the form of HDP. Because HDP now affect 10% of pregnancies in the United States, the American Heart Association has called for physicians who provide peripartum care to promote early identification and cardiovascular risk reduction. In this review, we discuss the epidemiology, pathophysiology, and outcomes of HDP-associated cardiovascular disease. In addition, we propose a multi-pronged approach to support cardiovascular risk reduction for women with a history of HDP. Additional research is warranted to define appropriate blood pressure targets in the postpartum period, optimize the use of pregnancy history in risk stratification tools, and clarify the effectiveness of preventive interventions. The highest rates of HDP are in populations with poor access to resources and quality health care, making it a major risk for inequity of care. Interventions to decrease long-term cardiovascular disease risk in women following HDP must also target disparity reduction.

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