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pile of plastic bottles

The linkage between chemicals used in plastics and cardiovascular disease

pile of plastic bottles

For people across the globe, plastics are synonymous with modern life and it’s impossible to avoid exposure to them, including clinical environments where a variety of frequently used materials, such as tubing and blood storage bags, are made from plastics.

For people across the globe, plastics are synonymous with modern life and it’s impossible to avoid exposure to them, including clinical environments where a variety of frequently used materials, such as tubing and blood storage bags, are made from plastics. Led by Nikki Posnack, Ph.D, principal investigator at The Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital, a team of Children’s National researchers has been studying the potential effects of chemicals found in plastics, such as BPA and DEHP, as possible contributors to cardiovascular disease.

Along with conducting proprietary studies of the potential effects, Posnack and her team recently reviewed available scientific studies to further identify and illuminate the potential links between exposure to the synthetic additives contained in plastics and cardiovascular mortality. The article was published this month in Nature Reviews Cardiology.

In the article Posnack cites a 10-year longitudinal study with the finding that high exposure to BPA was associated with a 46-49% higher hazard ratio for cardiovascular and all-cause mortality, compared with low exposure to BPA.

“Plastics may be indispensable materials, but their ubiquity does raise concerns about the effects of our continuous exposure to plasticizer additives like di(2-ethylhexyl) phthalate (DEHP) and synthetic chemicals used to create polymers like BPA,” said Posnack. “Although disease causation can be difficult to pinpoint in population and epidemiological studies, experimental work has clearly demonstrated a direct link to plastic chemicals and cardiac dysfunction. It is clear that future collaborative endeavors are necessary to bridge the gap between experimental, epidemiological and clinical investigations to resolve the impact of plastics on cardiovascular health.”

Nikki Gillum Posnack

Nikki Posnack, Ph.D, principal investigator at The Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital.

Posnack added that, given the omnipresence of plastics and their related chemicals, biomonitoring studies have reported detectable levels of DEHP and BPA in 75-90% of the population. Occupational or clinical environments can also result in elevated exposures to these dangerous chemicals. Previous epidemiological studies have reported links between elevated urinary levels of phthalate or bisphenol, common additives in plastic, and an increased risk of coronary and peripheral artery disease, chronic inflammation, myocardial infarction, angina, suppressed heart rate variability and hypertension.

Additionally, available research has shown that incomplete polymerization or degradation of BPA-based plastic products can result in unsafe human exposure to BPA. Despite these links, the article points out, both BPA and DEHP are still manufactured in high volumes and are used to produce a wide variety of consumer and commercial products.

Further exploring implications for pediatrics, a June 2020 article published by Posnack in Birth Defects Research looks at the potential effects of plastic chemicals on the cardiovascular health of fetal, infant and pediatric groups. The article highlighted experimental work that suggests plasticizer chemicals such as bisphenols and phthalates may exert negative influence on pediatric cardiovascular health. The article systematically called out areas of concern supported by research findings. Also addressing current gaps in knowledge, Posnack outlined future research endeavors that would be needed to resolve the relationship between chemical exposures and the impact on pediatric cardiovascular physiology.

In related work, Posnack and her team are expanding their work on plastics used in blood bags to also investigate the role of blood storage duration on health outcomes. A recently published first study demonstrates that “older” blood products (stored 35 or more days) directly impact cardiac electrophysiology, using experimental models. Published October 22, 2020 in the Journal of the American Heart Association, the study concludes that the cardiac effects are likely caused by biochemical alterations in the supernatant from red blood cell units that occur over time, including but not limited to, hyperkalemia (elevated potassium levels).

Asha Moudgil examines a young patient

Preventing cardiovascular disease after pediatric kidney transplant

Asha Moudgil examines a young patient

Pediatric nephrologist Asha Moudgil, M.D. examines a kidney transplant patient.

As obesity has continued to rise among children in the U.S., so has a condition called metabolic syndrome – a constellation of factors, including high abdominal fat, insulin resistance, high blood pressure, high triglycerides and low amounts of high-density lipoprotein (“good” cholesterol), that increase future risk of cardiovascular disease.

Although metabolic syndrome is dangerous in otherwise healthy children, it’s particularly so for those who’ve received kidney transplants due to chronic kidney disease, says pediatric nephrologist Asha Moudgil, M.D., medical director of transplant at Children’s National Health System. Dr. Moudgil and Children’s National co-authors, Registered Dietitian Kristen Sgambat, Ph.D., RD, and Cardiologist Sarah Clauss, M.D., published a literature review in the February 2018 Clinical Kidney Journal outlining recent research about the cardiovascular effects of metabolic syndrome after kidney transplantation.

“Simply having this transplant multiplies the risk of cardiovascular disease in this vulnerable population,” Dr. Moudgil says. “Combined with lifestyle factors that are driving up metabolic syndrome in general, it’s a ‘one-two punch’ for these patients.”

Dr. Moudgil explains that chronic kidney disease itself leads to poor growth, resulting in shorter stature that’s a risk factor for developing increased waist-to-height ratio upon becoming overweight. When children with this condition undergo long-awaited transplants, it reverses some factors that were suppressing appetite and keeping weight in check: The chronically high levels of urea in their blood decrease after transplant, improving their appetites; and there’s no need to maintain the restrictive diets they had been required to follow for kidney health prior to transplant.

The pharmaceutical regimen that patients follow post-transplant often includes steroids that independently contribute to weight gain and insulin resistance. Combined with the typical American high-fat, high-sugar, and high-sodium diet and low levels of physical activity, the majority of patients with chronic kidney disease gain significant weight after they receive transplants. The prevalence of obesity doubles the first year after transplantation, from about 15 percent to 30 percent, not only driving up cardiovascular disease risk but endangering the longevity of their transplant.

At the same time, says Sgambat, risk factors before and after transplantation drive up prevalence of other parts of metabolic syndrome. These include hypertension, which affects the majority of patients with chronic kidney disease before transplant and typically worsens due to sodium and water retention from immunosuppressive drugs. Dyslipidemia, or abnormal lipid concentrations in the blood, is also common among pediatric kidney transplant patients. One study included in the review showed that 71 percent of patients had high triglycerides three months post-transplant.

Ethnicity also can drive up risk for metabolic syndrome and cardiovascular disease. For example, the literature review says, individuals of African descent have a higher risk of these two conditions potentially due to genetic factors, such as high risk apolipoprotein L1 gene variants.

Together, these factors spur production of inflammatory molecules that trigger the development of early cardiovascular disease. Many kidney transplant recipients die from cardiovascular complications in early adulthood, Sgambat says, driving the need for early detection.

To that end, Dr. Moudgil says pediatric patients don’t typically show overt abnormalities in standard measures of cardiac functioning, such as echocardiography. As an alternative, she and colleagues cover three tools in the literature review that could offer advanced insight into whether patients have initial signs of cardiovascular disease. One of these is carotid intima-media thickness, a measure of the thickness of the carotid artery that can be obtained noninvasively by ultrasound. Another is myocardial strain imaging by speckle tracking echocardiography, a global measure of how the heart changes shape while beating. Cardiac magnetic resonance imaging (MRI), a relatively new technique, is already showing promise in detecting signs of early cardiovascular dysfunction.

A far simpler way to gauge cardiovascular risk, Sgambat adds, is calculating patients’ waist-to-height ratio. This measure doesn’t require sophisticated tools and can be tracked in any clinic over time, alerting patients to health-altering changes before it’s too late.

“It’s even more important to treat cardiovascular risk factors aggressively in this population,” Sgambat says. “Getting a concrete measure that something is trending in the wrong direction may motivate patients to change their diet or lifestyle in ways that a simple recommendation may not.”

Gram-positive-bacteria-Streptococcus-pyogenes

Assessing the risk factors in rheumatic heart disease

Gram-positive-bacteria-Streptococcus-pyogenes

Rheumatic heart disease is caused by untreated throat infections from the streptococcal bacterium. The infections progress into acute rheumatic fever and eventually weaken the valves of the heart.

Rheumatic heart disease (RHD) is the most commonly acquired cardiovascular disease in children and young adults. The devastating condition, which was endemic in the United States before 1950, is now relatively rare in the developed world due to social and economic development and the introduction of penicillin. But, in the developing world RHD remains nearly as common as HIV.

Fortunately, RHD is a cumulative disease and opportunities exist for early intervention. To further explore the utility of early diagnosis and intervention, a research team headed by Children’s National Heart Institute cardiologist Andrea Beaton, M.D., conducted a prospective natural history study of children with latent RHD.

RHD is caused by untreated streptococcal throat infections that progress into acute rheumatic fever (ARF) and eventually weaken the valves of the heart. While initial episodes of ARF occur almost exclusively during childhood, RHD most commonly presents in adolescents and young adults. This latent period between ARF and clinically apparent RHD is an ideal opportunity for early intervention, and screening echocardiography (echo) has emerged as a potentially powerful tool for early detection of RHD.

In their study published in the journal Circulation in September 2017, Dr. Beaton and her colleagues examined echocardiograms from children with latent RHD who were enrolled in the Ugandan National RHD registry. The researchers also developed models to search for risk factors and compare progression-free survival between patients who did and did not receive penicillin.

The team reports that children with moderate-to-severe latent RHD discovered by echo screening have poor outcomes. Children with both borderline and mild definite RHD have better outcomes but remain at substantial risk of progression. The researchers also found that children who are diagnosed at a younger age, and the presence of morphological mitral valve features, generally lead to unfavorable outcomes.

The authors conclude that children with moderate to severe RHD at screening should be considered for treatment as clinically diagnosed RHD, and that children with borderline or mild definite RHD at screening should, at a minimum, be maintained in close clinical follow up.

“It is clear that children found to have the earliest forms of RHD, seen only by echo, are at substantial risk for progression of disease. This study urges us forward to see if we can intervene to stop this progression once children are identified,” says Dr. Beaton.  “We are excited that our next project will be to do just that – a randomized clinical trial in Uganda to determine if penicillin can protect the hearts of children found to have latent RHD.”

child measuring belly with tape measure

Defining cardiovascular disease and diabetes risks in kids

child measuring belly with tape measure

In the Clinical Report, a study team describes the current state of play and offers evidence-based recommendations to guide clinicians on how to approach metabolic syndrome in children and adolescents.

For more than a decade and a half, researchers and clinicians have used the term “metabolic syndrome” (MetS) to describe a set of symptoms that can raise the risk of cardiovascular disease. Although this constellation of factors has proven to be a good predictor of cardiometabolic risk in adults, it has not been as useful for children. That’s why the American Academy of Pediatrics (AAP) now recommends that pediatricians instead focus on clusters of cardiometabolic risk factors that are associated with obesity, a condition that currently affects one in six U.S. children and adolescents.

In a new collaborative report, a study team from Children’s National Health System’s Division of Endocrinology and Diabetes, Harvard Medical School and Duke Children’s Hospital and Health Center describes the current state of play and offers evidence-based recommendations to guide clinicians on how to approach MetS in children and adolescents.

Adults with MetS have at least three of the following five individual risk factors:

  • High blood sugar (hyperglycemia)
  • Increased waist circumference (central adiposity)
  • Elevated triglycerides
  • Decreased high-density lipoprotein cholesterol (HDL-C), so-called “good” cholesterol and
  • Elevated blood pressure (hypertension).

This toxic combination ups adults’ odds of developing diabetes or heart disease. The process is set in motion by insulin resistance. Think Mousetrap, with each new development facilitating the next worrisome step. As fat expands, the cells become enlarged and become more resistant to insulin – a hormone that normally helps cells absorb glucose, an energy source. However, insulin retains the ability to stimulate fatty acids, which promotes even more fat cell expansion. Ectopic fat ends up stored in unexpected places, such as the liver. To top it off, the increased fat deposits end up causing increased inflammation in the system.

At least five health entities, including the World Health Organization, introduced clinical criteria to define MetS among adults, the study authors write. Although more than 40 varying definitions have been used for kids, there is no clear consensus whether to use a MetS definition for children at all, especially as adolescents mature into adulthood. Depending on the study, at least 50 percent of kids no longer meet the diagnostic criteria weeks or years after diagnosis.

“Given the absence of a consensus on the definition of MetS, the unstable nature of MetS and the lack of clarity about the predictive value of MetS for future health in pediatric populations, pediatricians are rightly confused about MetS,” the study authors write.

As a first step to lowering their patients’ cardiometabolic risks, pediatricians should prevent and treat obesity among children and adolescents, the study authors write. Each year, clinicians should perform annual obesity screening using body mass index (BMI) as a measure, and also should screen children once a year for elevated blood pressure. Nonfasting non-HDL-C or fasting lipid screening should be done for children aged 9 to 11 to identify kids whose cholesterol levels are out of line. The team also recommends screening for abnormal glucose tolerance and Type 2 diabetes in youth with BMI greater than or equal to the 85th percentile, 10 years or older (or pubertal), with two additional risk factors, such as family history, high-risk race/ethnicity, hypertension or a mother with gestational diabetes.

Pediatricians do not need to use cut points based on MetS definitions since, for many risk factors, the growing child’s risk lies along a continuum.

Treatments can include lifestyle modifications – such as adopting a negative energy balance diet, drinking water instead of sugar-sweetened beverages, participating in a moderate- to high-intensity weight-loss program, increasing physical activity and behavioral counseling.

“Identifying children with multiple cardiometabolic risk factors will enable pediatricians to target the most intensive interventions to patients who have the greatest need for risk reduction and who have the greatest potential to experience benefits from such personalized medicine,” the study authors conclude.

Link between population health and heart disease

Gerard Martin

Although clinical advances have improved treatments and mortality among patients with cardiovascular disease, heart disease remains the leading cause of death worldwide. Gerard Martin, M.D., cardiologist and medical director of Global Health at Children’s National and Chair of the American College of Cardiology’s Population Health Policy and Promotion Committee shares how cardiologists can improve outcomes by focusing on the link between population health and heart disease in a just-published article in Cardiology.

Read more.

How mindfulness can improve adolescent heart health

Could yoga, meditation, group support, or online video chats improve outcomes for adolescents with cardiac diagnoses? Vicki Freedenberg, Ph.D., R.N., electrophysiology nurse scientist at Children’s National Health System, shared insights from her research using these interventions at the American Heart Association (AHA) Scientific Sessions, held November 12-16 in New Orleans. The AHA Scientific Sessions featured the latest developments in science and cardiovascular clinical practice, including all aspects of basic, clinical, population, and translational science. In her presentation titled “Mindfulness Based Stress Reduction and Group Support Decrease Stress, Anxiety, and Depression in Adolescents with Cardiac Diagnoses: A Randomized Two-Group Study,” Freedenberg presented findings from her study comparing outcomes between cardiac patients who participated in a Mindfulness Based Stress Reduction program, which used meditation, yoga, and group support, and a second group that participated in a clinician-led online video support group with peers. Early results suggest that stress significantly decreased in both groups, and higher baseline anxiety and depression scores predicted lower levels of post-intervention anxiety and depression.

Read more about Children’s National AHA Scientific Sessions speakers.