Environmental Risk Factors Go Mainstream in Pediatric Cardiology

Cardiology has a long and distinguished history of undertaking research to discover the causes of cardiovascular disease (CVD) and of translating findings from this research into targeted strategies for disease detection and early intervention. This ‘upstream'-oriented strategy has proven highly successful. It has been a key driver of the more than 60% decline in CVD mortality achieved in the United States since the 1960s.^{1, 2} It appears to explain much of the contrast seen between the decades' long decline in global mortality rates from CVD versus the continuing rise in age-standardized mortality rates from cancer.³

Systematic search for the causes of CVD began with the launch of the prospective, longitudinal Framingham Heart Study in 1948.⁴ At that time, World War II had just ended; more than 50% of American men and 25% of American women smoked;⁵ many physicians believed that a permissible systolic blood pressure was a patient's age plus 100 in millimeters of mercury;⁶ and CVD mortality was at all all-time high. ^{1, 2} Within slightly more than a decade, the Framingham Heart Study discovered that hypertension, hyperlipemia, diabetes mellitus, and smoking are major preventable causes of coronary artery disease, stroke, and cardiac death. These discoveries gave rise to the CVD ‘risk factor' concept and laid the foundation for preventive cardiology.⁷

The cardiology and public health communities acted rapidly on the discoveries that emerged from Framingham and other longitudinal studies, ^{8, 9} and translated these findings into advances in both prevention and treatment. Preventive interventions included wide-scale public education about CVD risk factors, and the striking reductions in smoking prevalence that resulted from hard-fought bans on cigarette advertising, restrictions on smoking in public places, and high levels of tobacco taxation.⁵ Advances in treatment that further advanced CVD prevention included improvements in the management of hypertension; reductions in serum lipid levels through statins; and improvements in the control of arrhythmias.¹

Now a new generation of CVD risk factors has emerged. Unlike the risk factors of the 20^th century, which stemmed at least in part from lifestyle choices and personal behaviors, these newer risk factors are largely of external origin. They reflect changes in the global climate and the release into the environment of an estimated 350,000 novel manufactured chemicals and chemical mixtures,¹⁰ most of which have never been tested for toxicity.¹¹

The groundbreaking AHA Scientific Statement on Environmental Exposure and Pediatric Cardiology by Zachariah, et al.¹² in this issue of the journal addresses these risk factors and summarizes current knowledge of their impacts on cardiovascular health. This information is of great importance for CVD prevention in people of all ages, children as well as adults. Highlights are these:

• Climate change is linked to an increased incidence of congenital heart defects, particularly conotruncal and septal defects. Maternal heat exposure during pregnancy appears to be the principal mediating factor. Air pollution may further magnify risk.
• Airborne particulate matter pollution may contribute to an increased incidence of Kawasaki Disease.
• Lead exposure in infancy and childhood increases blood pressure and increases later morbidity and mortality from CVD, as well as from kidney disease.
• Endocrine-disrupting chemicals, such as bisphenols and phthalates, are associated with increased blood pressure and alterations in lipid profiles and thus with later increased risk for CVD.
• Per- and polyfluoroalkyl substances (PFAS) are associated with alterations in lipid profiles.¹² The American Heart Association's publication of this Scientific Statement is a step of great importance. It reflects the growing recognition that environmental exposures are important, yet preventable CVD risk factors. ¹³ And the emphasis on pediatric health that is central to this Statement reflects current understanding that infants and children are uniquely vulnerable to hazardous environmental exposures¹⁴ and underscores the recognition that exposures to environmental risk factors in early life can have negative impacts on cardiovascular health not only in childhood but across the lifespan.^{15, 16}

What comes next? First, there needs to be an acceleration of research in environmental cardiology. Of particular concern are the thousands of chemicals in the modern environment that have never been tested for toxicity.¹⁰ Because of extremely weak chemical safety legislation in the United States, these chemicals have been allowed to enter markets and remain on markets with almost no evaluation of their potential toxicity, and even less assessment of their potential toxicity to infants and children.¹¹ Almost certainly, there are additional manufactured chemicals in children's environments today whose risks to cardiovascular health have not yet been recognized. Prospective, multi-year epidemiologic studies have proven to be powerful tools for the discovery of associations between these chemicals and disease. An example of a previously unrecognized chemical hazard discovered through epidemiologic investigation is the recently reported finding that micro- and nanoplastic particles in vascular tissue may increase risk for CVD morbidity and mortality.¹⁷

In clinical practice, cardiologists and all health care professionals need to be aware of the pervasive impact of environmental factors on cardiovascular health.¹³ Physicians can act on this knowledge by obtaining a brief screening history of potentially harmful environmental exposures on each patient, and providing anticipatory guidance, as needed. A recent AHA statement on actions that patients can take to reduce air pollution exposure provides a template that could be extended to other hazards.¹⁸

Prevention of CVDs caused by hazardous environmental exposures will, however, require more than counseling individual patients. It will also necessitate action at a societal level to control these exposures at their root sources.

Climate change and air pollution can be addressed simultaneously, since both result mainly from the combustion of fossil carbon. Actions to control either will control both, thus producing a double benefit (or co-benefit). The most effective strategy for slowing climate change and reducing air pollution is rapid, wide-scale transition away from coal, gas, and oil to clean, renewable energy.¹⁹ Governments at every level have multiple tools, both carrots and sticks, to encourage this transition. These include creating incentives for non-polluting energy sources such as solar panels and windmills as well as for electric vehicles; preferential purchasing of green energy; reducing the enormous subsidies and tax breaks currently given to producers of fossil energy;²⁰ taxing carbon emissions; and strictly enforcing air pollution standards. Such actions have proven highly effective, and have saved thousands of lives. In the United States, air pollutant emissions have been reduced by 78% since passage of the Clean Air Act in 1970, and every dollar invested in air pollution control has yielded an estimated return of $30 through reductions in health care costs and the increased economic productivity of a healthier, longer-lived population.²¹

Preventing CVD caused by an ever-increasing volume and number of manufactured chemicals and plastics will require fundamental restructuring of national chemical policy to prioritize protection of human health, and specifically children's health.¹¹ Under this new policy, chemicals would no longer be presumed safe until they are proven to cause harm. Chemicals, chemical products, and plastics would not be allowed to enter markets and remain on markets until after independent assessment, not undertaken by their manufacturers, has established that they are safe. Consumer chemicals would thus be subjected to the same constraints that have been placed on the pharmaceutical industry since the thalidomide tragedy of the 1950s and 1960s.²² Because chemical production is a transnational enterprise, international efforts will also be required to protect children's health. International actions are of particular importance for protecting the health of children in low- and middle-income countries, where 60% of global chemical and plastic production is now concentrated.²³ A key strategy could be a legally binding Global Chemicals Treaty developed and implemented under UN auspices. Such a treaty would complement the UN Global Plastics Treaty now in negotiation.^{24, 25}

Cardiologists, other physicians, nurses, medical societies, and public health organizations are uniquely well positioned to advocate to governments on behalf of their patients to end pollution and prevent CVD.¹⁹ By pointing out to elected officials the well-documented links between air pollution, climate change and human health and calling for control of the release into children's environments of multiple new and untested manufactured chemicals each year, trusted health professionals are in a powerful position to catalyze enduring action, prevent disease and save lives.