Water, Soil, Noise, and Light Pollution: JACC Focus Seminar, Part 2.

Various forms of pollution carry a substantial burden with respect to increasing the risk of causing and exacerbating noncommunicable diseases, especially cardiovascular disease. The first part of this 2-part series on pollution and cardiovascular disease provided an overview of the impact of global warming and air pollution. This second paper provides an overview of the impact of water, soil, noise, and light pollution on the cardiovascular system. This review discusses the biological mechanisms underlying these effects and potential environmental biometrics of exposure. What is clear from both these pollution papers is that significant efforts and redoubled urgency are needed to reduce the sources of pollution in our environment, to incorporate environmental risk factors into medical education, to provide resources for research, and, ultimately, to protect those who are particularly vulnerable and susceptible.

Environmentally Not So Friendly: Global Warming, Air Pollution, and Wildfires: JACC Focus Seminar, Part 1.

Environmental stresses are increasingly recognized as significant risk factors for adverse health outcomes. In particular, various forms of pollution and climate change are playing a growing role in promoting noncommunicable diseases, especially cardiovascular disease. Given recent trends, global warming and air pollution are now associated with substantial cardiovascular morbidity and mortality. As a vicious cycle, global warming increases the occurrence, size, and severity of wildfires, which are significant sources of airborne particulate matter. Exposure to wildfire smoke is associated with cardiovascular disease, and these effects are underpinned by mechanisms that include oxidative stress, inflammation, impaired cardiac function, and proatherosclerotic effects in the circulation. In the first part of a 2-part series on pollution and cardiovascular disease, this review provides an overview of the impact of global warming and air pollution, and because of recent events and emerging trends specific attention is paid to air pollution caused by wildfires.

PAR4 Antagonism in Patients With Coronary Artery Disease Receiving Antiplatelet Therapies.

BACKGROUND: BMS-986141 is a novel potent highly selective antagonist of PAR (protease-activated receptor) type 4. PAR4 antagonism has been demonstrated to reduce thrombus formation in isolation and in combination with factor Xa inhibition in high shear conditions in healthy people. We sought to determine whether PAR4 antagonism had additive antithrombotic effects in patients with coronary artery disease who were receiving antiplatelet therapy. METHODS: Forty-five patients with stable coronary heart disease and 10 healthy volunteers completed a phase 2a open-label 4-arm single-center study. Patients were allocated to 1 of 3 treatment arms for 7 days: (1) ticagrelor (90 mg BID), (2) aspirin (75 mg QD), or (3) the combination of ticagrelor and aspirin. Agonist-induced platelet aggregation, platelet activation, and ex vivo thrombus formation were measured before and 2 and 24 hours after a single oral 4-mg dose of BMS-986141 on the first study visit day in all participants. RESULTS: BMS-986141 demonstrated highly selective inhibition of PAR4-AP (agonist peptide)-induced platelet aggregation, P-selectin expression, and platelet-monocyte aggregate expression (P≤0.001 for all), which were unaffected by concomitant antiplatelet therapies. PAR4 antagonism reduced ex vivo thrombus area in high shear conditions in healthy volunteers (-21%; P=0.001) and in patients receiving ticagrelor alone (-28%; P=0.001), aspirin alone (-23%; P=0.018), or both in combination (-24%; P≤0.001). Plasma concentration of BMS-986141 correlated with PAR4-AP-induced platelet responses (P≤0.001 for all) and total thrombus area under high shear stress conditions (P≤0.01 for all). CONCLUSIONS: PAR4 antagonism has additive antithrombotic effects when used in addition to ticagrelor, aspirin, or their combination, in patients with stable coronary heart disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05093790.

First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses.

Graphene oxide nanomaterials are being developed for wide-ranging applications but are associated with potential safety concerns for human health. We conducted a double-blind randomized controlled study to determine how the inhalation of graphene oxide nanosheets affects acute pulmonary and cardiovascular function. Small and ultrasmall graphene oxide nanosheets at a concentration of 200 µg m-3 or filtered air were inhaled for 2 h by 14 young healthy volunteers in repeated visits. Overall, graphene oxide nanosheet exposure was well tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected irrespective of graphene oxide particle size. Highly enriched blood proteomics analysis revealed very few differential plasma proteins and thrombus formation was mildly increased in an ex vivo model of arterial injury. Overall, acute inhalation of highly purified and thin nanometre-sized graphene oxide nanosheets was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures at a clinical setting for risk assessment of graphene oxide, and lay the foundations for investigating the effects of other two-dimensional nanomaterials in humans. Clinicaltrials.gov ref: NCT03659864.

Cardiovascular disease in low- and middle-income countries associated with environmental factors.

There is a growing recognition that the profound environmental changes that have occurred over the past century pose threats to human health. Many of these environmental factors, including air pollution, noise pollution, as well as exposure to metals such as arsenic, cadmium, lead, and other metals, are particularly detrimental to the cardiovascular health of people living in low-to-middle income countries (LMICs). Low-to-middle income countries are likely to be disproportionally burdened by cardiovascular diseases provoked by environmental factors. Moreover, they have the least capacity to address the core drivers and consequences of this phenomenon. This review summarizes the impact of environmental factors such as climate change, air pollution, and metal exposure on the cardiovascular system, and how these specifically affect people living in LMICs. It also outlines how behaviour changes and interventions that reduce environmental pollution would have significant effects on the cardiovascular health of those from LMICs, and globally.

New insights into the association of air pollution and kidney diseases by tracing gold nanoparticles with inductively coupled plasma mass spectrometry.

Exposure to particles from air pollution has been associated with kidney disease; however, the underlying biological mechanisms are incompletely understood. Inhaled particles can gain access to the circulation and, depending on their size, pass into urine, raising the possibility that particles may also sequester in the kidney and directly alter renal function. This study optimised an inductively coupled plasma mass spectrometry (ICP-MS) method to investigate the size dependency of particle accumulation in the kidneys of mice following pulmonary instillation (0.8 mg in total over 4 weeks) to gold nanoparticles (2, 3-4, 7-8, 14 or 40 nm or saline control). Due to the smallest particle sizes being below the limit of detection in single particle mode, ICP-MS was operated in total quantification mode. Gold was detected in all matrices of interest (blood, urine and kidney) from animals treated with all sizes of gold nanoparticles, at orders of magnitude higher than the methodological limit of detection in biological matrices (0.013 ng/mL). A size-dependent effect was observed, with smaller particles leading to greater levels of accumulation in tissues. This study highlights the value of a robust and reliable method by ICP-MS to detect extremely low levels of gold in biological samples for indirect particle tracing. The finding that nano-sized particles translocate from the lung to the kidney may provide a biological explanation for the associations between air pollution and kidney disease.