Impact of the Environment on Cardiovascular Health

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Global Footprint and Impact of Pollutants on Human Health

The global footprint of environmental pollution is very large, ranging from about 9 million deaths based on the most recent global burden of disease (GBD) estimate in 2019, to 12.6 million deaths based on a World Health Organization (WHO) estimate in 2012. These differences arise from variable definitions of the environment in the estimates. The GBD estimates are based on a more limited inventory of risk factors including air pollution: household, ambient (fine particulate matter [PM _2.5 ], and tropospheric ozone pollution); (2) water pollution: unsafe sanitation and unsafe water sources; (3) soil, chemical, and heavy metal pollution: lead (including contaminated sites polluted by lead from battery recycling operations), and mercury from gold mining; and (4) occupational pollution: occupational carcinogens, and occupational particulates, gases, and fumes. The WHO definition also includes noise, electromagnetic fields, occupational psychosocial risks, built environment, agricultural methods, and human-made climate and ecosystem change. It is important to emphasize that these estimates are likely a vast underestimate because all of these analyses are based on known risk factors (zone 1) for which there is convincing evidence of causal association ( Fig. 3.1 ). Total pollution is estimated to contribute to approximately 20% of all cardiovascular disease and 25% of ischemic heart diseases (IHDs) of which air pollution is the largest contributor, responsible for over 6 million deaths annually worldwide. As such, the global impact of environmental pollution is high and is expected to worsen as population-weighted exposures increase with urbanization and increased population density.

Air Pollution

The GBD 2019 lists air pollution as the fourth leading risk factor for global mortality, responsible for 6.67 million deaths globally. The disease burden attributable to ambient PM _2.5 estimated in disability-adjusted life-years (DALYs), increased from 70.5 (95% uncertainty interval [UI] 47.3 to 98.9) million DALYs in 1990, to 118.2 (95.9 to 138.4) million DALYs in 2019. Air pollution together with high body mass index and glucose are the only three risk factors among 87 others that account for greater than 1% of DALYs and continue in prevalence by greater than 1% per year. The increase globally is almost entirely attributable to urbanization and increasing exposures in Asia, parts of the Middle East, and Africa. Although many gaseous pollutants have been linked with health effects (e.g., ozone, nitrogen oxides, sulfur oxides), fine PM (particles ≤2.5 μm, PM _2.5 ), principally derived from fossil fuel combustion (for the purposes of power, residential energy use, and industry) is the most extensively implicated component, and has a disproportionate impact on adverse health effects. Over 50% of deaths attributable to air pollution is from cardiovascular causes ( Fig. 3.2 ).

Composition and Sources of Air Pollution

Air pollution is a complex mixture of gaseous phase and particulate constituents that varies spatially and temporally. From a regulation perspective, the Environmental Protection Agency (EPA) has set National Ambient Air Quality Standards (NAAQS) for six principal pollutants, which are called “criteria” air pollutants (carbon monoxide, lead, nitrogen dioxide, ozone, particulate matter, and sulfur dioxide, Table 3.1 ). Primary air pollutants are those that are released directly into the atmosphere, including both gaseous and particulates, whereas secondary pollutants are formed through chemical transformation through interaction with other constituents and/or in response to prevalent atmospheric conditions (sunlight, water, vapor, etc.). Many primary air pollutants such as nitrogen oxides (NO + NO ₂ ), carbon monoxide, sulfur dioxide (SO ₂ ), PM _2.5 , as well as carbon dioxide (CO ₂ ), originate from combustion of fuel or other anthropogenic processes. Combustion PM _2.5 is composed of many organic compounds, including organic carbon species (OC), elemental or black carbon, and trace metals ( Table 3.1 and eTable 3.3 ). In addition to O ₃ , which is the most prevalent secondary oxidant, a number of inorganic and organic acids and volatile organic carbons (VOCs) and semivolatile organic compounds (SVOCs) formed secondarily and are found in both the gas and particle phase, are an additional large class of pollutants. Key examples are benzene, toluene, xylene, 1,3- butadiene, and polycyclic aromatic hydrocarbons (PAHs). Many VOCs contribute to the formation of O ₃ and are oxidized in the atmosphere, becoming SVOCs and subsequently contribute to PM _2.5 mass. Examples of secondary pollutants include sulphates, nitrate, and ammonium which also contribute to the PM fraction of air pollution. The particulate fraction of air pollution may be broadly categorized by aerodynamic diameter: less than 10 μm (thoracic particles [PM ₁₀ ]), less than 2.5 μm (fine particles [PM _2.5 ]), less than 0.1 μm (ultrafine particles [UFPs]), and between 2.5 to 10 μm (coarse [PM _2.5–10 ]). Although most studies have focused on one or two pollutants at a time, the reality is that pollutants coexist and vary spatially and temporally. Even though some epidemiologic studies adjust for copollutants, the significant collinearity makes it complex to separate these effects.

TABLE 3.1

U.S. and European Standards for Air Pollutants

Adapted from Al-Kindi SG, Brook RD, Biswal S, et al. Environmental determinants of cardiovascular disease: lessons learned from air pollution. Nat Rev Cardiol . 2020;17:656–672.

ETABLE 3.3

Definitions and Description of Air Pollutants

Component	Notes
Sulphate (SO 4 2− )	Present mainly as a secondary ammonium sulphate component (NH 4 )2SO 4 from oxidation of SO 2 followed by reaction with NH 3 mainly from agricultural sources.
Nitrate (NO 3 − )	A secondary component normally present as ammonium nitrate (NH 4 NO 3 ), which results from the neutralization by NH 3 of HNO 3 vapor derived from oxidation of NOx emissions, or as sodium nitrate (NaNO 3 ) due to displacement of hydrogen chloride from NaCl by HNO 3 vapor.
Ammonium (NH 4 + )	Generally, in the form of (NH 4 ) 2 SO 4 or NH 4 NO 3 from NH 3 emissions.
Sodium (Na + ) and chloride (Cl − ) ions	From primary emissions of sea-salt particles.
Elemental carbon	Black, graphitic carbon formed during the high-temperature combustion of fossil and contemporary biomass fuels.
Organic carbon	Carbon in the form of organics either primary from automotive/industry from oxidation of volatile organic compounds (VOCs).
Mineral material	Crustal materials are rich in Al, Si, Fe, and Ca. These are present in crustal PM 10 . Nickel, cadmium, lead, and arsenic are present in combustion PM 2.5 .
Water	Water-soluble components, especially (NH 4 ) 2 SO 4 , NH 4 NO 3 , and NaCl, take up water from the atmosphere at high relative humidity, turning from crystalline solids into liquid droplets.

Particulate Air Pollutants

PM air pollution is by far the most studied and with the most evidence for health effects. The categorization of PM based on size thresholds reflects the ease of quantification and is a rough barometer of chemical composition, geographic distribution, and sources. Although regulatory thresholds exist for PM ₁₀ and PM _{2. 5} (see Table 3.1 ), no standards exist for UFP. PM ₁₀ and PM _2.5 often derive from different emissions sources and also have different chemical compositions. Emissions from combustion of gasoline, oil, diesel fuel, or wood produce much of the PM _2.5 pollution found in ambient air, as well as a significant proportion of PM ₁₀ . Dust from crustal material and agricultural and industrial practices contribute to the course (PM _10–2.5 ) or even larger particle (>PM ₁₀ ) size ranges and may dominate composition in certain environments. PM ₁₀ may also include dust from road dust, tire and road wear particles, dust from construction, agricultural emissions, wildfires and brush/waste burning, industrial sources, wind-blown dust from open lands, pollen, and fragments of bacteria and lipopolysaccharide (LPS). PM _0.1 or UFPs are generated through primary combustion of fossil fuels from automobile sources, are characterized by large surface area to size ratio, and can serve as a nidus for gaseous copollutants. UFPs are short lived and are highly influenced by proximity to the sources (typically <1 km from source). The spatial and temporal colocalization of gaseous copollutants with UFPs makes it difficult to separate the health effects in epidemiologic and mechanistic research. In addition, UFP monitoring is not widely available and requires specialized equipment. Recent studies have suggested heightened cardiovascular risk of UFP.

Gaseous Pollutants

Ground level ozone (O ₃ ) is the most studied gaseous pollutant with respect to health effects. It is a secondary pollutant which is created through reaction between nitrogen oxide and volatile organic compounds, facilitated by sunlight. Although high levels of ozone clearly confer adverse health effects including increased risk of mortality and asthma, recent evidence suggests a continued relationship between ozone and health effects at levels lower than the U.S. NAAQS of 70 ppb over 8 hours. The association between long-term ozone exposures and CV mortality is lower than other causes of mortality. The mechanisms of ozone-related cardiovascular and mortality effects appear to be related to oxidant stress and a prothrombotic response. There is paucity of data for other gaseous copollutants present in fossil fuel emissions such as VOCs and atherosclerotic cardiovascular disease (ASCVD) events, although mechanistically it is highly likely that these compounds may have important health effects. Copollutants such as NO ₂ and SO ₂ may not be directly toxic but function as surrogates for other copollutants and have been linked to cardiovascular events, including myocardial infarction (MI), stroke, and heart failure (HF). ^,

Particulate Matter Sources, Composition, and Cardiovascular Risk

Air pollution chemistry and hence health effects vary substantially by source. There is a substantial spatial and temporal variation of air pollution levels that may be important in health effects. Large urban-rural differences are found for primary combustion pollutants that originate from traffic such as nitrogen oxides (NO and NO ₂ ), and particulate black carbon, that may drive risk. Meteorologic conditions such as atmospheric stability can significantly alter the horizontal propagation of particles and thus the size of the population exposed. Given the fact that the dynamics of air pollution chemistry and concentration may vary substantially, the detailed chemical characterization of pollution is a static time frame that in addition to being expensive may not accurately portray the chemical composition particularly for components such as ultrafine. However, speciation of common pollutants such as sulfates and nitrates or the corresponding gaseous pollutants such as NO ₂ and SO ₂ have been shown to be predictive of health effects. A 2014 systematic review that quantified the associations between chemical components, such as sulfate, nitrate, and elemental and organic carbons, demonstrated that they were all linked to all-cause, cardiovascular, and respiratory mortality. In an analysis of the American Cancer Society Cancer Prevention Study II, mortality from ischemic heart disease (IHD) associated with PM _2.5 derived from coal combustion was fivefold higher than the risk with overall PM _2.5 mass, suggesting that the source of PM _2.5 may be important in determining cardiovascular risk. Examination of sources may sometimes represent a more efficient way of thinking about health effects, including regulation. For instance, traffic air pollution is perhaps the largest health threat from a source perspective in the West, with a sizeable proportion of the population living within 150 meters of a major highway and thus likely to be exposed to traffic-related ultrafine air pollution. The average Western adult spends 55 minutes a day exposed to vehicular emissions. Traffic air pollution peaks during the late morning and evening rush hours, with PM _0.1 and gaseous components demonstrating substantial variation within a span of 400 m. The substantial spatial variation and reactivity of PM _0.1 fraction pose challenges for accurate quantification, and thus a simple metric such as distance from a highway has been an effective surrogate for traffic-related exposures. Fossil fuel–burning coal power plants, shipping and airplane, and agricultural emissions (e.g., crop burning) may dominate emissions in certain environments. Most individuals across the globe spend preponderant majority of time indoors and are also exposed to indoor sources. Household air pollution (HAP) encompass a range of particles from diverse sources that vary dramatically depending on geography and socioeconomic and cultural factors. For instance, with exposure to high concentrations of emissions from wood/coal-burning stoves for cooking and heat, kerosene stoves may dominate the indoor environment in developing countries reliant on solid fuels for heat and cooking. In countries with high levels of ambient air pollution, it is estimated that up to 65% of inhalation of outdoor air particles occurs when people are indoors. In the West, cooking on gas stoves, burning incense and candles, use of aerosol sprays, and cleaning activities may contribute to indoor particle levels. Wood-burning communities in North America may experience high levels of UFPs during winter. The expansion of the human habitats and climate change have expanded the likelihood of exposure to air pollution from natural events such as wildfires and volcanic eruptions. Both PM and gaseous pollutants from these events can affect large populations and produce health effects in millions of people across the world. For instance, crustal material from dust storms can cause dramatic increases in outdoor and indoor PM counts. Mortality and respiratory morbidity have been the most frequently studied and most consistently reported outcomes of smoke exposure. Recent evidence suggests that smoke exposure from natural sources such as wildfires may be associated with cardiovascular effects with effect estimates comparable with ambient PM _2.5 from anthropogenic sources.

Household Versus Ambient Air Pollution

Although the vast majority of studies on air pollution have focused on ambient air pollution owing to exposure data availability, HAP is a major contributor to global mortality, particularly in developing countries. ^, The burden of disease attributable to HAP has been steadily decreasing, with the most recent GBD 2019 indicating that the percentage of DALYs attributable to HAP decreasing 56%, demoting HAP as the 4th leading risk factor in 1990 to the 10th leading risk factor in 2019. Although HAP is a significant cause of childhood morbidity including predisposition to respiratory tract infections and COPD, links between CVD have been recently elucidated, including association with hypertension and coronary artery disease. An issue with HAP has been the estimation of reliable exposure estimates and ascertainment of mortality causes, because the predominant majority of events occur in communities with limited access to health care and standardized reporting procedures. HAP encompasses gaseous and particulate pollution generated from solid fuel use for cooking and indoor heat in developing countries. In Western countries, wood-burning furnaces, indoor candle lighting, and aerosol spray use may all contribute to HAP. It is important to note that HAP and ambient air pollution also coexist, such as in developing countries and when outdoor ambient levels are very high. In these environments, the indoor environment may be dominated by outdoor levels (and hence sources). The translocation of particles from ambient (outdoor) air to indoor air is determined by house insulation and the method of ventilation. Smaller particles (UFPs) have higher likelihood of translocating indoors, and this has been documented in residential areas with proximity to major highways as well as wood-burning communities in the United States.