Both high arterial blood pressure (BP) and elevated levels of fine particulate matter (PM2.5) air pollution have been associated with an increased risk for several cardiovascular (CV) diseases, ...including stroke, heart failure, and myocardial infarction. Given that PM2.5 and high BP are each independently leading risk factors for premature mortality worldwide, a potential relationship between these factors would have tremendous public health repercussions. Therefore, the aim of this review is to summarize recent evidence linking air pollution and BP. Epidemiological findings demonstrate that particulate pollutants cause significant increases in BP parameters in relation to both short and long-term exposures, with robust evidence for exposures to PM2.5. Moreover, recent epidemiological studies suggest a positive association between residence within regions with higher levels of ambient PM and an increased incidence and prevalence of overt hypertension. Studies provide consistent results that elevated concentrations of pollutants increase hospital admissions and/or emergency visits for hypertensive disorders and also support that PM levels increases BP in vulnerable subsets of individuals (pregnant women, high CV risk individuals). In this context, PM-mediated BP elevations may be an important pathway which acts as a potential triggering factor for acute CV events. Mechanistic evidence illustrates plausible pathways by which acute and chronic exposures to air pollutants might disrupt hemodynamic balance favoring vasoconstriction, including autonomic imbalance and augmented release of various pro-oxidative, inflammatory and/or hemodynamically-active mediators. Together these responses may underlie PM-induced BP elevations; however, full details regarding the responsible mechanisms require further studies. As a consequence of the ubiquity of air pollution, even a small effect on raising BP and/or the prevalence of hypertension, i.e. the major risk factor for mortality and morbidity worldwide, would have enormous global public health implications.
Air pollution is a heterogeneous mixture of gases, liquids and PM (particulate matter). In the modern urban world, PM is principally derived from fossil fuel combustion with individual constituents ...varying in size from a few nanometres to 10 microm in diameter. In addition to the ambient concentration, the pollution source and chemical composition may play roles in determining the biological toxicity and subsequent health effects. Nevertheless, studies from across the world have consistently shown that both short- and long-term exposures to PM are associated with a host of cardiovascular diseases, including myocardial ischaemia and infarctions, heart failure, arrhythmias, strokes and increased cardiovascular mortality. Evidence from cellular/toxicological experiments, controlled animal and human exposures and human panel studies have demonstrated several mechanisms by which particle exposure may both trigger acute events as well as prompt the chronic development of cardiovascular diseases. PM inhaled into the pulmonary tree may instigate remote cardiovascular health effects via three general pathways: instigation of systemic inflammation and/or oxidative stress, alterations in autonomic balance, and potentially by direct actions upon the vasculature of particle constituents capable of reaching the systemic circulation. In turn, these responses have been shown to trigger acute arterial vasoconstriction, endothelial dysfunction, arrhythmias and pro-coagulant/thrombotic actions. Finally, long-term exposure has been shown to enhance the chronic genesis of atherosclerosis. Although the risk to one individual at any single time point is small, given the prodigious number of people continuously exposed, PM air pollution imparts a tremendous burden to the global public health, ranking it as the 13th leading cause of morality (approx. 800,000 annual deaths).
Fine particulate matter <2.5 μm (PM
) air pollution is the most important environmental risk factor contributing to global cardiovascular (CV) mortality and disability. Short-term elevations in PM
...increase the relative risk of acute CV events by 1% to 3% within a few days. Longer-term exposures over several years increase this risk by a larger magnitude (∼10%), which is partially attributable to the development of cardiometabolic conditions (e.g., hypertension and diabetes mellitus). As such, ambient PM
poses a major threat to global public health. In this review, the authors provide an overview of air pollution and health, including assessment of exposure, impact on CV outcomes, mechanistic underpinnings, and impact of air pollution reduction strategies to mitigate CV risk. The review concludes with future challenges, including the inextricable link between air pollution and climate change, and calls for large-scale trials to allow the promulgation of formal evidence-based recommendations to lower air pollution-induced health risks.
Abstract Background Considerable uncertainty exists as to whether lowering low-density lipoprotein cholesterol (LDL-C) by inhibiting the Niemann-Pick C1-Like 1 (NPC1L1) receptor with ezetimibe, ...either alone or in combination with a 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitor (statin), will reduce the risk of coronary heart disease (CHD). Objectives This study evaluated the effect of naturally random allocation to lower LDL-C mediated by polymorphisms in the NPC1L1 gene (target of ezetimibe), the HMGCR gene (target of statins), or both (target of combination therapy) on the risk of CHD. Methods We constructed NPC1L1 and HMGCR genetic LDL-C scores to naturally randomize participants into 4 groups: reference, lower LDL-C mediated by NPC1L1 polymorphisms, lower LDL-C mediated by HMGCR polymorphisms, or lower LDL-C mediated by polymorphisms in both NPC1L1 and HMGCR . We compared the risk of CHD (fatal or nonfatal myocardial infarction) among each group using a 2 × 2 factorial mendelian randomization study design. Results A total of 108,376 persons (10,464 CHD events) from 14 studies were included. There were no significant differences in baseline characteristics among the 4 groups, thus confirming that allocation was random. Compared to the reference group, the NPC1L1 group had 2.4 mg/dl lower LDL-C and 4.8% lower risk of CHD (odds ratio OR: 0.952, 95% confidence interval CI: 0.920 to 0.985); whereas the HMGCR group had 2.9 mg/dl lower LDL-C and a similar 5.3% lower risk of CHD (OR: 0.947, 95% CI: 0.909 to 0.986). The group with lower LDL-C mediated by both NPC1L1 and HMGCR polymorphisms had 5.8 mg/dl additively lower LDL-C and a 10.8% log-linearly additive lower risk of CHD (OR: 0.892, 95% CI: 0.854 to 0.932). Conclusions The effect of lower LDL-C on the risk of CHD mediated by polymorphisms in NPC1L1 , HMGCR, or both is approximately the same per unit lower LDL-C and log-linearly proportional to the absolute exposure to lower LDL-C.
Air pollution is well recognized as a major risk factor for chronic non-communicable diseases and has been estimated to contribute more to global morbidity and mortality than all other known ...environmental risk factors combined. Although air pollution contains a heterogeneous mixture of gases, the most robust evidence for detrimental effects on health is for fine particulate matter (particles ≤2.5 µm in diameter (PM
)) and ozone gas and, therefore, these species have been the main focus of environmental health research and regulatory standards. The evidence to date supports a strong link between the risk of cardiovascular events and all-cause mortality with PM
across a range of exposure levels, including to levels below current regulatory standards, with no 'safe' lower exposure levels at the population level. In this comprehensive Review, the empirical evidence supporting the effects of air pollution on cardiovascular health are examined, potential mechanisms that lead to increased cardiovascular risk are described, and measures to reduce this risk and identify key gaps in our knowledge that could help address the increasing cardiovascular morbidity and mortality associated with air pollution are discussed.
Since the publication of the last American Heart Association scientific statement on air pollution and cardiovascular disease in 2010, unequivocal evidence of the causal role of fine particulate ...matter air pollution (PM
, or particulate matter ≤2.5 μm in diameter) in cardiovascular disease has emerged. There is a compelling case to provide the public with practical personalized approaches to reduce the health effects of PM
. Such interventions would be applicable not only to individuals in heavily polluted countries, high-risk or susceptible individuals living in cleaner environments, and microenvironments with higher pollution exposures, but also to those traveling to locations with high levels of PM
. The overarching motivation for this document is to summarize the current evidence supporting personal-level strategies to prevent the adverse cardiovascular effects of PM
, guide the use of the most proven/viable approaches, obviate the use of ineffective measures, and avoid unwarranted interventions. The significance of this statement relates not only to the global importance of PM
, but also to its focus on the most tested interventions and viable approaches directed at particulate matter air pollution. The writing group sought to provide expert consensus opinions on personal-level measures recognizing the current uncertainty and limited evidence base for many interventions. In doing so, the writing group acknowledges that its intent is to assist other agencies charged with protecting public health, without minimizing the personal choice considerations of an individual who may decide to use these interventions in the face of ongoing air pollution exposure.
Particulate matter (PM) air pollution is a leading cause of global cardiovascular morbidity and mortality. Understanding the biological action of PM is of particular importance in improvement of ...public health. Recent Advances: Both fine (PM <2.5 μM) and ultrafine particles (<0.1 μM) are widely believed to mediate their effects through redox regulated pathways. A rather simplistic graded ramp model of redox stress has been replaced by a more sophisticated understanding of the role of oxidative stress in signaling, and the realization that many of the observed effects may involve disruption and/or enhancement of normal endogenous redox signaling and induction of a potent immune-mediated response, through entrainment of multiple reactive oxygen species (ROS).
The molecular events by which pulmonary oxidative stress in response to inhalational exposure to air pollution triggers inflammation, major ROS (e.g., superoxide, hydroxyl radical, nitric oxide, and peroxynitrite) generated in air pollution exposure, types of oxidative tissue damage in target organs, contributions of nonimmune and immune cells in inflammation, and the role of protective proteins (e.g., surfactant, proteins, and antioxidants) are highly complex and may differ depending on models and concomitant disease states.
While the role of oxidative stress in the lung has been well demonstrated, the role of oxidative stress in mediating systemic effects especially in inflammation and injury processes needs further work. The role of antioxidant defenses with chronic exposure will also need further exploration. Antioxid. Redox Signal. 28, 797-818.
Abstract
Fine particulate matter <2.5 µm (PM2.5) air pollution is a leading cause of global morbidity and mortality. The largest portion of deaths is now known to be due to cardiovascular disorders. ...Several air pollutants can trigger acute events (e.g., myocardial infarctions, strokes, heart failure). However, mounting evidence additionally supports that longer-term exposures pose a greater magnified risk to cardiovascular health. One explanation may be that PM2.5 has proven capable of promoting the development of chronic cardiometabolic conditions including atherosclerosis, hypertension, and diabetes mellitus. Here, we provide an updated overview of recent major studies regarding the impact of PM2.5 on cardiometabolic health and outline key remaining scientific questions. We discuss the relevance of emerging trials evaluating personal-level strategies (e.g., facemasks) to prevent the harmful effects of PM2.5, and close with a call for large-scale outcome trials to allow for the promulgation of formal evidence-base recommendations regarding their appropriate usage in the global battle against air pollution.
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