Exposome in ischaemic heart disease: beyond traditional risk factors

Abstract

Ischaemic heart disease represents the leading cause of morbidity and mortality, typically induced by the detrimental effects of risk factors on the cardiovascular system. Although preventive interventions tackling conventional risk factors have helped to reduce the incidence of ischaemic heart disease, it remains a major cause of death worldwide. Thus, attention is now shifting to non-traditional risk factors in the built, natural, and social environments that collectively contribute substantially to the disease burden and perpetuate residual risk. Of importance, these complex factors interact non-linearly and in unpredictable ways to often enhance the detrimental effects attributable to a single or collection of these factors. For this reason, a new paradigm called the 'exposome' has recently been introduced by epidemiologists in order to define the totality of exposure to these new risk factors. The purpose of this review is to outline how these emerging risk factors may interact and contribute to the occurrence of ischaemic heart disease, with a particular attention on the impact of long-term exposure to different environmental pollutants, socioeconomic and psychological factors, along with infectious diseases such as influenza and COVID-19. Moreover, potential mitigation strategies for both individuals and communities will be discussed.

Keywords: Atherosclerosis; Ischaemic heart disease; Mental stress; Pollution; Risk factors.

Graphical Abstract

Major non-traditional risk factors for ischaemic heart disease, including environmental pollution, mental health disorders, and infectious diseases. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 1

Impact of traditional and non-traditional risk factors on overall death, and death from ischaemic heart disease and DALYs. Data from the GBD 2019 reports

Figure 2

Percentage of ischaemic heart disease mortality burden attributable to air pollution for both sexes, all ages in 2019. Data from the GBD 2019 reports (Institute of Health and Metrics and Evaluation, IHME)

Figure 3

Air, light, and acoustic pollution represent relevant non-traditional risk factors for ischaemic heart disease. Air pollution through biological intermediates induces oxidative stress, inflammation which can generate insulin resistance and diabetes mellitus. Also, acoustic and light pollution and social stress enhance oxidative stress and inflammatory response through stress hormones imbalance and circadian rhythm disruption (sleep deprivation or fragmentation), respectively, leading to endothelial dysfunction and platelet aggregation. All these elements can promote ischaemic heart disease

Figure 4

Mental distress, depression, loneliness, and social isolation act as a trigger for ischaemic heart disease through the hypothalamic-pituitary-adrenal axis which induces the production of glucocorticoids by the adrenal cortex, generating insulin resistance and visceral obesity. An imbalance in the sympathetic nervous system promotes the fight or flight response with higher blood pressure and heart rate variability. SNS, sympathetic nervous system

Figure 5

Infectious diseases as risk factors in ischaemic heart disease. Respiratory infections, periodontal diseases, and recently SARS-CoV-2 infection through multiple mechanisms, such as platelet activation, lipopolysaccharide-mediated systemic, inflammation and oxidative stress, mediate ischaemic heart disease progression. Moreover, heightened gut permeability and successive low-grade endotoxaemia, through Toll-like receptors, affect atherosclerotic and thrombotic processes. EPCR, Endothelial protein C receptor; Fxa, Factor Xa; FVa, Factor Va; FVIIa, Factor VIIa; LPS, lipopolysaccharide; MO, monocyte; aPC, activated protein C; PC, protein C; PLT, platelet; TF, tissue factor; TLR, Toll-like receptor; TLR4, Toll-like receptor 4

Figure 6

Directed acyclic graph (DAG) illustrating the causal effect of the exposome on ischaemic heart disease (IHD). Being the exposome composed by air pollution, chemical exposure, light pollution, acoustic pollution, mental stress, depression, social isolation, infectious noxae, and pulmonary infections. Highlighting age, gender, and socioeconomic status as confounding factors. The green nodes indicate the exposure of interest, the green lines the exposures effect pathways, the blue node with ‘I’ indicates the outcome of interest, and the blue node without ‘I’ is an intermediate to the effect pathway. The pink nodes show the confounding factors since they are both ancestor of exposure and outcome and therefore, the pink lines identify the biasing path. This DAG was generated through dagitty.net