Invisible exposure, visible harm: air pollution and the global burden of cardiovascular disease

Background Air pollution is a major modifiable environmental risk factor for cardiovascular disease (CVD). In the Global Burden of Disease (GBD) 2021 study, air pollution was the second-leading risk factor for death worldwide, accounting for an estimated 8.1 million deaths from all causes in 2021, and particulate matter (PM) pollution (ambient plus household) was associated with approximately 4.5 million cardiovascular deaths. Main body This narrative review, based on a structured search of PubMed/MEDLINE, Scopus and Web of Science, summarizes evidence on the sources of the main pollutants (fine particulate matter [PM₂.₅], coarse particulate matter [PM₁₀], ultrafine particles [PM₀.₁/UFP], nitrogen dioxide [NO₂], sulfur dioxide [SO₂], ozone [O₃] and carbon monoxide [CO]); the global burden of pollution-attributable CVD; epidemiological evidence from major cohort and multi-city studies; biological mechanisms, distinguishing those supported by human data from those derived mainly from cell and animal models; the associations with specific cardiovascular phenotypes (ischemic heart disease, stroke, hypertension, heart failure, arrhythmia and vascular disease); susceptible populations; transcriptomic, proteomic, lipidomic, epigenetic and microRNA findings; and preventive strategies graded by strength of evidence. Observational studies consistently associate short- and long-term exposure to PM₂.₅ with cardiovascular events and mortality, and controlled-exposure, quasi-experimental and mechanistic studies support a causal interpretation for PM₂.₅. Evidence for individual gaseous pollutants is less consistent, and most multi-omics findings remain exploratory. Conclusion PM₂.₅ should be regarded as a cardiovascular risk factor in clinical and public-health practice. Key uncertainties include the shape of the exposure–response relationship at very low concentrations, the relative toxicity of particle components, and whether reducing individual exposure lowers hard cardiovascular outcomes. Priorities include prospective multi-omics studies with clinical endpoints in low- and middle-income countries, causal-inference designs, and trials testing exposure-reduction and targeted therapeutic strategies in highly exposed populations.