Beyond the lifestyle paradigm: environmental triggers and susceptible cardiovascular phenotypes

This commentary refers to ‘Air pollution before and during the COVID-19 pandemic: changes in risk of acute myocardial infarction’, by M. Ishii et al., https://doi.org/10.1093/eurheartj/ehag102 and the discussion piece ‘Beyond clinical phenotypes: endotype-specific environmental cardiovascular susceptibility’, by M. Ishii et al., https://doi.org/10.1093/eurheartj/ehag814. We read with interest the nationwide study by Ishii et al.1 on short-term fine particulate matter (PM2.5) exposure and acute myocardial infarction (AMI) before and during the COVID-19 pandemic. The most striking finding, in our view, was not the pollution–AMI association itself but how it behaved across phenotypes: PM2.5-associated risk of myocardial infarction with non-obstructive coronary arteries (MINOCA) fell during the pandemic, while no comparable change was seen for infarction with obstructive coronary disease.1 This selective attenuation raises a question that extends well beyond this dataset: can a single environmental exposure preferentially trigger different cardiovascular phenotypes, depending on the susceptibility of the individual exposed? MINOCA is not one disease but several—coronary vasospasm, microvascular dysfunction, thromboembolism, spontaneous coronary dissection, and other mechanisms.2 Each pathway could plausibly respond differently to the inflammation, endothelial dysfunction, autonomic imbalance, and prothrombotic tendency that air pollution is known to provoke.3 Read this way, the data from Ishii et al.1 support a susceptibility–trigger–phenotype model: pollution supplies the trigger, an individual's vascular or coronary substrate determines the susceptibility, and the clinical event is the resulting phenotype—a different starting point from treating PM2.5 as a generic risk factor that simply raises AMI incidence across the board.