First myocardial infarction: incorporating non-traditional risk factors to bridge the prevention gap

This commentary refers to ‘First myocardial infarction: risk factors, symptoms, and medical therapy’, by N. S. Nurmohamed et al., https://doi.org/10.1093/eurheartj/ehaf390 and the discussion piece ‘Preventing the First Myocardial Infarction: from Reaction to Action’, by N. S. Nurmohamed et al., https://doi.org/10.1093/eurheartj/ehaf852. We read with great interest the recent article by Nurmohamed et al.1 on the risk factors, symptoms, and medical therapy of first myocardial infarction (MI). This landmark real-world study powerfully exposes critical gaps in MI prevention, notably that 18% of first-MI patients lacked standard modifiable risk factors (SMuRFs). However, the exclusive reliance on SMuRFs overlooks compelling evidence that non-traditional risk factors (NTRFs), such as environmental exposures (air pollution and extreme temperatures), psychosocial stress, and circadian disruption, COVID-19, microplastics and polygenic risk score, significantly contribute to MI pathogenesis. Ignoring these factors perpetuates the very ‘unmet need for improved tools’ highlighted in your conclusion. Robust epidemiological data confirm NTRFs as independent MI predictors. Environmental stressors like PM₂.₅ (increased 1.32% risk of ACS in concentrations of 36.0 μg/m3), extreme cold (increased 32% incidence of MI) and microplastics (detected in 58.4% of plaques, with higher risk linked to MI) directly trigger plaque rupture.2–4 Behavioral/social drivers such as chronic sleep deprivation (reduction in sleep duration from 7.0 to 5.5 h/night, HR = 1.34), life stress, low socioeconomic status, and work-related stress induce endothelial dysfunction, inflammation and atherosclerosis.5–7 Additionally, COVID-19 is associated with a 5-fold higher risk of in-hospital definite stent thrombosis and an 8.7% increase in mortality.8 Polygenic risk scores, which aggregate genetic susceptibility, further contribute to MI risk by amplifying the pathogenic effects of these factors. Critically, these factors may explain which patients lack traditional risk factors and which patients fail to seek medical attention because they perceive themselves as SMuRFs-less. In Nurmohamed et al.’s1 cohort, NTRFs likely drove many ‘SMuRF–less’ cases, particularly in young males (a high-risk subgroup they identified).1