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Of genes, air pollution, and triple A

Comment by Giuseppe Biondi-Zoccai, Population Science and Public Health Section member

"We make the world we live in and shape our own environment." Orison Swett Marden

Risk Factors and Prevention

Preventive medicine rests solidly on identifying risk factors and acting accordingly at the population level as well as individually. (1) Thanks to the breakthroughs in molecular biology, our knowledge on the genetic determinants of cardiovascular disease is quite extensive, and a similar wealth of evidence has recently accrued on the adverse impact of air pollution on atherothrombosis. Yet, understanding their intricate interplay remains challenging, especially in everyday practice.

The European Journal of Preventive Cardiology showcases a very interesting cohort study which has explicitly focused on disentangling the complex interactions between genetic risk profile and pollution, namely exposure to nitric dioxide (NO2), nitrogen oxides (NOx), particulate matter with an aerodynamic diameter <2.5 μm (PM2.5), and particulate matter with an aerodynamic diameter <10 μm (PM10), on one hand, and the incidence of abdominal aortic aneurysm (AAA), on the other. (2) The study leveraged data on as many as 449,463 individuals aged 37-73 years from the UK Biobank, including more than 50%  females, and totaling as many as 1626 incident AAA cases during a median follow-up of nearly 13 years.

The main findings of the study were that, in keeping with other studies, (3) long-term exposure to such pollutants was significantly associated with an elevated risk of AAA onset. Most intriguingly, the detrimental effects of air pollutants were evident even for relatively low exposures (even if below the World Health Organization threshold, so for exposures that we consider as safe) yet protracted over a long period of time. Notably, those with both high levels of air pollutants exposure and high genetic risk had a quite higher risk of developing AAA compared with those with only increased exposure or increased genetic risk. Finally, Ma et al ventured into creating a novel polygenic risk score based on known AAA-related genetic markers, thus adding a novel sanctionable dimension to understanding how genetic predisposition interacts with air pollution to increase AAA risk. A key strength of this work rests in the reliance on detailed, annual average concentration data of air pollutants allowing for an accurate and individualized analytical framework.

Some limitations of this work should also be considered, including the potential for misclassification and bias of exposure levels due to variability in personal exposure and changes in residence not captured in the dataset, the lack of details on symptoms for minor AAA, which may lead to underdiagnosis, and the limited generalizability of the study findings to other ethnic groups different from the predominantly white population or areas without the specific patterns of pollutants such as those included in the UK Biobank cohort study. Finally, also it would be interesting to see analyses encompassing exposure to climate and other environmental factors (eg temperature, atmospheric pressure, humidity, rainfall, and sun exposure) which are well known to impact on atherothrombosis. (4-5)

In conclusion, we recommend perusing attentively the study by Ma and colleagues showing that incidence of AAA is strongly and synergistically impacted by genetic risk profile and pollution.  Notably, this study highlights the need for more stringent air quality standards and policies to reduce the population exposure to harmful pollutants, potentially mitigating AAA risk, especially among genetically susceptible individuals. In addition, the strong interaction between genetic risk and exposure to NO2, NOx, PM2.5, and PM10 suggests the possibility for tailored preventive measures and public health advisories for individuals at higher genetic risk of AAA.

Evidently, this UK Biobank analysis is a poignant reminder that the best way to tackle cardiovascular disease is to combine effectively and proactively collective and individual actions, aiming at preventing disease onset in an efficient and sustainable manner.

Figure 1. The role of air pollution on abdominal aortic aneurysm


Source: Eur Heart J, Volume 45, Issue 12, 21 March 2024, Pages 1030–1039,

Note: The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.


Giuseppe Biondi-Zoccai commented on:

2. Ma Y, Li D, Cui F, Wang J, Tang L, Yang Y, Liu R, Tian Y. Air pollutants, genetic susceptibility, and abdominal aortic aneurysm risk: a prospective study. Eur Heart J. 2024 Mar 27;45(12):1030-1039. doi: 10.1093/eurheartj/ehad886. PMID: 38241289.

Additional references:

1. Mensah GA, Fuster V, Murray CJL, Roth GA; Global Burden of Cardiovascular Diseases and Risks Collaborators. Global Burden of Cardiovascular Diseases and Risks, 1990-2022. J Am Coll Cardiol. 2023 Dec 19;82(25):2350-2473. doi: 10.1016/j.jacc.2023.11.007. PMID: 38092509.

3. de Bont J, Jaganathan S, Dahlquist M, Persson Å, Stafoggia M, Ljungman P. Ambient air pollution and cardiovascular diseases: An umbrella review of systematic reviews and meta-analyses. J Intern Med. 2022 Jun;291(6):779-800. doi: 10.1111/joim.13467. Epub 2022 Mar 8. PMID: 35138681; PMCID: PMC9310863.

4. Calcagno S, Di Pietro R, Dei Giudici A, Del Prete A, Sciarretta S, Versaci F. Air pollution, climate changes and cardiovascular diseases: a nightmare threesome! Minerva Cardioangiol. 2020 Aug;68(4):282-284. doi: 10.23736/S0026-4725.20.05122-1. Epub 2020 Feb 26. PMID: 32107894.

5. Biondi-Zoccai G, Rodriguez-Granillo GA, Mercade JM, Dawidowski L, Seropian IM, Cohen F, Sturmer-Ramos C, Descalzo A, Rubilar B, Sztejfman M, Zaidel E, Pazos C, Leguizamon J, Cafaro G, Visconti M, Baglioni P, Noya A, Fontana L, Rodriguez-Granillo M, Pavlovsky H, Alvarez JA, Lylyk P, Versaci F, Abrutzky R. Interplay between climate, pollution and COVID-19 on ST-elevation myocardial infarction in a large metropolitan region. Minerva Med. 2022 Dec;113(6):950-958. doi: 10.23736/S0026-4806.21.07748-X. Epub 2021 Jul 26. PMID: 34309338.

Notes to editor

Corresponding author: Prof. Giuseppe Biondi-Zoccai, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. Email