Sex-specific association between secondhand smoke exposure and acute coronary syndrome using KoGES epidemiological cohort data

1. Introduction

Acute coronary syndrome (ACS) signifies a spectrum of conditions that reflect a grave obstruction to coronary blood flow, embodying unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI) [1]. Representing a foremost cause of morbidity and mortality worldwide, ACS imposes a significant public health burden [2]. According to the Global Burden of Disease Study, ischemic heart disease, in which ACS is a major contributor, was responsible for an estimated 9 million deaths in 2021, symbolizing a striking 15.5% rise in the past decade [3]. ACS is not only a predominant driver of sudden cardiac events but is also critically implicated in the subsequent development of heart failure and related complications [4, 5]. The urgency of actively addressing Acute Coronary Syndrome (ACS) is underscored by its substantial impact on public health, necessitating directed efforts to reduce its incidence and enhance management strategies, particularly in populations bearing elevated risks due to various factors [6].

Secondhand smoke (SHS), comprising over 7000 chemicals, is a recognized risk factor for cardiovascular disease, including ACS [7, 8]. The toxic constituents of SHS lead to endothelial dysfunction, increased oxidative stress, and a pro-atherosclerotic environment, making even brief exposures hazardous [9]. Epidemiological data indicates that non-smokers exposed to SHS face a 25–30% higher risk of heart disease [10]. This highlights the urgent need for protective measures against SHS exposure, especially in high-risk environments [11].

Although there are ample studies detailing the sex differences in the harmful effects of direct smoking on both humans and animals [12, 13], research on sex disparities concerning the risks of diseases induced by SHS remains limited. We hypothesized that ACS, known to be significantly triggered by active smoking, might also be induced by SHS, with varying effects across sex. Utilizing prospective cohort data, we conducted an 18-year longitudinal study to determine whether SHS acts as a risk factor for ACS and to analyze if such a risk is modified by sex.

2. Methods

3. Results

4. Discussion

Our study provides an in-depth examination of the sex-specific relationships between SHS exposure and the risk of ACS. Over an 18-year follow-up, we identified that males exposed to SHS had a significantly elevated risk of developing ACS with an HR of 1.63, while females did not exhibit a significant association. Interestingly, even though SHS-exposed groups were younger with a larger female proportion and a higher prevalence of alcohol intake, the overall incidence of ACS did not display a significant difference between those exposed to SHS and those not. These findings underscore the importance of sex-specific approaches when evaluating the risk factors associated with ACS. For males, the pronounced risk associated with SHS exposure suggests an urgent need for targeted public health interventions, especially given the established harmful effects of direct smoking. The lack of association in females, on the other hand, offers avenues for further research to understand the underlying mechanisms and factors contributing to this discrepancy. Moreover, our research highlights the importance of considering other interacting factors, such as alcohol intake, when assessing the comprehensive effects of SHS. It is paramount for health professionals and policymakers to recognize these distinctions and tailor preventive strategies accordingly.

Several studies have established the association between smoking and an increased risk of Acute Coronary Syndrome (ACS). A study by Teo et al. [15] in 2006 demonstrated that smoking is a significant risk factor for ACS across different populations globally. Another study by Ambrose and Barua in 2004 explored the pathophysiological mechanisms linking smoking to coronary artery disease, further solidifying the relationship between smoking and ACS [16]. However, there are limited studies that specifically explore the sex differences in the effects of smoking on ACS risk. A study by Huxley and Woodward in 2013 did find that women smokers have a higher risk of coronary heart disease compared to their male counterparts, but this was focused on direct smoking rather than secondhand smoke (SHS) exposure [17].

In a comprehensive assessment of the global burden of disease from SHS, Öberg et al. [18] found that as of 2004, 40% of children, 35% of women, and 33% of men were regularly exposed to SHS worldwide. This widespread exposure was implicated in an estimated 603,000 deaths, making up about 1.0% of global mortality. Additionally, the link between SHS exposure and coronary heart disease has been established in prior studies. For instance, a 2015 meta-analysis revealed that exposure to SHS significantly increased the risk for all-cause mortality and cardiovascular disease (CVD) [19]. Another study noted that the risk of coronary heart disease almost doubled in those with the highest levels of SHS exposure compared to those unexposed [20]. While the deleterious effects of SHS are clear, the literature still has gaps in understanding sex-specific risks. Some investigations, like the one by Tan et al. [21], suggested a potentially heightened risk for women in relation to certain conditions, such as lung cancer, due to SHS exposure. The overarching narrative underscores the need for more refined studies, especially those exploring potential gender disparities in SHS-related health outcomes.

In our study, while SHS did not emerge as a principal risk factor for ACS across the entire cohort, it was discernibly a significant risk factor among male. This observed distinction between sexes can be attributed to the variable nature of SHS exposure, which, unlike active smoking, is less potent and more inconsistent [22]. This observed distinction can be elucidated by considering three main factors. Firstly, pathophysiological differences between male and female must be acknowledged. Specifically, the cardiovascular system in males might respond more adversely to certain components of SHS than females, potentially due to biological variations like hormonal differences or vascular reactivity [23]. Secondly, particular lifestyle habits prevalent among male could amplify the detrimental effects of SHS. For instance, male might be more exposed to occupational hazards or other harmful environments or may adopt specific dietary or activity patterns that enhance the risks associated with SHS [24]. Thirdly, sociological factors play a pivotal role. Male might, due to socio-cultural contexts, be more frequently exposed to SHS-rich environments or be influenced by other behavioral factors that coalesce to heighten the risk of ACS alongside SHS. Furthermore, social norms or expectations could shape the health-related behaviors and stress-coping mechanisms of male differently than female, and such distinctions could influence the ACS risk associated with SHS [25].

Our study conclusively demonstrated that SHS exposure serves as a risk factor for ACS specifically in men. Such findings provide substantial theoretical groundwork for healthcare and public health policymakers. It underscores the urgent need to tailor preventive strategies and interventions targeting male populations exposed to SHS.

Our study has several limitations. Firstly, our reliance on self-reported SHS exposure introduces potential recall bias, potentially leading to an underestimation or overestimation of actual SHS exposure levels. Secondly, we did not incorporate information on the severity or specific type of ACS, limiting the comprehensiveness of our results regarding the effects of SHS on particular ACS categories or severities. Thirdly, a critical limitation of our study is the lack of quantification regarding the level of SHS exposure. While we acknowledge the absence of specific data on the duration, frequency and concentration of SHS, the inability to precisely quantify the exposure level further impedes our capacity to assess its impact on ACS risk accurately. This quantification is essential for a more detailed and accurate evaluation of the relationship between SHS exposure and ACS risk, as the extent of exposure may vary significantly among individuals and can be a decisive factor in disease development. Fourthly, while we attempted to control for many variables, potential confounding factors such as diet, physical activity, and other environmental exposures that might interact with or influence the effects of SHS were not fully accounted for. Fifthly, the homogeneity of our cohort, specifically being Korean, could limit the generalizability of our findings to other ethnic or racial populations. Lastly, we did not consider potential changes in SHS exposure or smoking habits over time, which might influence the cumulative risk assessment of ACS related to SHS. Despite these limitations, our research provides substantial evidence for the role of SHS as a significant risk factor for ACS, particularly among males.

5. Conclusions

Our study provides compelling evidence that SHS exposure significantly elevates the risk of ACS in men. These findings underscore the urgent need for rigorous public health interventions and policies aimed at reducing secondhand smoke exposure, especially among male populations.

Availability of data and materials

Data in this study were from the Korean Genome and Epidemiology Study (KoGES; 6635-302), National Institute of Health, Korea Disease Control and Prevention Agency, Republic of Korea.

Author contributions

EJ and HHR—conceptualization, investigation, software, writing original draft, writing review and editing; EJ and HLK—data curation; EJ and HYK—formal analysis, supervision. All authors have read and agreed to the published version of the manuscript.

Ethics approval and consent to participate

The study protocol was reviewed and approved by the Institutional Review Board of Chonnam National University Hospital (CNUH-2018-297). The requirement for informed consent from patients was waived.

Acknowledgment

We express our sincere gratitude to all the dedicated staff members at the hospital who played an instrumental role in the collection of data for this study.

Funding

This study was supported by a grant (BCRI-21071) of Chonnam National University hospital biomedical research institute.

Conflict of interest

The authors declare no conflict of interest.