Aldehydes, a class of organic compounds characterized by a carbonyl group bonded to at least one hydrogen molecule [1], are ubiquitous in the environment. Aldehydes originate from diverse sources such as tobacco smoke, environmental pollutants, food consumption, and endogenous biological pathways [2, 3, 4]. Recent research has increasingly highlighted the detrimental effect of aldehydes on human health, leading to various health complications. Elevated hexanaldehyde levels, for instance, were reported to be associated with nasal obstruction and mild irritation, causing symptoms like frequent eye blinking and headaches [5]. Furthermore, the carcinogenic and mutagenic characteristics of aldehydes have been extensively documented [6]. Studies have found increased serum levels of hexanaldehyde and heptanaldehyde in patients with lung cancer [7], and higher concentrations of pentanaldehyde, nonanaldehyde, hexanaldehyde, and octanaldehyde in exhaled breath of patients with lung cancer [8].

The heart and blood vessels demonstrate increased sensitivity following aldehyde exposure [9, 10]. Studies have shown that aldehydes present in the blood vessel wall could induce hypercontraction, elevate the risk of vasospasm, and potentially result in myocardial necrosis [10]. Additionally, aldehydes are known to cause inflammation in blood vessels, promote intravascular thrombosis, and disturb the production of nitric oxide (NO) in vascular endothelial cells. This impairment of NO-mediated endothelial function and the disruption of NO’s cardioprotective effects may increase the risk of coronary artery disease [11]. Although the precise mechanisms are not yet fully understood, growing evidence suggests a potential link between aldehydes and cardiovascular diseases (CVD) [12, 13].

Given the widespread environmental exposure to aldehydes, there is growing concern about their adverse effects on the cardiovascular system. This study, therefore, aims to investigate the relationship between the concentrations of 12 specific aldehydes and CVD based on the representative population data.

This study investigated the relationship between aldehyde concentrations and CVD in 1529 participants from the 2013–2014 NHANES survey. To our knowledge, this is the first study to explore the association accounting for sample weights. Among the participants, those with CVD displayed a higher level of isopentanaldehyde than those without, though no significant differences were observed in the concentrations of the other 11 aldehyde types. In the unweighted logistic regression analysis, benzaldehyde concentration was significantly associated with CVD, showing an OR of 1.12 with 95% CI of 1.02–1.21, after adjusting for age, sex, race, education, hypertension, diabetes, smoking, and drinking. The significant association persisted in the weighted logistic regression analysis, with an OR (95% CI) of 1.17 (1.04–1.32). However, the levels of the other aldehydes did not show a significant association with CVD.

Aldehydes, a diverse class of organic compounds, are characterized by a carbonyl group where the carbon atom is bonded to a hydrogen atom and, typically, to another carbon or a hydrogen atom [17]. These compounds are omnipresent in nature and are commonly found in many foods, fragrances, and biological systems. Human exposure to aldehydes arises from multiple sources, such as air pollution, consumption of tobacco cigarettes and e-cigarettes, exposure to organic material, ingestion of food additives, alcohol intake, and endogenous metabolic activities [18, 19]. For example, crotonaldehyde and acrolein are significant aldehyde components of tobacco smoke. Primary exposure to these aldehydes in individuals occurs through inhalation of smoke from burning tobacco. Additionally, nonsmokers may also be exposed to these aldehydes indirectly through sidestream emissions, which are byproducts of smoking [20, 21].

These diverse sources necessitate an intricate understanding of their impact on public health. Aldehydes are significantly pervasive in our environment and show a close relationship with human health. In a recent study, Silva et al. [21] analyzed the 12 serum aldehydes in sera collected from 1843 participants in the 2013–2014 NHANES survey. Their data showed the widespread exposure of multiple types of aldehydes in the U.S. population, including isopentanaldehyde, propanaldehyde, butyraldehyde, heptanaldehyde, benzaldehyde, and hexanaldehyde. Different types of aldehydes can have distinct impacts on human health. Certain aldehydes, like formaldehyde, crotonaldehyde or hexanal, exhibit carcinogenic properties [22] or increase the risk of metabolic diseases [23]. In contrast, other aldehydes, such as cinnamaldehyde, have been demonstrated as protective factors against obesity, hyperglycemia, and non-alcoholic fatty liver disease [24, 25].

In our study, the weighted logistic regression analysis revealed a significant positive association between benzaldehyde concentration and CVD (OR = 1.17, 95% CI = 1.04–1.32) after adjusting for age, sex, race, education, hypertension, diabetes, smoking, and drinking. Benzaldehyde, a simple aromatic aldehyde, is prevalent both naturally and artificially [26]. It is found in many plant species, notably in bitter almond oil, and contributes to the characteristic almond scent. Benzaldehyde also results from environmental degradation processes, such as the breakdown of lignin, a key structural component in plant cell walls [27]. Besides its natural genesis, benzaldehyde is frequently synthesized for industrial use due to its appealing sweet aroma. Its applications are diverse, ranging from a flavor enhancer in food items and fragrance in personal care products to a precursor in synthesizing various organic compounds in chemical industries. Significantly, benzaldehyde is also present in vehicular exhaust and cigarette smoke, thus presenting a widespread exposure risk. Considering the pervasiveness of benzaldehyde, our results underscore the importance of managing benzaldehyde to mitigate its contribution to CVD development.

In a previous study by DeJarnett and colleagues, the epidemiological relationship between acrolein exposure and Framingham Risk Scores was investigated in 211 participants [28]. The findings indicated that acrolein exposure was linked to platelet activation and reduced levels of circulating angiogenic cells, thereby increasing the risk of CVD. Similarly, Liao et al. [13] investigated the association of benzaldehyde with CVD, discovering an increased risk (OR = 1.58, 95% CI = 1.15–2.17) at benzaldehyde concentrations $>$0.95 ng/mL. Additionally, compared with the lowest quartile (Q1), the Q2–Q4 isopentanaldehyde groups demonstrated increased ORs (95% CIs) of 1.48 (0.87, 2.52), 1.70 (1.01, 2.92), and 2.13 (1.19, 3.86), highlighting a graded relationship with CVD risk. However, their study did not account for the complex sampling design of NHANES survey, rendering their findings less robust. In contrast, our study incorporated survey weights according to the NHANES analytic guidance. We revealed a significant association between benzaldehyde and CVD but not in other aldehydes. The distinctive results are probably attributed to the difference in statistical analysis.

Our large-scale, nationally representative study demonstrated a positive relationship between benzaldehyde exposure and CVD. Nevertheless, several limitations should be mentioned. First, this study could only explore the association but not causality due to the cross-sectional continuous study design of NHANES survey. The following prospective study should be conducted to explore the longitudinal causal relationship. Second, there are various sources of aldehyde to explore. This study analyzed the serum aldehyde concentrations which suggested the overall exposure of aldehyde. However, the exact exposure sources of aldehyde were uncertain, thus limiting the clinical implication of this study. Third, the biological processes underlying the association between benzaldehyde exposure and CVD remains unclear. Forth, there exists a large difference in the number of patients between the two groups. Although we have applied the weighted statistics, the unbalanced distribution might result in potential bias. Last but not least, the outcome of this study is based on self-reported questionnaires. Although the interviewers have provided explanations for cardiovascular outcomes, the self-reported diseases might lead to inaccuracies in disease reporting. Therefore, our conclusion should be approached with caution. Further experiment analyses are warranted to elucidate the potential mechanisms underlying these associations.

In conclusion, this study highlights the potential role of benzaldehyde as a contributing factor to CVD. The observed association between benzaldehyde and CVD remained consistent in both unweighted and weighted logistic regression analyses, even after accounting for potential confounding factors such as age, sex, race, education, hypertension, diabetes, smoking and drinking. However, the study did not find a significant relationship between CVD risk and the concentrations of other examined aldehydes, including butyraldehyde, crotonaldehyde, decanaldehyde, heptanaldehyde, hexanaldehyde, isopentanaldehyde, nonanaldehyde, octanaldehyde, o-tolualdehyde, pentanaldehyde, and propanaldehyde. This indicates that the pathogenic effects of aldehydes on cardiovascular health may vary based on their distinct molecular structure and physicochemical properties. Future research should aim to validate these findings in diverse populations and delve deeper into understanding the biological mechanisms through which benzaldehyde may influence the development of CVD. Such studies will be crucial for developing targeted interventions and preventative strategies against CVD, particularly in the context of environmental and dietary exposure to specific aldehydes like benzaldehyde.

The data for this study can be found on the NHANES website (https://www.cdc.gov/nchs/nhanes/index.htm).

YF designed this study, acquired the data, and performed analysis. JZ supervise this research, performed analysis and interpreate the results. Both authors wrote the main manuscript text, prepared the tables/figures, reviewed the manuscript, and approved the final manuscript. Both authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Our study is based on the 2013–2014 survey. The 2013–2014 National Center for Health Statistics Ethics Review Board approved the NHANES survey (Ethics approval number: #2011-17). Written consent was obtained from all participants.

Not applicable.

This research received no external funding.

The authors declare no conflict of interest.