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Age, inflammation, alkaline phosphatase, and coronary artery calcification in firefighters
BMC Cardiovascular Disorders volume 25, Article number: 309 (2025)
Abstract
Background
Firefighting involves exposure to hazardous conditions that may contribute to adverse long term health outcomes, including cardiovascular disease. While coronary artery disease (CAD) is a leading cause of morbidity among firefighters, the specific occupational contributions to Coronary Artery Calcification (CAC), a reliable predictor of CAD, are not well understood.
Methods
We conducted a cross-sectional study involving 410 firefighters, aged 35–68, who underwent comprehensive health assessments, including CAC measurement using computed tomography. Multiple logistic regression models were built to examine the associations of demographic, lifestyle, and clinical variables with CAC score.
Results
Our analysis revealed statistically significant associations between several clinical indicators and CAC score. Age (odds ratio (OR): 1.12; 95% confidence interval (95% CI): [1.05, 1.19]) and percentage of monocytes (OR: 1.29; 95% CI: [1.06, 1.58]) were positively correlated with higher CAC score, highlighting the role of inflammation in CAD among firefighters. Moreover, the enzyme alkaline phosphatase emerged as an independent predictor of CAC score (OR: 1.02; 95% CI: [1.01, 1.04]), suggesting a novel biomarker of cardiovascular risk in this population.
Conclusion
Our study identified several risk factors associated with increased CAC score in firefighters, including age, inflammation, and alkaline phosphatase. These findings underscore the importance of tailored health monitoring and interventions to mitigate CAD risk in firefighters, considering both general and occupation-specific risk factors. This study contributes to a better understanding of the occupational health challenges faced by firefighters and provides a foundation for future research and preventive strategies in this high-risk group.
Key message
Although coronary artery disease (CAD) is a major cause of morbidity among firefighters, the specific occupational factors contributing to Coronary Artery Calcification (CAC), a reliable predictor of CAD, remain unclear. Our study identified age, inflammation, and alkaline phosphatase were associated with increased CAC in firefighters. This approach enhances our understanding of their occupational health challenges and lays the foundation for future research and preventive strategies.
Introduction
Firefighters play a critical role in public safety, but their profession exposes them to unique occupational hazards that may increase their long-term cardiovascular risk [1]. These hazards include burning materials, toxic chemicals, and structurally unstable environments, which pose immediate physical dangers [1,2,3]. In addition to these acute risks, they also experience chronic exposure to hazardous airborne pollutants, including fine particulate matter (PM2.5), polycyclic aromatic hydrocarbons (PAHs), and heavy metals [2, 3]. Even with the use of personal protective equipment (PPE), these exposures are unavoidable and have long-term implications for cardiovascular and metabolic health [4, 5].
Beyond environmental exposures, firefighters face physically demanding tasks, intense psychological stress, and irregular work schedules [4,5,6]. The cumulative effects of heat stress, sleep disruption from shift work, and repeated exposure to traumatic events can lead to systemic inflammation, oxidative stress, and autonomic nervous system dysregulation [1, 3, 7]. Over time, these stressors may contribute to the development of serious chronic conditions, including cardiovascular disease (CVD).
Cardiovascular disease (CVD) is a major health concern among firefighters, with coronary artery disease (CAD) being a particularly acute type that greatly contributes to mortality rates worldwide and in the United States [2, 4, 5, 7,8,9,10,11,12,13]. Extensive research has identified common risk factors for CVD, including hypertension, tobacco use, and elevated cholesterol. The CAC, obtained via computed tomography scans, is increasingly recognized as a crucial prognostic tool for assessing the risk of CAD. Large-scale cohort studies, such as the Multi-Ethnic Study of Atherosclerosis (MESA) and the Framingham Heart Study (FHS), have demonstrated that CAC is an independent predictor of future cardiovascular events [14, 15]. Given its strong predictive value, CAC assessment provides an opportunity for early detection and risk stratification of CAD [16,17,18].
A recent study in general population demonstrated that higher concentrations of PM2.5and nitrogen oxides (NO2), and increased physical exertion were associated with accelerated progression of CAC [19]. Given that firefighters are frequently exposed to air pollution and demanding physical activities, it is critical to investigate whether their clinical risk profile differs from that of the general population. However, few studies have systematically evaluated the clinical determinants of CAC in firefighters. To address this knowledge gap, our study systematically evaluates the clinical risk factors that contribute to elevated CAC among firefighters, providing insights into potential early detection and prevention strategies. Identifying these risk factors may improve risk stratification and targeted interventions to mitigate CVD burden in this high-risk occupational group.
Methods
Study design and population
This retrospective cross-sectional study analyzed electronic health records, clinical data, and laboratory reports from a cohort of firefighters who underwent occupational health assessments. The study data were collected at Ascension Public Safety Medical, a specialized occupational health clinic that administers pre-employment and routine annual health evaluations for a network of fire departments across the Midwest, with a primary focus on Indiana. Firefighters in this study were between 35 and 68 years old (n = 410). The inclusion criteria were precisely defined to include firefighters who undertook a comprehensive health assessment, which consisted of a physical examination, a thorough laboratory analysis, a fitness evaluation, and coronary artery calcium (CAC) imaging using CT scans. Firefighters were excluded if they had incomplete health records. Consent for the use of their data for research purposes was obtained at the time of the physical examination. The ethical framework of this study was strengthened by obtaining permission from the Indiana University Office of Research Compliance, under the protocol number 20,510.
Demographic characteristics
Demographic data were collected, including age (years), sex (female, male), self-identified race and ethnicity (Black, White, Hispanic, and Other), height (inches), weight (pounds), and body mass index (BMI) (kg/m²). Firefighters were classified as overweight if BMI \(\:\ge\:\) 25 kg/m2, the standard clinical cutoffs.
Lifestyle characteristics
Physical inactivity was assessed via a survey in which individuals were categorized into either an active or sedentary lifestyle group based on their self-reported responses. Current tobacco use was self-reported as either “yes” or “no”. The presence of cardiovascular disease in direct family members was recorded, as the firefighters had a family history of CVD.
Clinical characteristics
Participants underwent routine blood tests to evaluate their lipid profiles and other key indicators. The measurements included the levels of total cholesterol, triglycerides, HDL cholesterol, and low-density lipoprotein (LDL) cholesterol, all expressed in milligrams per deciliter (mg/dL). The total cholesterol to HDL cholesterol ratio was calculated. The measured electrolytes included sodium, potassium, chloride (all in mmol/L), and carbon dioxide (mmol/L). Mean corpuscular volume (MCV) was measured in femtoliters (fl.). The glomerular filtration rate (GFR) and creatinine levels were assessed. Fasting glucose levels were categorized as low (< 100 mg/dL), normal (100–125 mg/dL), and high (> 125 mg/dL). Creatinine levels were categorized as low (< 0.6 mg/dL), normal (0.6–1.1 mg/dL), and high (> 1.1 mg/dL).
Coronary artery calcification score assessment
CAC levels were assessed by precise computed tomography images, a safe way for estimating the severity of coronary atherosclerosis. Such assessments are recognized for their capability to predict the probability of cardiovascular events based on the score. The participants underwent scanning using an Imatron C Electron Beam Tomography (EBT) scanner, following a standardized protocol for coronary artery calcium quantification while minimizing radiation exposure. The CAC was calculated using the Agatston method, which assesses the volume of calcium and the calcium mass score. Sum of lesions were identified based on a threshold of density over 130 Hounsfield units and a minimum area of 1 mm², with the aggregate of these lesion scores constituting the individual’s total CAC score. A certified radiologist specializing in cardiovascular imaging, who was not informed about the participants’ health details to remain unbiased, examined the CT scans to confirm the accuracy of the scoring. Further methodological details are described in Hoff et al., 2001 [20].
Statistical analysis
In this study, we performed a comprehensive analysis of demographic, lifestyle, and clinical characteristics among firefighters to evaluate their association with CAC scores. For continuous variables, such as age, height, weight, body mass index (BMI), means and standard deviations were calculated. For categorical variables, including sex, race, ethnicity, overweight status, and sedentary lifestyle, counts (n) and percentages were calculated to describe their distribution within this cohort.
Independent t-tests were used to compare continuous variables between firefighters with CAC score of 0 and those with a CAC score greater than 0. Chi-squared tests were employed to assess differences in categorical variables across these two CAC score groups. If the expected frequency was less than 5, Fisher’s exact test was used instead.
To assess the multiple risk factors associated with the CAC score, we fit a logistic regression model, with binary outcome variable: CAC score = 0, and CAC score > 0. The selection of clinical variables in the logistic regression model was guided by a combination of statistical significance from univariate analyses and biological plausibility based on prior literature. Age is a well-established risk factor for CAC and was included in all models [21]. Monocyte percentage has been associated with systemic inflammation, which plays a critical role in atherosclerosis progression [22, 23]. Elevated glucose levels and hypertension are recognized risk factors for cardiovascular disease, making them key variables in our analysis [24]. Alkaline phosphatase has been linked to vascular calcification, providing a potential mechanistic connection to CAC progression [25, 26]. Platelet count, an indicator of coagulation activity and inflammation, has also been implicated in cardiovascular risk [27].
We used a forward stepwise selection method to identify the most significant variables in the model, including variables with p-value < 0.25 from univariate analyses. The variables selected in the forward selection model included age, percentage of monocytes in white blood cell count (monocyte percentage), glucose, hypertension, alkaline phosphatase, and platelet count. We then fit a multivariate logistic regression model with these selected variables, adjusting for race and other risk factors with p-value < 0.2 in univariate analyses, including, family history of cardiovascular disease, chloride, carbon dioxide, GFR, mean corpuscular volume, and prostate specific antigen. The model equation was as follows:
where p is the probability of the outcome with CAC score > 0, \(\:{{\upbeta\:}}_{0}\) is the constant term, \(\:{{\upbeta\:}}_{1},\:\dots\:\:{{\upbeta\:}}_{\text{k}\:\:}\)are the regression coefficients of each risk factor \(\:{\text{X}}_{1},\:\dots\:,\:{\text{X}}_{\text{k}},\:\text{a}\text{n}\text{d}\:\text{k}\:\)is the number of risk factors in the analysis. The final logistic regression model was built to elucidate the multiple risk factors that contribute to having a CAC score greater than zero in firefighters. This model provided estimates of odds ratios (ORs) and 95% confidence intervals (CIs) for each risk factor, determining the strength and direction of the associations between each risk factor and the likelihood of having a CAC score greater than zero.
We created the figure to visualize the ORs and 95% CIs from the multivariate logistic regression.
Results
In this study, we assessed the demographic and relevant characteristics of the 410 firefighters for whom the CAC were available, as summarized in Table 1. The outcome variable, CAC, was dichotomous into CAC = 0 and CAC > 0. Among these firefighters, 266 had a CAC of 0, while 144 had a CAC greater than zero. The p-values of these characteristics between two CAC groups were presented in Appendix A, Table a. The rest of characteristics of 410 firefighters were presented in Appendix B Table b.
The mean age of participants with a CAC > 0 was significantly higher at 52.2 years (SD = 6.3) compared to 47.2 years (SD = 6.0) for those with a CAC = 0 (p-value < 0.001). There was no significant difference in sex distribution between the two groups, with 6.0% female in the CAC = 0 group and 4.2% in the CAC > 0 group. However, it is notable that the majority of firefighters were male (about 95%) in both groups, while about 5% were female in both groups. There were no significant differences in mean values for height, weight, BMI, or the percentage of individuals classified as overweight or sedentary.
Hypertension was significantly more prevalent in the CAC > 0 group (33.3%) compared to the CAC score = 0 group (24.1%) (p-value = 0.05). There were no significant differences in the prevalence of tobacco use or family history of cardiovascular disease between the two groups. The percentage of participants with hyperlipidemia was nearly identical (51.5% in CAC score = 0, 51.4% in CAC score > 0) in both groups. There were no significant differences between the two groups regarding total cholesterol, triglyceride levels, HDL cholesterol, or LDL cholesterol.
Chloride levels were significantly lower in the CAC > 0 group (mean = 104.5 mmol/L) compared to the CAC = 0 group (mean = 105.2 mmol/L, p-value = 0.04), Similarly, GFR was also significantly lower in the CAC > 0 group (mean = 93.5 mL/min) compared to the CAC = 0 group (mean = 98.1 mL/min, p-value = 0.03). Low glucose levels (< 100 mg/dL) were more commonly observed in firefighters with a CAC = 0, with 70.9% of this group having low glucose levels, compared to 59.0% of those with a CAC > 0 had low glucose levels (p-value = 0.03). Normal glucose levels (100–125 mg/dL) were found in 31.7% of the CAC > 0 group, compared to 24.6% in the CAC = 0 group (p-value = 0.03). High glucose levels (> 125 mg/dL) were significantly more prevalent in the CAC > 0 group at 9.35% compared to 4.51% in the CAC = 0 group (p-value = 0.03).
The multivariable logistic regression analysis results with OR (95% CI) and p-value of each risk factor were presented in Table 2. The multivariable logistic regression analysis results with OR (95% CI) of each risk factor were visualized in Fig. 1. Our multivariable logistic regression analysis revealed some significant associations between various risk factors and the occurrence of CAC > 0. There was a significant positive association between age and CAC > 0 (OR: 1.12, 95% CI: [1.05, 1.19], p-value < 0.001). There was a significantly positive association between monocyte percentage and CAC > 0 (OR: 1.29, 95% CI: [1.06, 1.58], p-value = 0.01). There was a significant positive association between alkaline phosphatase and CAC > 0 (OR: 1.02, 95% CI: [1.01, 1.04], p-value = 0.04). While our model adjusted for key confounders, other potential confounders, such as dietary habits, environmental exposures, and occupational stress, were not directly accounted for due to data limitations. We acknowledge that potential residual confounding from unmeasured factors could contribute to the observed associations and should be explored in future research.
Adjusted ORs (95% CIs) for the associations between multiple risk factors and the risk of having CAC greater than zero among firefighters (N = 410)
Figure 1 visualizes the results of a multivariate logistic regression analysis, estimating the association between various demographic, clinical, and occupational risk factors, and the likelihood of having CAC > 0 among firefighters. Each dot represents the adjusted odds ratio (OR) for a given risk factor, while the horizontal lines indicate the 95% confidence intervals (CIs). ORs greater than 1.0 suggests a positive association with CAC, while an ORs less than 1.0 suggest an inverse association. Risk factors with CIs that do not cross 1.0 are statistically significant
Discussion
In this study, we aimed to identify the clinical risk factors related to coronary artery calcium score among firefighters, a population that is frequently exposed to work related risks that may increase their risk of cardiovascular disease. We identified that age, inflammation, and alkaline phosphatase were associated with increased CAC in firefighters. To the best of our knowledge, this is the first epidemiological study to determine multiple risk factors for CAC among firefighters, a population exposed to occupational hazards that may pose a threat of developing cardiovascular disease.
While most of our study population was male, which aligns with the overall demographic patterns in the firefighting field, it is important to highlight the presence of female firefighters (n = 22, Table 1). Despite the underrepresentation of women in the fire service, their numbers are increasing. In the United States, 75% of female firefighters have reported a lack of access to personal protective equipment designed specifically for female firefighters [9, 28]. Therefore, studies focusing on injuries, fatalities, and training unique to females are necessary [28,29,30]. While our findings did not show statistically significance differences in CAC > 0 between males and females, it is important to pay attention to the presence of female firefighters in the CAC > 0 groups. This is because there may be physiological and professional variations that can impact cardiovascular risk [9, 28, 30]. Female firefighters may face extra challenges due to the physical demands and protective gear primarily designated for men [29]. Research has demonstrated that CVD symptoms in women are frequently misunderstood, which can result in long delays or lack of in diagnosis or treatment [28, 30]. Recognizing the importance of identifying the risk factors for CAC in predicting cardiovascular events is very important. On the other hand, the presence of Hispanic firefighters (n = 3, Table 1) highlights the increasing ethnic diversity in Indiana’s firefighting workforce.
Our study identified multiple risk factors for CAC among firefighters in Indiana. There was a significant positive correlation between age and CAC > 0 (odds ratio: 1.12 [1.05, 1.19], p-value < 0.001, Table 2). This association highlights the gradual progression of coronary artery calcification with aging, which is particularly relevant for firefighters, as occupational stressors may accelerate this process [4, 5, 31, 32].
There was a significant positive association between monocyte percentage and the presence of CAC (odds ratio: 1.29 [1.06, 1.58], p-value < 0.001, Table 2), indicating inflammation’s role in the atherosclerotic process within this group. Monocytes play an active role in the development of atherosclerosis, a pathological process that can cause coronary calcification [12, 33, 34]. Once monocytes enter the bloodstream, they are drawn to the endothelial lining of arteries, particularly in locations where endothelial cells are damaged or dysfunctional [34,35,36,37]. The formation of these sites can be attributed to various factors, particularly exposure to environmental pollutants such as smoke, a prevalent occupational hazard in firefighting [34]. The positive relationship between monocytes and CAC can be viewed as indicative of a persistent systemic inflammatory response in firefighters [36, 38,39,40,41]. This heightened inflammatory state may be exacerbated by the persistent inhalation of irritating particles and chemicals, which may activate monocytes and other inflammatory pathways more frequently and intensely than in the general population. Firefighters are at risk of developing chronic low-grade inflammation due to inhaling smoke and pollutants, which can accelerate atherogenesis [38, 42,43,44]. The chronic inhalation of harmful particles and chemicals and exposure to heat can worsen the already heightened inflammatory state, leading to a more vigorous activation of monocytes and other inflammatory pathways compared to the general population [37, 38]. The chronic inhalation of harmful particles and chemicals and exposure to heat can worsen the already heightened inflammatory state, leading to a more vigorous activation of monocytes and other inflammatory pathways compared to the general population [36, 45,46,47]. The significant association between monocytes and CAC highlights the importance of developing tailored interventions to reduce firefighters’ exposure to toxic chemicals and to mitigate systemic inflammation [43].
There was a significant positive association between alkaline phosphatase and CAC > 0 (odds ratio: 1.02 [1.01, 1.04], p-value = 0.04, Table 2). We identified that higher alkaline phosphatase levels were positively associated with CAC in this firefighter cohort. Our findings suggest that alkaline phosphatase may serve as a biomarker of CAC in firefighters. Previous studies have shown that alkaline phosphatase is associated with CAD in the context of inflammation in the general population [48]. Inflammation is a factor that related to the progression of atherosclerosis, which will increase the CAC. Similarly, in our study, we also found that another inflammatory marker, monocytes, was associated with CAC. However, However, our findings demonstrate that alkaline phosphatase is independently associated with CAC in firefighters, even after adjusting for monocyte levels. This finding suggests that beyond inflammation, alkaline phosphatase may be directly involved in the progression of coronary artery calcification. The identification of alkaline phosphatase as a potential biomarker for CAC in firefighters aligns with emerging evidence on the role of lipid-related biomarkers in cardiovascular disease [49]. Recent studies, such as the role of lipoprotein(a) in cardiovascular diseases and premature acute coronary syndromes (RELACS) study, have highlighted the clinical significance of lipoprotein(a) in predicting premature acute coronary syndromes and refining cardiovascular risk stratification [49]. Incorporating such biomarkers into cardiovascular risk assessment models could enhance early detection and management of atherosclerotic burden, particularly in high-risk populations such as firefighters. We innovatively propose that alkaline phosphatase can be serve as an independent predictor of CAC in firefighters, which could be utilized as a biomarker of CVD risk in this occupational group. This finding could contribute to the early detection of CVD risks and enable the development of tailored programs to better prevent cardiovascular disease in firefighters.
Our study holds multiple strengths. First, the study has a relatively large sample size of firefighters, providing greater confidence in identifying the risk factors associated with CAC, compared to studies with smaller sample sizes. Additionally, this larger and diverse sample of firefighters enhances the generalizability of our findings to the broader occupational population. According to our best knowledge, this is the first epidemiological study to comprehensively examine risk factors for CAC specifically among firefighters. By focus on a distinct professional cohort that exposed to occupational hazards, this study offers new insights into the impact of occupational hazards on CAC and cardiovascular health. The study adds to our understanding of CAC in this population by thoroughly evaluating both clinical and lifestyle risk factors. Further studies are needed to expand on the results of this study to better understand the risk factors for CAC among firefighters.
The study has the well known limitations inherent to observational research designs, such as the possibility of unmeasured confounding factors that could impact the findings. We drew the conclusions from a cross-sectional analysis, which limits our ability to make causal inferences. The lack of longitudinal data prevents us from assessing temporal relationships between risk factors and CAC progression over time. Future studies with repeated measures would help establish the trajectory of CAC development in firefighters. Moreover, potential selection bias should be considered, as the study population consists of firefighters who attended routine health evaluations at a specialized occupational health clinic. Moreover, the majority of male participants in the sample may limit the applicability of the results to female firefighters, who are not adequately represented. Finally, the small sample size of Hispanic firefighters may limit the ability to assess potential relationships between risk factors and CAC in this subgroup.
Conclusion
In conclusion, our study found significant positive associations between age, monocyte percentage, and alkaline phosphatase with CAC in firefighters. These findings indicate that aging and inflammation play important roles in coronary artery calcification among this specific group. The study’s innovative discovery, particularly the positive relationships identified between alkaline phosphatase and CAC, highlighting the importance of considering a broader range of risk factors of cardiovascular risk evaluations for firefighters. These findings provide a foundation for further investigation into these connections and for the development of targeted interventions aimed at preventing cardiovascular disease in firefighters. Targeted firefighter health strategies should focus on reducing pollutant exposure through enhanced respiratory protection, decontamination protocols, and improved ventilation in fire stations. Additionally, routine biomarker assessments, anti-inflammatory dietary interventions, and structured fitness programs tailored to firefighters should be integrated into firefighter health programs to enable early detection of CAC and improved CVD risk stratification. Future research should focus on implementing these occupational health interventions to identify high-risk individuals early, which may help reduce CAC and prevent cardiovascular disease in firefighters.
Data availability
The study cannot be shared publicly due to privacy concerns for the individuals who participated in the study. The study data are available upon reasonable request.
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Contributions
We acknowledge the significant contributions of firefighters. All authors had full access to the data management and statistical analysis. HN and ML was responsible for the study concept and design. ML analyzed the data. ML drafted the manuscript. All authors (ML, JH, CM, TZ, LZ, PM, JW, VK, SM, HN) made significant contributions to the data analysis and review of the manuscript. All authors had responsibility for the data’s integrity and the precision of analyses.
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This study was approved by the Indiana University Office of Research Compliance (Approval Number: 20510) and Ascension Health Institutional Review Board (Approval Number: RIN20240002). Written informed consent was obtained from individual participants included in the study. The data collection and analysis adhered to the confidentiality and privacy standards.
Patient and public involvement
This study used secondary data analysis, so patient and public were not directly involved in this study. Therefore, no participants were specifically recruited for this study. Our study was approved by Indiana University Office of Research Compliance, as evidenced by the allocated protocol number 20510, and Ascension Health Institutional Review Board, as evidenced by RIN20240002.
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The authors declare no competing interests.
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Appendix
Appendix
Appendix A
Appendix B
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Li, M., Han, J., Muegge, C. et al. Age, inflammation, alkaline phosphatase, and coronary artery calcification in firefighters. BMC Cardiovasc Disord 25, 309 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12872-025-04750-4
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DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12872-025-04750-4