Association between Cardiovascular Disease Risk Factors and Cardiorespiratory Fitness in Firefighters: A Systematic Review and Meta-Analysis

Approximately 45% of on-duty related mortalities were due to sudden cardiac death, with many of these fatalities related to cardiovascular disease and overexertion, while performing emergency duties. Therefore, the aim of this systematic review was to determine the association between cardiovascular disease risk factors and cardiorespiratory fitness in firefighters. A literature search of PubMed, SCOPUS, Web of Science, Embase, EBSCOHost, and ScienceDirect was conducted; the Rayyan® intelligent systematic review tool was used to screen and select studies for inclusion. The appraisal tool for cross-sectional studies and the Critical Appraisal Skills Programme toolkit were used for methodological assessment of included studies. Data were analyzed using the Review Manager 5.3 and MedCalc® statistical softwares to determine the effects of obesity (Z = 10.29, p < 0.001) and aging (Z = 4.72, p < 0.001) on cardiorespiratory fitness. Furthermore, there was a significant effect for cardiorespiratory fitness level on systolic blood pressure (Z = 5.94, p < 0.001), diastolic blood pressure (Z = 2.45, p < 0.001), total cholesterol levels (Z = 3.80, p < 0.001), low-density lipoprotein cholesterol (Z = 4.44, p < 0.001), triglycerides (Z = 3.76, p < 0.001) and blood glucose concentration (Z = 4.78, p < 0.001). Cardiovascular disease risk factors and cardiorespiratory fitness were significantly and inversely associated in firefighters. Fire service departments should adopt behavioral intervention strategies to maintain optimum cardiovascular disease risk factor profiles and cardiorespiratory fitness among firefighters to ensure their occupational well-being.


Introduction
Firefighting is an extremely hazardous occupation, where firefighters not only are required to contend with severe temperatures but are also required to perform emergency rescues and are routinely exposed to hazardous chemicals and fumes [1][2][3][4]. The hazardous nature of the profession requires firefighters to wear personal protective equipment (PPE), and in some departments, PPE can weigh up to 29.3 kg [5], which places significant strain on firefighters [6][7][8]. In addition, many firefighters have been reported to have underlying cardiovascular disease (CVD) risk factors, which significantly predispose them to cardiovascular events while on duty [9][10][11][12]. This translates into an excessively high mortality rate of nearly 50% related to on-duty sudden cardiac death (SCD) [1][2][3]13]. This is largely due to the physically demanding nature of their occupation, which requires

Summary of Methods
The exposures assessed included CVD risk factors in relation to cardiorespiratory fitness in firefighters. There were no limitations to the publication year when considering studies for this review.
The inclusion criteria were as follows: (i) Studies that included full-time, part-time, and volunteer adult male and female firefighters between the ages of 18 and 65 years; (ii) Cross-sectional, observational, and experimental (intervention) study designs; (iii) Studies that investigated the association between CVD risk factors or health metrics and cardiorespiratory fitness in firefighters; (iv) Studies that were available in full text or that could be acquired through a request from the authors.

Critical Appraisal of Included Studies
The methodological evaluation of the included studies was carried out using the appraisal tool for cross-sectional studies (AXIS checklist) (Table S1, Supplementary File S4) [60] and The Critical Appraisal Skills Programme (CASP) toolkit (Middle Way, Oxford, UK) (Table S2 Supplementary File S4) ((https://casp-uk.net/casp-tools-checklists/) (accessed on 1 September 2021)). For evaluating the quality of cross-sectional studies, it has been demonstrated that the CASP toolkit (Middle Way, Oxford, UK) and the AXIS toolkit are relevant and dependable resources [60,61]. According to the AXIS checklist, each study that was given a score, between 15 and 17 points was considered to be "good" quality and a score from 18 to 19 points was considered to be "high" quality. For the CASP toolkit, all studies were considered to be high quality, as all boxes were ticked.

Study Selection
The database searches yielded a total of 1881 entries ( Figure 1). Of these, 1205 duplicates were removed. Of the remaining 677 studies screened via titles and abstracts, 56 studies met the inclusion criteria, and full texts were screened for final inclusion in the review. Reasons for exclusion included not investigating either the exploratory or outcome variables; studies that were qualitative in design, the main focus of the manuscript not being aligned with the current study, studies that were reviews, and studies that were not available in full-text. Following the full-text screening, 31 papers, in total, were eliminated, leaving 25 studies eligible to move forward with the data extraction and narrative synthesis. The reasons for exclusion included the association between the exploratory variable and the outcome variable not being analyzed. From this, 16 studies were suitable for inclusion in the metaanalysis after data extraction. Nine studies were excluded from the meta-analysis due to the data not being suitable for the analysis. The reasons for exclusion were, firstly, that studies did not include the means and standard deviation for both the CVD risk factors and the cardiorespiratory fitness measures. Secondly, there were no comparisons made between healthy firefighters and those with CVD risk factors and firefighters with good or poor cardiorespiratory fitness. total, were eliminated, leaving 25 studies eligible to move forward with the data extraction and narrative synthesis. The reasons for exclusion included the association between the exploratory variable and the outcome variable not being analyzed. From this, 16 studies were suitable for inclusion in the meta-analysis after data extraction. Nine studies were excluded from the meta-analysis due to the data not being suitable for the analysis. The reasons for exclusion were, firstly, that studies did not include the means and standard deviation for both the CVD risk factors and the cardiorespiratory fitness measures. Secondly, there were no comparisons made between healthy firefighters with CVD risk factors and firefighters with good or poor cardiorespiratory fitness.

Assessment of Overall Effect Size
The data were imported and analyzed using Review Manager 5.3 [59,[63][64][65]. The outcome measure (cardiorespiratory fitness) was analyzed as a continuous variable and dichotomous variable. The mean difference (MD), with a 95% confidence interval (CI) of

Data Analysis 2.5.1. Assessment of Overall Effect Size
The data were imported and analyzed using Review Manager 5.3 [59,[63][64][65]. The outcome measure (cardiorespiratory fitness) was analyzed as a continuous variable and dichotomous variable. The mean difference (MD), with a 95% confidence interval (CI) of estimation was used as effect estimates of the association between cardiovascular disease risk factors and cardiorespiratory fitness in firefighters [64]. For cardiorespiratory fitness measures that were dichotomous, the measure of 12 METS or greater was used to classify firefighters as being fit, and less than 12 METS as unfit. A meta-analysis of correlations was conducted using the MedCalc ® statistical software Ltd. (Ostend, Belgium, version 20.104). Using the inverse variance approach, the R values from the pooled studies were grouped based on correlation coefficients of similar exposures and outcomes and aggregated into a single, exemplary effect estimate [66]. The following formula was used to convert the original R values to a general test measure using Fisher's "R" to "Z" transformation [66]: To ascertain the correlation between the exposure and the outcome variables, the Fisher's Z values from the original studies were pooled using the random effect model [67].

Classification of Cardiovascular Disease Risk Factors and Cardiorespiratory Fitness
Across studies, similar criteria were used to classify CVD risk factors. Age, as a risk factor, was classified as an age ≥45 years for males and ≥55 years for females. Obesity was classified as a body mass index (BMI) ≥30 kg·m −2 . Hypertension was classified as a systolic blood pressure ≥140 mm Hg, or a diastolic blood pressure ≥90 mm Hg, or having been previously diagnosed with hypertension by a medical professional. Cigarette smoking was classified as being a current cigarette smoker or having quit within 6 months. Physical inactivity was classified as not exercising at a moderate intensity for at least 30 min, for at least three times a week. Dyslipidemia was classified as a total cholesterol concentration ≥5.18 mmol·L and a low-density lipoprotein ≥3.34 mmol·L or having been diagnosed by a medical professional. Diabetes was classified as a fasting blood glucose concentration ≥7.0 mmol·L or having a diagnosis by a medical professional. Firefighters were classified as being fit by meeting the minimum required cardiorespiratory fitness levels of 12 metabolic equivalents (METS), which is an oxygen consumption (VO 2 ) of 42 mL·kg·min, that has been accepted as the minimum required cardiorespiratory fitness level needed for the profession. Firefighters that did not meet the 12 METS cut-off were categorized as not meeting the minimum required cardiorespiratory fitness level. Studies using the 12 METs cut-off were categorized as dichotomous variables and the CVD risk factors were continuous. Studies using relative VO 2 were used as a continuous variable and CVD risk factors were used as dichotomous variables.

Assessment of Heterogeneity and Publication Bias
The I 2 and chi-square tests were employed as the two techniques to determine the degree of heterogeneity amongst the included studies [60]. These techniques have been used in previous meta-analyses to evaluate the effect of heterogeneity of the meta-analysis [60].
The following criteria were used to interpret I 2 statistics: (i) From 0% to 30%, indicated heterogeneity may not be important; (ii) From 31% to 60%, indicated that there was moderate heterogeneity; (iii) From 61% to 80%, indicated that there was substantial heterogeneity; (iv) From 81% to 100%, indicated that there was considerable heterogeneity.

Risk of Bias
The Begg's test and Egger's test were run using the Statistical Package for the Social Sciences (SPSS ® , Chicago, IL, USA) version 28 to evaluate the risk of bias in the studies included in the meta-analysis.

Subgroup Analysis and Investigation of Heterogeneity
To account for the presence of heterogeneity, a subgroup analysis was performed to explore the possible sources of the heterogeneity within studies [61]. The subgroup analysis was conducted on studies that used either a treadmill testing protocol, bicycle ergometer protocol, field tests, non-exercise measures, and direct VO 2max estimation using gas analysis.

Study Characteristics
The included studies encompassed 21 cross-sectional studies, three cohort studies, and one case-controlled study, conducted between 1991 and 2021, and included a total of 7822 firefighters. Studies were conducted on fire departments located in various regions globally, where multiple variations of cardiorespiratory fitness tests were used to estimate cardiorespiratory fitness. A summary of the included studies is found in Table 1. The detailed critical appraisal of the studies may be found in Supplementary File S4. The estimated VO 2max for subjects with two, three, or more metabolic abnormalities were found to be significantly lower than that of subjects with zero or one metabolic abnormality. There were significant differences among BMI (p < 0.01), BF% (p < 0.001), cholesterol (p < 0.05), triglycerides (p < 0.001), HDL-C (p < 0.05), and LDL-C (p < 0.01) between the low fit and high fit groups. There was a significant negative correlation between CRF and age (r = −0.50, p < 0.01).

The Effect of Cardiorespiratory Fitness on Blood Pressure in Firefighters
Systolic and diastolic blood pressure significantly and inversely influenced the cardiorespiratory fitness in firefighters [30,40,69,72,73,79]. Furthermore, higher blood pressure measurements reduced the overall cardiorespiratory fitness in firefighters since those with higher blood pressure were less likely to meet the minimum cardiorespiratory requirements for firefighting. In Figure 4A, not meeting the minimum cardiorespiratory fitness level had a significant positive pooled random effect on systolic blood pressure (MD = 5.69 mm Hg, Z = 5.94, p < 0.001) [30,40,69], with no heterogeneity between studies (I 2 = 0%) ( Figure S4C, Supplementary File S5). Not meeting the minimum cardiorespiratory fitness level had a significant positive pooled random effect on diastolic blood pressure in firefighters (MD = 3.43 mm Hg, Z = 2.45, p = 0.01) ( Figure 4B) [30,40,69] with considerable heterogeneity present (I 2 = 63%) between studies; however, there was no evidence of publication bias (Egger's test p = 0.269) ( Figure S4D, Supplementary File S5). After subgroup analysis, heterogeneity was reduced to 0% when a bicycle ergometer testing protocol was used. The effect remained significant for cardiorespiratory fitness levels on diastolic blood pressure after subgroup analysis (MD = 5.01 mm Hg, Z = 3.95, p < 0.001) [30,40]. [19,73,75,83,85]; (B) the association between cardiorespiratory fitness and BMI with subgroup analysis [30,40,69,79].

The Effect of Cardiorespiratory Fitness on Blood Pressure in Firefighters
Systolic and diastolic blood pressure significantly and inversely influenced the cardiorespiratory fitness in firefighters [30,40,69,72,73,79]. Furthermore, higher blood pressure measurements reduced the overall cardiorespiratory fitness in firefighters since those with higher blood pressure were less likely to meet the minimum cardiorespiratory requirements for firefighting. In Figure 4A, not meeting the minimum cardiorespiratory fitness level had a significant positive pooled random effect on systolic blood pressure (MD = 5.69 mm Hg, Z = 5.94, p < 0.001) [30,40,69], with no heterogeneity between studies (I 2 = 0%) ( Figure S4C, Supplementary File S5). Not meeting the minimum cardiorespiratory fitness level had a significant positive pooled random effect on diastolic blood pressure in firefighters (MD = 3.43 mm Hg, Z = 2.45, p = 0.01) ( Figure 4B) [30,40,69] with considerable heterogeneity present (I 2 = 63%) between studies; however, there was no evidence of publication bias (Egger's test p = 0.269) ( Figure S4D, Supplementary File S5). After subgroup analysis, heterogeneity was reduced to 0% when a bicycle ergometer testing protocol was used. The effect remained significant for cardiorespiratory fitness levels on diastolic blood pressure after subgroup analysis (MD = 5.01 mm Hg, Z = 3.95, p < 0.001) [30,40]. The association between cardiorespiratory fitness and systolic blood pressure [30,40,69]; (B) the association between cardiorespiratory fitness and diastolic blood pressure with subgroup analysis [30,40,69].

The Effect of Cardiorespiratory Fitness on Blood Cholesterol Concentration in Firefighters
Total cholesterol was significantly related to cardiorespiratory fitness in firefighters [30,40,69,79]. In addition, LDL-C [30,40,69,79] and triglycerides [30,40,69,79] were significantly and negatively related to cardiorespiratory fitness, with those firefighters being less likely to meet the minimum cardiorespiratory fitness requirements for firefighting. The meta-analysis indicated that there was a significant positive pooled random effect for not meeting the minimum cardiorespiratory fitness level on total The association between cardiorespiratory fitness and systolic blood pressure [30,40,69]; (B) the association between cardiorespiratory fitness and diastolic blood pressure with subgroup analysis [30,40,69].

Figure 6. The association between cardiorespiratory fitness and blood glucose in firefighters: (A)
The association between cardiorespiratory fitness and blood glucose concentration [30,69,79].

The Associations between Cigarette Smoking, Physical Inactivity, CVD Risk, and Heart Rate Variability and Cardiorespiratory Fitness in Firefighters
Punakallio et al. [82] and Durand et al. [35] reported that cigarette smoking was significantly associated with cardiorespiratory fitness in firefighters. Physical inactivity was significantly related to cardiorespiratory fitness in firefighters [35]. Li et al. [77] reported that overall, the 10-year ASCVD risk was not significantly related to cardiorespiratory fitness, after controlling for BF% in firefighters. Metabolic syndrome and an increasing number of cardiometabolic risk factors were significantly and negatively related to cardiorespiratory fitness in firefighters [41,70,78]. Porto et al. [80] reported that the number of times the change in successive normal sinus intervals exceeds 50 ms (PNN50), the root mean square of successive differences between normal heartbeats (rMSSD), and low-frequency and high-frequency ratio (LHR) were significantly different between cardiorespiratory fitness levels.

The Associations between Cigarette Smoking, Physical Inactivity, CVD Risk, and Heart Rate Variability and Cardiorespiratory Fitness in Firefighters
Punakallio et al. [82] and Durand et al. [35] reported that cigarette smoking was significantly associated with cardiorespiratory fitness in firefighters. Physical inactivity was significantly related to cardiorespiratory fitness in firefighters [35]. Li et al. [77] reported that overall, the 10-year ASCVD risk was not significantly related to cardiorespiratory fitness, after controlling for BF% in firefighters. Metabolic syndrome and an increasing number of cardiometabolic risk factors were significantly and negatively related to cardiorespiratory fitness in firefighters [41,70,78]. Porto et al. [80] reported that the number of times the change in successive normal sinus intervals exceeds 50 ms (PNN50), the root mean square of successive differences between normal heartbeats (rMSSD), and low-frequency and highfrequency ratio (LHR) were significantly different between cardiorespiratory fitness levels.

Summary of Evidence
To the best of the authors' knowledge, this is the first systematic review and metaanalysis performed to examine the relationship between CVD risk factors and cardiorespiratory fitness in firefighters. The results indicated that CVD risk factors had a statistically significant and inverse association with cardiorespiratory fitness in firefighters. This was particularly true for age, obesity, blood pressure, and blood lipid concentration. Collectively, having a better overall cardiovascular disease risk profile may have a compounded effect on firefighters' health, significantly improving their overall cardiorespiratory fitness and reducing their on-duty risks.

Cardiovascular Disease Risk Factors and Cardiorespiratory Fitness
Aged firefighters had poorer cardiorespiratory fitness as compared with younger firefighters. In addition, firefighters that did not meet the minimum required cardiorespiratory fitness were older than those who met the minimum required cardiorespiratory fitness level. Aging causes a decrease in vascular elasticity, which may negatively affect blood flow toward muscles [87,88]. In addition, the atrial and ventricular chambers of the heart show reduced elasticity [46,89], which negatively affects stroke volume and reduces blood flow toward the working muscles [88,89]. Furthermore, aging has been shown to reduce muscle functions, particularly those related to muscular force production [46]. Research has indicated that firefighters tend to become more physically inactive as they age, which may assist in the steady decline in cardiorespiratory fitness seen in this population with time [35,48,49].
The results of our systematic review and meta-analysis indicated that obese firefighters had a significantly lower cardiorespiratory fitness level as compared with non-obese firefighters. In addition, firefighters that did not meet the minimum cardiorespiratory fitness levels had a higher BMI than those that met the requirement. Previous systematic reviews have indicated that obesity significantly reduced cardiorespiratory fitness in sportsmen [90,91] and emergency occupations alike [8,92,93]. Moreover, obesity has been shown to increase the incidence of duty-related fatalities in firefighters [2]. Obesity increases non-functional mass in firefighters that are required to be carried. Increased peripheral resistance subsequently increases blood pressure, which reduces atrial preload, negatively affecting stroke volume and oxygen uptake to working muscles [47,94]. Increased fat mass increases the effort of respiratory muscles to expand the rib cage, reducing the available oxygen content toward working muscles [95]. Firefighters are required to carry additional weight while on duty [5], and therefore, firefighters are required to have a much higher cardiorespiratory fitness to cope with these stressors [6,83,96]. Obese firefighters who carry additional heavy protective gear may be significantly predisposed to poorer occupational performance [6,83,96] and significantly higher cardiorespiratory strain [3].
Firefighters that met the minimum cardiorespiratory standard had lower systolic and diastolic blood pressure than firefighters that did not meet the minimum requirements. Increased blood pressure, due to reduced vascular elasticity and increased total peripheral resistance, directly reduced stroke volume [97]. As mentioned previously, a reduction in stroke volume diminishes the quantity of oxygen transported to working muscles, limiting oxygen usage and energy production [43,97]. Firefighters should maintain normal and preferably optimal blood pressure levels throughout their careers to maintain adequate cardiorespiratory fitness levels, through multiple interventions.
In the present study, firefighters that did not meet the minimum cardiorespiratory fitness standard for firefighting had significantly higher concentrations for total cholesterol, LDL-C, triglycerides, and blood glucose. The current results were supported by previous literature that indicated physical fitness was significantly related to LDL-C and triglyceride concentrations [45,98,99]. Rumora et al. [100] reported that high LDL-C levels impaired mitochondrial function, by reducing oxygen uptake and subsequently reducing aerobic capacity. Physical activity was reported to improve blood lipid concentrations, specifically in reducing LDL-C and increasing HDL-C [99]. In addition, previous reviews have indicated that blood glucose and diabetes were significantly related to cardiorespiratory fitness [44,101]. The prevalence of diabetes is relatively low in firefighters; however, diabetes may have the highest overall impact on their overall cardiorespiratory fitness levels among the haematological parameters [9,12,27,30,33,69,102].
In previous studies, cigarette smoking and physical activity were investigated in relation to cardiorespiratory fitness in firefighters; however, insufficient studies were available to perform a meta-analysis. The results indicated that cigarette smoking was significantly related to declining cardiorespiratory fitness levels in firefighters over time. This was supported by the results of previous systematic reviews that indicated cigarette smoking negatively affected the cardiorespiratory fitness of healthy adult males [103]. In addition, exposure to passive smoke was also related to reduced cardiorespiratory fitness [103]. Physical inactivity, especially in obese firefighters, was significantly related to poorer cardiorespiratory fitness in firefighters. This is supported by a previous systematic review in young adults, where longer duration of physical activity sessions and higher frequency of physical activity were significantly related to cardiorespiratory fitness [104]. Only one study was found that investigated the overall effect of cardiovascular risk status on cardiorespiratory fitness in firefighters, indicating that a significant gap exists. This has been proven in previous research where higher cardiorespiratory fitness improved overall cardiovascular risk and all-cause mortality [105,106]. Similar to overall cardiovascular disease risk, only one study was found that investigated heart rate variability and cardiorespiratory fitness. The results indicated that heart rate variability increased as cardiorespiratory fitness increased, suggesting that optimal cardiovascular health was related to higher levels of cardiorespiratory fitness [80].

Strengths and Limitations
The overall quality of the studies that were included in our review was high, with most studies being above a score of eighteen. This study provided valuable evidence in an understudied research field in firefighters. An inherent weakness is that insufficient studies have investigated all the cardiovascular disease risk factors in firefighters, specifically cigarette smoking, physical inactivity, and a family history of cardiovascular disease. In addition, only one study used an overall risk score to determine cardiovascular risk on cardiorespiratory fitness. Several studies that were included did not include a selection procedure that would allow researchers to choose individuals who were representative of the intended population and the sample frame was not taken from an appropriate population base. A limited number of studies were available for many of the analyses, reducing the strength of the inferences that could be made. Lastly, cardiorespiratory fitness was not consistently measured in the same way, which likely contributed to the heterogeneity of results that could not be explained through subgroup analysis.

Conclusions
The current systematic review and meta-analysis support previous findings suggesting that firefighters need to maintain optimum cardiovascular health and cardiorespiratory fitness throughout their careers. As the reciprocal relationship indicated, this will reduce the likelihood of firefighters' cardiorespiratory fitness dropping below the minimum requirements for firefighting. Decreased cardiorespiratory fitness was attributed to the development and progression of CVD risk factors, which was most notable in firefighters not meeting the minimum recommended fitness level. Given that firefighters actively maintain their cardiorespiratory fitness levels, this is expected to have a positive effect on their cardiovascular health, subsequently reducing the risk of CVD-related morbidity and mortality. Fire and Rescue departments should promote regular physical activity and behavioral medication programs designed to not only increase the cardiorespiratory fitness of firefighters but improve their overall cardiovascular health status. It is recommended that fire departments should adopt scheduled physical activity or exercise programs while firefighters are on-duty and should ensure that firefighters are regularly assessed to measure their cardiorespiratory health. Future research should focus on the collective effect that an increased CVD risk status may have on cardiorespiratory fitness in firefighters. In addition, more studies should be conducted on cardiorespiratory fitness in relation to total fitness. i.e., muscular endurance, muscular strength, flexibility, and body composition. Few studies investigated the relationship between heart rate variability and cardiorespiratory fitness, indicating a significant research gap in this particular area.

Patents Protocol Registration
Details of the protocol for this systematic review were registered on PROSPERO (CRD42022330510) and can be accessed at: https://www.crd.york.ac.uk/prospero/display_ record.php?ID=CRD42022330510 (accessed on 18 December 2022).  Table S1. critical appraisal of cross-sectional studies (adapted from the appraisal tool for cross-sectional studies checklist); Table S2: Critical Appraisal Skills Programme of cohort and case-controlled studies (adapted from the Critical Appraisal Skills Programme). Supplementary File S5: Figure S2C: Funnel plot for publication bias; Figure S2D: Funnel plot for publication bias; Figure S3C: Forest plot for publication bias; Figure S3D: Forest plot for publication bias; Figure S4C: Forest plot for publication bias; Figure S4D: Forest plot for publication bias; Figure S5D: Forest plot for publication bias; Figure S5E: Forest plot for publication bias; Figure S5F: Forest plot for publication bias; Figure S6B: Forest plot for publication bias.  Data Availability Statement: All data generated or analyzed during this study are included in the published review article.

Conflicts of Interest:
The authors declare no conflict of interest.