Predicting the incidence of recurrent positive exercise stress tests among civilian pilots: a retrospective cohort study

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This study aimed to determine the incidence of recurrently positive EST and their predictors among civilian pilots in Indonesia. Methods This was a retrospective cohort study among civilian pilots who had the first positive EST test between January 2019 and June 2020 at the Aviation Medical Center, Jakarta. The data were retrieved from medical records. Subjects were included if there were data on subsequent ESTs at 6 and 12 months. Risk factors included total flight hours (TFH) in the last 6 months, license type, aircraft cabin pressurization system, flying limitation such as multicrew, cardiac intervention, age, smoking habit, family history of coronary artery disease, body mass index, blood pressure levels, lipid profile, and fasting blood glucose. Results Eighty-seven pilots were included; 54 of them (62.1%) had recurrent positive ESTs. All subjects were men, and the median age was 51 (range 40-64) years. Independent predictors of recurrent positive ESTs were age 60-65 years (adjusted odds ratio [ORadj]: 5.1, 95% CI: 1.12–23.16, p= 0.035), a TFH of > 275 hours (ORadj 5.1, 95% CI: 1.28–20.65, p= 0.021), and dyslipidemia (ORadj: 4.2 95% CI: 1.468–12.275, p=0.015). Having these three risk factors increased the probability of a recurrent positive EST up to 100%. Conclusion The incidence of recurrently positive ESTs among civilian pilots in Indonesia was high. Airlines may want to implement a more aggressive health policy for the prevention of cardiovascular diseases among their pilots. 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F1000Research 2024, 13 :1122 ( https://doi.org/10.12688/f1000research.155136.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Predicting the incidence of recurrent positive exercise stress tests among civilian pilots: a retrospective cohort study [version 1; peer review: 1 approved with reservations] Voltha Herry 1 , Indah Suci Widyahening https://orcid.org/0000-0002-7952-2893 2,3 , Ferdi Afian 2 , Ika Prasetya Wijaya 4 , Boon-How Chew 5,6 , Dewi Sumaryani Soemarko 2,7 Voltha Herry 1 , Indah Suci Widyahening https://orcid.org/0000-0002-7952-2893 2,3 , [...] Ferdi Afian 2 , Ika Prasetya Wijaya 4 , Boon-How Chew 5,6 , Dewi Sumaryani Soemarko 2,7 PUBLISHED 03 Oct 2024 Author details Author details 1 National Transportation Safety Committee, Ministry of Transportation, Republic of Indonesia, Jakarta, Indonesia 2 Department of Community Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia 3 Primary Health Care Research and Innovation Center, Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia 4 Department of Internal Medicine, Faculty of Medicine Universitas Indonesia Cipto Mangunkusumo Hospital, Jakarta, Indonesia 5 Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia 6 Clinical Research Unit, Hospital Pengajar Universiti Putra Malaysia (HPUPM Teaching Hospital), Serdang, Selangor, Malaysia 7 Occupational and Environmental Health Research Center, Indonesia Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia Voltha Herry Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Visualization, Writing – Original Draft Preparation Indah Suci Widyahening Roles: Formal Analysis, Funding Acquisition, Methodology, Supervision, Validation, Writing – Review & Editing Ferdi Afian Roles: Conceptualization, Investigation, Supervision, Validation, Writing – Review & Editing Ika Prasetya Wijaya Roles: Supervision, Validation, Writing – Review & Editing Boon-How Chew Roles: Methodology, Validation, Writing – Review & Editing Dewi Sumaryani Soemarko Roles: Methodology, Supervision, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Abstract* Background A positive exercise stress test (EST) is common among pilots, and it may indicate a greater risk of coronary artery disease (CAD). This study aimed to determine the incidence of recurrently positive EST and their predictors among civilian pilots in Indonesia. Methods This was a retrospective cohort study among civilian pilots who had the first positive EST test between January 2019 and June 2020 at the Aviation Medical Center, Jakarta. The data were retrieved from medical records. Subjects were included if there were data on subsequent ESTs at 6 and 12 months. Risk factors included total flight hours (TFH) in the last 6 months, license type, aircraft cabin pressurization system, flying limitation such as multicrew, cardiac intervention, age, smoking habit, family history of coronary artery disease, body mass index, blood pressure levels, lipid profile, and fasting blood glucose. Results Eighty-seven pilots were included; 54 of them (62.1%) had recurrent positive ESTs. All subjects were men, and the median age was 51 (range 40-64) years. Independent predictors of recurrent positive ESTs were age 60-65 years (adjusted odds ratio [ORadj]: 5.1, 95% CI: 1.12–23.16, p = 0.035), a TFH of > 275 hours (ORadj 5.1, 95% CI: 1.28–20.65, p = 0.021), and dyslipidemia (ORadj: 4.2 95% CI: 1.468–12.275, p=0.015). Having these three risk factors increased the probability of a recurrent positive EST up to 100%. Conclusion The incidence of recurrently positive ESTs among civilian pilots in Indonesia was high. Airlines may want to implement a more aggressive health policy for the prevention of cardiovascular diseases among their pilots. READ ALL READ LESS Keywords coronary artery disease, risk factors, airline pilot, electrocardiography Corresponding Author(s) Indah Suci Widyahening ( [email protected] ) Close Corresponding author: Indah Suci Widyahening Competing interests: No competing interests were disclosed. Grant information: This study received publication grants from Universitas Indonesia (number: NKB-1233/UN2.RST/HKP.05.00/2022). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2024 Herry V et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Herry V, Widyahening IS, Afian F et al. Predicting the incidence of recurrent positive exercise stress tests among civilian pilots: a retrospective cohort study [version 1; peer review: 1 approved with reservations] . F1000Research 2024, 13 :1122 ( https://doi.org/10.12688/f1000research.155136.1 ) First published: 03 Oct 2024, 13 :1122 ( https://doi.org/10.12688/f1000research.155136.1 ) Latest published: 03 Oct 2024, 13 :1122 ( https://doi.org/10.12688/f1000research.155136.1 ) Introduction Coronary artery disease (CAD) is a serious health problem in aviation. Acute coronary syndrome remains one of the most common causes of incapacitation among civilian pilots and can lead to incidents or fatal accidents. 1 Sudden incapacitation due to arrhythmia, myocardial infarction or heart failure can be catastrophic during a flight. There are several screening modalities for detecting CAD, including electrocardiography (ECG), echocardiography, coronary calcium scoring, coronary angiography, and ECG exercise stress test (EST) or treadmill tests with or without nuclear or stress imaging. ECG EST is often used as the first-line method to screen individuals at increased risk of CAD since it is readily available and may provide useful information on cardiac functional capacity, such as blood pressure response to exercise, assessment of exercise-related arrhythmias, and aerobic fitness. 2 However, EST is not recommended as a stand-alone screening tool to determine aeromedically significant CAD because it has low sensitivity and low positive predictive value. 3 , 4 Civilian pilots need medical assessment to obtain a first-class certificate that is valid for 6 months according to the Indonesian Civil Aviation Safety Regulation. 5 ECG EST for civilian pilots is performed once at the age of 35 years, annually between 40 and 60 years, and then every 6 months thereafter. Positive ESTs can be asymptomatic. 6 However, this finding requires further cardiovascular assessment while the pilot is grounded. Abnormal heart rhythm, either by resting or exercise ECG, must be considered unfit to fly until it is managed properly and the incapacitated pilot meets medical requirements. 5 If the pilot has a second positive EST, there will be more complicated management and assessment before the pilot can be returned to duty. Clearly, positive EST is an undesirable result that should always be prevented. Positive ESTs are commonly found among civilian pilots at the Aviation Medical Center, Jakarta, and some of them recur. However, the incidence and risk factors for recurring positive EST have not been well studied. Therefore, this study aimed to determine the incidence of recurrent positive EST and its risk factors among civilian pilots in Indonesia. A positive EST warrants further diagnostic management if it recurs. 7 Methods Study design and subjects This was a retrospective cohort study among civilian pilots who had a positive EST between January 2019 and June 2020. Subjects were selected from the medical records at the Aviation Medical Center, Directorate General of Air Transportation, Ministry of Transportation, Republic of Indonesia, Jakarta, which is currently the only institution mandated to perform the required periodical medical check-up for all civilian airline aircrews in Indonesia. The inclusion criteria were all civilian pilots with first-time positive EST results, aged 40–65 years, and who had EST results at 6 or 12 months after the first positive EST. Pilots with incomplete medical check-up data were excluded. Written informed consent was not required since all the data were obtained secondarily from the medical records. The sample size was calculated using the formula for a prevalence study with a confidence level of 95%, an expected prevalence of 23%, 8 and an error limit of 10%. The minimum sample size was 69 subjects. Ethics approval was granted by the Health Research Ethics Committee, Faculty of Medicine Universitas Indonesia on 12 July 2021 (No. KET-679/UN2. F1/ETIK/PPM.00.20/2021). This study complies with the Declaration of Helsinki and was performed according to ethics committee approval. A written request to use the medical record data was sent to the Aviation Medical Center, Directorate General of Air Transportation, Ministry of Transportation, Republic of Indonesia and approval was granted on 21 July 2021 (No. S1-132/UN2.F1S.14.3/2021). Exercise stress test data The exercise stress test was performed according to the Bruce protocol. The procedure consists of consecutive stages lasting 3 minutes each, where the patient is required to walk at an increased speed and on a steeper incline. The testing methodology can be modified according to the patient’s tolerance, with the goal of achieving an exercise duration of 6 to 12 minutes. A modified version of the Bruce protocol has been developed for individuals who are unable to engage in intense exercise. This modified protocol includes two additional stages at the beginning, both of which include lower workloads than stage 1. 9 A positive result was defined by one of these criteria on the ECG result: ST segment depression >1 mm below the isoelectric line at 60 milliseconds after the J point (if horizontal or down sloping ST segment depression); ST segment depression >1.5 mm below the isoelectric line at 80 milliseconds after the J point (if upsloping ST segment depression); ST segment elevation >1 mm at 80 milliseconds after the J point; or ST segment elevation on the AVR lead. This condition was regarded as similar to horizontal ST-segment depression. 10 A cardiologist assessed and determined the result based on the ECG. Risk factor assessment Risk factors tested were total flight hours (TFH) in the last six months (≤275 hours vs. >275 hours; 275 hours being the midpoint of maximum flying hours for pilots in six months according to the International Civil Aviation Organization [ICAO]), license type (Commercial Pilot License [CPL] or Air Transport Pilot License [ATPL]), aircraft cabin system (pressurized vs. unpressurized), limitation (not flying as pilot in command), cardiac intervention (either percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) after the positive EST soon after being evaluated by an aviation medical examiner, age group (40-49 vs. 50-59 vs. 60-65 years), smoking habit, family history of CAD, body mass index (BMI), blood pressure, lipid profile, and fasting blood glucose. Limitation was defined as not flying as a pilot in command. BMI was categorized based on the World Health Organization (WHO) criteria as normal (18.5-24.9 kg/m 2 ), overweight (25.0-29.9 kg/m 2 ) or obese (above 30.0 kg/m 2 ). 11 Blood pressure was categorized according to the Joint National Committee VII criteria as hypertension (systole of ≥140 or diastole of ≥90 mmHg) or not hypertension. 12 Lipid profiles were classified according to the Indonesian Society of Endocrinology Guideline into dyslipidemia (total cholesterol ≥240 mg/dl, LDL ≥160 mg/dl, or HDL ≤40 mg/dl) and normal. 13 Fasting blood glucose was classified according to the Indonesian Society of Endocrinology Guideline as <126 mg/dl or ≥126 mg/dl. 7 Statistical analyses The baseline characteristics of the pilots and risk factors are presented descriptively. The associations between independent and dependent variables were analyzed using the chi-square test. Multivariate logistic regression analyses were performed for variables with a p value of <0.25 based on the univariate analysis to identify independent predictors for one recurrently positive EST at six or 12 months, expressed by the adjusted odds ratio (OR adj ) and its corresponding 95% confidence intervals (CIs). The probability of a recurrently positive EST was then calculated based on the number of risk factors. Statistical analyses were performed using IBM ® SPSS ® Statistics version 20. Results A total of 87 civilian pilots had a positive EST between January 2019 and June 2020, all of whom were men with a median age of 51 (range 40-64) years. There were 33 (37.9%) pilots who received a cardiac intervention to confirm CAD. Other characteristics are shown in Table 1 . Table 1. Characteristics of the civilian pilots (n=87). Characteristic n (%) Median (Min–Max) Age (years old) 51 (40-64) 40-49 37 (42.5) 50-59 32 (36.8) 60-65 18 (20.7) Body mass index (kg/m 2 ) 26.6 (22.4-44.7) Normal 20 (23.0) Overweight 52 (59.8) Obese 15 (17.2) Systole (mmHg) 130 (109-150) Diastole (mmHg) 83 (64-100) High systole or diastole 59 (67.8) Normal 28 (32.2) Total cholesterol level (mg/dL) 161 (99-301) Cholesterol-HDL level (mg/dL) 40 (24-86) Cholesterol LDL level (mg/dL) 94 (30-210) Dyslipidemia No 35 (40.2) Yes 52 (59.8) Fasting Glucose (mg/dL) 104 (77-173) <126 71 (81.6) ≥126 16 (18.4) Smoking habit No 54 (62.1) Yes 33 (37.9) Family history of CAD No 83 (95.4) Yes 4 (4.6) License type CPL 6 (6.9) ATPL 81 (93.1) Total flight hours (hours) 149 (0-550) ≤275 63 (72.4) >275 24 (27.6) Aircraft cabin system Pressurized 80 (92.0) Unpressurized 7 (8.0) Limitation Yes 33 (37.9) No 54 (62.1) Cardiac intervention Yes 33 (37.9) No 54 (62.1) Recurrently positive EST was found in 54 (62.1%) pilots. It was significantly associated with age, TFH in the last 6 months, and dyslipidemia ( Table 2 ). Multivariate analyses revealed that age 60-65 years, a TFH of >275 hours in the last six months, and dyslipidemia were independent predictors of recurrent positive EST (Nagelkerke R 2 = 0.319; Hosmer and Lemeshow test p = 0.227). The adjusted OR was 5.1 for the 60-65 years and TFH >275 hours, whereas dyslipidemia was associated with a 4.2-fold increased risk for recurrent EST ( Table 3 ). The probability of recurrently positive EST was 100% for pilots with all three risk factors ( Table 4 ). Table 2. Associations between risk factors and recurrent positive exercise stress tests among pilots, n = 87. Risk factors Recurrent positive EST OR (95% CI) p value Yes (n = 54) No (n = 33) n (%) n (%) Total flight hours in the last 6 months ≤275 hours 33 (52.4) 30 (47.6) Reference >275 hours 21 (87.5) 3 (12.5) 6.36 (1.72-23.51) 0.003 * License CPL 2 (33.3) 4 (66.7) Reference ATPL 52 (64.2) 29 (35.8) 3.59 (0.62-20.78) 0.195 ^ Aircraft cabin system Pressurized 51 (63.8) 29 (36.3) Reference Unpressurized 3 (42.9) 4 (57.1) 0.43 (0.09-2.04) 0.419 ^ Limitation Yes 22 (66.7) 11 (33.3) Reference No 32 (59.3) 22 (40.7) 0.73 (0.29-1.80) 0.490 * Cardiac intervention Yes 20 (60.6) 13 (39.4) Reference No 34 (63.0) 20 (37.0) 1.11 (0.45-2.69) 0.826 * Age 40-49 years old 17 (45.9) 20 (54.1) Reference 50-59 years old 22 (68.8) 10 (31.3) 2.59 (0.96-6.95) 0.057 * 60-65 years old 15 (83.3) 3 (16.7) 5.88 (1.45-23.81) 0.008 * Nutritional status Normal 13 (65.0) 7 (35.0) Reference Overweight 32 (61.5) 20 (38.5) 0.86 (0.29-2.53) 0.786 * Obese 9 (60.0) 6 (40.0) 0.81 (0.20-3.22) 0.762 * Hypertension No 39 (66.1) 20 (33.9) Reference Yes 15 (53.6) 13 (46.4) 0.59 (0.24-1.48) 0.260 * Dyslipidemia No 16 (45.7) 19 (54.3) Reference Yes 38 (73.1) 14 (26.9) 3.22 (1.31-7.96) 0.010 * Fasting blood glucose <126 mg/dL 42 (59.2) 29 (40.8) Reference ≥126 mg/dL 12 (75.0) 4 (25.0) 2.07 (0.61-7.06) 0.238 * Smoking habit No 33 (61.1) 21 (38.9) Reference Yes 21 (63.6) 12 (36.4) 1.11 (0.46-2.73) 0.814 * Family history of CAD No 52 (62.7) 31 (37.3) Reference Yes 2 (50.0) 2 (50.0) 0.60 (0.08-4.45) 0.632 ^ * Chi square test. ^ Fisher’s exact test. Table 3. Independent risk factors for recurrent positive exercise stress test results, n = 87. Variable OR adj 95% CI p value Age Age 50-59 years 2.797 0.878–8.908 0.082 Age 60-65 years 5.094 1.121–23.157 0.035 TFH >275 hours 5.134 1.277–20.645 0.021 Dyslipidemia 4.245 1.468–12.275 0.015 Table 4. Risk prediction of recurrent positive exercise stress test results based on the number of risk factors. Number of risk factors Subjects, n (%) Recurrent positive EST, n (%) 1 39 (44.8) 23 (59.0) 2 23 (26.4) 14 (60.9) 3 5 (5.7) 5 (100.0) Discussion Our study evaluated the EST follow-up data as the primary outcome. We found that the incidence of recurrent positive EST among civilian pilots in Indonesia was high at 62.1%. Positive EST recurred despite flying limitations or cardiac intervention (PCI or CABG), which some of the pilots underwent after the first positive EST. The independent predictors were an age of 60-65 years, a TFH of >275 hours in the last 6 months, and dyslipidemia. If the pilot had all 3 risk factors, he would definitely have a positive result on the next EST. There are no other reports specifically addressing recurrent positive EST in the aerospace medicine literature. A study in Turkey on 26 cases (pilots and aircrew) with a history of CAD revealed that 6 (23.1%) of them had subsequent positive ESTs. 6 Positive ESTs based on ST segment changes, either depression or elevation, are beneficial for risk stratification in people with intermediate-risk symptoms of CAD. 14 However, pilots are usually asymptomatic, and according to the American Heart Association guidelines, asymptomatic individuals have very low (<5%) or low (5-10%) pretest probabilities of CAD. 15 Therefore, positive EST warrants further diagnostic management, especially if it recurs. During the period of assessment, which was conducted immediately as the EST showed a positive result, a pilot was considered unfit to fly. Grounded pilots create additional burdens to airlines, such as increased medical costs and loss of working hours for at least 6 months. Returning pilots with known CAD to flight duties requires a comprehensive evaluation and control of modifiable risk factors. 2 Knowing the risk factors and predictors of recurring positive EST will be valuable as potential health nudges for prevention. Our study showed that older age was a risk factor for recurrent positive EST. Aging is a well-known nonmodifiable risk factor for CAD. 16 Pilots aged >60 years are also classified as having a high risk of CAD. 17 The mechanisms of aging and cellular physiological alterations leading to increased cardiovascular risk have been reviewed elsewhere. 18 We found that a total flight time >275 hours in the last six months significantly increased the risk of recurrent positive EST. Another study revealed that a total flight time ≥5000 hours is among the independent predictors of a high risk of atherosclerotic cardiovascular disease. 19 Some researchers have suggested that flight time is associated with cosmic radiation and intermittent hypoxia, which affect lipid metabolism and trigger coronary stenosis. Cosmic radiation exposure triggers oxidative stress and continuously accelerates changes in lipoprotein structure and lipid metabolism. The body responds by increasing the release of lipid molecules into the bloodstream as a protective mechanism against damage to the cell membrane induced by lipid peroxidation, which disturbs lipid metabolism. 20 , 21 Repetitive intermittent hypoxia inhibits the absorption of cholesterol through hypoxia-inducible factor 1 (HIF-1). Hypoxia affects adipose tissue by activating inflammation and releasing inflammatory mediators into the bloodstream. This will cause systemic inflammation and disruption of nitrite oxide production, causing epithelial and endothelial dysfunction. 22 , 23 Dyslipidemia also emerged as an independent predictor of recurrent positive EST in this study. It is associated with fat accumulation in the arterial wall, accelerating the atherosclerosis process by narrowing the lumen and blocking the blood supply. 24 Airline pilots consumed more dyslipidemia medication than did the general population; the prevalence of statin treatment among pilots also increased with age. 25 Pharmacologic intervention for hyperlipidemia among pilots should be initiated based on the Indonesian Society of Endocrinology recommendation for individuals in Indonesia when the LDL-cholesterol level is more than 130 mg/dL. This approach is more aggressive than many other guidelines, as pilots are classified as having intermediate cardiovascular risk. 26 Our findings imply that pilots with positive EST should control their modifiable cardiovascular risk factors more stringently, particularly their lipid profile. Older age and increased flying time also increase the risk of recurrent EST, but these factors cannot be controlled and are associated with increased flying responsibility and expertise. At best, pilots aged more than 60 years should check their lipid profile more often and reduce their flying time to less than 275 hours within 6 months. Nutritional assessment and intervention may be needed. However, risk mitigation in aerospace medicine should be considered in the context of an abnormal working environment, i.e., a dry and pressurized cabin, hypoxia and hypobaric, spatial disorientation, and heightened stress. 27 , 28 No risk scoring system has been developed for civilian pilots. Lifestyle modifications and pharmacological interventions at lower risk thresholds may be useful for traditional assessments of pilots who are considered to be at low risk. 20 The limitation of our study was the retrospective cohort design with secondary data from the medical records. Therefore, several potential risk factors, such as physical activity, dietary patterns, and current medication, could not be evaluated. However, basic information on modifiable and occupational risk factors for CAD was available for further analyses. Conclusion The incidence of recurrently positive EST among civilian pilots in Indonesia was high. The independent risk factors were an age of 60-65 years, more than 275 cumulative flight hours in the last six months, and dyslipidemia. Pilots were advised to control their risk factors, particularly their lipid profile, to prevent recurrent positive EST. Among pilots, airlines may want to have more aggressive health policies for the prevention of cardiovascular diseases, such as enhanced cardiovascular screening for those with risk factors. A medical specialist who obtained competencies in maintaining the health of pilots and all aviation personnel at an airline, such as an aviation medicine specialist, would be expected to have a better understanding of aviation cardiology. Ethical considerations Ethics approval was granted by the Health Research Ethics Committee, Faculty of Medicine Universitas Indonesia on 12 July 2021 (No. KET-679/UN2. F1/ETIK/PPM.00.20/2021). This study complies with the Declaration of Helsinki and was performed according to ethics committee approval. A written request to use the medical record data was sent to the Aviation Medical Center, Directorate General of Air Transportation, Ministry of Transportation, Republic of Indonesia and approval was granted on 21 July 2021 (No. S1-132/UN2.F1S.14.3/2021). Data availability The data belong to the Directorate General of Air Transportation, Ministry of Transportation, Republic of Indonesia and access was restricted for security reason. Data access will be granted once users have consented to the data sharing agreement and provided written plans and justification for what is proposed with the data. Data access may be obtained by submitting a request to the corresponding author (Indah Suci Widyahening) and will be reviewed by the Aviation Medical Center, Directorate General of Air Transportation, Ministry of Transportation of the Republic of Indonesia 5 and subjected to the Regulation of the Ministry of Health of the Republic of Indonesia no. 85/2020, on Data Sharing. Extended data Open Science Framework: Predicting the incidence of recurrent positive exercise stress tests among civilian pilots: a retrospective cohort study. https://doi.org/10.17605/OSF.IO/4B9FQ . File included: STROBE checklist. Acknowledgements The authors would like to express their gratitude to the Aviation Medical Center, Directorate General of Air Transportation, Ministry of Transportation, Republic of Indonesia, Jakarta, for their support in this study and Dr. Sunu Budhi Raharjo from the National Cardiovascular Center Harapan Kita, Jakarta for his valuable inputs in the development of this manuscript. References 1. Lord D, Conlon HA: Cardiovascular risk factors in airline pilots. Workplace Health Saf. 2018; 66 : 471–474. PubMed Abstract | Publisher Full Text 2. Gray G, Davenport ED, Bron D, et al. : The challenge of asymptomatic coronary artery disease in aircrew; detecting plaque before the accident. Heart. 2019; 105 : s17–s24. PubMed Abstract | Publisher Full Text | Free Full Text 3. Detrano R, Gianrossi R, Froelicher V: The diagnostic accuracy of the exercise electrocardiogram: a meta-analysis of 22 years of research. Prog. Cardiovasc. Dis. 1989; 32 : 173–206. PubMed Abstract | Publisher Full Text 4. Wilson RF, Marcus ML, Christensen BV, et al. : Accuracy of exercise electrocardiography in detecting physiologically significant coronary arterial lesions. Circulation. 1991; 83 : 412–421. PubMed Abstract | Publisher Full Text 5. Ministry of Transportation, Republic of Indonesia: Regulation Number PM 69 Year 2017 on Civil Aviation Safety Regulation Part 67 on Medical Standard and Certification. Reference Source 6. Lauer M, Froelicher ES, Williams M, et al. : Exercise testing in asymptomatic adults. Circulation. 2005; 112 : 771–776. Publisher Full Text 7. Ministry of Transportation, Republic of Indonesia: Regulation Number KP 238 Year 2018 on Staff Instruction Part 67-02 on Manual of Aviation Medical Assessment. 8. Erdal M, Aparci M, Isilak Z, et al. : Clinical Features of Aviators with Coronary Artery Disease Diagnosed by Multislice CT Angiography. Anatol. J. Cardiol. 2014; 14 : 150–154. PubMed Abstract | Publisher Full Text 9. Vilcant V, Zeltser R: Treadmill Stress Testing. [Updated 2023 Jun 20]. StatPearls. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Reference Source 10. Indonesian Heart Association: Guidelines of Treadmill Test: Procedure and Interpretation. Jakarta: Indonesian Heart Association; 2016. Reference Source 11. World Health Organization: Body mass index (BMI).2022. Reference Source 12. Chobanian AV, Bakris GL, Black HR, et al. : Seventh Report of The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. American Heart Association; 2003. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (ahajournals.org) 13. Indonesian Society of Endocrinology: Guidelines of Dyslipidemia Management in Indonesia. Jakarta: Indonesian Endocrinologist Association; 2021. 23-11-21-Website-Panduan-Dislipidemia-2021-Ebook.pdf Reference Source 14. Bourque JM, Beller GA: Value of exercise ECG for risk stratification in suspected or known CAD in the era of advanced imaging technologies. JACC Cardiovasc. Imaging. 2015; 8 : 1309–1321. PubMed Abstract | Publisher Full Text | Free Full Text 15. Gibbons RJ, Balady GJ, Bricker JT, et al. : American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Committee to Update the 1997 Exercise Testing Guidelines. ACC/AHA 2002 guideline update for exercise testing: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). J. Am. Coll. Cardiol. 2002; 40 : 1531–1540. PubMed Abstract | Publisher Full Text 16. Hajar R: Risk factors for coronary artery disease: Historical perspectives. Heart Views. 2017; 18 (3): 109–114. PubMed Abstract | Publisher Full Text | Free Full Text 17. 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PubMed Abstract | Publisher Full Text | Free Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 03 Oct 2024 ADD YOUR COMMENT Comment Author details Author details 1 National Transportation Safety Committee, Ministry of Transportation, Republic of Indonesia, Jakarta, Indonesia 2 Department of Community Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia 3 Primary Health Care Research and Innovation Center, Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia 4 Department of Internal Medicine, Faculty of Medicine Universitas Indonesia Cipto Mangunkusumo Hospital, Jakarta, Indonesia 5 Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia 6 Clinical Research Unit, Hospital Pengajar Universiti Putra Malaysia (HPUPM Teaching Hospital), Serdang, Selangor, Malaysia 7 Occupational and Environmental Health Research Center, Indonesia Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia Voltha Herry Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Visualization, Writing – Original Draft Preparation Indah Suci Widyahening Roles: Formal Analysis, Funding Acquisition, Methodology, Supervision, Validation, Writing – Review & Editing Ferdi Afian Roles: Conceptualization, Investigation, Supervision, Validation, Writing – Review & Editing Ika Prasetya Wijaya Roles: Supervision, Validation, Writing – Review & Editing Boon-How Chew Roles: Methodology, Validation, Writing – Review & Editing Dewi Sumaryani Soemarko Roles: Methodology, Supervision, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information This study received publication grants from Universitas Indonesia (number: NKB-1233/UN2.RST/HKP.05.00/2022). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (1) version 1 Published: 03 Oct 2024, 13:1122 https://doi.org/10.12688/f1000research.155136.1 Copyright © 2024 Herry V et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Herry V, Widyahening IS, Afian F et al. Predicting the incidence of recurrent positive exercise stress tests among civilian pilots: a retrospective cohort study [version 1; peer review: 1 approved with reservations] . F1000Research 2024, 13 :1122 ( https://doi.org/10.12688/f1000research.155136.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 03 Oct 2024 Views 0 Cite How to cite this report: Sonaglioni A. Reviewer Report For: Predicting the incidence of recurrent positive exercise stress tests among civilian pilots: a retrospective cohort study [version 1; peer review: 1 approved with reservations] . F1000Research 2024, 13 :1122 ( https://doi.org/10.5256/f1000research.170268.r331311 ) The direct URL for this report is: https://f1000research.com/articles/13-1122/v1#referee-response-331311 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 15 Oct 2024 Andrea Sonaglioni , MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.170268.r331311 In this interesting paper, the Authors found that an age of 60-65 yrs, a THF of >275 hours in the last 6 months and dyslipidemia were independently correlated with recurrently positive EST among civilian pilots In Indonesia. The Authors ... Continue reading READ ALL In this interesting paper, the Authors found that an age of 60-65 yrs, a THF of >275 hours in the last 6 months and dyslipidemia were independently correlated with recurrently positive EST among civilian pilots In Indonesia. The Authors stated that 37.9% of pilots with positive EST underwent a cardiac intervention to confirm CAD. How many pilots had obstructive CAD on subsequent coronary angiography? Could the Authors add in the Results section the percentage of false positive EST results? It is known that EST has a low specificity for detecting CAD, due to a great number of false positive EST results. At the end of the Discussion section, the Authors could add a paragraph concerning the potential causes of false positive EST results. I suggest the Authors to discuss a number of exercise-induced ST-segment changes simulating myocardial ischemia, such as those described in individuals with exaggerated atrial repolarization waves (Ta wave), in hyperventilating individuals, in individuals with mitral valve prolapse and finally in individuals with concave-shaped chest wall and/or pectus excavatum. The Authors could cite and discuss the following references: Sapin P, et al., 1995 (Ref 1) Gardin J, et al.,1980 (Ref 2) Tebbe U, et al., 1985 (Ref 3) Sonaglioni A, et al., 2020 (Ref 4) Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes References 1. Sapin P, Blauwet M, Koch G, Gettes L: Exaggerated atrial repolarization waves as a predictor of false positive exercise tests in an unselected population. Journal of Electrocardiology . 1995; 28 (4): 313-321 Publisher Full Text 2. Gardin J, Isner J, Ronan J, Fox S: Pseudoischemic “false positive” S-T segment changes induced by hyperventilation in patients with mitral valve prolapse. The American Journal of Cardiology . 1980; 45 (5): 952-958 Publisher Full Text 3. Tebbe U, Schicha H, Neumann P, Voth E, et al.: Mitral valve prolapse in the ventriculogram: scintigraphic, electrocardiographic, and hemodynamic abnormalities. Clin Cardiol . 1985; 8 (6): 341-7 PubMed Abstract | Publisher Full Text 4. Sonaglioni A, Nicolosi GL, Lombardo M, Anzà C, et al.: False-positive electrocardiographic changes during exercise test in a patient with pectus excavatum. J Clin Ultrasound . 2020; 48 (9): 579-584 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Cardiology, echocardiographiy, exercise stress echocardiography, heart failure, mitral valve prolapse, pectus excavatum, atrial fibrillation, heart failure, aortic stenosis, pulmonary hypertension, coronary artery disease I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Sonaglioni A. Reviewer Report For: Predicting the incidence of recurrent positive exercise stress tests among civilian pilots: a retrospective cohort study [version 1; peer review: 1 approved with reservations] . F1000Research 2024, 13 :1122 ( https://doi.org/10.5256/f1000research.170268.r331311 ) The direct URL for this report is: https://f1000research.com/articles/13-1122/v1#referee-response-331311 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 03 Oct 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 Version 1 03 Oct 24 read Andrea Sonaglioni , MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Sonaglioni A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 15 Oct 2024 | for Version 1 Andrea Sonaglioni , MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy 0 Views copyright © 2024 Sonaglioni A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions In this interesting paper, the Authors found that an age of 60-65 yrs, a THF of >275 hours in the last 6 months and dyslipidemia were independently correlated with recurrently positive EST among civilian pilots In Indonesia. The Authors stated that 37.9% of pilots with positive EST underwent a cardiac intervention to confirm CAD. How many pilots had obstructive CAD on subsequent coronary angiography? Could the Authors add in the Results section the percentage of false positive EST results? It is known that EST has a low specificity for detecting CAD, due to a great number of false positive EST results. At the end of the Discussion section, the Authors could add a paragraph concerning the potential causes of false positive EST results. I suggest the Authors to discuss a number of exercise-induced ST-segment changes simulating myocardial ischemia, such as those described in individuals with exaggerated atrial repolarization waves (Ta wave), in hyperventilating individuals, in individuals with mitral valve prolapse and finally in individuals with concave-shaped chest wall and/or pectus excavatum. The Authors could cite and discuss the following references: Sapin P, et al., 1995 (Ref 1) Gardin J, et al.,1980 (Ref 2) Tebbe U, et al., 1985 (Ref 3) Sonaglioni A, et al., 2020 (Ref 4) Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes References 1. Sapin P, Blauwet M, Koch G, Gettes L: Exaggerated atrial repolarization waves as a predictor of false positive exercise tests in an unselected population. Journal of Electrocardiology . 1995; 28 (4): 313-321 Publisher Full Text 2. Gardin J, Isner J, Ronan J, Fox S: Pseudoischemic “false positive” S-T segment changes induced by hyperventilation in patients with mitral valve prolapse. The American Journal of Cardiology . 1980; 45 (5): 952-958 Publisher Full Text 3. Tebbe U, Schicha H, Neumann P, Voth E, et al.: Mitral valve prolapse in the ventriculogram: scintigraphic, electrocardiographic, and hemodynamic abnormalities. Clin Cardiol . 1985; 8 (6): 341-7 PubMed Abstract | Publisher Full Text 4. Sonaglioni A, Nicolosi GL, Lombardo M, Anzà C, et al.: False-positive electrocardiographic changes during exercise test in a patient with pectus excavatum. J Clin Ultrasound . 2020; 48 (9): 579-584 PubMed Abstract | Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Cardiology, echocardiographiy, exercise stress echocardiography, heart failure, mitral valve prolapse, pectus excavatum, atrial fibrillation, heart failure, aortic stenosis, pulmonary hypertension, coronary artery disease I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Sonaglioni A. Peer Review Report For: Predicting the incidence of recurrent positive exercise stress tests among civilian pilots: a retrospective cohort study [version 1; peer review: 1 approved with reservations] . 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