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

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

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.

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 R² = 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).

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.