Air Travel and Cardiovascular Disease

Stephen E. Possick, MD; Michèle Barry, MD, FACP

Disclosures

J Travel Med. 2004;11(4) 

In This Article

Pulmonary Embolism and Deep Venous Thromboembolism During Air Travel

DVT and thromboembolism have long been proposed as possible complications of air travel. Pulmonary embolism (PE) has been suggested as a culprit in deaths related to air travel, although evidence linking air travel to DVT has been somewhat elusive.[28,29,30] Sarvesvaran found that 18% of sudden deaths among long-distance travelers over a 3-year period at Heathrow were attributable to PE.[28] Lapostolle et al. recently described 56 cases of PE discovered at Charles de Gaulle Airport from 1993 to 2000.[30] They found that distance traveled was a significant risk factor for the development of PE, with those who traveled over 5,000 km being at the highest risk.[30] Perez-Rodriguez et al. documented an incidence of 1.65 PEs per million in passengers traveling for more than 8h between January 1995 and December 2000 at Madrid-Barajas airport.[31] Scurr et al. demonstrated that the risk of symptomless calf DVT was as high as 10% in subjects over 50 years of age on flights longer than 8h.[32] Subjects with cardiorespiratory disease, however, were excluded from the study population. Schwarz et al. found a somewhat lower risk of isolated calf venous thrombosis in a population of 964 travelers flying for an average of 8h or more:[33] 2.1% of travelers vs. 0.8% of controls were diagnosed with symptomless calf venous thrombosis. The rate of DVT in the traveling cohort was 0.7%, compared to 0.2% in the control group. Travelers with cardiovascular disease were not excluded. Although calf DVT may not lead to significant morbidity, others have shown that calf DVT can extend to more proximal sites in up to 20% of patients and is associated with a risk of PE as high as 10%.[34]

The Lonflit 1 study was planned to evaluate the incidence of DVT as a consequence of long fights in economy class. DVT diagnosis was made by comparing ultrasound scans 48h before flying and 24h after flying.[35] The study evaluated 355 subjects at low risk for DVT and 389 at high risk, defined as prior DVT, malignancy within 2 years, limited mobility, coagulation disorders or large varicose veins.[35] Subjects with artificial cardiac valves, diabetes, hypertension, renal or hepatic insufficiency and pacemakers were excluded.[35] No DVTs were found in the low-risk group, whereas 2.8% of the high-risk group were found to have evidence of new thrombosis after an average of 12.4h of flying; almost all cases (94.7%) were observed in subjects sitting in window or central seats. The putative mechanisms of increased risk during air travel include venous stasis, fluid retention, hemoconcentration secondary to dehydration, and increased erythropoietin levels.[36] Decreased PaO2 may also play a role by interfering with fibrinolysis and activating the coagulation cascade.[37,38] Congestive heart failure has long been proposed as a risk factor for venous thromboembolism (VTE). Chronic hypercoagulability and venous stasis have both been proposed as possible mechanisms. Howell et al. found that a left ventricular ejection fraction (LVEF) between 20% and 44% was associated with an increased risk of VTE, with an odds ratio of 2.8 (95% CI 1.4-5.7%) in a population of Veteran's administration patients.[39] LVEF <20% was associated with an odds ratio of 38.3 (95% CI 9.6-152.5%) for VTE.[39]

Although it has been difficult to draw significant conclusions regarding the prevalence of DVT and PE secondary to air travel, compression stockings have been proven to decrease the incidence of calf DVT and may decrease the overall risk of more proximal DVT and PE. Scurr et al. presented compelling evidence that superficial calf DVT may be prevented by the use of graduated elastic compression stockings.[32] The selection criteria excluded patients with cardiorespiratory disease, malignancy, and prior venous thrombosis. All subjects were over 50 years of age. None of the 115 patients who wore compression stockings were found to have calf DVTs after flights of more than 8h.[32] The Lonflit 4 trial provided further evidence of the efficacy of compression stockings in the prevention of lower extremity venous thrombosis in low- to medium-risk patients.[40] No lower extremity venous thromboses were detected among 184 subjects in the group randomized to compression stockings, whereas four deep venous thromboses and two superficial thromboses were discovered in the control group of 188 patients. All subjects traveled for 7 to 8h by air in economy class. The Lonflit 2 trial supports the use of compression stockings in populations at high risk for DVT.[35] In Lonflit 2, 833 subjects believed to be at high risk for DVT based on prior DVT, coagulation disorders, neoplastic disease, large varicose veins or limited mobility were prospectively randomized to below-the-knee compression stockings or no intervention during air travel lasting for an average of 12.4h. Twenty-two DVTs were identified in 19 of the 422 subjects in the control group, whereas only one DVT was found in the 411 subjects who wore below-the-knee elastic compression stockings.[35] In both groups, all subjects were seated in window or central seats.

The role of aspirin therapy in the prevention of VTE has been a subject of considerable debate. The most recent guidelines from the American College of Chest Physicians do not recommend the use of aspirin as prophylaxis for venous thrombosis, although the guidelines do not specifically address the issue of air travel and venous thrombosis.[41] The authors cite the superior efficacy of other agents, notably low-molecular-weight heparin (LMWH), unfractionated heparin and warfarin, in making their recommendations. The prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial randomized 13,356 patients undergoing surgery for hip fracture and 4,088 patients undergoing elective arthroplasty to 160mg daily aspirin therapy or placebo started preoperatively and continued for 35 days.[42] The use of other thromboprophylactic measures was permitted. Eighteen percent of patients were treated with unfractionated heparin, 26% with LMWH, and 30% with thromboembolic-deterrent stockings. Aspirin therapy reduced the risk of PE and DVT by 34% in the combined groups, with a similar proportional risk reduction in those treated with heparin. In those patients taking aspirin alone vs. placebo, the risk of bleeding was 2.6% vs. 2.5%. The concomitant use of other thromboprophylaxis and the high-risk nature of the patient population make any extrapolation to other populations quite difficult.

Lonflit 3 evaluated the efficacy of aspirin and LMWH in the prevention of DVT in 300 high-risk subjects traveling for more than 10h by air.[43] Patients were defined as high risk if they had had prior DVT, a coagulation disorder, obesity or severely limited mobility, malignancy within the preceding 2 years, or large varicose veins. Patients with cardiovascular disease, diabetes and hypertension were excluded. The control group received no intervention. The aspirin group received 400mg of aspirin daily for 3 days, beginning 12h before the start of air travel. The LMWH group received one dose of enoxaparin 2 to 4h prior to the flight, based on a weight-adjusted protocol. Six DVTs were discovered in the control group involving four patients, whereas three DVTs involving three patients were found in the aspirin arm. The p-value for number of limbs involved was <.05, but was not statistically significant when the number of patients with DVT was analyzed. No DVTs were identified in the enoxaparin arm. The p-value was <.002 for limbs affected when compared to controls. The statistical significance of enoxaparin compared to aspirin was not given. It is difficult to make inferences for either the population in question or air travelers as a whole based on this study. The small size of the study, the small number of patients with DVT and the lack of statistical significance when numbers of patients with DVT are compared in the aspirin and placebo groups do not allow justification of aspirin therapy in this group. The PEP trial would support the use of a 160-mg dose rather than 400mg in any subsequent study. The use of LMWH has been shown to be efficacious in the prevention of DVT in high-risk populations and is recommended for DVT prophylaxis in high-risk postoperative patients.[41] Lonflit 3 supports the utility of LMWH in high-risk populations during air travel.

Compression stockings appear to represent a reasonable measure in all travelers over the age of 50 years who fly for more than 8h or further than 5,000km in a single journey. Whereas Lonflit 3 excluded patients with cardiovascular disease, many travelers with cardiac disease will be on chronic aspirin therapy prior to embarking on air travel. The appropriate dose of aspirin and its specific role in this population remain unclear. Lonflit 3 suggests that aspirin would not be of great utility in a moderate-risk population, as it did not significantly alter the incidence of DVT in a high-risk population. A retrospective trial analyzing the incidence of symptomatic DVT and PE in patients on chronic aspirin therapy would require a large number of patients, but is quite feasible. LMWH may prove useful in patients at particularly high risk for DVT who are not maintained on chronic anticoagulation. Avoidance of constrictive clothing, avoidance of leg crossing and participation in minor physical activity during flights are likely to have some efficacy as well, although this has not been proven. Aisle seating, avoidance of tobacco and alcohol-containing beverages, and increased consumption of fluids may also be of benefit. Based on the best available evidence, we recommend a risk stratification system for travelers with cardiac disease and prophylactic measures to prevent thromboembolism in Table 5 .

Future randomized prospective trials identifying high-risk patients who may require anticoagulation are needed in travelers with cardiac disease.

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