Reduced lung function in patients with abdominal aortic aneurysm is associated with activation of inflammation and hemostasis, not smoking or cardiovascular disease.
OBJECTIVE
Abdominal aortic aneurysms often coexist with reduced lung function and chronic obstructive pulmonary disease (COPD). These conditions are each associated with cigarette smoking, cardiovascular disease, and evidence of increased inflammatory and hemostatic activity. The aim of this study was to determine if these factors accounted for the link between aneurysms and pulmonary disease.


METHODS
The design was a case-control study comparing patients with an asymptomatic abdominal aortic aneurysm with population-based controls without an aneurysm. Aneurysms were diagnosed by ultrasound scan, and pulmonary function was measured by respiratory questionnaire and spirometry. Activation of inflammation and hemostasis was measured by assay of plasma interleukin-6 (IL-6), fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator (tPA) antigen, fibrin D-dimer, and plasmin antiplasmin complexes.


RESULTS
Cases with an abdominal aortic aneurysm (n = 89) had more COPD and worse expiratory lung function as measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) than controls (n = 98) (FEV1, 1.9 vs 2.2 L, P < .01; FEV1/FVC, 0.67 vs 0.75, P < .001) and did not differ in restrictive function (FVC, 2.9 vs 3.0 L, P = .33). Cases also had higher levels of lifetime cigarette smoking (30 vs 24 pack-years, P < 0.01), cardiovascular disease (35% vs 18%, P = .01), plasma fibrinogen (3.5 vs 3.1 g/L, P = .02), IL-6 (2.8 vs 1.8, pg/mL, P < .001), plasmin antiplasmin complexes (596 vs 384 microg/L, P = .01), and D-dimer (442 vs 93 ng/mL, P < .001). On multiple logistic regression analysis of lung function and COPD on the risk of aneurysm, both cigarette smoking and cardiovascular disease had little effect on the relationships. For the markers of activated inflammation and hemostasis, plasmin antiplasmin complexes and D-dimer had the most important confounding effect on the odds ratios. All markers combined had a substantial effect: odds ratio of aneurysm for a one standard deviation decrease in FEV1 fell from 2.3 (95% confidence interval [CI], 1.5 to 3.5) (P < .01) to 1.3 (95% CI, 0.55 to 2.4) (P > or = .05).


CONCLUSIONS
The association between reduced respiratory function and abdominal aortic aneurysm was not accounted for by cigarette smoking or cardiovascular disease. We hypothesize that activation of inflammation and hemostasis in response to injury may be an important explanation of the association between aneurysm formation and reduced respiratory function. Further studies are required to test this hypothesis.
Fowkes
F Gerald R
FG
Wolfson Unit for Prevention of Peripheral Vascular Diseases, University of Edinburgh, Edinburgh, United Kingdom. Gerry.Fowkes@ed.ac.uk
Anandan
Chantelle L C
CL
Lee
Amanda J
AJ
Smith
Felicity B
FB
Tzoulaki
Ioanna
I
Rumley
Ann
A
Powell
Janet T
JT
Lowe
Gordon D O
GD
D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000150:complications; D016022:Case-Control Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D005541:Forced Expiratory Volume / Q000502:physiology; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology*; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications; D012907:Smoking / Q000009:adverse effects; D013147:Spirometry; D011795:Surveys and Questionnaires; D014463:Ultrasonography; D014797:Vital Capacity / Q000502:physiology; D000979:alpha-2-Antiplasmin / Q000032:analysis
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D000979:alpha-2-Antiplasmin; C036309:fibrin fragment D; D005340:Fibrinogen