Association of Differential Leukocyte Count With Incident Abdominal Aortic Aneurysm Over 22.5 Years: The ARIC Study

Objective: Leukocytes contribute to the development of abdominal aortic aneurysm (AAA). We evaluated whether associations of differential leukocyte counts with AAA persist after accounting for traditional risk factors of AAA. Approach and Results: Among 11 217 adults from the Atherosclerosis Risk in Communities Study, we evaluated associations of differential leukocyte counts at baseline (1987-1989) with incident AAAs over a median follow-up of 22.5 years, using Cox proportional hazards regression. Each differential leukocyte count was categorized into 5 groups - below normal, tertiles within the normal range, and above normal, with the first tertile serving as the referent. We identified 377 incident AAAs through 2011, using hospital discharge diagnoses, linked Medicare records, or death certificates. At baseline, higher neutrophil, monocyte, and eosinophil counts were associated with higher risk of AAA, independent of smoking, other differential leukocyte counts, and other traditional risk factors. The association with incident AAA was the strongest for above normal neutrophil count, with an adjusted hazard ratio (95% CI) of 2.17 (1.29-3.64). Below normal neutrophil, lymphocyte, eosinophil and basophil counts were associated with higher risk of AAA with adjusted hazard ratio (95% CI) between 1.86 (1.04-3.35) and 1.62 (1.10-2.39). Conclusions: Higher neutrophil, monocyte, and eosinophil counts in midlife are associated with higher risk of AAA, even after accounting for traditional risk factors such as smoking, obesity, and atherosclerosis. This suggests the need to identify nontraditional risk factors and treatment strategies to mitigate the residual risk of AAA conferred by midlife inflammation. Whether immunosuppression is associated with higher risk of AAA needs further investigation.