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

Abstract

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.

PI3Kgamma promotes neutrophil extracellular trap formation by noncanonical pyroptosis in abdominal aortic aneurysm

“…Among inflammatory cells, neutrophils are recruited to the aortic wall at early stage of AAA formation 8 . A prospective cohort study showed a strong positive association between neutrophil count and AAA development, independent of other traditional risk factors such as smoking, obesity, and atherosclerosis 9 . Limiting neutrophil recruitment to the arterial wall significantly reduced the incidence of elastase-perfusion AAA 10 , and inhibition of neutrophils using anti-neutrophil antibodies can be also effective in limiting the progression of experimental AAA 8 .…”

Research Advances in Abdominal Aortic Aneurysms: Triglyceride-Rich Lipoproteins as a Therapeutic Target

“…In the landmark ARIC study (Atherosclerosis Risk in Communities) of >10 000 diverse participants from 3 communities, >300 individuals developed AAA over a median follow-up of ≈23 years. 2,3 Among the risk factors for incident AAAs included elevated plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations. 2 Despite strong epidemiological evidence linking LDL-C to AAAs, connecting pharmacological LDL-C lowering with the prevention of AAA growth and rupture has remained elusive.…”

“…2,3 Among the risk factors for incident AAAs included elevated plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations. 2 Despite strong epidemiological evidence linking LDL-C to AAAs, connecting pharmacological LDL-C lowering with the prevention of AAA growth and rupture has remained elusive. Several observational studies have suggested associations between statin use and lower rates of AAA growth and rupture, 4–7 but findings have not been consistent.…”