Our observation of only a small, but statistically insignificant, decrease in annual AAA growth rates does not preclude meaningful clinical effects, because the growth rate reduction estimated from natural genetic variation does not necessarily relate to the magnitude of the benefit that might result from pharmacological treatment directed at the IL-6 trans-signaling pathway.36 Selective blocking of the IL-6 trans-signaling pathway using sgp130Fc is being investigated in phase II clinical trials in patients with inflammatory bowel disease.14 Here, IL6 is linked to triple-A syndrome.