Increased intermediate CD14++CD16++ monocyte subset levels associate with restenosis after peripheral percutaneous transluminal angioplasty

- Monocyte subset distributions are differentially affected by angioplasty of lower limb arteries in patients with and without restenosis.
- Increased frequencies of CD14++CD16++ 'intermediate' monocytes are predictive for the development of restenosis after percutaneous transluminal angioplasty of lower limb arteries.
- 'Intermediate' monocytes display an upregulated intracellular myeloperoxidase content, associated with a higher restenosis risk.
- Monocyte subset distributions and phenotype may indicate individuals at higher risk for restenosis.

Background and aimsWe aimed at studying the association of three major human monocyte subsets after percutaneous transluminal angioplasty (PTA) in patients with femoropopliteal disease.MethodsWe prospectively studied 67 sequential patients (40 male, 27 female; mean age 71 ± 11 years) treated with femoropopliteal angioplasty. Multi-color flow cytometry characterized monocyte subsets from venous blood for expression of CD14 and CD16 and intracellular myeloperoxidase (MPO) prior to, and 3, 6 and 12 months post PTA. Analyses tested associations between monocyte subsets and risk for restenosis.Results16/67 patients (24%) developed restenosis within 12 months after PTA. Patients with hyperlipidemia had increased risk for restenosis (HR = 1.7, 95% CI 0.7-2.9, p = 0.001). Increased baseline monocytes associated with an increased risk of late restenosis (HR = 4.9, 95% CI: 1.3-18.6, p = 0.047). CD14++CD16++ 'intermediate' monocytes assessed at baseline, and after 3, 6, and 12 months significantly associated with the risk for subsequent restenosis: HR = 3.9 (95% CI: 2.4-6.5, p = 0.029), HR = 5.7 (95% CI = 0.7-44.7, p = 0.013), HR = 6.5 (95% CI: 2.5-16.9, p = 0.001) and HR = 1.5 (95% CI = 1.4-15.5 p = 0.001), respectively. Moreover, the probability for freedom of restenosis decreased with increased levels of intermediate subsets at 12 months after PTA. Additionally, intracellular MPO expression in CD14++CD16++ measured at 3, 6 and 12 months associated with an increased restenosis risk (HR = 1.5, 95% CI: 0.8-2.1, p = 0.214, HR = 1.9, 95% CI: 1.0-2.3 p = 0.051 and HR = 1.4, 95% CI: 1.0-1.8, p = 0.052).ConclusionsOur results imply altered innate immunity after angioplasty. Elevated CD14++CD16++ intermediate monocyte frequencies and increased MPO expression may identify individuals at heightened risk for restenosis.