The ARIC carotid MRI study of blood cellular markers: an inverse association of monocyte myeloperoxidase content with peripheral arterial disease

Abstract

We evaluated the association of blood monocyte and platelet activation markers with the risk of peripheral artery disease (PAD) in a multicenter study of atherosclerosis among African American and Caucasian patients. Flow cytometric analysis of blood cells was performed in 1791 participants (209 cases with PAD and 1582 noncases) from the cross-sectional Atherosclerosis Risk in Communities Carotid Magnetic Resonance Imaging ([MRI] ARIC Carotid MRI) Study to assess platelet glycoproteins IIb and IIIa, P-selectin, CD40 ligand, platelet-leukocyte aggregates, monocyte lipopolysaccharide receptor, toll-like receptors (TLRs) 2 and 4, P-selectin glycoprotein ligand 1, cyclooxygenase 2, and myeloperoxidase. Multivariate regression analyses evaluated the association of cellular markers with the risk of PAD. After adjusting for age, race, and gender, platelet CD40L, and monocyte myeloperoxidase (mMPO) levels were significantly lower (P < .001), and monocyte TLR-4 levels were higher (P = .03) in patients with PAD. With additional adjustments for conventional risk factors, mMPO remained inversely and independently associated with the risk of PAD (odds ratio [OR]: 0.35, P = .01).

Figure 1

A, Adjusted odds ratios (ORs) of PAD by tertile of monocyte myeloperoxidase (mMPO, MFI). Tertile 1 (white bars): 6.1–79.9; tertile 2 (shaded bars): 79.9–100; tertile 3 (black bars): 100–209.1. B, Adjusted odds ratios (ORs) of PAD by tertile of monocyte TLR-4 (%). Tertile 1 (white bars): 49.3–63.4; tertile 2 (shaded bars): 63.4–66.7; tertile 3 (black bars): 66.7–95.0. Model 1: Adjusted for age, race, and gender. Model 2: Also adjusted for diabetes, waist-to-hip ratio, TC, HDL, CRP, smoking status, hypertension and lipid-lowering medication use. PAD indicates peripheral arterial disease; MFI, median fluorescent intensity; TLR, toll-like receptor; TC, total cholesterol; HDL, high-density lipoprotein; CRP, C-reactive protein.