Association of Markers of Intravascular Cellular Interaction with Carotid Intima Medial Thickness in Postmenopausal Women

Abstract

Objective: Increases in carotid intima medial thickness (CIMT) reflect unwanted intravascular cellular interactions and activations and increased risk of stroke. This study aimed to evaluate interactions among intravascular cells and cellular origin of microvesicles (MV) released from activated cells that might contribute to increased cardiovascular disease risk in postmenopausal women. Methods: Postmenopausal women (n=75) who completed the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic, Rochester MN, were invited to participate for follow-up evaluation. Blood samples were drawn into protease inhibitors anticoagulant tubes. CIMT was evaluated by B-mode ultrasound at study baseline, years 1-4 during KEEPS and at 3 year follow-up. Intravascular cells interactions and cellular origin of MV in peripheral blood were measured by digital flow cytometer. Results: The average age and month past menopause is 60 ± 2 years and 103 ± 9 months respectively. Conventional cardiovascular risk factors were within the normative ranges. CIMT increased 9.8 ± 8.7% from year 1 to 7 and positively correlated with age (ρ = 0.36, P<0.0001) and month past menopause (ρ = 0.23, P<0.0001). CIMT also positively correlated with mean platelet volume (ρ = 0.24, P=0.02), total leukocytes-derived MV (ρ = 0.26, P=0.004), percentage of circulating lymphocytes carrying platelet antigen (ρ = 0.26, P=0.03), and endothelial antigen (ρ = 0.25, P=0.003). Conclusion These results suggest that intravascular cellular activations and interactions may contribute to vascular remodeling with age in apparently healthy postmenopausal women. Funding: Aurora Foundation and NIH AG044170.