Juan Lin1, Xiaonan Xue1, Kathryn Anastos1,2, Mardge H Cohen3, Stephen J Gange4, Jason M Lazar5, Chenglong Liu6, Wendy J Mack7, Phyllis C Tien8,9, Cathy Tilley10, Howard N Hodis7, Alan L Landay11, Russell P Tracy10, Robert C Kaplan1,12, David B Hanna1. 1. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY. 2. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY. 3. Department of Medicine, John H. Stroger Hospital, Chicago, IL. 4. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 5. Department of Medicine, SUNY-Downstate Medical Center, Brooklyn, NY. 6. Department of Medicine, Georgetown University Medical Center, Washington, DC. 7. Department of Preventive Medicine, University of Southern California, Los Angeles, CA. 8. Department of Veterans Affairs, University of California, San Francisco, San Francisco, CA. 9. Department of Medicine, University of California, San Francisco, San Francisco, CA. 10. Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT. 11. Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL. 12. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Abstract
BACKGROUND: Expression of tissue factor (TF) on the surface of activated monocytes may trigger thrombosis, leading to clotting risk, inflammation, and atherosclerosis. TF-positive microparticles (MP-TF) represent a functionally active form of TF that may be promulgated by long-term HIV infection. We hypothesized that greater MP-TF activity is associated with carotid artery plaque in HIV+ women. SETTING: In a case-control study nested within the Women's Interagency HIV Study (WIHS), eligible HIV+ participants underwent B-mode carotid artery ultrasound at 2 study visits occurring 7 years apart. Cases were defined by the presence of at least 1 carotid artery plaque assessed at either visit. Cases were matched 1:2 to controls who were found not to have carotid artery plaques. METHODS: Conditional logistic regression estimated the association of MP-TF activity with the presence of carotid artery plaque, adjusting for demographic and behavioral characteristics, HIV-related factors, cardiometabolic risk factors, and serum inflammation biomarkers (high-sensitivity C-reactive protein, IL-6, sCD14, sCD163, Gal-3, and Gal-3BP). RESULTS: Elevated MP-TF activity (>0.537 pg/mL) was found to be significantly associated with greater odds of plaque (adjusted odds ratio 3.86, 95% confidence interval: 1.06 to 14.07, P = 0.04). The association was attenuated after further adjustment for IL-6 but was unaffected by adjustment for other biomarkers including those denoting monocyte activation. CONCLUSIONS: Our findings suggest a link among HIV infection, innate immune system perturbation, coagulation, and atherosclerosis.
BACKGROUND: Expression of tissue factor (TF) on the surface of activated monocytes may trigger thrombosis, leading to clotting risk, inflammation, and atherosclerosis. TF-positive microparticles (MP-TF) represent a functionally active form of TF that may be promulgated by long-term HIV infection. We hypothesized that greater MP-TF activity is associated with carotid artery plaque in HIV+ women. SETTING: In a case-control study nested within the Women's Interagency HIV Study (WIHS), eligible HIV+ participants underwent B-mode carotid artery ultrasound at 2 study visits occurring 7 years apart. Cases were defined by the presence of at least 1 carotid artery plaque assessed at either visit. Cases were matched 1:2 to controls who were found not to have carotid artery plaques. METHODS: Conditional logistic regression estimated the association of MP-TF activity with the presence of carotid artery plaque, adjusting for demographic and behavioral characteristics, HIV-related factors, cardiometabolic risk factors, and serum inflammation biomarkers (high-sensitivity C-reactive protein, IL-6, sCD14, sCD163, Gal-3, and Gal-3BP). RESULTS: Elevated MP-TF activity (>0.537 pg/mL) was found to be significantly associated with greater odds of plaque (adjusted odds ratio 3.86, 95% confidence interval: 1.06 to 14.07, P = 0.04). The association was attenuated after further adjustment for IL-6 but was unaffected by adjustment for other biomarkers including those denoting monocyte activation. CONCLUSIONS: Our findings suggest a link among HIV infection, innate immune system perturbation, coagulation, and atherosclerosis.
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