Role of T‐Cell Dysfunction, Inflammation, and Coagulation in Microvascular Disease in HIV
Background Compared to uninfected adults, HIV‐infected adults on antiretroviral therapy are at increased risk of cardiovascular disease. Given the increase in T‐cell dysfunction, inflammation, and coagulation in HIV infection, microvascular dysfunction is thought to contribute to this excess cardiov...
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| Language: | English |
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Wiley
2016-12-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.116.004243 |
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| author | Arjun Sinha Yifei Ma Rebecca Scherzer Sophia Hur Danny Li Peter Ganz Steven G. Deeks Priscilla Y. Hsue |
| author_facet | Arjun Sinha Yifei Ma Rebecca Scherzer Sophia Hur Danny Li Peter Ganz Steven G. Deeks Priscilla Y. Hsue |
| author_sort | Arjun Sinha |
| collection | DOAJ |
| description | Background Compared to uninfected adults, HIV‐infected adults on antiretroviral therapy are at increased risk of cardiovascular disease. Given the increase in T‐cell dysfunction, inflammation, and coagulation in HIV infection, microvascular dysfunction is thought to contribute to this excess cardiovascular risk. However, the relationships between these variables remain undefined. Methods and Results This was a cross‐sectional study of 358 HIV‐infected adults from the SCOPE cohort. Macrovascular endothelial function was assessed using flow‐mediated dilation of the brachial artery and microvascular function by reactive hyperemia. T‐cell phenotype was determined by flow cytometry. Plasma markers of inflammation (tumor necrosis factor‐α, interleukin‐6, high‐sensitivity C‐reactive protein, sCD14) and coagulation (fibrinogen, D‐dimer) were also measured. In all HIV+ subjects, markers of inflammation (tumor necrosis factor‐α, high‐sensitivity C‐reactive protein), coagulation (D‐dimer) and T‐cell activation (CD8+PD1+, CD4+interferon+cytomegalovirus‐specific) were associated with worse reactive hyperemia after adjusting for traditional cardiovascular risk factors and co‐infections. In treated and suppressed subjects, tumor necrosis factor‐α and CD8+PD1+ cells remained associated with worse reactive hyperemia after adjustment. Compared to the untreated subjects, CD8+PD1+ cells were increased in the virally suppressed group. Reactive hyperemia was predictive of flow‐mediated dilation. Conclusions CD8+PD1+ cells and tumor necrosis factor‐α were associated with microvascular dysfunction in all HIV+ subjects and the treated and suppressed group. Additionally, D‐dimer, high‐sensitivity C‐reactive protein, sCD‐14, and interleukin‐6 were associated with microvascular dysfunction in all HIV+ subjects. Although T‐cell dysfunction, inflammation, and microvascular dysfunction are thought to play a role in cardiovascular disease in HIV, this study is the first to look at which T‐cell and inflammatory markers are associated with microvascular dysfunction in HIV‐infected individuals. |
| format | Article |
| id | doaj-art-36d4bfd0b8134a559c57c853df794d89 |
| institution | DOAJ |
| issn | 2047-9980 |
| language | English |
| publishDate | 2016-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-36d4bfd0b8134a559c57c853df794d892025-08-20T02:44:29ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-12-0151210.1161/JAHA.116.004243Role of T‐Cell Dysfunction, Inflammation, and Coagulation in Microvascular Disease in HIVArjun Sinha0Yifei Ma1Rebecca Scherzer2Sophia Hur3Danny Li4Peter Ganz5Steven G. Deeks6Priscilla Y. Hsue7Department of Medicine University of California San Francisco CADepartment of Medicine San Francisco Veterans Affairs Medical Center University of California San Francisco CADepartment of Medicine San Francisco Veterans Affairs Medical Center University of California San Francisco CADivision of Cardiology Department of Medicine San Francisco General Hospital University of California San Francisco CADivision of Cardiology Department of Medicine San Francisco General Hospital University of California San Francisco CADivision of Cardiology Department of Medicine San Francisco General Hospital University of California San Francisco CAThe Positive Health Program San Francisco General Hospital San Francisco CADivision of Cardiology Department of Medicine San Francisco General Hospital University of California San Francisco CABackground Compared to uninfected adults, HIV‐infected adults on antiretroviral therapy are at increased risk of cardiovascular disease. Given the increase in T‐cell dysfunction, inflammation, and coagulation in HIV infection, microvascular dysfunction is thought to contribute to this excess cardiovascular risk. However, the relationships between these variables remain undefined. Methods and Results This was a cross‐sectional study of 358 HIV‐infected adults from the SCOPE cohort. Macrovascular endothelial function was assessed using flow‐mediated dilation of the brachial artery and microvascular function by reactive hyperemia. T‐cell phenotype was determined by flow cytometry. Plasma markers of inflammation (tumor necrosis factor‐α, interleukin‐6, high‐sensitivity C‐reactive protein, sCD14) and coagulation (fibrinogen, D‐dimer) were also measured. In all HIV+ subjects, markers of inflammation (tumor necrosis factor‐α, high‐sensitivity C‐reactive protein), coagulation (D‐dimer) and T‐cell activation (CD8+PD1+, CD4+interferon+cytomegalovirus‐specific) were associated with worse reactive hyperemia after adjusting for traditional cardiovascular risk factors and co‐infections. In treated and suppressed subjects, tumor necrosis factor‐α and CD8+PD1+ cells remained associated with worse reactive hyperemia after adjustment. Compared to the untreated subjects, CD8+PD1+ cells were increased in the virally suppressed group. Reactive hyperemia was predictive of flow‐mediated dilation. Conclusions CD8+PD1+ cells and tumor necrosis factor‐α were associated with microvascular dysfunction in all HIV+ subjects and the treated and suppressed group. Additionally, D‐dimer, high‐sensitivity C‐reactive protein, sCD‐14, and interleukin‐6 were associated with microvascular dysfunction in all HIV+ subjects. Although T‐cell dysfunction, inflammation, and microvascular dysfunction are thought to play a role in cardiovascular disease in HIV, this study is the first to look at which T‐cell and inflammatory markers are associated with microvascular dysfunction in HIV‐infected individuals.https://www.ahajournals.org/doi/10.1161/JAHA.116.004243coagulationHIVimmune systeminflammationmicrocirculation |
| spellingShingle | Arjun Sinha Yifei Ma Rebecca Scherzer Sophia Hur Danny Li Peter Ganz Steven G. Deeks Priscilla Y. Hsue Role of T‐Cell Dysfunction, Inflammation, and Coagulation in Microvascular Disease in HIV Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease coagulation HIV immune system inflammation microcirculation |
| title | Role of T‐Cell Dysfunction, Inflammation, and Coagulation in Microvascular Disease in HIV |
| title_full | Role of T‐Cell Dysfunction, Inflammation, and Coagulation in Microvascular Disease in HIV |
| title_fullStr | Role of T‐Cell Dysfunction, Inflammation, and Coagulation in Microvascular Disease in HIV |
| title_full_unstemmed | Role of T‐Cell Dysfunction, Inflammation, and Coagulation in Microvascular Disease in HIV |
| title_short | Role of T‐Cell Dysfunction, Inflammation, and Coagulation in Microvascular Disease in HIV |
| title_sort | role of t cell dysfunction inflammation and coagulation in microvascular disease in hiv |
| topic | coagulation HIV immune system inflammation microcirculation |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.116.004243 |
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