HIV patients today experience an increasing burden of coronary artery disease (CAD). Although it has been postulated that increased inflammation interacts with traditional risk factors to accelerate atherosclerosis in HIV patients, the importane of inflammation per se in the pathogenesis of CAD in HIV patients is not known. This critical gap in knowledge about CAD pathogenesis was identified by the NHLBI Working Group on """"""""Advancing HIV/AIDS Research in Heart, Lung, and Blood Diseases"""""""" last year and it is important not only for our understanding of in vivo vascular biology in the setting of HIV but also for defining the role, if any, for anti- inflammatory approaches in altering CAD in HIV patients. Anti-inflammatory strategies have been associated with lower cardiovascular event rates in individuals with inflammatory autoimmune disease and are appealing in HIV populations but are not currently used in practice because of the lack of an established and easily obtained measure of the effect of inflammation on the processes which result in coronary atherosclerosis and because no clinical trial has established whether an anti-inflammatory strategy alone alters these processes. Inflammation contributes to the process of coronary endothelial dysfunction which plays a pivotal role in the development, progression, and clinical manifestations of CAD, and is a marker for sub-clinical disease, an independent predictor of adverse cardiovascular events, and a potential target for medical interventions. We recently developed noninvasive, reproducible MRI-based methods to measure coronary endothelial function (CEF). We propose a placebo-controlled, double blind, single-center mechanistic trial to test the hypothesis that the anti-inflammatory approach, low dose colchicine (LDC), improves impaired local CEF in HIV patients with subclinical CAD. The studies will provide novel much-needed mechanistic insight into the potential of anti- inflammatory strategies to reduce coronary endothelial dysfunction, which inflammatory biomarkers herald the CEF response, the relationship of CAD and CEF with epicardial adipose tissue (a purported local paracrine source of inflammatory mediators), and whether a heterogeneous CEF response occurs with differential effects in more severely than mildly diseased coronary vessels, suggesting local anti-inflammatory effects. In addition to this novel mechanistic information, the findings with a clinically available drug could be more rapidly translated to practice.

Public Health Relevance

Inflammation, the body's immune response, is thought to contribute, along with cholesterol, high-blood pressure and other risk factors, to coronary artery heart disease in patients with HIV. However anti-inflammatory treatment strategies are not used in clinical practice for patients with HIV and heart disease. This study proposes to test the effec of an anti-inflammatory strategy, currently used for noncardiac diseases, to determine whether it can reduce inflammation and improve the biologic health and the response of diseased coronary arteries in patients with HIV and heart disease.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
High Priority, Short Term Project Award (R56)
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Special Emphasis Panel (ZHL1-CSR-B (M1))
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Kirby, Ruth
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Johns Hopkins University
Schools of Medicine
United States
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Bonanno, Gabriele; Hays, Allison G; Weiss, Robert G et al. (2018) Self-gated golden angle spiral cine MRI for coronary endothelial function assessment. Magn Reson Med 80:560-570
Hays, Allison G; Iantorno, Micaela; Schär, Michael et al. (2017) Local coronary wall eccentricity and endothelial function are closely related in patients with atherosclerotic coronary artery disease. J Cardiovasc Magn Reson 19:51
Iantorno, Micaela; Schär, Michael; Soleimanifard, Sahar et al. (2017) Coronary artery endothelial dysfunction is present in HIV-positive individuals without significant coronary artery disease. AIDS 31:1281-1289
Iantorno, Micaela; Hays, Allison G; Schär, Michael et al. (2016) Simultaneous Noninvasive Assessment of Systemic and Coronary Endothelial Function. Circ Cardiovasc Imaging 9:e003954
Hays, Allison G; Iantorno, Micaela; Soleimanifard, Sahar et al. (2015) Coronary vasomotor responses to isometric handgrip exercise are primarily mediated by nitric oxide: a noninvasive MRI test of coronary endothelial function. Am J Physiol Heart Circ Physiol 308:H1343-50