Abstract P327: Inflammation Associates With Lower Myocardial Function Among Antiretroviral-Treated Persons Living With HIV in South Africa

Abstract

Introduction: HIV-associated inflammation contributes to higher CVD risk among persons living with HIV (PLWH). Heart failure (HF) is a prominent CVD manifestation in sub-Saharan Africa where HIV prevalence is high. Systolic dysfunction is a well-known complication of untreated, advanced HIV disease, but it is unknown if ongoing inflammation contributes to myocardial dysfunction during antiretroviral therapy (ART). We evaluated myocardial function via cardiac magnetic resonance (CMR) and studied associations with inflammatory biomarkers among ART-treated PLWH residing in Khayelitsha township near Cape Town, South Africa. Methods: CMR images were ascertained via a large bore 3T Siemens Skyra MRI scanner using standardized protocols. Biomarkers were measured from stored plasma using immunoassays and were log 2 -transformed for analyses. Linear regression was used to evaluate cross-sectional associations between CMR parameters and biomarker concentrations, adjusted for age, sex, current smoking, and hypertension. Results: Among 133 ART-treated PLWH without known CVD, 64% (85) were female, 99% (132) were Black African, 29% (39) were smokers, 92% (123) had undetectable HIV viral load, mean (SD) age was 50 (9) years, and current and nadir CD4+ count were 535 (270) and 271 (213) cells/μL, respectively. Higher TNFR1, TNF-α, and IFN-γ were associated with lower left ventricular ejection fraction (p=0.03, 0.05, and 0.03, respectively) and systolic global circumferential strain (p=0.01, 0.04, and 0.02) ( Table ). Higher TNFR1 was also associated with lower diastolic strain rate in circumferential (p=0.02), longitudinal (p=0.05), and radial (p=0.01) planes. Conclusion: These data suggest inflammation may contribute to lower myocardial function among ART-treated PLWH prior to development of clinical HF. The magnitude of this effect was modest, but potential long-term effects on myocardial tissue remodeling and subsequent HF risk warrant further investigation among a growing ART-treated population in South Africa.

Cardiovascular Disease Among Persons Living With HIV: New Insights Into Pathogenesis and Clinical Manifestations in a Global Context

“…Fibrosis is a common pathway of remodeling resulting from injury, stress, and inflammation. 88,89 82,83,85,[90][91][92][93][94][95][96][97][98] Compared with uninfected controls, the presence of diffuse or patchy fibrosis indicated by late gadolinium enhancement is severalfold higher among PLWH. 90,[92][93][94] The degree of fibrosis estimated by extracellular volume fraction index, using pre-and postcontrast T1 mapping, is also higher among PLWH compared with controls, but the magnitude varies greatly by study.…”

“…[92][93][94]96,98 Second, 2 studies specifically assessed monocyte activation through soluble biomarkers (eg, sCD163) or cell phenotypes reflecting proinflammatory monocytes with tissue migration markers, and demonstrated positive associations with extracellular volume fraction. 82,83 Last, an important thread through these data is that women with HIV often had higher extracellular volume fraction estimates of myocardial fibrosis than men with HIV, 85,91,95,97 and this difference may account for some of the overall effect reported by HIV status. 85 Research is needed to better characterize the potential interaction of sex and HIV status, considering underlying cardiometabolic risk, for myocardial fibrosis and clinical risk.…”

“…The second is recent data from studies of PLWH reporting associations between cardiac magnetic resonance imaging (CMR) estimates of myocardial fibrosis with circulating levels of sCD163 and monocyte phenotypes reflecting tissue migration. 82,83 In summary, the proposed pathophysiology of HFpEF (Figure 4) may be amplified by well-described features of chronic HIV disease, including systemic inflammation, microvascular dysfunction, and proinflammatory monocytes and tissue macrophages.…”

HIV-Associated Cardiovascular Disease Pathogenesis: An Emerging Understanding Through Imaging and Immunology

“…However, a South African study failed to identify a link between circulating inflammatory proteins (TNFR-I [tumor necrosis factor receptor 1], IL-6, sCD14, and sCD163) and myocardial fibrosis as measured by extracellular volume fraction. 49 Myocardial fibrosis has been positively associated with percentages of circulating nonclassical and intermediate monocyte phenotypes that reflect inflammation and tissue injury. 49…”

“…49 Myocardial fibrosis has been positively associated with percentages of circulating nonclassical and intermediate monocyte phenotypes that reflect inflammation and tissue injury. 49…”