Abstract 15132: Proteomic Signatures of Human Immunodeficiency Virus-Associated Subclinical Left Atrial Dilation

Abstract

Introduction: Persons living with HIV (PLWH) receiving combination antiretroviral therapy (cART) are at higher risk of heart failure (HF) and preceding cardiac abnormalities, including left atrial (LA) dilation, compared to persons without HIV (PWOH). Mechanisms of this excess risk are unclear. We assessed whether plasma proteomic signatures of immune activation are cross-sectionally associated with LA volume index (LAVi) and augmented among PLWH. Methods: We performed Olink proteomics on plasma obtained concurrently with cardiac magnetic resonance among PLWH and PWOH. Proteins were analyzed individually and as clusters agnostically defined using weighted gene co-expression network analysis. Associations with HIV serostatus and LAVi were estimated using multivariable linear regression with robust variance. We explored protein relationships using annotated enrichment analysis. Results: Among 352 participants (age 55±6 years; 25% female; 70% Black), mean LAVi was 29±9 mL/m 2 and 60% were PLWH (88% on cART; 73% with undetectable plasma HIV RNA). Of 2594 proteins, 104 were independently associated with LAVi (false discovery rate, FDR<0.05). We identified 49 of these as candidate contributors to the association between HIV seropositivity and higher LAVi (36 when excluding PLWH with detectable HIV RNA), enriched in T-cell activation and leukocyte cell adhesion regulators. We identified one protein cluster positively associated with LAVi and HIV seropositivity regardless of HIV suppression status, enriched in TNF signaling, ephrin signaling and extracellular matrix (ECM) organization. Conclusion: Proteomic signatures that may in part account for HIV-associated elevation in LAVi are enriched in pathways of immune activation, cytokine signaling and ECM organization, even among virally suppressed PLWH on cART. These findings support a link between persistent immune activation and subclinical LA dilation which may portend future risk for HF among PLWH.