Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure.

People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure.

Proteomics of left ventricular structure in the Multi-Ethnic Study of Atherosclerosis.

Aims: Proteomic profiling offers an expansive approach to biomarker discovery and mechanistic hypothesis generation for LV remodelling, a critical component of heart failure (HF). We sought to identify plasma proteins cross-sectionally associated with left ventricular (LV) size and geometry in a diverse population-based cohort without known cardiovascular disease (CVD).

Methods And Results: Among participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we quantified plasma abundances of 1305 proteins using an aptamer-based platform at exam 1 (2000-2002) and exam 5 (2010-2011) and assessed LV structure by cardiac magnetic resonance (CMR) at the same time points.

Relationship Between Myocardial NPPB Expression and Serum NT-proBNP in Heart Failure With Preserved Ejection Fraction.

“Low serum NT-proBNP in obese #HFpEF is related to lower myocardial synthesis at same hemodynamic load. #HFpEF thresholds for serum proBNP bias towards worse renal dz, less severe #obesity, worse #PH, impacting efficacy/generalizability.”

Proteomic Signature of HIV-Associated Subclinical Left Atrial Remodeling and Incident Heart Failure.

Background: People living with HIV (PLWH) are at higher risk of heart failure (HF) and preceding subclinical cardiac abnormalities, including left atrial dilation, compared to people without HIV (PWOH). Hypothesized mechanisms include premature aging linked to chronic immune activation. We leveraged plasma proteomics to identify potential novel contributors to HIV-associated differences in indexed left atrial volume (LAVi) among PLWH and PWOH and externally validated identified proteomic signatures with incident HF among a cohort of older PWOH.

Association Between Left Ventricular Scar and Ventricular Ectopy in People Living With and Without HIV.

Background: People living with HIV (PLWH) have greater risk for arrhythmic sudden death and heart failure than people without HIV (PWOH), though risk identifiers remain understudied. Higher ventricular ectopy (VE) burden reflects increased arrhythmic susceptibility and cardiomyopathy risk.

Objectives: The purpose of this study was to test if myocardial scar measured by late gadolinium-enhancement cardiovascular magnetic resonance (LGE-CMR) associates with VE by ambulatory electrocardiographic monitoring among PLWH and PWOH with risk factors for HIV, and if the association differs by HIV.

Myocardial extracellular volume fraction is positively associated with activated monocyte subsets among cART-treated persons living with HIV in South Africa.

Background: Despite treatment with combination antiretroviral therapy (cART), persons living with HIV (PLWH) are at higher risk of cardiac structural abnormalities that may presage clinical heart failure, including myocardial fibrosis. This study assessed whether circulating cellular and soluble protein markers of immune activation cross-sectionally associate with myocardial fibrosis among cART-treated PLWH in South Africa.

Methods: Participants were enrolled in Khayelitsha township near Cape Town, SA.

Circulating biomarker correlates of left atrial size and myocardial extracellular volume fraction among persons living with and without HIV.

Background: Infection with human immunodeficiency virus (HIV) is associated with higher risk for myocardial disease despite modern combination antiretroviral therapy (cART). Factors contributing to this excess risk, however, remain poorly characterized. We aimed to assess cross-sectional relationships between elevations of left atrial volume index (LAVI) and myocardial extracellular volume (ECV) fraction that have been reported in persons living with HIV and levels of circulating biomarkers of inflammation, fibrosis, and myocyte stretch among persons living with and without HIV (PLWH, PLWOH).

Myocardial Fibrosis Among Antiretroviral Therapy-Treated Persons With Human Immunodeficiency Virus in South Africa.

Background: Heart failure is a prominent cardiovascular disease (CVD) manifestation in sub-Sarahan Africa. Myocardial fibrosis is a central feature of heart failure that we aimed to characterize among persons with human immunodeficiency virus (PWH) in South Africa.

Methods: Cardiovascular magnetic resonance (CMR) imaging was performed among PWH with viral suppression and uninfected controls, both free of known CVD.

Elevated N-terminal prohormone of brain natriuretic peptide among persons living with HIV in a South African peri-urban township.

Aims: Efforts to improve access to antiretroviral therapy (ART) have shifted morbidity and mortality among persons living with HIV (PLWH) from AIDS to non-communicable diseases, such as cardiovascular disease (CVD). However, contemporary data on CVD among PLWH in sub-Saharan Africa in the current ART era are lacking. The aim of this study was to assess the burden of cardiac stress among PLWH in South Africa via measurement of N-terminal prohormone of brain natriuretic peptide (NT-proBNP).

Factor Xa Inhibition Reduces Coagulation Activity but Not Inflammation Among People With HIV: A Randomized Clinical Trial.

Background: Coagulation activity among persons with HIV is associated with end-organ disease risk, but the pathogenesis is not well characterized. We tested a hypothesis that hypercoagulation contributes to disease risk, in part, via upregulation of inflammation.

Methods: Treatment effects of edoxaban (30 mg), a direct factor Xa inhibitor, vs placebo were investigated in a randomized, double-blind crossover trial among participants with HIV and viral suppression and D-dimer levels ≥100 ng/mL.

Assessing inflammation and its role in comorbidities among persons living with HIV.

Purpose Of Review: This article describes the use of biomarkers in expanding our understanding of chronic non-AIDS comorbidities among persons living with HIV (PLWH) receiving antiretroviral therapy (ART).

Recent Findings: We review current evidence that biomarkers of chronic immune activation and inflammation associate with a broad spectrum of end-organ diseases in PLWH. We discuss how ART may impact inflammation associated with HIV infection and the degree to which inflammation persists despite effective suppression of viral replication in plasma.

Inflammation Associates With Impaired Small Arterial Elasticity Early in HIV Disease.

We estimated small arterial elasticity and used linear regression to evaluate its association with inflammatory biomarkers among antiretroviral therapy-naïve, HIV-positive patients with high CD4+ counts. After adjustment, high-sensitivity C-reactive protein and interleukin-6 were inversely associated with small arterial elasticity. These data suggest that systemic inflammation may contribute to vascular dysfunction even in very early HIV disease.