Fig. 3: HIV-associated proteomic signature of left atrial size among people living with and without HIV in the United States (n = 352).

a Volcano plot of mean differences in left atrial volume index (LAVi) per standard deviation (SD) increment in plasma abundance of 439 HIV-associated proteins vs. -log₁₀ false discovery rate (FDR; Benjamini-Hochberg) estimated using linear regression with robust variance. Purple indicates proteins only associated in Model 1 (M1) when adjusting for sociodemographics, HIV, hepatitis C virus (HCV) infection, and renal function. Orange indicates proteins associated in Model 2 (M2) following further adjustment for education, cardiovascular risk factors, and substance use. The threshold for significance is indicated by a gray dotted line, FDR < 0.05. The most saturated model (orange) yielded 69 proteins positively associated with LAVi and 4 proteins inversely associated. Complete modeling results can be found in Supplementary Data 3. b Beta-beta plot of mean differences in standardized protein abundances comparing persons living with vs. without HIV (PLWH, PWOH) vs. mean differences in LAVi per SD increment in plasma protein abundances. All associations were estimated using linear regression with robust variance, and proteins depicted (n = 73) are restricted to those significantly associated with both parameters with an FDR < 0.05. HIV point estimates (y-axis) were adjusted for sociodemographics, substance use, HCV, and renal function. LAVi point estimates (x-axis) were adjusted for the same covariates, plus HIV and cardiovascular risk factors. c Enriched biological processes among proteins associated with both positive HIV serostatus and higher LAVi (concordant directionality), estimated using a two-sided Fisher’s exact test, Gene Ontology: Biological Processes annotations, and a threshold for significance of FDR < 0.05. Protein ratio = proportion of total signature proteins (n = 73) that map to the given annotation. TNF = tumor necrosis factor; NK = natural killer; PDGF = platelet-derived growth factor. Proteins mapping to each annotation can be found in Supplementary Table S7. d Mean differences in LAVi per SD increment in plasma protein abundances among strata of PLWH and PWOH, estimated using linear regression with robust variance adjusting for sociodemographics, substance use, cardiovascular risk factors, HCV, and renal function. Proteins depicted are limited to those with HIV×protein multiplicative interactions with an FDR < 0.10 (n = 73 proteins tested). Error bars indicate 95% confidence intervals.