Urinary Proteomic Profile of Arterial Stiffness Is Associated With Mortality and Cardiovascular Outcomes

Figures

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  Figure 1. Associations of pulse wave velocity (PWV) with PWV‐derived urinary proteomic score (PWV‐UP) and clinical variables. A, Scatterplot of PWV and PWV‐UP. The solid line represents the regression line. The band with 2 solid lines indicates the 95% confidence limits of the regression line, and the transparent band refers to the 95% prediction limits of the regression model. The gray dotted line represents the identity line that had a slope of 1. B, Scatterplot of PWV and the predicted values of the clinical variables. The clinical variables included age, sex, heart rate, mean arterial pressure, blood glucose, urine microalbumin, and current smoking. C, Scatterplot of PWV and the predicted value of PWV‐UP and the clinical variables together. D, Bar plot illustrating the proportion of explained variance in PWV by 3 models. The error bars denote the upper 95% confidence limit.

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  Figure 2. Volcano plot of significant peptides of pulse wave velocity–derived urinary proteomic score (PWV‐UP). Of the 743 peptides with parental protein, 276 peptides (37 proteins) significantly contributed to PWV‐UP with a variable importance in the projection (VIP) ≥1.2 as the threshold. Peptides in the top left quadrant (202) and top right quadrant (74) of the plots were inversely or positively associated with pulse wave velocity, respectively. ANXA1 indicates annexin A1; APOA, apolipoprotein A; APOC, apolipoprotein C; CHGB, secretogranin‐1; COL, collagen; LMAN2, vesicular integral‐membrane protein VIP36; MGP, matrix Gla protein; PCDH, protocadherin‐9; PGRMC1, membrane‐associated progesterone receptor component; PKD1L2, polycystic kidney disease protein 1‐like 2; PLG, plasminogen; POTEF, POTE ankyrin domain family member F; S100A9, protein S100‐A9; SERPINA1, α1‐antitrypsin; SERPINA3, α1‐antichymotrypsin; and TMSB4X, thymosin β4.

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  Figure 3. Bioinformatic analysis for the significant proteins in the urinary proteomic profile. A, Top 20 Reactome pathways annotated by the urinary proteomic profile. The bar length of every pathway indicates the corresponding −log10 (false discovery rate). B, The network of enriched Gene Ontology (GO) biological processes. GO terms are clustered and colored by different functional groups. Each dot represents a GO term with adjusted P<0.05. Dot size indicates their corresponding adjusted P value, whereas the edge width and transparency suggest the κ score. ECM indicates extracellular matrix; MET, mesenchymal‐epithelial transition factor; NCAM1, neural cell adhesion molecule 1; PDGF, platelet‐derived growth factor receptor; and PTK, protein‐tyrosine kinase.

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  Figure 4. Cumulative incidence of all‐cause mortality and cardiovascular events in 669 participants. The participants were divided into 2 groups according to the median of pulse wave velocity–derived urinary proteomic score (PWV‐UP) (A and B) and the median of pulse wave velocity (PWV) (C and D). The colored bands represent the SE. P values express the significance of the log‐rank test or the Gray method for the difference across the groups.