Figure 1. Increment in AUC with addition of clinical risk factors and each protein in turn from logistic regression model

Model adjusted for the matching variables (age, sex, cohort, follow-up time) and for clinical risk factors (smoking, diabetes, history of coronary artery disease, antihypertensive treatment, body mass index, systolic blood pressure, heart rate and creatinine). Matching variables (age, sex, cohort and follow-up time) are accounted for in the study design and in the statistical model. CRF, clinical risk factors; NT-pro BNP, N-terminal prohormone brain natriuretic peptide; TRAILR2, TNF-related apoptosis-inducing ligand receptor 2; TWEAK, tumor necrosis factor-like weak inducer of apoptosis; CASP8, caspase-8 precursor.

Figure 2. Correlation matrix between the top proteins identified in the Random forest analysis

Figure 3. Main biological networks inherent to the 39 top biomarker proteins

Figure 4. Decision tree for incident heart failure

Legend: BNP was the major discrimination factor to split between heart failure case and control. In the case of low BNP, TWEAK and TRAILR2 may be suitable for confirming HF cases in smaller populations. In the case of high BNP, PON3 and GDF15 offer little classification improvement.Values in criteria are log2-normalized protein expression (NPX) measured by Olink Proseek® Multiplex panels.