Blood proteins improve early cardiometabolic risk prediction
In 43,709 adults with early-stage disease, outcome-specific proteomic signatures improved clinical risk discrimination across 11 incident outcomes, boosting C-index values by 0.024 to 0.070.
Diabetes, Obesity & Metabolism
The study evaluated 43,709 UK Biobank participants with early cardiovascular-kidney-metabolic stages 0 to 2. Researchers measured 2,920 plasma proteins and modeled their links to 11 incident cardiovascular, kidney, and mortality outcomes. A total of 157 proteins showed concordant associations across all outcomes, with 155 positive and two inverse links. Differences in markers such as GDF15, TNFRSF10B, WFDC2, and NT-proBNP emerged between incident cases and reference participants. Eleven proteins were consistently elevated across baseline stages 0 to 2. Outcome-specific proteomic panels improved discrimination beyond standard clinical models, increasing C-index values by 0.024 to 0.070. A recurrent 12-protein panel also raised C-index values by 0.018 to 0.052.
Why it matters
Cardiovascular-kidney-metabolic dysfunction reflects interconnected systems of age-related systemic decline before clinical disease manifests. Identifying early circulating proteomic shifts offers a molecular window to assess and potentially track multiorgan deterioration.
Caveats
The study is observational and relied on internal validation within a single cohort. External studies are needed to determine if these proteomic panels generalize to broader, more diverse populations.
The paper
University of Science and Technology of China
Diabetes, Obesity & Metabolism · 30 Sep 2026