Key result
A 125-protein score improves aortic stenosis risk prediction over clinical factors alone.
Why the study?
Proteomic signatures might be a novel risk marker for AS, so investigators explored whether a protein risk score derived from large-scale proteomics data would improve risk prediction.
Does a protein risk score derived from plasma proteins improve risk prediction of aortic stenosis in the general population compared to clinical risk factors alone?
Cohort (n=52,598)
Yes
Does a protein risk score derived from plasma proteins improve risk prediction of aortic stenosis in the general population compared to clinical risk factors alone?
Effect estimate: HR 2.24 (95% CI 1.77-2.84)
A novel 125-protein risk score significantly improves the prediction of incident aortic stenosis beyond standard clinical risk factors in the general population.
Background Proteomic signatures might be a novel risk marker for aortic stenosis (AS). We explored whether a protein risk score derived from large-scale proteomics data would improve risk prediction of AS. Methods A total of 52,598 individuals with 1,459 unique plasma protein measurements and without a history of stroke, transient ischemic attack, or atrial fibrillation (AF) were included from the UK Biobank Pharma Proteomics Project. Protein risk score was developed with lasso penalized Cox regression on participants enrolled at the English centre (40,653 individuals; 98.2% white) and validated on participants enrolled at the remaining centre (11,945 individuals; 77.1% white). Results The protein risk score formula developed from the derivation set was composed of 125 unique plasma proteins. In the test set (54.6% women, median 59 [51-64] years), per SD increase in protein risk score was associated with a hazard ratio of 2.24 (95% CI, 1.77-2.84) for incident AF. C-index for a model including clinical risk factors and protein risk score was 0.833 (95% CI, 0.798-0.868). The change in C-index when protein risk score was added to clinical risk factors was 0.040 (95% confidence interval [CI], 0.033-0.057) and when protein risk score was added to a joint model including clinical risk factors and lipoprotein A was 0.037 (95% CI, 0.011 to 0.068). Protein risk score added to clinical risk factors resulted in a risk reclassification of 9.7% (95% CI, 2.8-16.7) using a 10-year risk threshold of 5%. In the decision curve, a greater predicted net benefit was found after adding protein risk score to clinical risk factors across 10-year risk thresholds. Conclusions Protein risk score derived from a single plasma sample significantly improved risk prediction of aortic stenosis. Further research is needed to determine whether a protein risk score is useful in clinical practice.Cumulative event rate of aortic stenosis
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Park et al. (2025) conducted a cohort in Aortic stenosis (n=52,598). Protein risk score vs. Clinical risk factors was evaluated on Incident AF / Aortic stenosis (HR 2.24, 95% CI 1.77-2.84). A 125-protein risk score significantly improved risk prediction of aortic stenosis when added to clinical risk factors, increasing the C-index by 0.040 (95% CI, 0.033-0.057).
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