Key result
Plasma infrared fingerprinting plus age outperforms SMART2 for mortality discrimination in CAD with ~0.79 C-index.
Why the study?
Residual cardiovascular risk remains substantial in CAD patients despite optimal secondary prevention, and while CHIP contributes causally to this risk, its detection requires sequencing. Plasma infrared molecular fingerprinting was evaluated as a sequencing-free tool for residual risk stratification and CHIP-aligned phenotyping.
Does plasma infrared molecular fingerprinting (IMF) improve mortality risk discrimination compared to the SMART2 score in patients with angiographically confirmed coronary artery disease?
Cohort (n=1,341)
Yes
Does plasma infrared molecular fingerprinting (IMF) improve mortality risk discrimination compared to the SMART2 score in patients with angiographically confirmed coronary artery disease?
Answers are grounded in this paper and cite their sources.
Plasma infrared molecular fingerprinting provides a rapid, low-cost, sequencing-free assessment of residual mortality risk in patients with coronary artery disease that outperforms the guideline-recommended SMART2 score while capturing clonal haematopoiesis-associated biology.
Background Residual cardiovascular risk remains substantial in patients with coronary artery disease (CAD) despite optimal secondary prevention. Clonal haematopoiesis of indeterminate potential (CHIP) contributes causally to this risk but requires sequencing for detection. Plasma infrared molecular fingerprinting (IMF), a spectroscopy-based assay, was evaluated as a sequencing-free tool for residual risk stratification and CHIP-aligned phenotyping. Methods A total of 1,341 patients with angiographically confirmed CAD (mean age 73 years, 76% male) were analysed over a follow-up of up to 11 years. Plasma IMF spectra, comprehensive clinical data, and targeted sequencing of 13 CHIP driver genes were measured. Penalised Cox regression models using IMF features were benchmarked against the guideline-recommended SMART2 score. Model performance was assessed by discrimination, reclassification, calibration, and decision-curve analysis. External validations were performed in two independent cohorts (KORA, n = 3,169; Lasers4Life, n = 2,123). Results The IMF+Age model demonstrated superior mortality discrimination compared with SMART2 (C-index 0.79 vs. 0.74, P<0.01) and significant reclassification improvement (10-year IDI 0.05, 95% CI 0.03-0.08, P<0.001; NRI 0.69, 95% CI 0.35-1.02, P<0.001). Decision-curve analysis showed greater net benefit across clinical thresholds. IMF-derived risk strata differentiated 11-year survival (3.4%, 11.7%, and 27.1%; log-rank P<0.001) and were enriched for CHIP carriers, particularly spliceosome mutations. External validation reproduced expected risk patterns and comorbidity associations. Conclusion Plasma IMF provides a rapid, low-cost, sequencing-free assessment of residual mortality risk in CAD, outperforming guideline-based scores while reflecting CHIP-associated biology. IMF constitutes a scalable phenotypic platform for precision secondary prevention and biology-guided trial design.
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Scheidt et al. (2026) conducted a cohort in Coronary artery disease (n=1,341). Plasma infrared molecular fingerprinting (IMF) + Age model vs. Guideline-recommended SMART2 score was evaluated on Mortality discrimination and 10-year risk reclassification (C-index 0.79 vs 0.74; NRI 0.69, 95% CI 0.35-1.02, p=<0.01). Plasma infrared fingerprinting plus age showed superior mortality discrimination vs SMART2 in CAD (C-index 0.79 vs 0.74, P<0.01) and improved reclassification (NRI 0.69, 95% CI 0.35-1.02, P<0.001).
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