Scientists identified 27 plasma proteins associated with hypertrophic cardiomyopathy (HCM) severity in 144 carriers of pathogenic MYBPC3 genetic variants, then successfully replicated 21 of these proteins in the UK Biobank's 6,492 participants. Five proteins emerged as top candidates: NT-proBNP, GDF-15, FGF-23, ADM, and NCAM1, with four having existing drugs that could be repurposed for treatment. This represents a significant advance in personalized cardiac medicine. Currently, predicting which MYBPC3 carriers will develop severe HCM remains challenging, forcing families to live with uncertainty about their cardiac future. These biomarkers could transform clinical practice by enabling earlier intervention and more precise monitoring of disease progression. The proteins also associated with heart failure, dilated cardiomyopathy, and sudden cardiac arrest risk, suggesting broader cardiovascular applications. However, this preprint awaits peer review, and the findings require validation in larger, more diverse populations before clinical implementation. The discovery that these biomarkers work across different HCM genotypes, not just MYBPC3 carriers, suggests they capture fundamental disease mechanisms rather than variant-specific effects, potentially benefiting all HCM patients regardless of their genetic profile.