A 27-protein cardiovascular risk score (Prot-CVR) derived from plasma protein measurements demonstrated superior predictive capability compared to coronary artery calcium (CAC) scoring alone for four-year cardiovascular events in 2,122 Multi-Ethnic Study of Atherosclerosis participants. The protein test achieved a higher C-index (0.68 vs 0.63) and stronger hazard ratios for composite outcomes including heart attack, stroke, heart failure, and death. Most significantly, among the 49.6% of participants with zero calcium scores—traditionally considered low-risk—the protein test successfully identified those who would experience cardiovascular events. This addresses a critical clinical gap, as nearly half of heart attacks occur in patients with minimal coronary calcium deposits. The combined approach of protein testing plus calcium scoring plus age achieved the strongest predictive performance with a 4-year AUC of 0.72. However, this preprint study awaits peer review, and the modest improvement over existing methods raises questions about cost-effectiveness in clinical practice. While the protein test shows promise for refining risk assessment in the substantial population with zero calcium scores, real-world implementation would require validation of the complex 27-protein panel's reproducibility and accessibility across diverse healthcare settings.