Analysis of 16,600 hypertensive patients revealed plasma renin activity follows a U-shaped curve for major adverse cardiovascular events, with optimal levels at 1.17 ng/mL/h. Both low renin (<0.3 ng/mL/h) and high renin (>3.0 ng/mL/h) increased cardiovascular risk by 29% and 19% respectively compared to optimal levels. The study demonstrates precision medicine potential in hypertension management. Patients with low renin achieved 25% lower cardiovascular risk when treated with mineralocorticoid receptor antagonists like spironolactone, while those with high renin benefited most from standard ACE inhibitors or ARBs with 24% risk reduction. This represents a paradigm shift from one-size-fits-all hypertension treatment toward biomarker-guided therapy selection. The renin-guided approach could transform cardiovascular prevention by matching specific drug classes to individual renin profiles. However, this preprint awaits peer review, and the retrospective design limits causal inferences. The findings need validation in prospective randomized trials before clinical implementation, as treatment assignment wasn't randomized and confounding factors may influence outcomes.