The exact role of SIRT7 in hypertensive patients with coronary artery disease (CAD) remains elusive. This study aimed to explore plasma SIRT7 levels and their clinical significance in this population. From July 2022 to June 2024, 222 hypertensive patients (106 with isolated hypertension and 116 with hypertension plus CAD) were enrolled. Plasma SIRT7 was measured by ELISA, and participants were followed for rehospitalization (median 804 days). ROC curves, LASSO regression, and Cox proportional hazards models were used for statistical analysis. Hypertensive CAD patients had significantly higher SIRT7 levels than those without CAD (P < 0.001). Plasma SIRT7 levels were positively correlated with CK (R = 0.36, P < 0.001) and CK-MB (R = 0.50, P < 0.001), and negatively with HDL-C (R = -0.23, P < 0.001). The optimal cutoff of SIRT7 for diagnosing CAD demonstrated 94.0% sensitivity and 75.5% specificity, exhibiting an AUC of 0.917, superior to CK, CK-MB, and HDL-C. Multivariate analysis identified SIRT7 as an independent CAD risk factor (adjusted OR = 1.97, 95% CI 1.48-2.63). Restricted cubic spline (RCS) analysis revealed a linear correlation between SIRT7 and rehospitalization (P for overall = 0.038), but no non-linear relationship (P for non-linear = 0.164). Elevated SIRT7 predicted rehospitalization risk (HR = 1.15, 95% CI 1.02-1.29) and improved risk prediction, with an integrated discrimination index (IDI) of 21.8% and net reclassification improvement (NRI) of 51.0%. Plasma SIRT7 acts as both a diagnostic marker for CAD and a predictor of rehospitalization in hypertensive patients, indicating its dual role in pathogenesis and clinical monitoring. Targeting SIRT7 signaling may offer a new therapeutic strategy for hypertension-associated CAD.