Abstract / Summary
Background: The prognostic significance of renin activity and its role in identifying patients who may benefit from mineralocorticoid receptor antagonists (MRAs) remain incompletely defined. Methods: In a multicentre retrospective cohort of 16,600 adults with hypertension, we evaluated associations between baseline plasma renin activity and major adverse cardiovascular events (MACE), comprising ischaemic stroke, intracranial haemorrhage, myocardial infarction, and all-cause death. Renin was analysed using restricted cubic splines and categories. Time-dependent Cox models assessed associations between MRA use and outcomes across renin strata, treating MRA exposure as time-varying. Findings: Renin showed a U-shaped association with MACE, with the lowest estimated risk at 1.17 ng/mL/h. Compared with renin 0.3-.0 ng/mL/h, both low renin (<0.3 ng/mL/h; adjusted hazard ratio [HR] 1.29, 95% CI 1.15-1.45) and high renin (>3.0 ng/mL/h; HR 1.19, 1.06-1.33) were associated with higher MACE risk. MRA use was associated with lower MACE risk when renin was low (<0.3 ng/mL/h [HR 0.59, 95% CI 0.46-0.74] and 0.3-1.0 ng/mL/h [0.71, 0.55-0.92]), but not when renin was high (>3.0 ng/mL/h [1.07, 0.76-1.52]). MRA use was associated with lower all-cause mortality across renin categories [≤]3.0 ng/mL/h, whereas no significant association was observed at renin >3.0 ng/mL/h. Interpretation: Baseline renin showed a U-shaped association with MACE. The use of MRAs was associated with lower risk of MACE only when renin was low. These findings provide support for renin-guided MRA therapy in hypertension.