Background: Several lines of evidence suggest that aldosterone can have an adverse blood pressure independent effect on heart and blood vessels including hypertrophy, vascular inflammation, myocyte necrosis and fibrosis. This study set out to evaluate whether spironolactone had a beneficial effect on arterial stiffness (in comparison to bendrofluthiazide) and to what extent this could be predicted by the aldosterone renin ratio (ARR).

Methods: This is a substudy of a double-blind, randomised, crossover, trial in hypertensive subjects with either a high ARR (> 750 and a plasma aldosterone > 250pmol/l), or low ARR (< 300 and a plasma renin activity <10ng/ml/h). Each group underwent 12 weeks treatment with spironolactone 50mg OD and bendroflumethiazide (BFZ) 2.5mg OD in random order, separated by a 2-week washout. Brachial pulse wave velocity (Br-PWV) and pulse wave analysis for central blood pressure, augmentation index (AIx) and time of reflection (Tr) measurements using Sphygmocor technique was conducted at the end of each treatment.

Result: 98 subjects (59 high and 39 low ARR) completed the sub-study. Reduction in central SBP was significantly greater after spironolactone compared with BFZ for both the high and low ARR groups (Delta (Δ) −3.39 mmHg P< 0.035) with no difference between the groups in relative response to spironolactone and BFZ. There were no differences in Br-PWV, AIx or Tr between treatments or the ARR groups (P> 0.05 for all).

Conclusion: The result of this study suggests that the benefit of spironolactone on blood pressure is not influenced by the prevailing state of activation of the RAAS. There was no convincing evidence that mineralocorticoid antagonism had a beneficial effect on arterial stiffness independent of blood pressure lowering.