Does aldosterone-to-renin ratio predict the antihypertensive effect of the aldosterone antagonist spironolactone?

Am J Hypertens. 2005 Dec;18(12 Pt 1):1631-5. doi: 10.1016/j.amjhyper.2005.06.010.

Abstract

Background: The recognition that some 10% to 15% of the hypertensive population may have aldosterone excess has increased the frequency of measurement of the aldosterone-to-renin ratio (ARR) and the use of aldosterone antagonists. Whether this ratio will predict the blood pressure (BP) response to spironolactone is not clear.

Methods: We correlated the BP response to spironolactone 50 mg/day to baseline ARR in 69 hypertensive patients (mean [+/-SD] age 57 +/- 2 years, 65% male), consisting of 39 subjects with long-standing hypertension (4.0 +/- 0.2 years) whose hypertension was uncontrolled on at least three antihypertensive medications and 30 previously untreated patients who were randomized in a cross-over design to receive either spironolactone 50 mg/day or bendroflumethiazide 2.5 mg/day for 4 weeks.

Results: After 4 weeks of spironolactone, BP in patients with never-treated hypertension was reduced by 18 +/- 3 / 11 +/- 1 mm Hg. There was a highly significant correlation between log ARR and the fall in systolic BP (r = 0.69, P < .001) and diastolic BP (r = 0.45, P < .05). Nine of ten patients with low renin activity (< or =0.5 ng/mL/h) showed a >20-mm Hg fall in systolic BP. No such correlations were seen when BP was reduced by bendroflumethazide 2.5 mg. For patients with resistant hypertension, despite a BP reduction of 28 +/- 3 / 13 +/- 2 mm Hg after 14 weeks of spironolactone, there was no relationship between the reduction in BP and the ARR; however, subjects with pretreatment potassium <4.0 mmol/L had a greater response than those with levels > or =4.0 mmol/L (34 +/- 3 / 16 +/- 2 v 20 +/- 6 / 8 +/- 3 mm Hg, P < .05)

Conclusions: Based on the study results, ARR and low renin activity may predict the response to spironolactone in never-treated hypertensive patients but not in patients taking antihypertensive drugs, possibly because of the effect of these agents on ARR. In such patients a trial of spironolactone is required to assess the BP response.

Publication types

  • Comparative Study

MeSH terms

  • Aldosterone / blood*
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use*
  • Bendroflumethiazide / administration & dosage
  • Bendroflumethiazide / therapeutic use
  • Blood Pressure / drug effects
  • Female
  • Humans
  • Hypertension / blood*
  • Hypertension / drug therapy*
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / administration & dosage
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Renin / blood*
  • Renin-Angiotensin System / drug effects
  • Spironolactone / administration & dosage
  • Spironolactone / therapeutic use*

Substances

  • Antihypertensive Agents
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Aldosterone
  • Bendroflumethiazide
  • Renin