Does aldosterone-to-renin ratio predict the antihypertensive effect of the aldosterone antagonist spironolactone?
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.
Mahmud
Azra
A
Department of Therapeutics and Hypertension Clinic, Trinity Centre for Health Sciences, St. James' Hospital, Dublin, Ireland.
Mahgoub
Mohammed
M
Hall
Mary
M
Feely
John
J
D000450:Aldosterone / Q000097:blood*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001539:Bendroflumethiazide / Q000008:administration & dosage / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D012083:Renin / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013148:Spironolactone / Q000008:administration & dosage / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D001539:Bendroflumethiazide; D012083:Renin