Low-dose spironolactone, added to long-term ACE inhibitor therapy, reduces blood pressure and urinary albumin excretion in obese patients with hypertensive target organ damage.
BACKGROUND
For some hypertensive patients, conventional blockade of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers does not adequately protect against target organ damage. This may be particularly true for hypertensive patients with obesity, a condition often associated with elevated aldosterone levels.


METHODS
We conducted a pre-post study of fixed, low-dose spironolactone (12.5 mg/d), added to chronic ACE inhibitor-based antihypertension regimens, in obese subjects with essential hypertension and preexistent target organ damage. Outcomes of interest were changes in blood pressure (office, 24-h, and nocturnal), urinary albumin excretion, and potassium.


RESULTS
21 subjects with mean age 57.3 +/- 7.1 years, BMI 32.4 +/- 3.4 kg/m2 and 12.0 +/- 7.0 years of antihypertensive therapy were enrolled. The mean aldosterone level before spironolactone treatment was 10.1 +/- 7.3 ng/dl, and over 40% of subjects had baseline levels greater than mean population levels. During 4 weeks of low-dose spironolactone, mean office (110.6 +/- 7.8 to 105.0 +/- 8.1 mmHg, p = 0.004), 24-hour ambulatory (100.6 +/- 9.4 to 95.5 +/- 7.1 mmHg, p = 0.03) and nocturnal (95.3 +/- 11.5 to 87.5 +/- 8.2, p = 0.004) blood pressures all declined significantly. Log urine albumin : creatinine ratios also significantly dropped during spironolactone treatment (p = 0.002); in multivariate analysis, this decline did not appear to be due to changes in blood pressure but was influenced by concomitant changes in estimated glomerular filtration rate. Both the reductions in blood pressure and albumin excretion reversed after withdrawal of spironolactone. Serum potassium levels were essentially unchanged by low-dose spironolactone (p = 0.9).


CONCLUSIONS
A fixed, low-dose of spironolactone, added to chronic ACE inhibitor therapy, reduced blood pressure and urinary albumin excretion in obese subjects with hypertension and preexistent target organ damage. A relative hyperaldosteronism due to aldosterone escape and/or obesity may explain the beneficial effects of spironolactone therapy in this study.
Bomback
A S
AS
Department of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons, 622 West 168th Street, PH 4-124, New York, NY 10032, USA. asb68@columbia.edu
Muskala
P
P
Bald
E
E
Chwatko
G
G
Nowicki
M
M
D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control* / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D009765:Obesity / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D013148:Spironolactone / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone