Spironolactone Improves Cardiac Function in Resistant Hypertension
Last Updated: 2010-04-20 10:56:16 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Low doses of spironolactone can improve cardiac physiology in patients with resistant hypertension, new research shows.
The treatment seems to work in two different ways, depending on whether patients also have high aldosterone levels. But with or without hyperaldosteronism, within three months the hypertensive patients in the study had regression of left ventricular hypertrophy and intracardiac volume overload, the researchers report in the May issue of Hypertension.
The study initially involved 108 patients with persistent hypertension above 140/90 despite the use of three antihypertensive drugs, including 37 who had urinary aldosterone levels of at least 12 mcg/24 hours and plasma renin activity less than 1 ng/mL/hr.
Cardiac MRI showed that while both sets of patients had similar blood pressure and left ventricular mass, the patients with hyperaldosteronism had significantly higher left and right ventricular end-diastolic volumes. They also had high plasma levels of brain natriuretic peptide, even with chronic use of thiazide diuretics.
Forty-four patients went on to receive therapy with spironolactone, starting at 25 mg/day and rising after four weeks to 50 mg/day, with other antihypertensive medications adjusted as necessary. Thirty-four patients (19 with high aldosterone and 15 with normal levels) were re-evaluated three and six months later. (Reasons for dropping out included uncontrolled hypertension in three patients, transient hyperkalemia in one, and transient high creatinine in one. Both of the transient conditions resolved when spironolactone was withdrawn.)
At three and six months, all patients had significant decreases in blood pressure and left ventricular mass. Furthermore, spironolactone produced significant reductions in left and right ventricular end-diastolic volume, left atrial volume, and brain natriuretic peptide level -- but only in the patients with high aldosterone levels. Treatment did not affect these parameters when the aldosterone level was normal.
"In subjects with high aldosterone, mineralocorticoid receptor blockade induces a prominent diuretic effect compared with a greater vasodilatory effect in subjects with normal aldosterone status," said lead author Dr. Krishna Gaddam of the University of Alabama at Birmingham and colleagues.
An estimated 10% to 20% of patients with hypertension are resistant to treatment, and aldosterone has been implicated as a factor. "Our study suggests that aldosterone is a potential mediator of resistance to treatment of hypertension by at least two separate mechanisms," Dr. Gaddam told Reuters Health by email.
When present in excess, aldosterone causes intravascular and intracardiac volume overload. At lower levels, it contributes to increases in vascular resistance; in that case, spironolactone produces a greater vasodilatory effect.
"The current study indicates that both effects are overcome with low doses of spironolactone, which could potentially translate to improved cardiovascular outcomes," Dr. Gaddam continued, "thus demonstrating the benefit of aldosterone blockade regardless of underlying aldosterone status."
The researchers also found that high aldosterone is associated with intracardiac volume overload, as shown by increased right and left ventricular end-diastolic volumes and by plasma brain natriuretic peptide levels, even in patients using thiazide diuretics.
Hypertension 2010;55:1137-1142.Copyright © 2010 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
