Suppression of aldosterone mediates regression of left ventricular hypertrophy in patients with hypertension

J Renin Angiotensin Aldosterone Syst. 2011 Dec;12(4):483-90. doi: 10.1177/1470320311414453. Epub 2011 Jul 11.

Abstract

Background: High circulating aldosterone levels stimulate myocardial fibrosis and left ventricular hypertrophy (LVH). However, it is not clear whether suppression of aldosterone directly contributes to LVH regression in hypertensive patients.

Methods: The Aliskiren in Left Ventricular Hypertrophy (ALLAY) trial randomised 465 hypertensive overweight subjects with LVH to the direct renin inhibitor aliskiren 300 mg, losartan 100 mg or the combination and followed patients for 9 months. All patients were treated to standard blood pressure targets. Left ventricular (LV) mass index (LVMI) and LV wall thickness (LVWT) were assessed by cardiac magnetic resonance. A subset of 136 patients who had plasma aldosterone concentration (ALDO) measured at baseline and study end was analysed.

Results: At baseline, plasma ALDO was modestly related to systolic blood pressure, LVMI, and wall thickness (all, p < 0.05). Aliskiren, either alone or in combination, was associated with a significantly greater reduction from baseline to 9 months in plasma aldosterone than losartan alone (p < 0.02). Reduction in ALDO was related to reduction in LVMI even after adjustment for baseline ALDO, BP reduction and treatment group (p for trend = 0.042).

Conclusion: In hypertensive patients with increased LVWT, aliskiren alone or in combination with the angiotensin receptor blocker losartan provides greater reduction in aldosterone compared to losartan alone. Moreover, suppression of aldosterone was associated with reduction of LVH, independently of the change in SBP, suggesting that suppression of aldosterone, a known mediator of LVH, may be particularly important for LVH regression and as a target for therapy.

Trial registration: ClinicalTrials.gov NCT00219141.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aldosterone / blood*
  • Amides / administration & dosage
  • Amides / pharmacology
  • Amides / therapeutic use
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure / drug effects
  • Demography
  • Female
  • Fumarates / administration & dosage
  • Fumarates / pharmacology
  • Fumarates / therapeutic use
  • Heart Ventricles / drug effects
  • Heart Ventricles / pathology
  • Humans
  • Hypertension / blood*
  • Hypertension / complications*
  • Hypertension / drug therapy
  • Hypertension / physiopathology
  • Hypertrophy, Left Ventricular / blood
  • Hypertrophy, Left Ventricular / complications*
  • Hypertrophy, Left Ventricular / pathology*
  • Hypertrophy, Left Ventricular / physiopathology
  • Losartan / administration & dosage
  • Losartan / pharmacology
  • Losartan / therapeutic use
  • Male
  • Middle Aged
  • Organ Size / drug effects
  • Systole / drug effects

Substances

  • Amides
  • Antihypertensive Agents
  • Fumarates
  • Aldosterone
  • aliskiren
  • Losartan

Associated data

  • ClinicalTrials.gov/NCT00219141