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Long-term BP control and vascular health in patients with hyperaldosteronism treated with low-dose, amiloride-based

Joseph L Izzo1,2, Michael Hong1,2, Tanveer Hussain1,2

  • 1Department of Medicine, Jacobs School of Medicine, University at Buffalo, Buffalo, New York.

Journal of Clinical Hypertension (Greenwich, Conn.)
|June 7, 2019
PubMed

Insights

Long-term blockade of the epithelial sodium channel (ENaC) with amiloride normalized blood pressure and protected vascular function in patients with hyperaldosteronism. This suggests ENaC, not mineralocorticoid receptor activation, mediates aldosterone

Area of Science:

  • Cardiovascular Medicine
  • Endocrinology
  • Nephrology

Background:

  • The direct role of aldosterone in macro- and microcirculatory disease and cardiovascular outcomes in humans remains unclear.
  • Hyperaldosteronism (HA) is associated with severe resistant hypertension and potential vascular complications.
  • Epithelial sodium channel (ENaC) is a key mediator of aldosterone's effects on sodium reabsorption.

Purpose of the Study:

  • To investigate the long-term effects of amiloride, a specific ENaC blocker, on blood pressure and vascular function in patients with chronic hyperaldosteronism.
  • To determine if ENaC blockade can prevent or reverse aldosterone-induced vascular damage.

Main Methods:

  • A long-term, single-practice study of 5 patients with chronic hyperaldosteronism (including 3 with glucocorticoid-remediable aldosteronism) treated with low-dose amiloride (mean 7 mg daily) for a mean of 20 years.
  • Assessment of blood pressure, vascular studies (pulse wave analysis, pulse wave velocities, augmentation index, reflection magnitude, pulse stiffening ratio, ankle-brachial index), and renal function (serum creatinine, estimated glomerular filtration rate, albumin:creatinine ratio) after a mean of 18 years.
  • Monitoring for cardiovascular events throughout the 20-year follow-up period.

Main Results:

  • Amiloride normalized or near-normalized blood pressure within 1-4 weeks, with sustained control for 20 years.
  • All vascular and renal function indicators were completely normal after 18 years of amiloride treatment.
  • No cardiovascular events occurred in any patient during the mean 20-year follow-up.

Conclusions:

  • Long-term ENaC blockade with amiloride can normalize blood pressure and protect macro- and microvascular function in patients with hyperaldosteronism.
  • These findings suggest that aldosterone's vasculopathic effects are mediated via ENaC, and are preventable or reversible with ENaC blockade.
  • Alternatively, aldosterone may not have a significant BP-independent role in human vascular diseases, highlighting the need for further research.

Keywords:
AmilorideENaCalbuminuriaarterial stiffnessepithelial sodium channelglucocorticoid remediable aldosteronismhyperaldosteronismpulse wave velocityserum creatinine

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