Maintenance of long-term blood pressure control and vascular health by low-dose amiloride-based therapy in...

Area of Science:

• Endocrinology
• Cardiovascular Medicine
• Nephrology

Background:

• The direct role of aldosterone in macro- and microcirculatory disease and cardiovascular outcomes in humans remains unclear.
• Chronic hyperaldosteronism (HA) is associated with severe resistant hypertension and potential vascular complications.

Purpose of the Study:

• To investigate the long-term effects of low-dose amiloride, an epithelial sodium channel (ENaC) blocker, on blood pressure and cardiovascular/renal function in patients with hyperaldosteronism.
• To explore the potential mechanisms by which aldosterone may influence vascular health.

Main Methods:

• A single-practice, long-term observational study of five patients with chronic HA (including three with glucocorticoid-remediable aldosteronism, GRA) treated with amiloride (5-10 mg daily) for 14-28 years.
• Comprehensive assessment included office and 24-hour ambulatory blood pressure monitoring, pulse wave analysis, pulse wave velocities, ankle-brachial index, renal function tests, and urinary albumin-to-creatinine ratio after a mean of 18 years.

Main Results:

• Amiloride normalized blood pressure within 1-4 weeks in all patients, with sustained control over two decades.
• Long-term follow-up (mean 18 years) revealed essentially normal vascular and renal function indicators.
• No cardiovascular or renal events occurred during 100 patient-years of total observation.

Conclusions:

• Long-term epithelial sodium channel (ENaC) blockade with amiloride effectively normalizes blood pressure and preserves macro- and microvascular function in patients with hyperaldosteronism.
• These findings suggest that aldosterone's potential vasculopathic effects may be mediated via ENaC, or that aldosterone's role in age-dependent vasculopathy is dependent on blood pressure.
• Further research is warranted to elucidate the precise mechanisms and clinical implications.