Background:
Primary aldosteronism (PA) is a widely under-diagnosed, potentially curable and specifically treatable cause of hypertension. PA screening involves measuring the aldosterone-to-renin-ratio (ARR), but false negative results can occur in the setting of medications, which block the renin-angiotensin system (RAS). Withdrawing RAS blockers from patients with resistant hypertension is not without cardiovascular risk. A novel diagnostic approach, the aldosterone-to-angiotensin-II-ratio (AA2-Ratio), has the potential for less drug interference and improved reliability in PA screening and confirmation of diagnosis.
Methods:
Serum samples from 80 patients undergoing PA confirmation testing were analyzed. Sampling was performed in a recumbent (7 a.m.) and in an upright (10 a.m.) position before and after 4 days of oral administration of fludrocortisone and salt loading. The concentrations of renin, aldosterone and equilibrium Angiotensin-II were determined and ARR and AA2-Ratios were calculated. The interference of ACE-inhibition with the AA2-Ratio was investigated in healthy volunteers receiving 10mg enalapril daily for 8 days.
Results:
Renin concentration was undetectable in more than 40% of samples, while equilibrium Angiotensin-II was measurable in 98% of all 320 samples analyzed. Angiotensin-II levels were significantly higher in upright collected samples compared to samples collected in a recumbent position. Comparison of the ARR with the AA2-Ratio revealed a significantly larger diagnostic window for the AA2-Ratio. While the ARR was significantly suppressed by ACE-inhibitor treatment, the AA2-Ratio remained unaffected by ACE-inhibition.
Conclusion:
The AA2-Ratio may be superior to the ARR in PA screening among hypertensive patients. Equilibrium Angiotensin-II levels show expected responses to posture and appear to outperform renin concentration as a marker for RAS activation in terms of sensitivity, giving a measurable readout even in clinical states characterized by markedly suppressed RAS activity. The stability of the AA2-Ratio in the presence of ACE-inhibition points to a potential use of the AA2-Ratio PA screening in hypertensive patients without ACE-inhibitor discontinuation.
The efficacy of angiotensin converting enzyme inhibitors versus angiotensin II receptor blockers on insulin resistance in hypertensive patients
