Confounders of the aldosterone‐to‐renin ratio when used as a screening test in hypertensive patients: A critical analysis of the literature

Alnazer

Leeuw

et al. 2021

Cardiovasc Drugs Ther

Self Cite

Purpose Hydralazine, doxazosin, and verapamil are currently recommended by the Endocrine Society as acceptable bridging treatment in those in whom full cessation of antihypertensive medication is infeasible during screening for primary aldosteronism (PA). This is under the assumption that they cause minimal to no effect on the aldosterone-to-renin ratio, the most widely used screening test for PA. However, limited evidence is available regarding the effects of these particular drugs on said ratio. Methods In the present study, we retrospectively assessed the changes in aldosterone, renin, and aldosterone-to-renin values in essential hypertensive participants before and after treatment with either hydralazine (n = 26) or doxazosin (n = 20) or verapamil (n = 15). All samples were taken under highly standardized conditions. Results Hydralazine resulted in a borderline significant rise in active plasma renin concentration (19 vs 25 mIU/L, p = 0.067) and a significant fall in the aldosterone-to-renin ratio (38 vs 24, p = 0.017). Doxazosin caused declines in both plasma aldosterone concentration (470 vs 330 pmol/L, p = 0.028) and the aldosterone-to-renin ratio (30 vs 20, p = 0.020). With respect to verapamil, we found no statistically significant effect on any of these outcome variables. Conclusion We conclude that the assumption that these drugs can be used with little consequence to the aldosterone-to-renin cannot be substantiated. While it is possible that they are indeed the best option when full antihypertensive drug cessation is infeasible, the potential effects of these drugs must still be taken into account when interpreting the aldosterone-to-renin ratio.

Section: Discussionmentioning

confidence: 85%

The Effects of Verapamil, Hydralazine, and Doxazosin on Renin, Aldosterone, and the Ratio Thereof

Alnazer

Leeuw

et al. 2021

Cardiovasc Drugs Ther

Self Cite

“…However, we deliberately wanted to avoid posture-related variations in renin and aldosterone levels. Previous research has indicated that the ARR is less variable when measured in the supine position [16], thus, the difference between successive measurements of the ARR may have even been greater when measured in the seated position. Additionally, research regarding posture and systematically higher or lower ARR values have been inconclusive [16], thus, we felt comfortable maintaining the widely used value of 30 as our cut-off.…”

Section: Discussionmentioning

confidence: 96%

“…Previous research has indicated that the ARR is less variable when measured in the supine position [16], thus, the difference between successive measurements of the ARR may have even been greater when measured in the seated position. Additionally, research regarding posture and systematically higher or lower ARR values have been inconclusive [16], thus, we felt comfortable maintaining the widely used value of 30 as our cut-off. Our population was additionally placed on a fixed low sodium diet, as opposed to the recommended ad libitum diet according to current guidelines [1].…”

Section: Total=116mentioning

confidence: 96%

Variability of aldosterone, renin and the aldosterone-to-renin ratio in hypertensive patients without primary aldosteronism

Journal of Hypertension

Alnazer²,

Leeuw³

2022

Self Cite

Objectives: The aldosterone-to-renin ratio (ARR) is commonly used in the screening of primary aldosteronism. However, limited information is available with regard to the intra-patient variability in this ratio. Our objective is to determine whether ARR measurements are reliably consistent over both the short-and long-term. Methods:We assessed the short-term variability of the aldosterone-to-renin ratio in 116 unmedicated, essential hypertensive participants who had two blood samples taken in the morning of the same day for measurement of aldosterone and active plasma renin concentration. Longterm variability was studied in 22 unmedicated, essential hypertensive participants who had two blood samples taken approximately 1 year apart. All samples were taken under highly standardized conditions.Results: Our data show that renin, aldosterone and the aldosterone-to-renin ratio show marked variations, both when measured on the same day and when assessed at a longer interval. The ARR becomes increasingly variable as its mean value increases. Its degree of variability is similar in both the short-term and the long-term.Conclusions: Based on our findings, we conclude that the aldosterone-to-renin has acceptable short-term variability in the lower ranges, but increasingly dubious reliability as aldosterone-to-renin values rise. Thus, in a clinical context, great caution should be taken in interpreting pointmeasurements of moderate to high aldosterone-to-renin ratio values.

“…Previous research has indicated that the ARR is less variable when measured in the supine position. [41] An additional limitation was our somewhat small population sizes. Having larger sample sizes would have Informed consent was obtained from all individuals who participated in the studies described in this paper.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Verapamil, Hydralazine and Doxazosin on Renin, Aldosterone and The Ratio Thereof

Alnazer

Leeuw

2021

Preprint

Self Cite

PURPOSE Hydralazine, doxazosin and verapamil are currently recommended by the Endocrine Society as acceptable bridging treatment in those in whom full cessation of antihypertensive medication is infeasible during screening for primary aldosteronism (PA). This is under the assumption that they cause minimal to no effect on the aldosterone-to-renin ratio, the most widely used screening test for PA. However, limited evidence is available regarding the effects of these particular drugs on said ratio. METHODS In the present study, we retrospectively assessed the changes in aldosterone, renin and aldosterone-to-renin values in essential hypertensive participants before and after treatment with either hydralazine (n = 26), or doxazosin (n = 20) or verapamil (n = 15). All samples were taken under highly standardised conditions. RESULTS Hydralazine resulted in a borderline significant rise in active plasma renin concentration (19 vs 25 mIU/L, p = 0.067) and a significant fall in the aldosterone-to-renin ratio (38 vs 24, p = 0.017). Doxazosin caused declines in both plasma aldosterone concentration (470 vs 330 pmol/L, p = 0.028) and the aldosterone-to-renin ratio (30 vs 20, p = 0.020). With respect to verapamil, we found no statistically significant effect on any of these outcome variables. CONCLUSION We conclude that the assumption that these drugs can be used with little consequence to the aldosterone-to-renin cannot be substantiated. While it is possible that they are indeed the best option when full antihypertensive drug cessation is infeasible, the potential effects of these drugs must still be taken into account when interpreting the aldosterone-to-renin ratio.