The aldosterone-to-renin ratio (ARR) is a widely used screening test for primary aldosteronism (PA). However, there are various confounding factors, including medication, that may influence the levels of renin and/or aldosterone and consequently the ARR. While withdrawal of antihypertensive treatment prior to screening is advisable, this is not always practical or safe. When it is not possible to interrupt treatment, medications with a neutral, or at least a negligible effect on the ARR are required for bridging the diagnostic period. Current guidelines recommend the use of non-dihydropyridine calcium channel blockers, alpha-adrenoceptor blocking drugs, and the vasodilator hydralazine as noninterfering medications, as these drugs allegedly do not influence the results of ARR testing. 1,2 Although several investigators have reported the effect of these medications on average levels of renin and aldosterone in groups of patients, the calculation of the magnitude of effect on the ARR cannot be inferred by simply dividing the mean values of the entire study population. Thus, drawing conclusions about whether or not the individual ARR is modified by such medication is not a sound approach. The objective of the present review is to identify medications that do and do not impact the ARR on the basis of robust evidence. Addressing the effects of these medications could help researchers and clinical practitioners in choosing a safe drug to use in severe hypertensives in whom temporary treatment withdrawal is not an option, while not significantly hampering the interpretations of the ARR.

The aldosterone-to-renin ratio (ARR) is a common screening test for primary aldosteronism in hypertensives. However, there are many factors which could confound the ARR test result and reduce the accuracy of this test. The present review's objective is to identify these factors and to describe to what extent they affect the ARR. Our analysis revealed that sex, age, posture, and sodium-intake influence the ARR, whereas assay techniques do not. Race and body mass index have an uncertain effect on the ARR. We conclude that several factors can affect the ARR. Not taking these factors into account could lead to misinterpretation of the ARR. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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.

The aldosterone-to-renin ratio (ARR) is widely used as a screening test for primary aldosteronism, but its determinants in patients with essential hypertension are not fully known. The purpose of the present investigation is to identify the impact of age, sex and BMI on renin, aldosterone and the ARR when measured under strict, standardized conditions in hypertensive patients without primary aldosteronism.Methods: We analysed the data of 423 consecutive hypertensive patients with no concomitant cardiac or renal disorders from two different hospitals (Rotterdam and Maastricht) who had been referred for evaluation of their hypertension. Those who were diagnosed with secondary causes of hypertension, including primary aldosteronism, were excluded from analysis. Patients who used oral contraceptives or had hormonal replacement therapy were excluded as well. Plasma aldosterone concentration (PAC), active plasma renin concentration (APRC) and the ARR were measured under standardized conditions. All measurements were taken in the supine position at 10.00 h in the morning, with one subgroup of patients adhering to a sodium-restricted diet (55 mmol/day) for no less than 3 weeks, and the other subgroup maintaining an ad libitum diet. In those who were receiving antihypertensive treatment, all medications were discontinued at least 3 weeks before testing.Results: In neither group did aldosterone correlate with age. Renin, however, was inversely related to age both during low-salt diet (P < 0.001) and during ad lib salt intake (P ¼ 0.05). This resulted in a significant positive correlation between age and the ARR in both groups. Although on both dietary regimens, PAC and APRC were significantly higher in men when compared with women, the ARR was not significantly different between the two sexes. The age-relationships of renin and the ARR were comparable in men and women on both diets, albeit with greater variability in women. There was an upward trend between BMI and the ARR, which reached statistical significance only in men on low-salt diet. In multivariable regression analysis, age remained the only independent determinant of the ARR. Conclusion:In our essential hypertensive population, the ARR increased significantly with age but was not affected by sex or BMI.

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Objective: The aldosterone-to-renin ratio (ARR) is widely used as a screening test for primary aldosteronism (PA) in patients with hypertension. The purpose of the present investigation is to identify the impact of age, body mass index (BMI) and sex on renin, aldosterone, and the ARR, when measured under strictly standardised conditions. Design and method: We measured plasma aldosterone, plasma renin concentration and the ARR in 190 essential hypertensive patients (120 males, 70 females). All measurements were taken in the supine position at 9am. A low sodium diet (55mmol/day) was in place for no less than two weeks prior to screening. In those who were receiving antihypertensive medications, all medications were discontinued at least 2 week before testing. Results: Renin and aldosterone were significantly higher in men, and remained so when controlling for BMI and age. However, the ARR was not significantly affected by sex. Aldosterone was not significantly influenced by age but renin correlated inversely with age, with and without controlling for BMI (r = -0.285, p < 0.001). The ARR was positively correlated with age (r = 0.236, p < 0.001), with and without controlling for BMI. Subgroup analysis demonstrated a significant effect on the ARR in males only, with and without controlling for BMI (p < 0.001 and p0.004, respectively). Although renin and aldosterone individually were not significantly influenced by BMI, the ARR showed a positive correlation (p = 0.022). However, this effect was not seen when age was controlled for nor was it seen in the subgroup analysis of males and females (p = 0.125, p = 0.515, p = 0.207, respectively) Conclusions: Under strictly standardized conditions, advanced age is associated with an increased ARR in male essential hypertensives. BMI when controlling for age does not influence the ARR. The impact of sex on the ARR appears negligible.

Objective: The aldosterone-to-renin ratio (ARR) is widely used as a screening test for primary aldosteronism (PA) in patients with hypertension. The purpose of the present original investigation is to identify the impact hormonal changes have on renin, aldosterone, and the ARR during the menstrual cycle of premenopausal women when measured in strict standardised conditions. Design and method: We analysed 59 women with a history of preeclampsia and 6 healthy parous controls. Blood values were determined during both follicular and luteal phases of the menstrual cycle (days 1 and 14 respectively). Plasma aldosterone, active plasma renin concentration (APRC) and the ARR were measured under standardised conditions. All measurements were taken in the supine position at 9am, all patients maintained a standardised sodium diet (100 mmol/day) for no less than two weeks. In those who were receiving antihypertensive medications (n = 2), all medications were discontinued at least 1 week prior to screening. Results: When performing the Friedman's Test and the Wilcoxon signed rank test in formerly preeclamptic women (n = 59), aldosterone and renin were both significantly elevated in the luteal phase (mean rank aldosterone 1.2 and 1.8 p0.000 Z-4.7, mean rank renin 1.23 and 1.77 p0.000 Z -4.5, respectively), however the ARR values did not significantly differ between phases (mean rank 1.53 and 1.47 p0.7 Z-0.14). When performing the Friendman's Test in the control group (n = 6), the difference in aldosterone, renin and the ARR between the follicular and luteal phase was not significant (p0.059 for all parameters). Wilcoxon signed test revealed a significant difference in aldosterone (Z-2.02 p0.04), but the difference in renin and the ARR remained insignificant (p0.06). Conclusions: In this study of premenopausal women we found that both renin and aldosterone are significantly affected by the menstrual cycle. However the resulting ARR was not statistically significantly altered. Our study indicates that it is not necessary to take the menstrual phase of patients into account when performing and interpreting the ARR as a screening test for PA in patients with a history of preeclampsia.

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