Is the aldosterone:renin ratio truly reproducible?

Letters to the Editor will be published, if suitable, as space permits. They should not exceed 1000 words (typed double-spaced) in length and may be subject to editing or abridgment. Rossi et al recently concluded that the aldosterone:renin ratio (ARR) is reproducible. 1 However, we think that several common errors were performed in their data interpretation, as described below. In the Bland-Altman plot B (Figure 1 in Reference 1), the large differences in repeat measurements are overlooked on the basis that only 7% of points lay outside of the between-test " 95% CIs, " by which they imply the Bland-Altman " limits of agreement. " These are constructed using the mean difference Ϯ1.96 SDs, and so by definition alone, will always contain Ϸ95% of the data and should certainly not, therefore, be regarded as evidence for good reproducibility. The latter should instead be qualitatively assessed by a careful clinical consideration of the magnitude of the 2 calculated limits. This step is often omitted, as was the case here. The upper of the 2 " limits of agreement " 2 in plot B is 2.1. This equates to a ratio of 8.2 between the 2 measures because, log(e)ARR1Ϫlog(e)ARR2ϭlog(e)(ARR1/ARR2), and exp(2.1)ϭ 8.2. Therefore, the ratio of repeat measurements may differ by as much as 8.2. Had the authors drawn confidence limits for the limits of agreement, sometimes termed " tolerance limits, " 3 the ratios of repeat measures would be as high as Ϸ10. This follows from the formula for the SE for the limits of agreement of ͌(3s 2 /n)ϭ0.097, where " s " is the SD of the differences [Ϸ0.92, ie, (2.1Ϫ0.3)/1.96], and " n " is the sample size (268). The upper confidence limit for the upper limit of agreement is then calculated as exp[2.1ϩ(1.96*0.097)]ϭ9.9. In plot B, ratios of this magnitude are observed across the low to midrange of (log)ARR values, reflecting absolute ARR differences (as well as ratios) that are far too large in clinical terms to provide any convincing evidence for good reproducibility. In plot D, absolute differences of Ϫ30 and ϩ30 occur around the 10th and 85th percentiles, indicating that approximately one fourth of subjects had differences Ն30, the mean ARR value itself among primary hypertensive subjects, the majority of those studied. The second Bland-Altman plot (plot C) confirms the large differences of plot B, because several points have ratios Ͼ8. However, this is distorted …