OR02-5 The Aldosterone-to-Renin Ratio and False-Negative Case Detection for Primary Aldosteronism

Program: Abstracts - Orals, Poster Previews, and Posters
Session: OR02-Renin-Angiotensin-Aldosterone - Bench to Bedside
Basic/Translational
Friday, April 1, 2016: 11:45 AM-1:15 PM
Presentation Start Time: 12:45 PM
Room 156 (BCEC)
Rene Baudrand*1, Jasmine Torrey2, Gordon H Williams2 and Anand Vaidya3
1Pontificia Universidad Catolica de Chile, Santiago, Chile, 2Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 3Brigham and Women's Hospital/Harvard Medical School, Boston, MA
Context: Primary aldosteronism (PA) is the most common cause of secondary hypertension and increases cardiovascular morbidity; therefore, case detection for PA is of public health importance. Broad screening for PA using the aldosterone-to-renin ratio (ARR) is recommended; however, specific dietary considerations and cutoffs for serum aldosterone and plasma renin activity (PRA) when measuring the ARR are not well defined.

Objective: To evaluate the hypotheses that dietary sodium intake variability and insufficiently suppressed PRA can result in inaccurate interpretation of the ARR for PA screening.

Methods: 241 untreated stage I hypertensives with ARR > 20, underwent one week of high sodium diet (HS) such that 24h urine sodium was >200 mmol/d, and subsequently one week of low sodium diet (LS), such that 24h urine sodium was <50 mmol/d. All ARR measurements were taken in the morning after overnight supine rest. Subjects were considered to have a “positive screen” for PA if they had ARR > 20 in addition to PRA ≤ 1.0 ng/mL/h and serum aldosterone ≥ 6 ng/dL. PA was considered to be “confirmed” if positive screens also had a 24h urine aldosterone of ≥12 mcg/d on HS.

Results: 33% (79/241) of the population met criteria for a positive screen for PA; the remaining 67% had a negative screen for PA despite having ARR>20 due to a combination of low aldosterone (< 6 ng/dL) and a highly suppressed PRA. When the 79 subjects with a positive screen for PA underwent LS diet, 56% (44/79) no longer met criteria for a positive screen. This subset of “false negative” screens for PA on LS were characterized as having: higher PRA on LS (2.03 ± 1.9 vs. 0.44 ± 0.3 ng/mL/h; P<0.001) and on HS (0.25 ± 0.13 vs. 0.16 ± 0.1 ng/mL/h; P=0.001), Caucasian race predominance (90 vs. 62%; P=0.002), but no difference in serum aldosterone levels, when compared to subjects whose screen remained positive on LS. Multivariable logistic regression showed that odds for false-negative PA screening on LS were associated with a PRA > 0.3 ng/mL/h on HS (OR=3.7 [1.1–12.5]) and Caucasian race (OR = 8.3 [CI 2.1–32.2]). Most notably, among the 48/79 subjects who had confirmed PA, 52% (25/48) no longer met criteria for a positive screen for PA when placed on LS.

Conclusions: Among individuals with untreated stage I hypertension, we observed that substantial inaccuracies in PA screening can occur if dietary sodium balance and absolute values of PRA and aldosterone are not considered. Our findings suggest that case-detection for PA could be markedly improved by: 1) ensuring a high dietary sodium intake when measuring ARR; and 2) interpreting the ARR in the context of a sufficiently suppressed PRA.

Nothing to Disclose: RB, JT, GHW, AV

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