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Plasma aldosterone level within the normal range is less associated with cardiovascular and cerebrovascular risk in primary aldosteronism

Murata, Masahikoa; Kitamura, Tetsuhiroa; Tamada, Daisukea; Mukai, Kosukea; Kurebayashi, Shogob; Yamamoto, Tsunehikoc; Hashimoto, Kunihikod; Hayashi, Reiko D.e; Kouhara, Haruhikoe; Takeiri, Sachif; Kajimoto, Yoshitakaf; Nakao, Makotog; Hamasaki, Toshimitsuh; Otsuki, Michioa; Shimomura, Iichiroa

doi: 10.1097/HJH.0000000000001251
ORIGINAL PAPERS: Primary aldosteronism

Background: Previous studies showed higher risk of cardiovascular and cerebrovascular (CCV) events in primary aldosteronism compared with essential hypertension, but the patients of these studies were limited to primary aldosteronism patients with high plasma aldosterone concentration (PAC). The introduction of the aldosterone–renin ratio as the screening test for primary aldosteronism led to the recognition of primary aldosteronism patients with normal PAC (nPA). However, there is no information on the risk of primary aldosteronism including nPA.

Method: In this retrospectively and cross-sectional study, the clinical features and CCV event risk of primary aldosteronism at diagnosis including nPA were investigated and compared with essential hypertension. The study included 292 consecutive primary aldosteronism patients and 498 essential hypertension outpatients. All primary aldosteronism patients were diagnosed by autonomous aldosterone secretion using confirmatory tests, and then divided into nPA (n = 130) and primary aldosteronism patients with high PAC (hPA: n = 162) using a PAC cutoff level of less than 443 pmol/l (16 ng/dl), representing the normal upper limit of PAC.

Results: nPA patients were significantly older at diagnosis of primary aldosteronism and at onset of hypertension compared with hPA patients. They had milder hypokalemia and easier-to-control blood pressure. The results suggested that nPA could be considered a mild type of primary aldosteronism but not an early-stage hPA. Moreover, the risk of all CCV events in nPA was significantly lower than that in hPA (odds ratio 0.42, 95% confidence interval 0.18–0.90, P < 0.05) and not significantly higher than that in essential hypertension (odds ratio 0.95, 95% confidence interval 0.43–1.94, P = 0.899).

Conclusion: This study suggests that aggressive diagnostic workout for nPA is less effective to prevent CCV events.

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aDepartment of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka

bDepartment of Internal Medicine, Nishinomiya Municipal Central Hospital, Nishinomiya

cDepartment of Internal Medicine, Kansai Rosai Hospital, Amagasaki, Hyogo

dDepartment of Internal Medicine of Endocrinology and Metabolism, NTT West Osaka Hospital, Osaka

eDepartment of Internal Medicine of Endocrinology and Metabolism, National Hospital Organization, Osaka Minami Medical Center, Kawachinagano

fSenrichuo Ekimae Clinic, Toyonaka

gNakao Naika Clinic, Osaka

hOffice of Biostatistics and Data Management, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan

Correspondence to Tetsuhiro Kitamura, MD, PhD, Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Osaka, Japan. Tel: +81 6 6879 3742; fax: +81 6 6879 3739; e-mail:

Abbreviations: Af, atrial fibrillation; ARR, aldosterone–renin ratio; CCV, cardiovascular and cerebrovascular; CH, cerebral hemorrhage; CI, cerebral infarction; CAD, coronary artery disease; EH, essential hypertension; HF, heart failure; hPA, PA patients with high PAC; nPA, PA patients with normal PAC; PA, primary aldosteronism; PAC, plasma aldosterone concentration; PRA, plasma renin activity

Received 30 September, 2015

Revised 27 October, 2016

Accepted 15 December, 2016

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