title: Parathyroid hormone, aldosterone-to-renin ratio and fibroblast growth factor-23 as determinants of nocturnal blood pressure in primary hyperparathyroidism: the eplerenone in primary hyperparathyroidism trial.
abstract: The high prevalence of arterial hypertension in primary hyperparathyroidism (pHPT) is largely unexplained. Apart from parathyroid hormone (PTH), the mineral hormones fibroblast growth factor (FGF)-23 and aldosterone-to-renin ratio (ARR) are upregulated in pHPT. We aimed to determine whether nocturnal blood pressure (BP) is related with PTH, FGF-23 or ARR in a relatively large sample of pHPT patients.
  
  
  
  Cross-sectional data of the single-center "Eplerenone in Primary Hyperparathyroidism" trial were used. All patients with a biochemical diagnosis of pHPT who had both available 24-h ambulatory BP monitoring and valid laboratory data were included.
  
  
  
  Full data were available in 136 patients (mean age 67 ± 10 years, 78% women). Median PTH was 99 (interquartile range: 82-124) pg/ml and mean calcium was 2.63 ± 0.15 mmol/l. ARR, but not PTH or FGF-23, was significantly and directly related with nocturnal SBP (Pearson's r = 0.241, P < 0.01) and DBP (r = 0.328, P < 0.01). In multivariate regression analyses, with adjustment for age, sex, PTH, FGF-23, traditional cardiovascular risk factors, antihypertensive medication and parameters of calcium metabolism ARR remained significantly and directly related with nocturnal BP (SBP: adjusted β-coefficient = 0.289, P < 0.01; DBP: β = 0.399, P < 0.01). The relationship between ARR and nocturnal SBP was exclusively present in patients with PTH levels above the median of 99 pg/ml.
  
  
  
  ARR, but not FGF-23 or PTH, was independently and directly related with nocturnal BP parameters in patients with pHPT, and this relationship was dependent on pHPT disease severity. Inappropriately, elevated aldosterone may partially explain the high prevalence of arterial hypertension in pHPT.
authors.affiliation: aDepartment of Cardiology bDepartment of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria cMedizinische Klinik mit Schwerpunkt Kardiologie, Campus Virchow-Klinikum, Charité-Universitaetsmedizin Berlin, Berlin, Germany dClinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria eSwiss Cardiovascular Center Bern, Department of Cardiology, Bern University Hospital, Bern, Switzerland fHypertension Unit, Internal Medicine, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy gDepartment of Health Sciences and the EMGO Institute, VU University, Amsterdam, The Netherlands hDepartment of Cardiology, University Hospital of the RWTH Aachen, Aachen iSynlab Academy, Synlab Services LLC jMedical Clinic V (Nephrology, Hypertensiology, Endocrinology), Medical Faculty Mannheim, Ruperto Carola University Heidelberg, Mannheim, Germany kDepartment of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands lSpecialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Verheyen
authors.forename: Astrid
authors.initials: A
authors.lastname: Fahrleitner-Pammer
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.forename: Evgeny
authors.initials: E
authors.lastname: Belyavskiy
authors.forename: Julia
authors.initials: J
authors.lastname: Wetzel
authors.forename: Martin
authors.initials: M
authors.lastname: Gaksch
authors.forename: Martin R
authors.initials: MR
authors.lastname: Grübler
authors.forename: Cristiana
authors.initials: C
authors.lastname: Catena
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Sechi
authors.forename: Adriana J
authors.initials: AJ
authors.lastname: Van Ballegooijen
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Brandenburg
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.forename: Sabine
authors.initials: S
authors.lastname: Perl
authors.forename: Helmut
authors.initials: H
authors.lastname: Brussee
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D002118:Calcium / Q000097:blood; D002940:Circadian Rhythm; D003430:Cross-Sectional Studies; D003971:Diastole; D000077545:Eplerenone; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D006973:Hypertension / Q000097:blood / Q000209:etiology; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D010281:Parathyroid Hormone / Q000097:blood*; D016032:Randomized Controlled Trials as Topic; D012083:Renin / Q000097:blood*; D012307:Risk Factors; D012737:Sex Factors; D013148:Spironolactone / Q000031:analogs & derivatives / Q000627:therapeutic use; D013599:Systole
chemical_list: D000959:Antihypertensive Agents; C000717427:FGF23 protein, human; D000451:Mineralocorticoid Receptor Antagonists; D010281:Parathyroid Hormone; D013148:Spironolactone; D000450:Aldosterone; D005346:Fibroblast Growth Factors; D000077545:Eplerenone; D000089703:Fibroblast Growth Factor-23; D012083:Renin; D002118:Calcium