title: Interrelated aldosterone and parathyroid hormone mutually modify cardiovascular mortality risk.
abstract: BACKGROUND
  Inappropriate aldosterone and parathyroid hormone (PTH) secretion is associated with increased cardiovascular risk. Accumulating evidence suggests bidirectional interplay between aldosterone and PTH.
  
  
  METHODS
  We evaluated the cross-sectional relationship between plasma aldosterone concentration (PAC), aldosterone to renin ratio (ARR) and PTH and subsequently tested whether the interaction between PAC and PTH modified the risk of cardiovascular death. PAC [78.0 (48.0-123.0) pg/mL], ARR [6.4 (2.9-12.9) pg/mL/pg/mL] and PTH concentration [median: 29.0 (22.0-40.0) pg/mL] were measured in 3074 patients (mean age: 62.5 ± 10.6 years; 30.3% women) referred to coronary angiography in a tertiary care center in Southwest Germany.
  
  
  RESULTS
  Using multiple linear regression analysis, PAC and ARR emerged as an independent predictor of higher PTH concentrations (β=0.12 and 0.21, P<0.001 for both) irrespective of intake of antihypertensive treatment, 25(OH)D, kidney function, serum calcium, phosphate, magnesium, cortisol, NT-pro-BNP, soluble α-klotho and FGF-23 concentration. After a median follow-up of 9.9 years, 512 (16.7%) participants had died due to fatal cardiovascular events. Multivariate Cox proportional hazard analysis revealed that both PAC and PTH were independently associated with cardiovascular mortality, with a potential synergistic interaction (P=0.028). PAC and PTH are exclusively associated with cardiovascular death in subjects with PTH and PAC concentrations above the median, respectively (PAC: HR per log SD: 1.14; 95% CI 1.02-1.29; P=0.026; PTH: HR per log SD: 1.18; 95% CI 1.02-1.37; P=0.031).
  
  
  CONCLUSIONS
  Higher PAC and ARR were independently associated with PTH. PAC was independently related to incident cardiovascular mortality exclusively in patients with elevated PTH and vice versa.
authors.affiliation: Specialist Clinic for Rehabilitation Bad Aussee, Bad Aussee, Austria; Department of Cardiology, Medical University of Graz, Graz, Austria; Department of Internal Medicine - Cardiology, Charité University Hospital Berlin, Campus Virchow Klinikum, Berlin Germany. Electronic address: andreas.tomaschitz@gmx.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria; Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, 1081 BT Amsterdam, The Netherlands. Electronic address: stefan.pilz@chello.at.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.affiliation: Specialist Clinic for Rehabilitation Bad Aussee, Bad Aussee, Austria.
authors.forename: Jutta
authors.initials: J
authors.lastname: Rus-Machan
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.affiliation: Department of Cardiology, University Hospital of the RWTH, Aachen, Germany.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Brandenburg
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.affiliation: Department of Cardiology, Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Kapl
authors.affiliation: Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Grammer
authors.affiliation: University Hospital Heidelberg, Department of Medicine, Division of Nephrology, Heidelberg, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Medical University of Graz, Graz, Austria.
authors.forename: Jörg H
authors.initials: JH
authors.lastname: Horina
authors.affiliation: Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: Department of Cardiology, Medical University of Graz, Graz, Austria; Department of Internal Medicine - Cardiology, Charité University Hospital Berlin, Campus Virchow Klinikum, Berlin Germany.
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
authors.affiliation: Department of Cardiology, Medical University of Graz, Graz, Austria; Department of Internal Medicine - Cardiology, Charité University Hospital Berlin, Campus Virchow Klinikum, Berlin Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kraigher-Krainer
authors.affiliation: Department of Radiology, Dalio Institute of Cardiovascular Imaging, New York-Presbyterian Hospital and the Weill Cornell Medical College, New York, USA; Department of Internal Medicine, Section of Geriatrics, Yale School of Medicine, Adler Geriatric Center, New Haven, USA.
authors.forename: Bríain Ó
authors.initials: BÓ
authors.lastname: Hartaigh
authors.affiliation: Department of Internal Medicine, Diabetes and Metabolism, Medical University of Graz, Austria.
authors.forename: Hermann
authors.initials: H
authors.lastname: Toplak
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
authors.forename: Adriana J
authors.initials: AJ
authors.lastname: van Ballegooijen
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Amrein
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
authors.forename: Astrid
authors.initials: A
authors.lastname: Fahrleitner-Pammer
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany; Synlab Academy, Synlab Services LLC, Mannheim, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis*; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D000450:Aldosterone; D000089703:Fibroblast Growth Factor-23
keywords: Aldosterone; Cardiovascular mortality; Parathyroid hormone