Interrelated aldosterone and parathyroid hormone mutually modify cardiovascular mortality risk

Andreas Tomaschitz; Stefan Pilz; Jutta Rus-Machan; Andreas Meinitzer; Vincent M Brandenburg; Hubert Scharnagl; Martin Kapl; Tanja Grammer; Eberhard Ritz; Jörg H Horina; Marcus E Kleber; Burkert Pieske; Elisabeth Kraigher-Krainer; Bríain Ó Hartaigh; Hermann Toplak; Adriana J van Ballegooijen; Karin Amrein; Astrid Fahrleitner-Pammer; Winfried März

doi:10.1016/j.ijcard.2015.03.062

Interrelated aldosterone and parathyroid hormone mutually modify cardiovascular mortality risk

Int J Cardiol. 2015 Apr 1:184:710-716. doi: 10.1016/j.ijcard.2015.03.062. Epub 2015 Mar 4.

Authors

Andreas Tomaschitz¹, Stefan Pilz², Jutta Rus-Machan³, Andreas Meinitzer⁴, Vincent M Brandenburg⁵, Hubert Scharnagl⁴, Martin Kapl⁶, Tanja Grammer⁷, Eberhard Ritz⁸, Jörg H Horina⁹, Marcus E Kleber⁷, Burkert Pieske¹⁰, Elisabeth Kraigher-Krainer¹⁰, Bríain Ó Hartaigh¹¹, Hermann Toplak¹², Adriana J van Ballegooijen¹³, Karin Amrein¹⁴, Astrid Fahrleitner-Pammer¹⁴, Winfried März¹⁵

Affiliations

¹ 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.
² 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.
³ Specialist Clinic for Rehabilitation Bad Aussee, Bad Aussee, Austria.
⁴ Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
⁵ Department of Cardiology, University Hospital of the RWTH, Aachen, Germany.
⁶ Department of Cardiology, Medical University of Graz, Graz, Austria.
⁷ Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
⁸ University Hospital Heidelberg, Department of Medicine, Division of Nephrology, Heidelberg, Germany.
⁹ Department of Internal Medicine, Division of Nephrology, Medical University of Graz, Graz, Austria.
¹⁰ Department of Cardiology, Medical University of Graz, Graz, Austria; Department of Internal Medicine - Cardiology, Charité University Hospital Berlin, Campus Virchow Klinikum, Berlin Germany.
¹¹ 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.
¹² Department of Internal Medicine, Diabetes and Metabolism, Medical University of Graz, Austria.
¹³ Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
¹⁴ Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
¹⁵ 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.

PMID: 25777071
DOI: 10.1016/j.ijcard.2015.03.062

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.

Keywords: Aldosterone; Cardiovascular mortality; Parathyroid hormone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aldosterone / blood*
Biomarkers / blood
Cardiovascular Diseases / blood*
Cardiovascular Diseases / diagnosis*
Cross-Sectional Studies
Female
Fibroblast Growth Factor-23
Follow-Up Studies
Humans
Male
Middle Aged
Parathyroid Hormone / blood*
Risk Factors

Substances

Biomarkers
FGF23 protein, human
Parathyroid Hormone
Aldosterone
Fibroblast Growth Factor-23