Sieglinde Zelzer1, Dietmar Enko2, Stefan Pilz3, Andreas Tomaschitz4, Winfried März5, Andreas Meinitzer6. 1. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. Electronic address: sieglinde.zelzer@klinikum-graz.at. 2. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Clinical Chemistry and Laboratory Medicine, General Hospital Steyr, Sierningerstraße 170, 4400 Steyr, Austria. Electronic address: dietmar.enko@gespag.at. 3. Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. Electronic address: stefan.pilz@medunigraz.at. 4. Department of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Specialist Clinic for Rehabilitation Bad Gleichenberg, Schweizereiweg 4, 8344 Bad Gleichenberg, Austria; Department of Cardiology, Charité University Medicine Berlin, Hindenburgdamm 30, 12203 Berlin, Germany. Electronic address: andreas.tomaschitz@gmx.at. 5. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Theodor Kutzer-Ufer 1 - 3, 68167 Mannheim, Germany; Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim and Augsburg, Gubenerstraße 39, 86156 Augsburg, Germany. Electronic address: Winfried.Maerz@synlab.com. 6. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. Electronic address: andreas.meinitzer@klinikum-graz.at.
Abstract
OBJECTIVES: The leukocyte-derived myeloperoxidase (MPO), the nitric oxidase synthase (NOS) inhibitor asymmetrical dimethyl-arginine (ADMA) and the renin-angiotensin-aldosterone-system (RAAS) are associated with cardiovascular diseases (CVD). This study aimed to investigate potential interactions between the RAAS, ADMA and MPO in cardiovascular risk patients. DESIGN AND METHODS: All in all, 1446 patients, who were referred to coronary angiography, were included in this prospective study. MPO, ADMA and circulating serum markers of the RAAS system were measured. Additionally, all-cause and CVD mortality, cardiovascular risk factors, inflammatory and endothelial markers, and medication use were investigated. RESULTS: MPO concentrations were significantly associated with ADMA (P=0.002), renin (P=0.001) and angiotensin II levels (P=0.015), whereas ADMA was in tendency associated with renin (P=0.059) and significantly with angiotensin II (P=0.001). Both, ADMA and MPO were inversely correlated with angiotensinogen, angiotensin I and the angiotensin I/angiotensin II ratio. ADMA and angiotensin II were found stronger independent risk factors for all-cause and CVD mortality compared to MPO. CONCLUSIONS: MPO concentrations were significantly associated with higher ADMA levels and an up-regulated circulating RAAS in patients with CVD. Moreover, serum levels of ADMA and angiotensin II were shown to be more predictive for all-cause and CVD mortality compared to MPO.
OBJECTIVES: The leukocyte-derived myeloperoxidase (MPO), the nitric oxidase synthase (NOS) inhibitor asymmetrical dimethyl-arginine (ADMA) and the renin-angiotensin-aldosterone-system (RAAS) are associated with cardiovascular diseases (CVD). This study aimed to investigate potential interactions between the RAAS, ADMA and MPO in cardiovascular risk patients. DESIGN AND METHODS: All in all, 1446 patients, who were referred to coronary angiography, were included in this prospective study. MPO, ADMA and circulating serum markers of the RAAS system were measured. Additionally, all-cause and CVD mortality, cardiovascular risk factors, inflammatory and endothelial markers, and medication use were investigated. RESULTS:MPO concentrations were significantly associated with ADMA (P=0.002), renin (P=0.001) and angiotensin II levels (P=0.015), whereas ADMA was in tendency associated with renin (P=0.059) and significantly with angiotensin II (P=0.001). Both, ADMA and MPO were inversely correlated with angiotensinogen, angiotensin I and the angiotensin I/angiotensin II ratio. ADMA and angiotensin II were found stronger independent risk factors for all-cause and CVD mortality compared to MPO. CONCLUSIONS:MPO concentrations were significantly associated with higher ADMA levels and an up-regulated circulating RAAS in patients with CVD. Moreover, serum levels of ADMA and angiotensin II were shown to be more predictive for all-cause and CVD mortality compared to MPO.