Myeloperoxidase, asymmetric dimethyl-arginine and the renin-angiotensin-aldosterone-system in cardiovascular risk patients: Cross-sectional findings from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.
OBJECTIVE
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.


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.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. Electronic address: sieglinde.zelzer@klinikum-graz.at.
Sieglinde
S
Zelzer
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.
Dietmar
D
Enko
Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. Electronic address: stefan.pilz@medunigraz.at.
Stefan
S
Pilz
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.
Andreas
A
Tomaschitz
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.
Winfried
W
März
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. Electronic address: andreas.meinitzer@klinikum-graz.at.
Andreas
A
Meinitzer
D000368:Aged; D000450:Aldosterone / Q000097:blood*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001317:Austria / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000401:mortality; D015331:Cohort Studies; D017023:Coronary Angiography; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D005979:Glutathione Peroxidase / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009195:Peroxidase / Q000097:blood*; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D012084:Renin-Angiotensin System; D012307:Risk Factors; D000094765:Glutathione Peroxidase GPX1
D015415:Biomarkers; D000450:Aldosterone; C018524:N,N-dimethylarginine; D001120:Arginine; D009195:Peroxidase; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human
Asymmetric dimethyl-arginine; Cardiovascular disease; Myeloperoxidase; Renin-angiotensin-aldosterone-system