Asymmetric and symmetric dimethylarginine and risk of secondary cardiovascular disease events and mortality in patients with stable coronary heart disease: the KAROLA follow-up study
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- 作者：Bob Siegerink (1) (2)
Renke Maas (3)
Carla Y. Vossen (2) (4)
Edzard Schwedhelm (5)
Wolfgang Koenig (6)
Rainer B?ger (5)
Dietrich Rothenbacher (1) (7)
Hermann Brenner (1)
Lutz P. Breitling (1) (8) - 关键词：ADMA ; SDMA ; Cardiovascular disease ; Mortality ; Prospective cohort study
- 刊名：Clinical Research in Cardiology
- 出版年：2013
- 出版时间：March 2013
- 年：2013
- 卷：102
- 期：3
- 页码：193-202
- 全文大小：404KB
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Renke Maas (3)
Carla Y. Vossen (2) (4)
Edzard Schwedhelm (5)
Wolfgang Koenig (6)
Rainer B?ger (5)
Dietrich Rothenbacher (1) (7)
Hermann Brenner (1)
Lutz P. Breitling (1) (8)
1. German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research C070, Heidelberg, Germany
2. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
3. Friedrich-Alexander Universit?t Erlangen-Nürnberg, Institute of Experimental and Clinical Pharmacology and Toxicology, Erlangen, Germany
4. Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
5. Clinical Pharmacology Unit, Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
6. Department of Internal Medicine II-Cardiology, Ulm University, Ulm, Germany
7. Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
8. Clinic for Gastroenterology, Hepatology and Infectiology, University Hospital Düsseldorf, Düsseldorf, Germany
文摘
Background Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor, which has been associated with total and cardiovascular mortality in various clinical settings. Studies on its structural isomer, symmetric dimethylarginine (SDMA), are scarce. This study aimed to determine the associations of both ADMA and SDMA levels with secondary cardiovascular disease events and all-cause mortality in patients with stable coronary heart disease (CHD). Methods In the observational prospective cohort study KAROLA, 1,148 CHD patients were followed for a median of 8.1?years. ADMA and SDMA were determined by liquid chromatography–tandem mass spectrometry. Baseline ADMA and SDMA levels were categorized in quartiles or standardized by their respective standard deviation, and appropriate hazard ratios and 95?% confidence intervals (HR [95?% CI]) were estimated in Cox proportional hazards models. Results 150 patients experienced secondary cardiovascular disease events (CVD) and 121 patients died. After adjustment for confounders, ADMA was not associated with the risk of secondary CVD events (HR per standard deviation increase: 1.02 [95?%CI: 0.86-.21]), whereas an association was suggested for SDMA (HR 1.17 [1.00-.37]). Higher hazard ratios were observed in all-cause mortality models (ADMA: HR 1.15 [0.95-.37]; SDMA: HR 1.29 [1.09-.52]). Conclusions Our results suggest that especially SDMA might possibly have potential as a risk marker for all-cause mortality and to a lesser extent for secondary cardiovascular events. Future studies are needed to quantify these associations more precisely and should, in particular, further address the possibility of residual confounding by impaired kidney function.