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. 2013

Bob Siegerink, and Renke Maas, and Carla Y Vossen, and Edzard Schwedhelm, and Wolfgang Koenig, and Rainer Böger, and Dietrich Rothenbacher, and Hermann Brenner, and Lutz P Breitling
German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research C070, Heidelberg, Germany.

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: 0.86-1.21]), whereas an association was suggested for SDMA (HR 1.17 [1.00-1.37]). Higher hazard ratios were observed in all-cause mortality models (ADMA: HR 1.15 [0.95-1.37]; SDMA: HR 1.29 [1.09-1.52]). 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.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011237 Predictive Value of Tests In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test. Negative Predictive Value,Positive Predictive Value,Predictive Value Of Test,Predictive Values Of Tests,Negative Predictive Values,Positive Predictive Values,Predictive Value, Negative,Predictive Value, Positive
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D012008 Recurrence The return of a sign, symptom, or disease after a remission. Recrudescence,Relapse,Recrudescences,Recurrences,Relapses
D002423 Cause of Death Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. Causes of Death,Death Cause,Death Causes
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D003327 Coronary Disease An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. Coronary Heart Disease,Coronary Diseases,Coronary Heart Diseases,Disease, Coronary,Disease, Coronary Heart,Diseases, Coronary,Diseases, Coronary Heart,Heart Disease, Coronary,Heart Diseases, Coronary
D005260 Female Females

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