Asymmetric Dimethylarginine (Adma) Is Related to the Severity of Atherosclerosis and Predicts Mortality in End Stage Renal Disease (Esrd)

Zoccali, Carmine; Boeger, S.; Mallamaci, Francesca; Benedetto, Francesco; Tripepi, Giovanni; Malatino, Lorenzo; Cataliotti, A.; Bellanuova, Ignazio; Böeger, Rainer

doi:10.1097/00004872-200006001-00096

Cited by 21 publications

(25 citation statements)

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“…Moreover, prospective clinical studies have convincingly shown that high ADMA plasma levels are associated with an increased incidence of major cardiovascular events and with total mortality. This was found in high-risk populations such as haemodialysis patients, 63 in patients with multi-organ failure treated on a multidisciplinary intensive care unit, 64 and in patients after acute myocardial infarction. 65 ADMA was also reported to be a risk marker for cardiovascular disease and mortality in medium-risk populations such as patients with stable coronary artery disease, [66][67][68] chronic heart failure, 69 peripheral arterial disease 70 and type 2 diabetes mellitus.…”

Section: Adma and Cardiovascular Diseasementioning

confidence: 92%

Review article: Asymmetric dimethylarginine as a mediator of vascular dysfunction and a marker of cardiovascular disease and mortality: an intriguing interaction with diabetes mellitus

Anderssohn

Schwedhelm

Lüneburg

et al. 2010

Diabetes and Vascular Disease Research

114

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Asymmetric dimethylarginine (ADMA) has evolved as an important regulator of nitric oxide (NO) synthesis in recent years. Elevated levels of ADMA have been reported in many conditions associated with a high cardiovascular risk. Moreover, ADMA is a biomarker for major cardiovascular events and mortality in cohorts with high, intermediate and low overall cardiovascular risk. Discrepant data have been reported on cardiovascular risk in people with and without diabetes mellitus, and the association of ADMA with diabetes mellitus per se has also remained controversial, possibly relating to type and stage of diabetes. Clinical and experimental data suggest that there is a multifaceted link between ADMA and insulin metabolism and action on one hand, and ADMA and glucose utilisation on the other. This interplay may be regulated by the enzyme involved in the metabolic degradation of ADMA, dimethylarginine dimethylaminohydrolase (DDAH). Recent data from prospective clinical studies suggest that whilst ADMA may be a marker for total mortality in patients without diabetes, elevated ADMA may exert beneficial effects in patients with diabetes. In this respect, ADMA could serve as a re-coupling agent overcoming endothelial nitric oxide synthase (eNOS) uncoupling in patients with diabetes. Anticipated advances in clinical and experimental investigation will help us to better understand this complex interrelationship between diabetes, eNOS, DDAH and ADMA.

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Section: Adma and Cardiovascular Diseasementioning

confidence: 92%

Review article: Asymmetric dimethylarginine as a mediator of vascular dysfunction and a marker of cardiovascular disease and mortality: an intriguing interaction with diabetes mellitus

Anderssohn

Schwedhelm

Lüneburg

et al. 2010

Diabetes and Vascular Disease Research

114

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“…On average, plasma E2 concentrations were greater than 2000 pg/ml. The mean age of these participants was 31.07 years (range [25][26][27][28][29][30][31][32][33][34][35][36]. The fasting glucose, total cholesterol and triglyceride concentrations were 81.57 Ϯ 14.50 mg/dl, 154.642 Ϯ 44.89 mg/dl and 93.64 Ϯ 42.54 mg/dl, respectively.…”

Section: Participantsmentioning

confidence: 99%

Plasma markers of NO synthase activity in women after ovarian hyperstimulation: influence of estradiol on ADMA

et al. 2006

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Abstract:The beneficial effects of estrogen on vasculature are partially explained by an estrogen-induced increase in nitric oxide (NO) synthesis. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase. In the present study, the effect of 17␤-estradiol (E2) on ADMA and NO synthesis was investigated both in vivo and in vitro. Plasma NO and ADMA levels were measured in healthy women at a low menstrual estrogenic stage (E2 Ͻ 100 pg/ml) and in women who were undergoing ovarian hyperstimulation (E2 Ͼ 2000 pg/ml) before in vitro fertilization embryo transfer. Primary human umbilical vein endothelial cell (HUVEC) cultures were incubated with and without 100 nM E2 for 24 hours and the NO and ADMA levels of the media were measured. A nitric oxide analyzer was used for the detection of NO metabolites. ADMA and L-arginine were measured by high-performance liquid chromatography after precolumn derivatization with o-phthaldialdehyde. The IVF patients with high plasma E2 concentrations had significantly lower (48%, n ϭ 12) plasma ADMA and higher (56%, n ϭ 14) NO levels than the women at a low estrogenic stage. The incubation of HUVEC cultures with estradiol resulted in a significant decrease (47%, n ϭ 10) in ADMA and an increase (46%, n ϭ 10) in NO concentration in the culture media. Estradiol, by reducing ADMA, may therefore facilitate NO synthesis in endothelial cells. The protective effects of estradiol on vasculature may partly be related to a reduction in ADMA levels.

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“…In theory the model is perfect when predicted and observed risk coincide. Here I will use the cardiovascular risk extended evaluation in dialysis (CREED) study database [2] to make an exercise on cardiovascular risk modelling. We start with a fundamental variable, age.…”

Section: Cardiovascular Risk Modellingmentioning

confidence: 99%

“…In this analysis the plasma concentration of ADMA was appropriately corrected for age and plasma homocysteine because these factors, like ADMA, were independently related to IMT [11]. Secondly we examined the relationship between ADMA and all causes and cardiovascular mortality [2]. Interestingly, this analysis showed that patients with a relatively higher plasma concentration of ADMA had a shorter survival than those with a relatively lower plasma concentration.…”

Section: Esrd As a Vasculotoxic State: Asymmetric Dimethylarginine Asmentioning

confidence: 99%

Endothelial Damage, Asymmetric Dimethylarginine and Cardiovascular Risk in End-Stage Renal Disease

Zoccali¹

2002

Blood Purif

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To be appropriately labelled as a ‘risk factor’ any putative risk factor should increase the prediction power of standard statistical models based on ‘traditional’ (Framingham) risk factors. In end-stage renal disease (ESRD), Framingham risk factors do not fully explain the cardiovascular burden of these patients. Inflammation, hyperhomocysteinemia and anemia contribute to the high cardiovascular risk of ESRD, but knowledge is still incomplete. We suspected that asymmetric dimethylarginine (ADMA) is an important cardiovascular risk factor in dialysis patients. This substance inhibits nitric oxide synthase thus triggering a series of pathophysiological events leading to atherosclerosis. To test this hypothesis, we studied the relationship between ADMA and intima media thickness (IMT) in the carotid artery. ADMA was found to be strongly and independently related to IMT. More importantly we found that patients with relatively higher plasma ADMA had shorter survival and a higher rate of incident cardiovascular complications in comparison to those with a relatively lower plasma concentration. These data represent a sound basis for intervention studies aimed at modifying the plasma ADMA concentration in ESRD patients.

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Asymmetric Dimethylarginine (Adma) Is Related to the Severity of Atherosclerosis and Predicts Mortality in End Stage Renal Disease (Esrd)

Cited by 21 publications

References 0 publications

Review article: Asymmetric dimethylarginine as a mediator of vascular dysfunction and a marker of cardiovascular disease and mortality: an intriguing interaction with diabetes mellitus

Review article: Asymmetric dimethylarginine as a mediator of vascular dysfunction and a marker of cardiovascular disease and mortality: an intriguing interaction with diabetes mellitus

Plasma markers of NO synthase activity in women after ovarian hyperstimulation: influence of estradiol on ADMA

Endothelial Damage, Asymmetric Dimethylarginine and Cardiovascular Risk in End-Stage Renal Disease

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