Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics, and Subclinical Vascular Disease

Chirinos, Julio A.; David, Robert; Bralley, J. Alexander; Zea‐Diaz, Humberto; Muñoz-Atahualpa, Edgar; Corrales-Medina, Fernando F.; Cuba-Bustinza, Carolina; Chirinos-Pacheco, Julio; Medina‐Lezama, Josefina

doi:10.1161/hypertensionaha.108.120352

Cited by 57 publications

(43 citation statements)

References 47 publications

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“…On multiple stepwise regression analysis, carotid IMT was conspicuously related with the concentrations of ADMA [74] and the generation of carotid IMT, over a 6-year period, was associated with serum concentrations of ADMA [75] . In the PREVENCION study of 922 grown-up subjects, ADMA remarkably prognosticated carotid IMT even after adaptation for CV hazard parameters, CRP, and kidney function, but did not prefigure carotid-femoral pulse wave velocity, BP, or hemodynamic abnormality [76] . Kocak et al [77] determined higher ADMA concentrations in people without alreadyknown arteriosclerotic disease who were on continuous ambulatory peritoneal dialysis and revealed a remarkable positive correlational statistics between the concentrations of ADMA and carotid IMT in these subjects.…”

Section: Adma and Carotid Intima-media Thicknessmentioning

confidence: 90%

Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus

Konya

Miuchi

Satani

et al. 2015

WJEM

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Cardiovascular (CV) complications are an essential causal element of prospect in diabetes mellitus (DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine (ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM (T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin (U-Alb), mean intimal-medial thickness (IMT) and ankle brachial index (ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA (standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects. Core tip: Asymmetric dimethylarginine (ADMA) is an emerging independent biomarker for prospective cardiovascular (CV) complications. In our study, the results show that the cases with a high level of ADMA could have diabetes mellitus CV (DMCV) complications in the future within five years. Furthermore, not only ADMA but also urinary albumin was associated with DMCV complications in the multiple regression analyses. The clinical acceptation of this parameter will rely on the availability of therapies to immediately reduce ADMA such as incretin-based drugs, which could support the part of ADMA as an etiologic risk factor.

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Section: Adma and Carotid Intima-media Thicknessmentioning

confidence: 90%

Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus

Konya

Miuchi

Satani

et al. 2015

WJEM

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“…8 These data support the clinical observations that ADMA plasma levels are elevated in subclinical inflammation states, such as in patients with multiple risk factors for atherosclerosis. 9 However, our knowledge regarding the ef-fects of inflammation on circulating ADMA in humans is mainly derived from cross-sectional data. Furthermore, despite its putative link between inflammation and endothelial dysfunction, the potential role of ADMA as a mediator of inflammation-induced endothelial dysfunction has not been demonstrated until now.…”

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confidence: 99%

Role of Asymmetrical Dimethylarginine in Inflammation-Induced Endothelial Dysfunction in Human Atherosclerosis

et al. 2011

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Abstract-We explored the role of asymmetrical dimethylarginine (ADMA) as a cause of endothelial dysfunction induced by systemic inflammation. In vitro data suggest that ADMA bioavailability is regulated by proinflammatory stimuli, but it is unclear whether ADMA is a link between inflammation and endothelial dysfunction in humans. In study 1 we recruited 351 patients with coronary artery disease (CAD) and 87 healthy controls. In study 2 we recruited 69 CAD, 69 healthy, and 10 patients with rheumatoid arthritis, whereas in study 3, 22 healthy and 70 CAD subjects were randomly assigned to Salmonella typhii vaccination (nϭ11 healthy and nϭ60 CAD) or placebo (nϭ11 healthy and nϭ10 CAD). Circulating interleukin 6/ADMA and flow-mediated dilation (FMD) were measured at 0 and 8 hours. In study 1, ADMA was inversely correlated with FMD in healthy individuals and CAD patients (PϽ0.0001 for both). However, interleukin 6 was inversely correlated with FMD (PϽ0.0001) in healthy subjects but not in CAD patients. The positive correlation between ADMA and interleukin 6 was stronger in healthy (rϭ0.515; PϽ0.0001) compared with CAD (rϭ0.289; Pϭ0.0001) subjects. In study 2, both patients with rheumatoid arthritis and CAD had higher interleukin 6 (PϽ0.0001) and ADMA (Pϭ0.004) but lower FMD (Pϭ0.001) versus healthy subjects. In study 3, vaccination increased interleukin 6 in healthy (PϽ0.001) and CAD (PϽ0.001) subjects. FMD was reduced in healthy subjects (PϽ0.05), but its reduction in CAD was borderline. Vaccination increased ADMA only in healthy subjects (PϽ0.001). Systemic, low-grade inflammation leads to increased ADMA that may induce endothelial dysfunction. This study demonstrated that ADMA may be a link between inflammation and endothelial dysfunction in humans. (Hypertension. 2011;58:93-98.) • Online Data Supplement Key Words: ADMA Ⅲ endothelium Ⅲ inflammation Ⅲ interleukin 6 Ⅲ atherosclerosis Ⅲ coronary artery disease T he development of endothelial dysfunction is considered to be the initial step in atherogenesis. 1 A healthy endothelium is responsible for NO generation through oxidation of L-arginine by endothelial NO synthase (eNOS). 1 NO maintains vascular tone and acts, per se, as an important intracellular messenger, inducing divergent anti-inflammatory, antithrombotic, and antiapoptotic effects. 1 Asymmetrical dimethylarginine (ADMA), an endogenous L-arginine analog, has been associated with impaired endothelial function in humans. 2 ADMA has also been associated with eNOS uncoupling that results in increased eNOSderived superoxide production in human vessels. 2 Clinical evidence suggests that ADMA plasma levels are associated with endothelial function, particularly in patients with coronary atherosclerosis 3 or atherosclerosis risk factors, 4 whereas this association is significant but weak in healthy individuals. 5 Furthermore, in prospective studies, plasma ADMA has been independently associated with clinical outcome and mortality in diabetic subjects and patients with atherosclerosis. 6 ADMA is derived from ...

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“…We studied 1639 adults aged 18 to 80 years enrolled in the PREVENCION (Estudio Peruano de Prevalencia de Enfermedades Cardiovasculares, for Peruvian Study of the Prevalence of Cardiovascular diseases) study 8, 9, 10, 11, 12, 13, 14. PREVENCION is a study undertaken in Arequipa, the second largest city in Peru, which occurred in 2 phases: the first phase, which focused on population‐based prevalence estimates of cardiovascular disease/risk factors, and the second phase, which focused on increasing the sample size for prospective analyses regarding the relationship between baseline cardiovascular phenotypes and mortality.…”

Section: Methodsmentioning

confidence: 99%

Hemodynamic Patterns Identified by Impedance Cardiography Predict Mortality in the General Population: The PREVENCION Study

Medina‐Lezama

Narvaez‐Guerra

Herrera‐Enriquez

et al. 2018

JAHA

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BackgroundBlood pressure is determined by the interactions between the heart and arterial properties, and subjects with identical blood pressure may have substantially different hemodynamic determinants. Whether arterial hemodynamic indices quantified by impedance cardiography (ICG), a simple operator‐independent office procedure, independently predict all‐cause mortality in adults from the general population, and specifically among those who do not meet criteria for American College of Cardiology/American Heart Association stage 2 hypertension, is currently unknown.Methods and ResultsWe studied 1639 adults aged 18 to 80 years from the general population. We used ICG to measure hemodynamic parameters and metrics of cardiac function. We assessed the relationship between hemodynamic parameters measured at baseline and all‐cause mortality over a mean follow‐up of 10.9 years. Several ICG parameters predicted death. The strongest predictors were total arterial compliance index (standardized hazard ratio=0.38; 95% confidence interval=0.31–0.46; P<0.0001) and indices of cardiac contractility: velocity index (standardized hazard ratio=0.45; 95% confidence interval=0.37–0.55; P<0.0001) and acceleration index (standardized hazard ratio=0.44; 95% confidence interval=0.35–0.55; P<0.0001). These remained independently predictive of death after adjustment for multiple confounders, as well as systolic and diastolic blood pressure. Among subjects without stage 2 hypertension (n=1563), indices of cardiac contractility were independently predictive of death and identified a subpopulation (25% of non‐stage‐2 hypertensives) that demonstrated a high 10‐year mortality risk, equivalent to that of stage 2 hypertensives.ConclusionsHemodynamic patterns identified by ICG independently predict mortality in the general population. The predictive value of ICG applies even in the absence of American College of Cardiology/American Heart Association stage 2 hypertension and identifies higher‐risk individuals who are in earlier stages of the hypertension continuum.

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Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics, and Subclinical Vascular Disease

Cited by 57 publications

References 47 publications

Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus

Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus

Role of Asymmetrical Dimethylarginine in Inflammation-Induced Endothelial Dysfunction in Human Atherosclerosis

Hemodynamic Patterns Identified by Impedance Cardiography Predict Mortality in the General Population: The PREVENCION Study

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