dimethylarginine and Carotid-Artery-Diseases

To examine associations between asymmetric (ADMA), symmetric dimethylarginine (SDMA) and ADMA:SDMA ratio with assessments of endothelial function and coronary artery perfusion in RA patients.. ADMA and SDMA levels were measured in 197 RA individuals [144 (77.4%) females, median age: 66 years (quartiles: 59-73)]. Patients underwent assessments of microvascular endothelium-dependent and endothelium-independent function, macrovascular endothelium-dependent and endothelium-independent function and vascular morphology (pulse wave analysis, carotid intima-media thickness (cIMT), and carotid plaque). Coronary perfusion was assessed by subendocardial viability ratio (SEVR).. SEVR correlated with SDMA (r = 0.172, p = 0.026) and ADMA:SDMA (r = -0.160, p = 0.041) in univariable analysis, but not in multivariable analysis accounting for confounding factors. Neither ADMA:SDMA ratio nor SDMA were significantly correlated with microvascular or macrovascular endothelial function, or with arterial stiffness and cIMT. Within subgroup of patients (n = 26) with high inflammatory markers, a post-hoc analysis showed that SDMA and the ADMA:SDMA ratio were significantly associated with endothelium-dependent microvascular function in univariable analysis, with Pearson's r correlation coefficients of -0.440 (p = 0.031) and 0.511 (p = 0.011), respectively. Similar finding were established between ADMA:SDMA ratio and arterial stiffness in univariable analysis, with Pearson's r of 0.493, (p = 0.024).. Dimethylarginines were not found to be significantly associated with several assessments of vascular function and morphology in patients with RA, however, post-hoc analysis indicates that there may be associations in patients with raised inflammatory markers. Our results suggest that dysregulated NO metabolism may not be the sole mechanism for the development of preclinical atherosclerosis in RA.

Topics: Aged; Arginine; Arthritis, Rheumatoid; Atherosclerosis; Carotid Artery Diseases; Carotid Intima-Media Thickness; Endothelium, Vascular; Female; Humans; Immunoenzyme Techniques; Microvessels; Middle Aged; Models, Biological; Prospective Studies; Pulse Wave Analysis; Ultrasonography

Symmetric (SDMA) and asymmetric (ADMA) dimethylarginines have emerged as novel biomarkers of cardiovascular disease (CVD) in several disease settings associated with atherosclerosis. Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by high CVD mortality and morbidity. ADMA and SDMA levels are abnormal in RA patients, but their correlation with assessments of endothelial function and structure remains unknown. We aimed to investigate whether SDMA and ADMA are associated with carotid intima media thickness (cIMT) and arterial stiffness as well as non-invasive assessments of in vivo micro- and macrovascular endothelial function in RA patients with high systemic inflammatory load.. ADMA and SDMA levels were measured using immunoassays in 197 RA individuals. Twenty-six of these [23 (86.4%) females, median age 70, quartiles (60, 73)] were identified as having high inflammatory markers [erythrocyte sedimentation rate (ESR) >25 mm/hr and C-reactive protein (CRP) > 5 mg/L], and were compared to the remainder of the cohort. Patients underwent assessments of microvascular endothelium-dependent and endothelium-independent function [laser Doppler imaging with iontophoresis of acetylcholine (Ach) and sodium-nitroprusside (SNP) respectively], macrovascular endothelium-dependent and endothelium-independent function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilation respectively), and vascular morphology [pulse wave analysis, and carotid intima media thickness (cIMT)].. Significant interactions with inflammation were detected in the associations between ACh and both SDMA (p = 0.014) and ADMA:SDMA ratio (p = 0.027), as well as between SNP and SDMA (p = 0.042) and between arterial stiffness and ADMA:SDMA (p = 0.036), with the associations being stronger in the patients with high inflammatory markers in each case.. Besides their emerging role as markers of endothelial dysfunction SDMA and ADMA may promote endothelial injury in RA as mediators of the adverse effects of systemic inflammation on micro- and macrovasculature respectively in patients with active disease.

Topics: Aged; Arginine; Arthritis, Rheumatoid; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cohort Studies; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoassay; Inflammation; Laser-Doppler Flowmetry; Male; Middle Aged; Pulse Wave Analysis; Receptor Cross-Talk; Vascular Stiffness

Higher plasma concentrations of the endogenous nitric oxides synthase inhibitor asymmetrical dimethylarginine (ADMA) are associated with increased risk of cardiovascular and cerebrovascular events and death, presumably by promoting endothelial dysfunction and subclinical atherosclerosis. We hypothesized that plasma ADMA concentrations are positively related to common carotid artery intimal-media thickness (CCA-IMT) and to internal carotid (ICA)/bulb IMT.. We investigated the cross-sectional relations of plasma ADMA with CCA-IMT and ICA/bulb IMT in 2958 Framingham Heart Study participants (mean age, 58 years; 55% women).. In unadjusted analyses, ADMA was positively related to both CCA-IMT (beta per SD increment, 0.012; P<0.001) and ICA/bulb IMT (beta per SD increment, 0.059; P<0.001). In multivariable analyses (adjusting for age, sex, systolic blood pressure, antihypertensive treatment, smoking status, diabetes, BMI, total-to-HDL cholesterol ratio, log C-reactive protein, and serum creatinine), plasma ADMA was not associated with CCA-IMT (P=0.991), but remained significantly and positively related to ICA/bulb IMT (beta per SD increment, 0.0246; P=0.002).. In our large community-based sample, we observed that higher plasma ADMA concentrations were associated with greater ICA/bulb IMT, but not with CCA-IMT. These data are consistent with the notion that ADMA promotes subclinical atherosclerosis in a site-specific manner, with a greater proatherogenic influence at known vulnerable sites in the arterial tree.

Topics: Adult Children; Aged; Arginine; Biomarkers; Carotid Artery Diseases; Carotid Artery, Common; Carotid Artery, Internal; Cohort Studies; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Nitric Oxide Synthase; Tunica Intima; Tunica Media

Topics: Arginine; Blood Pressure; Carotid Artery Diseases; Causality; Cell Membrane; Endothelial Cells; Hemodynamics; Humans; Hypertension; Membrane Fluidity; Nitric Oxide; Regional Blood Flow

To determine the association between asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, with atherosclerosis in patients with chronic kidney disease (CKD).. One hundred thirty-eight CKD patients were enrolled in this study. Serum levels of L-arginine, ADMA, and SDMA were measured by high-performance liquid chromatography (HPLC). Common carotid arteries intimae-medial thickness (CCA-IMT), cross-sectional calculated intimae-medial thickness (cIM area) and atherosclerotic plaque were detected by noninvasive high-resolution B-mode ultrasonography.. Serum levels of ADMA and SDMA were significantly increased in CKD patients (n=138) compared with age matched healthy subjects (n=42, P<0.01). ADMA and SDMA levels increased with the progression of renal dysfunction and were negatively related to creatinine clearance (Ccr) in pre-dialysis patients (r=-0.315, P<0.05; r=-0.426, P<0.01). Serum levels of ADMA and SDMA in dialysis patients (n=74) were significantly higher than those in pre-dialysis patients (P<0.05). Patients with carotid artery plaques showed significantly higher levels of ADMA compared with those without plaques. Serum levels of ADMA closely correlated with the mean IMT (r=0.471, P<0.01) and cIM area value (r=0.430, P<0.01). These correlations remained significant even after adjusting GFR, age, gender ,and other risk factors for atherosclerosis in the multiple regression analysis.. Serum levels of ADMA increased with the progression of CKD and may play a role in the pathogenesis of accelerated atherosclerosis in CKD patients.

Topics: Adult; Arginine; Carotid Artery Diseases; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nitric Oxide Synthase; Renal Dialysis