Relationship of asymmetric dimethylarginine and homocysteine to vascular aging in systemic lupus erythematosus patients.

Weill Cornell Medical College and Hospital for Special Surgery, New York, New York 10021, USA.
Arthritis & Rheumatology (Impact Factor: 7.48). 02/2010; 62(6):1718-22. DOI: 10.1002/art.27392
Source: PubMed

ABSTRACT Systemic lupus erythematosus (SLE) is independently associated with accelerated atherosclerosis and premature arterial stiffening. Asymmetric dimethylarginine (ADMA) and homocysteine are mechanistically interrelated mediators of endothelial dysfunction and correlates of atherosclerosis in the general population. The aim of this study was to assess the relationship of ADMA and homocysteine to subclinical vascular disease in patients with SLE.
One hundred twenty-five patients with SLE who were participating in a study of cardiovascular disease underwent clinical and laboratory assessment, carotid artery ultrasonography to detect atherosclerosis, and radial artery applanation tonometry to measure arterial stiffness.
Neither ADMA nor homocysteine correlated with the presence or extent of carotid atherosclerosis. In contrast, ADMA was significantly related to the arterial stiffness index. Independent correlates of arterial stiffening included the ADMA concentration, the presence of diabetes mellitus, older age at the time of diagnosis, longer disease duration, and the absence of anti-Sm or anti-RNP antibodies. A secondary multivariable analysis substituting homocysteine for ADMA demonstrated comparable relationships with arterial stiffness (r(2) = 0.616 for homocysteine and r(2) = 0.595 for ADMA).
ADMA and homocysteine are biomarkers for and may be mediators of premature arterial stiffening in patients with SLE. Because arterial stiffness has independent prognostic value for cardiovascular morbidity and mortality, its predictors may identify patients who are at increased risk of cardiovascular disease.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To determine whether demographic, inflammatory, and metabolic factors predict elevated asymmetric dimethylarginine (ADMA) levels in rheumatoid arthritis (RA). Method: A total of 67 RA patients [mean age 56 ± 12 years, median disease duration 8 (3-15) years] were assessed. Routine biochemistry tests, lipid profile, glycaemic profile [glucose, insulin, homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI)], and inflammatory markers were measured in all patients. ADMA levels were measured by enzyme-linked immunosorbent assay (ELISA). Regression analyses were performed to identify predictors of ADMA in RA. Results: Regression analysis revealed that HOMA (β = 0.149, p = 0.003) was an independent predictor of ADMA in RA. From the drug factors, anti-hypertensive medication use was associated with lower ADMA levels (β = -0.081, p = 0.004). ADMA was not associated with RA disease-related parameters or any of the other cardiovascular risk factors that were assessed. Conclusions: HOMA, a strong indicator of insulin resistance, seems to be the main predictor of elevated ADMA levels in RA patients; ADMA may reflect an important pathway linking abnormal insulin metabolism with endothelial dysfunction in RA.
    Scandinavian journal of rheumatology 01/2013; 42(3). · 2.51 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Serum homocysteine, when studied singly, has been reported to be positively associated both with the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine [ADMA, via inhibition of dimethylarginine dimethylaminohydrolase (DDAH) activity] and with symmetric dimethylarginine (SDMA). We investigated combined associations between transsulfuration pathway thiols, including homocysteine, and serum ADMA and SDMA concentrations at population level. Data on clinical and demographic characteristics, medication exposure, C-reactive protein, serum ADMA and SDMA (LC-MS/MS), and thiols (homocysteine, cysteine, taurine, glutamylcysteine, total glutathione, and cysteinylglycine; capillary electrophoresis) were collected from a sample of the Hunter Community Study on human ageing [n = 498, median age (IQR) = 64 (60-70) years]. REGRESSION ANALYSIS SHOWED THAT: a) age (P = 0.001), gender (P = 0.03), lower estimated glomerular filtration rate (eGFR, P = 0.08), body mass index (P = 0.008), treatment with beta-blockers (P = 0.03), homocysteine (P = 0.02), and glutamylcysteine (P = 0.003) were independently associated with higher ADMA concentrations; and b) age (P = 0.001), absence of diabetes (P = 0.001), lower body mass index (P = 0.01), lower eGFR (P<0.001), cysteine (P = 0.007), and glutamylcysteine (P<0.001) were independently associated with higher SDMA concentrations. No significant associations were observed between methylated arginines and either glutathione or taurine concentrations. After adjusting for clinical, demographic, biochemical, and pharmacological confounders the combined assessment of transsulfuration pathway thiols shows that glutamylcysteine has the strongest and positive independent associations with ADMA and SDMA. Whether this reflects a direct effect of glutamylcysteine on DDAH activity (for ADMA) and/or cationic amino acid transport requires further investigations.
    PLoS ONE 01/2013; 8(1):e54870. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of atherosclerosis (ATH) is higher in patients with systemic lupus erythematosus (SLE) and occurs at an earlier age. The lupus-related factors that account for this increased risk are likely numerous and related to the factors described in this article. Identifying of at-risk subjects and increasing the understanding of pathogenesis of ATH in SLE is critical for improving the quality of care and improving mortality in this vulnerable population.
    Rheumatic Disease Clinics of North America 08/2014; · 1.74 Impact Factor