Associations of methylarginines and homoarginine with diastolic dysfunction and cardiovascular risk factors in patients with preserved left ventricular ejection fraction

J Card Fail. 2014 Dec;20(12):923-30. doi: 10.1016/j.cardfail.2014.09.004. Epub 2014 Sep 16.

Abstract

Background: Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and homoarginine are considered to modulate nitric oxide synthesis. We evaluated whether ADMA, SDMA, and homoarginine are associated with diastolic dysfunction.

Methods and results: We investigated primary care patients at cardiovascular risk with preserved left ventricular ejection fraction from the multicenter DIAST-CHF study. We measured serum concentrations of ADMA, SDMA, and homoarginine and performed standardized echocardiographic examinations. Among 1,396 patients (mean age 65.3 ± 8.3 y, 54.6% women), diastolic dysfunction was ruled out in 261 patients (18.7%). Mild and moderate/severe grades of diastolic dysfunction were present in 900 (64.5%) and 235 (16.8%) study participants, respectively. After adjustments for cardiovascular risk factors, ADMA and SDMA were positively and homoarginine negatively associated with N-terminal pro-B-type natriuretic peptide and midregional pro-adrenomedullin (P < .05 for all). Lower homoarginine levels were associated with diastolic dysfunction, and higher ADMA and SDMA levels were associated with the severity of diastolic dysfunction (P < .05 for all).

Conclusions: Higher levels of ADMA and SDMA and lower levels of homoarginine are associated with an adverse cardiovascular risk profile and diastolic dysfunction. Further studies should clarify the potential of these amino acid derivatives for the therapy of cardiovascular diseases.

Keywords: Homoarginine; cardiovascular risk; diastolic dysfunction; methylarginines.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / diagnostic imaging
  • Echocardiography, Doppler
  • Female
  • Heart Failure, Diastolic / blood*
  • Heart Failure, Diastolic / diagnostic imaging
  • Homoarginine / blood*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Reference Values
  • Risk Factors
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Stroke Volume / physiology*

Substances

  • Biomarkers
  • Homoarginine
  • Nitric Oxide
  • symmetric dimethylarginine
  • Arginine