Asymmetric Dimethylarginine versus Proton Pump Inhibitors Usage in Patients with Stable Coronary Artery Disease: A Cross-Sectional Study

Abstract

A recent experimental study suggested that proton pump inhibitors (PPI), widely used to prevent gastroduodenal complications of dual antiplatelet therapy, may increase the accumulation of the endogenous nitric oxide synthesis antagonist asymmetric dimethylarginine (ADMA), an adverse outcome predictor. Our aim was to assess the effect of PPI usage on circulating ADMA in coronary artery disease (CAD). Plasma ADMA levels were compared according to PPI use for ≥1 month prior to admission in 128 previously described non-diabetic men with stable CAD who were free of heart failure or other coexistent diseases. Patients on PPI tended to be older and with insignificantly lower estimated glomerular filtration rate (GFR). PPI use was not associated with any effect on plasma ADMA (0.51 ± 0.11 (SD) vs. 0.50 ± 0.10 µmol/L for those with PPI (n = 53) and without PPI (n = 75), respectively; p = 0.7). Additionally, plasma ADMA did not differ between PPI users and non-users stratified by a history of current smoking, CAD severity or extent. The adjustment for patients’ age and GFR did not substantially change the results. Thus, PPI usage does not appear to affect circulating ADMA in non-diabetic men with stable CAD. Whether novel mechanisms of adverse PPI effects on the vasculature can be translated into clinical conditions, requires further studies.

No Association of Proton Pump Inhibitor Use with Fasting or Postload Glycaemia in Patients with Cardiovascular Disease: A Cross-Sectional Retrospective Study

“…In particular, L-N G -nitroarginine methyl ester may affect glycaemia also via adrenal epinephrine release 36 , and the inhibition of the insulin-degrading enzyme through S-nitrosylation was demonstrated only in vitro at high concentrations of artificial putative NO donors and consequent exposure to supraphysiological levels of NO liberated from these compounds 35 . Moreover, in a recent clinical observational study 37 , we did not confirm the PPI-ADMA interaction.…”

Systematic review with meta‐analysis: risk of adverse cardiovascular events with proton pump inhibitors independent of clopidogrel

“…Although PPI use was associated with an increase in plasma ADMA, no adverse effect on vascular function was evident . A further study conducted by Kruszelnicka et al suggested that PPI use did not appear to increase plasma ADMA in a study cohort of nondiabetic men with coronary artery disease. Due to this conflicting evidence, the association between PPIs and subsequent dysregulation of NO as a potential explanation for the observed increase in cardiovascular risk remains controversial.…”

Long‐term use of proton pump inhibitors, dose–response relationship and associated risk of ischemic stroke and myocardial infarction

“…ADMA inhibits the nitric oxide synthase, which may lead to an acceleration of atherosclerosis . However, clinically relevant impacts of PPIs on plasma ADMA levels have been inconsistent . It has also been hypothesized that the elevated gastric pH, caused by either PPI or H2RA, decreases conversion of dietary nitrate and nitrite to nitric oxide (NO), leading to endothelial dysfunction .…”