Association between Body Mass Index, Asymmetric Dimethylarginine and Risk of Cardiovascular Events and Mortality in Norwegian Patients with Suspected Stable Angina Pectoris

PLoS One. 2016 Mar 22;11(3):e0152029. doi: 10.1371/journal.pone.0152029. eCollection 2016.

Abstract

Background: Asymmetric dimethylarginine (ADMA) is associated with increased risk of atherosclerotic cardiovascular disease and mortality through inhibition of nitrogen oxide (NO) synthesis. As positive correlations between serum concentrations of NO and body mass index (BMI) have been observed, we aimed to explore whether the potential associations between plasma ADMA levels and the risk of acute myocardial infarction (AMI) and mortality were modified by BMI.

Methods: Multivariable Cox proportional hazard models were used to estimate the hazard ratios (HR) for AMI, cardiovascular death and all-cause mortality according to baseline plasma ADMA levels in 4122 patients with suspected stable angina pectoris. Analyses were subsequently repeated in patients with BMI below (low BMI) or above (high BMI) median.

Results: A total of 2982 patients (72%) were men. Median (range) age, plasma ADMA level and BMI were 62 (21-88) years, 0.54 (0.10-1.25) μmol/L and 26.3 (18.5-54.3) kg/m2, respectively. During a mean (standard deviation) follow-up time of 4.7 (1.4) years, 337 (8%) patients suffered from an AMI, 300 (7%) died, whereof 165 (55%) due to cardiovascular disease. Each 0.1 μmol/L increment in plasma ADMA level was associated with an increased risk of AMI (HR (95% CI) 1.21 (1.08, 1.35) and cardiovascular death 1.30 (1.13, 1.49) in participants with low BMI only. Interactions were significant for AMI (p = 0.04) and CV death (p = 0.03). BMI did not modify the association between plasma ADMA levels and all-cause mortality.

Conclusion: Plasma ADMA levels were associated with risk of AMI and cardiovascular death among patients with low BMI only.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angina, Stable / blood*
  • Angina, Stable / metabolism
  • Angina, Stable / physiopathology
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Body Mass Index
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology*
  • Nitrogen Oxides / metabolism
  • Norway
  • Risk Factors

Substances

  • Nitrogen Oxides
  • N,N-dimethylarginine
  • Arginine

Grants and funding

The study was funded by the Norwegian Ministry of Health and Care Services, the Western Norway Regional Health Authority, the Department of Heart Disease at Haukeland University Hospital, Bergen, and the Meltzer Foundation, Bergen, Norway.