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

Abstract

BackgroundAsymmetric 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.MethodsMultivariable 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.ResultsA 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.ConclusionPlasma ADMA levels were associated with risk of AMI and cardiovascular death among patients with low BMI only.

Asymmetric Dimethylarginin (ADMA) as a Marker of Endothelial Dysfunction in Primary Aldosteronism

“…Moreover, elevated plasma ADMA concentration has been identified as a predictor of acute coronary events, and an independent risk factor for all-cause and cardiovascular mortality (8, 9). Although elevated concentrations of ADMA have been found in several cardiovascular and metabolic diseases (10-13, 22-24), to our knowledge, to date, there have been no reports on ADMA levels in cases with PA. Recent studies have demonstrated a higher frequency of cardiovascular events in PA compared to patients with EH (3, 4).…”

Relationship between asymmetric dimethylarginine in umbilical cord plasma and birth weight follows a U-shaped curve

“…Increased circulating ADMA levels occur in adult patients with diabetes mellitus and vascular diseases [10][11][12][13]15]. We tested whether the origin of ADMA dysregulation starts in fetal life.…”

“…Braekke et al reported that not only maternal concentrations of ADMA, but also L-arginine, are significantly higher in women with preeclampsia than in controls [9]. Elevation of ADMA has also been reported in adult cardiovascular diseases [10][11][12][13]. Oxidative stress is also responsible for the increased synthesis and/or inhibition of catabolism of ADMA [14] that are observed in patients with hypercholesterolemia, hyperglycemia, diabetes and hypertension [10,[15][16][17].…”

Asymmetric dimethylarginine exacerbates cognitive dysfunction associated with cerebrovascular pathology

“…Recently, asymmetric dimethylarginine (ADMA) has been regarded as an independent risk factor and prospective biomarker for cardiovascular diseases because of its elevation in blood in a variety of cardiac and metabolic diseases, including hypertension, 5,6 diabetes, 7,8 obesity, 9,10 hyperlipidemia, 11 and hypercholesterolemia, 12 all of which are well‐established primary risk factors of VCID and AD. ADMA as an endogenous inhibitor of cationic amino acid transporter (CAT) and endothelial nitric oxide synthase (eNOS) causes disturbances in cellular L‐Arg uptake and cellular synthesis and bioavailability of NO 13 .…”