Differential associations of angiographic extent and severity of coronary artery disease with asymmetric dimethylarginine but not insulin resistance in non-diabetic men with stable angina: a cross-sectional study

Abstract

BackgroundAsymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthesis inhibitor, and insulin resistance (IR) have been implicated in atherogenesis. Our aim was to estimate relations between ADMA, the magnitude of IR and angiographic indices of extent and severity of coronary atherosclerosis in non-diabetic men with stable coronary artery disease (CAD).MethodsWe studied 151 non-diabetic men (mean age 57 ± 11 years) with stable angina, obstructive CAD (at least 1 luminal diameter stenosis of ≥70% in major coronary segments) and without heart failure, and 34 age-matched controls free of ≥50% coronary narrowings. The following CAD indices were computed: the number of major epicardial vessels with ≥70% stenosis, Sullivan extent score representing a proportion of the visible coronary tree with vessel wall irregularities, and Gensini score which reflects both CAD severity and extent, yet assigning a heavier weight to proximal segments and to the more severe narrowings by a non-linear point system. An estimate of IR was derived by homeostasis model assessment (HOMA-IR) from fasting insulin and glucose.ResultsAmong the CAD patients, the proportions of subjects with 1-vessel, 2- vessel and 3-vessel CAD were 26%, 25% and 49%, respectively. ADMA levels were higher in patients with obstructive CAD compared to the controls (0.51 ± 0.10 vs. 0.46 ± 0.09 μmol/L [SD], P = 0.01), whereas HOMA-IR was similar (median, 3.2 [interquartile range: 2.4–4.9] vs. 2.9 [2.3–4.7], P = 0.2). Within the CAD group, ADMA increased across ascending quartiles of Sullivan score (Spearman’s rho = 0.23, P = 0.004), but not with Gensini score (rho = 0.12, P = 0.15) or the number of vessels involved (rho = 0.08, P = 0.3). ADMA correlated to log-transformed Sullivan score (Pearson's r = 0.21, P = 0.008), which was only slightly attenuated upon multivariate adjustment (β = 0.19 ± 0.08 [SEM], P = 0.015). HOMA-IR did not differ according to any measure of angiographic CAD (P ≥ 0.2). ADMA and log (HOMA-IR) were mutually unrelated (r = 0.07, P = 0.4).ConclusionsADMA is associated with diffuse but not focal coronary atherosclerosis in non-diabetic men with stable CAD irrespectively of the degree of IR. The independent relationship between ADMA and coronary atherosclerotic burden may contribute to the well-recognized prognostic effect of ADMA in CAD.

Correlation Between Insulin Resistance and Severity of Coronary Artery Disease in Non-Diabetes

“…Our study showed that the severity of CAD is not associated with IR in the non-diabetic population, which is similar to a study by Kruszelnicka et al where no correlation was seen between the IR as measured by HOMA and Gensini score in 151 non-diabetic men [19].…”

Asymmetric dimethylarginine and long-term adverse cardiovascular events in patients with type 2 diabetes: relation with the glycemic control

“…Elevated ADMA level was reported to be associated with the development and progression of diabetic complications [ 12 - 14 ] as well as worse long-term cardiovascular prognosis in diabetic patients [ 15 - 17 ]. Furthermore, ADMA was associated with the coronary atherosclerosis and its extent and severity both in non-diabetic and diabetic patients [ 34 , 35 ]. However, in a large-scale study of 3238 individuals scheduled for coronary angiography, the plasma ADMA levels of patients with type 2 diabetes were only marginally higher than those of the patients without diabetes (0.83 μmol/l versus 0.82 μmol/l, p = 0.032) [ 36 ].…”

Association of circulating angiogenesis inhibitors and asymmetric dimethyl arginine with coronary plaque burden

“…Relatively few studies have examined associations with coronary atherosclerosis. However, in a recent study of 152 non-diabetic men with obstructive coronary disease (≥1 vessel with 70 % atherosclerosis), ADMA was correlated with the proportion of the length of the coronary tree occupied by luminal irregularities, but not with number of diseased vessels or the Gensini score [ 24 ]. Another study of 997 participants found that ADMA concentration was higher in individuals with ≥50 % coronary stenosis of a coronary artery compared to those without significant atherosclerosis.…”