Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris

Yunpeng Ding, Gard F T Svingen, Eva R Pedersen, Jesse F Gregory, Per M Ueland, Grethe S Tell, Ottar K Nygård, Yunpeng Ding, Gard F T Svingen, Eva R Pedersen, Jesse F Gregory, Per M Ueland, Grethe S Tell, Ottar K Nygård

Abstract

Background: Glycine is an amino acid involved in antioxidative reactions, purine synthesis, and collagen formation. Several studies demonstrate inverse associations of glycine with obesity, hypertension, and diabetes mellitus. Recently, glycine-dependent reactions have also been linked to lipid metabolism and cholesterol transport. However, little evidence is available on the association between glycine and coronary heart disease. Therefore, we assessed the association between plasma glycine and acute myocardial infarction (AMI).

Methods and results: A total of 4109 participants undergoing coronary angiography for suspected stable angina pectoris were studied. Cox regression was used to estimate the association between plasma glycine and AMI, obtained via linkage to the CVDNOR project. During a median follow-up of 7.4 years, 616 patients (15.0%) experienced an AMI. Plasma glycine was higher in women than in men and was associated with a more favorable baseline lipid profile and lower prevalence of obesity, hypertension, and diabetes mellitus (all P<0.001). After multivariate adjustment for traditional coronary heart disease risk factors, plasma glycine was inversely associated with risk of AMI (hazard ratio per SD: 0.89; 95% CI, 0.82-0.98; P=0.017). The inverse association was generally stronger in those with apolipoprotein B, low-density lipoprotein cholesterol, or apolipoprotein A-1 above the median (all Pinteraction≤0.037).

Conclusions: Plasma glycine was inversely associated with risk of AMI in patients with suspected stable angina pectoris. The associations were stronger in patients with apolipoprotein B, low-density lipoprotein cholesterol, or apolipoprotein A-1 levels above the median. These results motivate further studies to elucidate the relationship between glycine and lipid metabolism, in particular in relation to cholesterol transport and atherosclerosis.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00354081.

Keywords: amino acids; apolipoprotein; atherosclerosis; glycine; lipids and lipoprotein metabolism; myocardial infarction.

© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1
Figure 1
Dose–response associations between (log‐transformed) plasma glycine and risk of acute myocardial infarction. Generalized additive regressions are used with the adjustment for age and sex in the simple model (A), and additional adjustment for smoking, obesity, hypertension, diabetes mellitus, angiographic extent of coronary artery disease (ordinal), estimated glomerular filtration rate, apolipoprotein A‐1, apolipoprotein B, and statin treatment in the multivariate model (B). The solid lines and the shaded areas represent hazard ratios of plasma glycine and their 95% CI, respectively. The areas under the curve along the X‐axes represent the distributions of the plasma glycine concentrations (μmol/L) in the total population. The vertical white lines denote the 25th, 50th, and 75th percentiles of plasma glycine, respectively.
Figure 2
Figure 2
Risk associations between plasma glycine and AMI according to the median values of prespecified lipid parameters. The black squares represent the hazard ratios and their areas are proportional to the subgroup sizes. Horizontal lines represent the 95% CI. AMI indicates acute myocardial infarction; ApoA‐1, apolipoprotein A‐1; ApoB, apolipoprotein B; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein.

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