Mannose as a biomarker of coronary artery disease: Angiographic evidence and clinical significance

Abstract

Background: High mannose has previously associated with insulin resistance and cardiovascular disease (CVD). Our objective is to establish whether mannose is associated with anatomical evidence of coronary artery disease (CAD). Methods: Plasma mannose concentrations were measured by liquid chromatography/tandem mass spectrometry in a discovery cohort (n = 513) and a validation cohort (n = 221) of carefully phenotyped individuals. In both cohorts CAD was quantitated using state-of-the-art imaging techniques (coronary computed coronary tomography angiography (CCTA), invasive coronary angiography and optical coherence tomography). Information on subsequent CVD events/death was collected. Associations of mannose with angiographic variables and biomarkers were tested using univariate and multivariate regression models. Survival analysis was performed using the Kaplan-Meier estimator. Results: Mannose was related to indices of CAD and features of plaque vulnerability. In the discovery cohort, mannose was a marker of quantity and quality of CCTA-proven CAD and subjects with a mannose level in the top quartile had a significantly higher risk of CVD events/death (p = 3.6e-5). In the validation cohort, mannose was significantly associated with fibrous cap thickness < 65 μm (odds ratio = 1.32 per each 10 μmol/L mannose change [95% confidence interval, 1.05-1.65]) and was an independent predictor of death (hazard ratio for mannose≥vs < 84.6 μmol/L: 4.0(95%CI, 1.4-11.3), p = 0.006). Conclusion:The current data add novel evidence that high mannose is a signature of CAD with a vulnerable plaque phenotype, consistently across measures of severity of vessel involvement and independent of the traditional correlates of CVD, and that it is an independent predictor of incident adverse outcomes.

Plasma mannose as a novel marker of myocardial infarction across different glycaemic states: a case control study

“…Even though there is no reference range for mannose concentrations, mainly because of different assay methods, our findings in patients with known DM, 98.0 (79.4−120.7) μmol/L, are comparable to the concentrations measured by assays based on mass spectrometry [ 18 , 20 ]. Consistent with previous observations [ 9 , 12 , 20 , 21 ], we noted a positive linear correlation between mannose and glucose concentrations in the total population. Taken together, this strongly supports the hypothesis that mannose is a strong marker of insulin resistance [ 11 , 12 , 22 ].…”

“…A large prospective cohort study reported an association between mannose levels and incident T2DM and CV outcomes including CHD and MI [ 9 ]. A validation study, including patients with varying CV risk whose CAD was quantitated by coronary computed angiography, invasive coronary angiography and optical coherence tomography, found an association between plasma mannose and CAD with a vulnerable plaque phenotype, which was independent of traditional CV risk factors [ 12 ]. In the effort to minimize the effect of additional confounders the present study selected patients with a first MI, i.e.…”

“…Hence, this metabolite may be a new marker able to early identify insulin-resistant people at high CV risk [ 10 , 11 ]. That mannose is related to incident CVD and glucose perturbations is reinforced by a recent validation study comprising patients with prevalent coronary artery disease (CAD), where plasma mannose was correlated not only with CAD severity but also with adverse CV outcomes and mortality [ 12 ].…”

Effect of acute high-intensity exercise on myocardium metabolic profiles in rat and human study via metabolomics approach

“…Disorders of glucose metabolism will reduce angiogenesis and cardiac antioxidant capacity by affecting molecular signaling pathways, which ultimately lead to heart disease 20 . Studies showed ultramarathon runners had been detected high levels of d -mannose in their urine with the risk of myocardial ischemia 21 . d -mannose-1-phosphate easily reacts with proteins or lipids through the glycosylation process and generates glycosylation end products (AGEs) which easily cause myocardial lipid metabolism disorders, myocardial chronic inflammation, and cardiomyocyte apoptosis 19 , 22 .…”

Network preservation analysis reveals dysregulated metabolic pathways in human vascular smooth muscle cell phenotypic switching

“…Mannose supplementation in chow-fed mice, however, did not have as pronounced of an effect on weight gain attenuation suggesting that mannose has a greater impact in pathological conditions. In addition, plasma levels of mannose have recently been shown to be a biomarker of CAD and a more vulnerable plaque phenotype 55 . It is not clear whether mannose is related to CAD because it marks insulin resistance or because of an intrinsic biological property 56 .…”