Abstract
BackgroundHigh 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). MethodsPlasma 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. ResultsMannose 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). ConclusionThe 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.
Highlights
Previous work – using cell-specific analysis of genome-scale meta bolic models, transcriptional regulatory networks, and protein-protein interaction networks – identified elevated circulating mannose con centrations as a novel marker of insulin resistance [1]
In a multivariate logistic model of presence of coronary artery disease (CAD) with the same covariates, the odds ratio (OR) for 1 standard deviation (SD) plasma mannose concentrations (= 22 μmol/L) was 1.51 [95% CI: 1.07–2.15], with an area-under-receiver operating characteristics (ROC) of 0.833
We extend the current knowledge by showing that higher plasma mannose levels are associated with a lower Minimal fibrous cap thickness (MinFCT) and trended to have more macrophage accumulation, suggesting a more vulnerable plaque
Summary
Previous work – using cell-specific analysis of genome-scale meta bolic models, transcriptional regulatory networks, and protein-protein interaction networks – identified elevated circulating mannose con centrations as a novel marker of insulin resistance [1]. In epidemiological co horts higher plasma mannose concentrations have been associated with insulin resistance and with risk of developing diabetes, diabetic kidney disease, and cardiovascular disease (CVD) [3] The mechanisms underlying these associations have not been explored. 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 tomog raphy angiography (CCTA), invasive coronary angiography and optical coherence tomography). 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
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