Why Do High-Risk Patients Develop or Not Develop Coronary Artery Disease? Metabolic Insights from the CAPIRE Study.

Martino Deidda,Daniele Andreini,Roberto Latini,Christian Cadeddu Dessalvi,Giuseppe Mercuro,Eleuterio Ferrannini,Aldo Maggioni,Antonio Noto,Marco Magnoni,Felicita Andreotti,On Behalf Of The Capire Investigators

doi:10.3390/metabo12020123

Abstract

Traditional cardiovascular (CV) risk factors (RFs) and coronary artery disease (CAD) do not always show a direct correlation. We investigated the metabolic differences in a cohort of patients with a high CV risk profile who developed, or did not develop, among those enrolled in the Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation (CAPIRE) study. We studied 112 subjects with a high CV risk profile, subdividing them according to the presence (CAD/High-RFs) or absence of CAD (No-CAD/High-RFs), assessed by computed tomography angiography. The metabolic differences between the two groups were identified by gas chromatography-mass spectrometry. Characteristic patterns and specific metabolites emerged for each of the two phenotypic groups: high concentrations of pyruvic acid, pipecolic acid, p-cresol, 3-aminoisobutyric acid, isoleucine, glyceric acid, lactic acid, sucrose, phosphoric acid, trimethylamine-N-oxide, 3-hydroxy-3-methylglutaric acid, erythritol, 3-hydroxybutyric acid, glucose, leucine, and glutamic acid; and low concentrations of cholesterol, hypoxanthine, glycerol-3-P, and cysteine in the CAD/High-RFs group vs the No-CAD/High-RFs group. Our results show the existence of different metabolic profiles between patients who develop CAD and those who do not, despite comparable high CV risk profiles. A specific cluster of metabolites, rather than a single marker, appears to be able to identify novel predisposing or protective mechanisms towards CAD beyond classic CVRFs.

Highlights

We previously investigated the functional-metabolic correlations of coronary artery disease (CAD), CVRFs, both or neither in a 2 × 2 phenotypic observational study [6]
We focused on patients with high-risk CV profiles, with or without widespread CAD
Some intermediates of the glycolysis pathways were found to be the major contributors to the cluster differences between the CAD/high-risk factors (RFs) and no-CAD/high-RF groups, indicating a significant alteration of energy metabolism

Summary

Introduction

A risk factor (RF) is a specific condition, behavior or biological substrate statistically associated with a disease and shown to contribute to its pathogenesis, development or accelerated course. Seventy years later, CV disease (CVD) is still a major problem, causing disability and premature death around the world. The latter consideration suggests that additional and unknown mechanisms may act independently of CVRFs or modulate the pathophysiological response to traditional. CVRFs. despite the well known genetic influence on the development of CAD, as demonstrated by its high rate of inheritance (40–50%) [2,3], CAD cannot be considered as the expression of a transmitted predisposition, but, rather, as the result of multiple factors and genetic, epigenetic and environmental/behavioral interactions

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Conclusion