Innovative Approaches to Assess Intermediate Cardiovascular Risk Subjects: A Review From Clinical to Metabolomics Strategies

Abstract

Current risk stratification strategies for coronary artery disease (CAD) have low predictive value in asymptomatic subjects classified as intermediate cardiovascular risk. This is relevant because not all coronary events occur in individuals with traditional multiple risk factors. Most importantly, the first manifestation of the disease may be either sudden cardiac death or acute coronary syndrome, after rupture and thrombosis of an unstable non-obstructive atherosclerotic plaque, which was previously silent. The inaccurate stratification using the current models may ultimately subject the individual to excessive or insufficient preventive therapies. A breakthrough in the comprehension of the molecular mechanisms governing the atherosclerosis pathology has driven many researches toward the necessity for a better risk stratification. In this Review, we discuss how metabolomics screening integrated with traditional risk assessments becomes a powerful approach to improve non-invasive CAD subclinical diagnostics. In addition, this Review highlights the findings of metabolomics studies performed by two relevant analytical platforms in current use–mass spectrometry (MS) hyphenated to separation techniques and nuclear magnetic resonance spectroscopy (NMR) –and evaluates critically the challenges for further clinical implementation of metabolomics data. We also discuss the modern understanding of the pathophysiology of atherosclerosis and the limitations of traditional analytical methods. Our aim is to show how discriminant metabolites originated from metabolomics approaches may become promising candidate molecules to aid intermediate risk patient stratification for cardiovascular events and how these tools could successfully meet the demands to translate cardiovascular metabolic biomarkers into clinical settings.

Defining atherosclerotic plaque biology by mass spectrometry-based omics approaches

“…Despite the recent advancements in the diagnosis, interventions, preventive measurements and management, vascular diseases, especially CAD, are the primary reason for mortality and morbidity worldwide. 7 A deeper understanding of atherosclerotic plaque biology is essential for finding new efficient strategies for addressing the issue.…”

Application of a novel index for understanding vascular health following pharmacological intervention in a pre-clinical model of metabolic disease

“…The role and relevance of microvascular dysfunction as a significant contributor to the functional or clinical outcomes under the broader umbrella of cardio- or cerebrovascular disease risk has long been an area of great focus in both basic and translational research. However, although many diverse efforts have been made to investigate individual correlative measures and predictive biomarkers of vascular dysfunction, far fewer have attempted to understand and frame integrated vascular function within the context of health, disease, and treatment ( Martins et al, 2021 ; Amal et al, 2022 ).…”

Role of dysregulated macrophage subpopulation ratios and functional changes in the development of coronary atherosclerosis

“…In the early stage, LDL accumulates in the endothelium and possesses pro‐inflammatory and immunogenic properties after oxidation 2 . In recent years, there has been growing evidence that abnormal lipid metabolism is the ignition point for atherosclerosis, triggering numerous inflammatory events that play an important role in the development and progression of coronary heart disease 3–5 . The consumption of lipids can alter the behavior of macrophages, 6 such as apoptosis, migration, proliferation, etc., but its impact on the formation of atherosclerotic plaques is not yet clear.…”