Clinical staging to guide management of metabolic disorders and their sequelae: a European Atherosclerosis Society consensus statement
Conclusions & future perspectives
Future perspectives
Estimating the risk of systemic metabolic disorder progression
Clinical risk scores
- Future clinical risk scores may help predict the progression of SMD and allow personalized interventions.
- These scores could include lifestyle factors, lifetime exposure, molecular markers (metabolites, cytokines, microRNA), and use big data and AI for precise risk prediction across diverse populations.
- Non-invasive imaging (e.g., plaque burden, coronary artery calcium) may refine risk assessment, especially for sub-clinical heart and kidney disease.
Polygenic risk scores
- PRS quantify genetic risk for SMD components like obesity, Type 2 diabetes, hypercholesterolaemia, and MASLD.
- They can identify high-risk individuals early, even before symptoms appear, and predict responsiveness to lifestyle or pharmacological interventions.
- Challenges include ancestral diversity and discordant variant effects, but pathway-specific PRS may improve prediction accuracy.
Microbiome-based treatments
- The gut microbiome is linked to obesity, insulin resistance, dyslipidaemia, and diabetes.
- Therapeutic strategies under study include personalized diets, prebiotics, postbiotics, symbiotics, and fecal microbiota transfer.
- These approaches are promising but require further research and standardization before clinical use.
Consensus key points
- SMD is a multi-factorial disorder caused by visceral obesity, genetic predisposition, and lifestyle factors.
- It progresses through stages, from metabolic abnormalities (Stage 1) to early organ damage (Stage 2) and more advanced organ dysfunction (Stage 3).
- Visceral fat drives insulin resistance, MASLD, dyslipidaemia, hypertension, and inflammation, affecting multiple organs.
- Lifestyle changes are the cornerstone of treatment at all stages, with pharmacotherapy and metabolic surgery for severe cases.
Conclusions
- A three-stage SMD system helps guide holistic, stage-specific management.
- Stage 1 affects 58% of European participants in the UK Biobank (6% increased mortality), and Stage 2 affects 19% (49% increased mortality).
- Management should combine lifestyle, medications, and, if needed, surgery, targeting multiple metabolic abnormalities.
- Effective SMD care requires individualized, multi-faceted strategies to prevent progression and organ damage.