Metabolic Health Phenotypes and Cardiovascular Risk

Metabolic health phenotypes describe the varied cardiometabolic profiles observed across individuals with similar degrees of adiposity. While excess weight is widely recognised as a driver of cardiovascular risk, a subset of people with obesity display normal insulin sensitivity, favourable lipid profiles and absence of hypertension, a state often termed metabolically healthy obesity. Conversely, metabolically unhealthy normal‐weight individuals experience elevated risk of heart disease and stroke despite a body mass index within accepted ranges. The categorisation of metabolic phenotypes has shifted emphasis from weight alone towards clusters of biochemical, genetic and lifestyle factors that modulate cardiovascular risk. Refining these phenotypes enhances early identification of high‐risk groups and supports targeted prevention strategies, from dietary modification to pharmacotherapy. As cardiovascular disease remains the leading cause of global mortality, elucidating metabolic health heterogeneity is essential for precision public health and equitable clinical care.

Research from Nature Portfolio

Recent studies have introduced a lipidomic‐based metabolic BMI score that quantifies dysregulation independent of measured body mass index. By evaluating the difference between metabolic and anthropometric BMI, researchers have identified individuals at elevated risk of cardiovascular events despite normal body mass, and conversely those with obesity but preserved metabolic resilience. Lifestyle factors such as exercise and diet were shown to modulate the metabolic BMI score, indicating potential to reverse adverse profiles. Another large‐scale population analysis demonstrated that poor metabolic health confers greater mortality and cardiovascular risk than adiposity per se. In this nationwide cohort, metabolically unhealthy status predicted higher all‐cause and cardiovascular mortality across BMI categories, whereas metabolically healthy individuals with obesity exhibited mortality rates comparable to metabolically healthy normal‐weight peers. These findings underscore that maintaining metabolic integrity may offset some risks associated with elevated body mass.

Metabolic Health Phenotypes and Cardiovascular Risk publication trend

The graph below shows the total number of articles in metabolic health phenotypes and cardiovascular risk across all publications each year (not limited to Nature Index journals).

Technical terms

Body mass index (BMI): A measure of weight adjusted for height, calculated as weight in kilograms divided by height in metres squared.

Metabolically healthy obesity (MHO): An obesity phenotype characterised by normal insulin sensitivity, favourable lipid levels and absence of hypertension.

Metabolically unhealthy obesity (MUO): An obesity phenotype marked by insulin resistance, dyslipidaemia, elevated blood pressure or glucose abnormalities.

Polygenic risk score (PRS): A quantitative metric of genetic predisposition to a trait or disease, derived from multiple genetic variants.

Metabolic BMI score (mBMI): An index based on metabolite profiles that estimates metabolic dysregulation associated with adiposity.

Metabotype: A distinct metabolic phenotype reflecting differences in tissue‐specific insulin resistance, lipid turnover or other biochemical pathways.

References

1. Metabolic phenotyping of BMI to characterize cardiometabolic risk: evidence from large population-based cohorts. Nature Communications (2023).
2. Associations of metabolic changes and polygenic risk scores with cardiovascular outcomes and all-cause mortality across BMI categories: a prospective cohort study. Cardiovascular Diabetology (2024).
3. Metabolic phenotyping in people living with obesity: Implications for dietary prevention. Reviews in Endocrine and Metabolic Disorders (2023).
4. Metabolically Healthy Obesity. Endocrine Reviews (2020).
5. Obesity, metabolic health, and mortality in adults: a nationwide population-based study in Korea. Scientific Reports (2016).
6. Are people with metabolically healthy obesity really healthy? A prospective cohort study of 381,363 UK Biobank participants. Diabetologia (2021).