The 'Slow Burn' Phenotype: How Relative Caloric Intake Reveals Hidden Cardiovascular Risk Beyond BMI

Area of Science:

• Cardiology
• Metabolic Health
• Biostatistics

Background:

• Body mass index (BMI) is a common but limited metric for assessing cardiovascular (CV) risk.
• Individual metabolic responses and energy balance vary significantly, leading to heterogeneity in CV risk not captured by BMI alone.

Purpose of the Study:

• To investigate a 'Slow Burn' phenotype, defined by lower-than-expected energy intake relative to BMI, age, and sex.
• To determine if this phenotype is associated with elevated cardiovascular risk across different BMI categories.

Main Methods:

• Analysis of 160,905 White/European participants from the UK Biobank.
• Categorization of relative caloric intake into low (LI; 'Slow Burn'), normal (NI), and high (HI) groups based on residuals from a predictive model.
• Definition of nine phenotypes combining intake groups with BMI categories (normal weight, overweight, obese) to assess 3-point major adverse cardiovascular events (3P-MACE).

Main Results:

• The LI phenotype showed a higher risk of 3P-MACE and myocardial infarction (MI) compared to the NI group.
• The Normal-Weight LI (NW-LI) phenotype exhibited increased 3P-MACE risk, with low muscle strength mediating a portion of this excess risk.
• NW-LI participants were more likely to experience future weight gain compared to their NI counterparts.

Conclusions:

• The 'Slow Burn' phenotype identifies individuals at increased cardiovascular risk, independent of their BMI.
• These findings underscore the limitations of BMI-based risk stratification and advocate for incorporating energy balance and functional status into risk assessment strategies.