The Association Between Relative Caloric Intake and Cardiovascular Outcomes

Background: Obesity is a major risk factor for cardiovascular (CV) disease, but body mass index (BMI) alone inadequately captures CV risk heterogeneity. We hypothesized that relative caloric intake status —energy intake relative to physiological needs— is associated with long-term CV risk. <div> <br> </div> <div> Methods: We analyzed 165,640 participants from the UK Biobank. Relative caloric intake status was derived using residuals from a linear model predicting energy intake from BMI, age, and sex and categorized as low (LI, &lt;30th percentile), normal (NI, 30th–70th), or high (HI, &gt;70th). In secondary analyses, intake groups were combined with BMI categories (normal weight [NW], overweight [OW], obese [OB]) to define nine phenotypes. The primary outcome was 3-point major adverse cardiovascular events (3P-MACE: myocardial infarction [MI], stroke, and CV mortality). </div> <div> <br> </div> <div> Findings: Compared with the NI group, the LI phenotype showed a higher risk of 3P-MACE (adjusted hazard ratio [aHR] 1.07, 95% confidence interval [CI] 1.01–1.14, P = 0.027) and MI (aHR 1.16, 95% CI 1.07–1.25, p &lt; 0.001), whereas the HI group showed no increased risk. In BMI-stratified analyses, the NW-LI phenotype demonstrated an increased risk of 3P-MACE (aHR 1.15; 95% CI 1.02–1.30) versus the NW-NI reference. LI status was consistently associated with low muscle strength independent of BMI, whereas metabolic dysfunction–associated steatotic liver disease risk was primarily associated with absolute BMI. </div> <div> <br> </div> <div> Interpretation: Relative caloric intake identifies heterogeneous CV risk profiles. The high-risk LI phenotype likely reflects sarcopenic vulnerability rather than metabolic health, highlighting BMI limitations and the need for strategies promoting metabolic and muscular health beyond simple caloric restriction. </div>