Does the obesity paradox truly exist? A study on the relationship between different degrees of obesity and stroke incidence and mortality based on the UK Biobank

BACKGROUND: Obesity has been associated with increased incidence and severity of various cardiovascular risk factors, as well as an elevated risk of stroke. However, the evidence of its effect on outcomes in stroke patients has been equivocal. Previous studies have documented the obesity paradox in stroke, characterized by a negative correlation between BMI and stroke mortality. To address the limitations of relying solely on BMI in previous investigations, notably the documented obesity paradox linking BMI to stroke mortality, our study incorporates additional obesity metrics beyond BMI. We aimed to comprehensively evaluate the relationship between obesity and stroke outcomes, thereby providing a more holistic understanding of their association. METHODS: The present study included 502,128 participants from the UK Biobank database. Cox proportional hazard models were performed to determine the associations of indicators, including BMI, WC, WHR, WHtR and BFP with the incidence and mortality of stroke. RESULTS: Increased BMI was associated with elevated stroke incidence and mortality, with the lowest risk observed in the BMI range of 18-24 kg/m². Both lower BMI (17≤BMI<18.5 kg/m²) and higher BMI (BMI≥25 kg/m²) were linked to higher incidence and mortality of stroke. In contrast, other obesity-related indicators (WC, WHR, WHtR and BFP) exhibited more pronounced linear relationships with the incidence of stroke, all-cause mortality in the total population, stroke mortality in the total population and all-cause mortality in stroke patients. However, no significant differences were found in stroke-specific mortality among underweight, normal weight, overweight and obese groups in stroke patients across various obesity indicators, suggesting no obvious association between obesity and stroke-specific mortality in stroke patients under the current definitions and adjustments in this study. Notably, stroke severity, acute care, and complications were not available in the analysis, and residual confounding from these unmeasured factors cannot be ruled out. Furthermore, our analyses on the relationships between several obesity subtypes with different metabolic health statuses and stroke incidence and mortality revealed that, regardless of normal weight or not, individuals with metabolic abnormalities had significantly higher incidence and mortality of stroke compared to those with normal metabolism. This highlights the importance of metabolic status in the onset and prognosis of stroke. CONCLUSIONS: Our findings demonstrate that stroke-specific mortality in stroke patients was not associated with obesity severity when assessed using multiple obesity indicators including BMI, WC, WHR, WHtR and BFP. This is inconsistent with previous observations of the obesity paradox. Meanwhile, the observation that individuals with metabolic abnormalities exhibit significantly higher stroke incidence and mortality compared to those with normal metabolism further confirms the adverse impact of metabolic disturbances on stroke risk and prognosis, underscoring the pivotal role of metabolic health in stroke management.