Development of a Predictive Model for Metabolic Syndrome Using Noninvasive Data and its Cardiovascular Disease Risk Assessments: Multicohort Validation Study (Preprint)

BACKGROUND Metabolic syndrome is a cluster of metabolic abnormalities, including obesity, hypertension, dyslipidemia, and insulin resistance, that significantly increase the risk of cardiovascular disease (CVD) and other chronic conditions. Its global prevalence is rising, particularly in aging and urban populations. Traditional screening methods rely on laboratory tests and specialized assessments, which may not be readily accessible in routine primary care and community settings. Limited resources, time constraints, and inconsistent screening practices hinder early identification and intervention. Developing a noninvasive and scalable predictive model could enhance accessibility and improve early detection. OBJECTIVE This study aimed to develop and validate a predictive model for metabolic syndrome using noninvasive body composition data. Additionally, we evaluated the model’s ability to predict long-term CVD risk, supporting its application in clinical and public health settings for early intervention and preventive strategies. METHODS We developed a machine learning–based predictive model using noninvasive data from two nationally representative cohorts: the Korea National Health and Nutrition Examination Survey (KNHANES) and the Korean Genome and Epidemiology Study. The model was trained using dual-energy x-ray absorptiometry data from KNHANES (2008-2011) and validated internally with bioelectrical impedance analysis data from KNHANES 2022. External validation was conducted using Korean Genome and Epidemiology Study follow-up datasets. Five machine learning algorithms were compared, and the best-performing model was selected based on the area under the receiver operating characteristic curve. Cox proportional hazards regression was used to assess the model’s ability to predict long-term CVD risk. RESULTS The model demonstrated strong predictive performance across validation cohorts. Area under the receiver operating characteristic curve values for metabolic syndrome prediction ranged from 0.8338 to 0.8447 in internal validation, 0.8066 to 0.8138 in external validation 1, and 0.8039 to 0.8123 in external validation 2. The model’s predictions were significantly associated with future cardiovascular risk, with Cox regression analysis indicating that individuals classified as having metabolic syndrome had a 1.51-fold higher risk of developing CVD (hazard ratio 1.51, 95% CI 1.32-1.73; P<.001). The ability to predict long-term CVD risk highlights the potential utility of this model for guiding early interventions. CONCLUSIONS This study developed a noninvasive predictive model for metabolic syndrome with strong performance across diverse validation cohorts. By enabling early risk identification without laboratory tests, the model enhances accessibility in primary care and large-scale screenings. Its ability to predict long-term CVD risk supports proactive intervention strategies, potentially reducing the burden of cardiometabolic diseases. Further research should refine the model with additional clinical factors and broader population validation to maximize its clinical impact.