Association between Changes in Status Based on Multiple Metabolic Syndrome Criteria and Cardiovascular Disease Risk

Background: Although metabolic syndrome (MetS) changes over time, the association between MetS remission and cardiovascular disease risk has not been adequately evaluated by diagnostic criteria or sex. Using current (National Cholesterol Education Program-Adult Treatment Panel III, International Diabetes Federation, Japan) and new criteria, with previously optimized thresholds for predicting cardiovascular disease, we examined whether changes in MetS status alter cardiovascular disease risk in men and women. Methods: A total of 201,007 men and 99,579 women, aged 20 to 72 years who underwent annual physical examinations between 2008 and 2020 and with no history of cardiovascular disease, were divided into four groups according to a changed MetS status over a 2-year baseline period (MetS-free, MetS-developed, MetS-remission, MetS-persisted). Subsequent cardiovascular disease was observed and multivariate Cox regression analysis was used to calculate each group's hazard ratio (HR). Results: During a median follow-up of 5.0 years, 2,831 men (1.41%) and 330 women (0.33%) developed cardiovascular disease. MetS-developed showed significantly increased risk, from 1.5- to 1.8-fold in men and 1.6- to 2.6-fold in women, across all criteria. MetS-remission, by new criteria, showed significantly reduced risk compared to MetS-persisted in both men and women (HR for optimized criteria-1, 0.58; 95% confidence interval CI, 0.51 to 0.67 for men; and HR for optimized criteria-1, 0.56; 95% CI, 0.35 to 0.91 for women). These risk modifications were greater for obesity and younger age. Conclusion: MetS onset was associated with increased cardiovascular disease risk by all criteria. MetS remission showed reduced risk, by approximately 40%, in both men and women for optimized criteria only. Thus, efforts to prevent and resolve MetS to reduce the risk of cardiovascular disease are supported.