Persistent status of metabolic syndrome and risk of cholangiocarcinoma: A Korean nationwide population- based cohort study

Objective: It is unknown whether persistent metabolic syndrome (MetS) is associ-ated with an increased risk of cholangiocarcinoma (CCA). Therefore, we investigated the risk of CCA according to changes in MetS status. Research design and methods: This nationwide cohort study included 8,581,407 adults who un-derwent anthropometric measurements and laboratory tests in two consecutive national health screenings during 2009-2012 and observed the subjects until 2017. Individuals with cancer, or follow-up duration <1 year were excluded (n Z 377,915). Subjects were classified into the MetS-free, MetS-developed, MetS-improved, and MetS-persistent groups. The outcome was the incidence of CCA, identified using the claims database. Multivariable Cox proportional hazards regression models were used. Results: Among the 8,203,492 subjects (mean age 48.9 +/- 12.8 years; 56.7% male), 7506 CCA patients were newly identified during a median follow-up of 5.1 years. The probability of CCA was consistently higher in the MetS-persistent group than in the MetS-free group (P < 0.001). MetS-persistent status was significantly associated with an increased risk of CCA compared with the MetS-free status (unadjusted hazard ratio [HR] 2.8, 95% confidence interval [CI] 2.66-2.95), even after adjusting for multiple covariates (adjusted HR 1.07, 95% CI 1.01-1.13). Improved or newly developed MetS was not associated with CCA risk in the fully adjusted model (aHR 1.02, 95% CI 0.94-1.10 and aHR 0.99, 95% CI 0.92-1.06, respectively). Conclusions: MetS was associated with an increased risk of CCA if it persisted for >2 years. Our finding suggests that MetS may be a potentially modifiable risk factor for CCA. (c) 2021 Elsevier Ltd. All rights reserved.