Association of total cholesterol variability with risk of venous thromboembolism: A nationwide cohort study

Background The effects of total cholesterol (TC) on coagulation and hemostatic systems could contribute to the development of venous thromboembolism (VTE). We investigated this possible association using TC variability. Methods From the Korean NHIS-HEALS database, 1,236,589 participants with health screenings between 2003 and 2008 were included. TC variability was assessed using various parameters, including the coefficient of variation (CV), standard deviation (SD), and variability independent of mean (VIM). Occurrence of VTE was established by identifying at least two medical claims with a diagnostic code including various types of VTE: deep vein thrombosis (DVT) (I80.2-80.3), pulmonary embolism (PE) (I26, I26.0, I26.9), intraabdominal VTE (I81, I82, I82.2-82.3), and other VTE (I82.8-82.9). Results Throughout the study's median follow-up period of 12.4 years (interquartile range 12.2-12.6) years, TC levels were assessed a total of 5,702,800 times. VTE occurred in 11,769 (1.08%) patients (DVT (4,708 (0.43%)), PE (3,109 (0.29%)), intraabdominal VTE (5,215 (0.48%)), and other VTE (4,794, (0.44%)). As a result, there was gradual association was observed between higher TC variability and occurrence of VTE. Multivariable analysis showed that quartile of TC variability using CV showed a positive correlation with the occurrence of VTE (adjusted hazard ratio (the highest versus lowest quartile), 1.14, 95% confidence interval, 1.08-1.20, p < 0.001). This result remained consistent applying to SD and VIM. In addition, higher quartile of TC variability was consistently associated with the development of various types of VTE in subgroup analysis. Conclusions Increased TC variability may be associated with increased VTE risk. This analysis highlights the importance of maintaining stable TC levels to prevent the development of VTE.