Association Between Lipid Profile and Risk of Incident Systemic Sclerosis: A Nationwide Population-Based Study

Background and Aims: Lipid metabolism is altered in systemic sclerosis (SSc), mediating activation of immune cells and fibroblasts. However, it is unclear whether altered lipid profile is associated with a risk of developing SSc. We aimed to assess the association between lipid profile and risk of incident SSc. Methods: From a Korean nationwide database, individuals without SSc who underwent national health check-ups in 2009 were selected and followed-up through 2019. Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride were measured on the health check-up date in 2009. Individuals who developed SSc during follow-up were identified. Multivariable Cox models were performed to estimate the risk of incident SSc according to TC, HDL-C, LDL-C, and triglyceride levels, respectively. Results: Of the 9,894,996 individuals selected, 1355 individuals developed SSc during a mean follow-up of 9.2 years (incidence rate=1.49 per 100,000 person-years). Levels of TC (adjusted hazard ratio [aHR] 0.959, 95% confidence interval [CI] 0.945-0.974), HDL-C (aHR 0.968, 95% CI 0.950-0.987), LDL-C (aHR 0.968, 95% CI 0.952-0.983) were inversely associated with the risk of incident SSc, whereas no significant association was observed between levels of triglyceride (aHR 1.004, 95% CI 0.998-1.011) and risk of incident SSc. Conclusion: Serum levels of TC, HDL-C, and LDL-C were inversely associated with the risk of incident SSc. Our findings provide new insights that altered lipid profile could be considered a non-causal biomarker associated with incident SSc, which could help early diagnosis. The underlying mechanism for this association needs further studies. Plain Language Summary: Lipid metabolism is altered in patients with systemic sclerosis (SSc), mediating activation of immune cells and fibroblasts. In this large population-based cohort study, we found that levels of TC, HDL-C, and LDL-C were inversely associated with the risk of incident SSc. Our findings suggest that levels of TC, HDL-C, and LDL-C could be considered in detecting individuals at high risk of incident SSc. Keywords: systemic sclerosis, risk factor, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol