Low HDL Cholesterol and High Risk of Autoimmune Disease: Two Population-Based Cohort Studies Including 117341 Individuals.

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HDL is quantitatively the most important lipoprotein in most species and mechanistic evidence points toward a role for HDL in normal immune function. We tested the hypothesis that concentrations of HDL cholesterol are associated with risk of autoimmune disease. From 2 studies of the general population-the Copenhagen General Population Study and the Copenhagen City Heart study-we included 107954 and 9387 individuals with baseline measurements of HDL cholesterol. These were followed with the national Danish Patient Registry from baseline in 2003-2015 or 1991-1994 through 2017, during which time 4078 and 1101 individuals developed autoimmune disease in the 2 studies. In the Copenhagen General Population Study, compared to individuals with HDL cholesterol ≥2.0 mmol/L (77 mg/dL), the multifactorially adjusted hazard ratios for any autoimmune disease were 1.06 (95% CI, 0.94-1.19) for individuals with HDL cholesterol of 1.5-1.99 mmol/L (58-77 mg/dL), 1.18 (95% CI, 1.04-1.35) for individuals with HDL cholesterol of 1.0-1.49 mmol/L (39-58 mg/dL), and 1.84 (95% CI, 1.52-2.22) for individuals with HDL cholesterol <1.0 mmol/L (39 mg/dL) (P for trend <0.001). These results were similar when excluding events within 5 years of baseline, in women and men separately, for events at baseline, irrespective of low-grade inflammation or triglyceride concentrations, for the apolipoprotein A1 part of HDL, and for more restrictive end point definitions. Finally, the Copenhagen City Heart Study provided independent confirmation. Low HDL cholesterol level is associated with high risk of autoimmune disease in individuals from the general population. Our observational findings cannot determine causality.