Hydroxychloroquine alters lipoprotein particle concentrations and composition

Hydroxychloroquine (HCQ) is an immunomodulatory agent used in autoimmune conditions. Observational studies suggest that HCQ may lower circulating cholesterol and triglyceride levels, indicating a potential cardiovascular benefit. However, the specific changes in lipoprotein particle concentrations driving these effects have not been characterized in detail.

To evaluate the effects of HCQ on circulating lipids and on lipoprotein concentration and composition.

A post hoc analysis was conducted within a randomized, placebo-controlled, double-blind trial investigating the effects of HCQ on glucose metabolism in adults at risk for type 2 diabetes. Outcomes were analyzed as changes from baseline (placebo-adjusted) using mixed-effects models, with adjustments for sex, age, body mass index, and statin use.

Compared with placebo, HCQ reduced total cholesterol (10.4%), low-density lipoprotein (LDL) cholesterol (12.9%), and non-high-density lipoprotein (HDL) cholesterol (15.0%). LDL particle concentration decreased by 15.1% and apolipoprotein B (ApoB) by 9.7%. HCQ had no effect on HDL cholesterol, HDL particle concentration, or apolipoproteinA1 (ApoA1). However, small HDL particle concentrations fell by 20.0%, while large HDL particle concentrations increased by 17.1%. HCQ reduced triglycerides by 27.8%, which was associated with a 20.6% reduction in triglyceride content per very low-density lipoprotein (VLDL) particle. Lipoprotein(a) levels were unaffected.

HCQ changes lipoprotein concentration and composition, though the effects are distinct for each lipoprotein class. Our results suggest that HCQ lowers total cholesterol by reducing LDL particle concentration, decreases triglyceride by reducing the triglyceride content of VLDL particles, and alters the relative distribution of small vs large HDL particle concentration. These findings suggest protective benefits against atherosclerosis that warrant further investigation.