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Moxonidine is centrally acting imidazoline type-1 receptor agonist that significantly lowers blood pressure and has some insulin-sensitising actions. Its effects on plasma lipid profiles are uncertain. This study examined the effects of moxonidine on detailed lipid and lipoprotein profiles in 12 patients with hypertension and type 2b Fredricksen hyperlipidaemia. Treatment with moxonidine in six patients who completed the study resulted in a 10/5 mmHg reduction in 24-h ambulatory blood pressure (p = 0.01). A significant reduction in total and low-density-lipoprotein cholesterol (LDL-C) of 10% (p = 0.04) and 18% (p = 0.03), respectively, was seen. Triglycerides were reduced non-significantly by 23%, and high-density-lipoprotein cholesterol (HDL-C) was increased by 16%. There were no significant changes in apolipoprotein (apo) A-1 and B concentrations. No significant shifts were seen in HDL-C, LDL-C, very-low-density-lipoprotein cholesterol (VLDL-C) or apolipoprotein peak positions with therapy. Analysis of area under curve for each subfraction showed that moxonidine therapy resulted in a redistribution within the apoB profile. A slight non-significant reduction in VLDL apoB was seen. There was a reduction in the dense LDL apoB peak (p = 0.02) but less in the buoyant LDL apoB peak (p = 0.17) with a countervailing increase in LDL-C in the buoyant fraction (p = 0.01). The HDL-C and apoA-1 profile showed a shift from dense HDL apoA-1 (p = 0.01) to a buoyant HDL apoA-1sub-species (p = 0.01). These changes are consistent with a tendency for moxonidine to improve atherogenic lipid and lipoprotein profiles by actions on insulin-sensitisation and possibly through a direct cholesterol-reducing effect as seen with other imidazoles.