The aim of this study was to explore the effects of a single lipoprotein apheresis session on myocardial stress/rest (S/R) perfusion in patients with elevated lipoprotein(a) (Lp(a)) and coronary artery disease using cardiac magnetic resonance imaging. Twenty patients with Lp(a) > 60 mg/dL and coronary artery disease were randomized into a control or a treatment group. Both groups underwent cardiac magnetic resonance imaging with assessment of left ventricular function, perfusion and viability, and the treatment group underwent lipoprotein apheresis immediately afterwards. Repeat magnetic resonance imaging was performed at 24 h for both groups and at 96 h for just the treatment group. The transmyocardial perfusion gradient (i.e. endo-epi ratio [EER]) was determined and a comprehensive parameter of resting and adenosine-induced stress perfusion was derived (EER-S/R). While the hematocrit remained unchanged, apheresis reduced lipoproteins and rheological parameters: Lp(a) - 55.1%, total cholesterol - 34.5%, low density lipoprotein (LDL) - 54.6%, Lp(a)-corrected LDL - 54.3%, high density lipoprotein - 17.4%, apolipoprotein B - 39.2%, plasma viscosity - 10.7%, and fibrinogen - 30.6% at 24 h (P < 0.05 for all). At 96 h these parameters, except for plasma viscosity, apolipoprotein B and Lp(a)-corrected LDL, recovered but did not reach baseline values (P < 0.05 for all). The EER-S/R at 24 h was lowered by therapy (DeltaEER-S/R 5%; P < 0.03), whereas this effect disappeared at 96 h. The ejection fraction (EF) was slightly improved at 24 h (67.07 +/- 6.28% vs. 64.89 +/- 6.39%; DeltaEF 2.2%, P < 0.05) and returned to baseline at 96 h. In the control group no corresponding changes were detected. In conclusion, cardiac magnetic resonance imaging detects subtle treatment-related changes in regional myocardial perfusion in patients with elevated Lp(a) and coronary artery disease undergoing lipoprotein apheresis.