Acute and Chronic Impact of Bariatric Surgery on Plasma LDL Cholesterol and PCSK9 Levels in Patients With Severe Obesity

Context: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol (LDL-C) concentrations. In patients with severe obesity, biliopancreatic diversion with duodenal switch (BPD-DS) surgery induces substantial weight loss and influences lipoprotein metabolism. The effect of BPD-DS on PCSK9 levels is unknown. Objectives: To determine the acute and chronic impact of BPD-DS on PCSK9 levels and whether the acute impact of BPD-DS could be explained by BPD-DS-associated caloric restriction (CR). Design, Settings, and Participants: PCSK9 levels were measured in 20 men and 49 women (age, 41.5 +/- 11.1 years) with severe obesity before, 24 hours, 5 days, and 6 and 12 months after BPD-DS and in a comparable control group (n = 31) at baseline and at 6 and 12 months. PCSK9 levels were also measured during 3-day CR in patients (n = 7) with severe obesity and type 2 diabetes. Results: PCSK9 levels increased 13.4% after 24 hours (248.7 +/- 64.8 to 269.7 +/- 63.8 ng/mL; P = 0.02) and decreased 9.5% at 12 months compared with baseline (217.6 +/- 43.0 ng/mL; P < 0.0001). LDL-C levels decreased 36.2% after 24 hours (2.6 +/- 0.7 to 1.7 +/- 0.6 mmol/L; P < 0.0001) and 30% at 12 months compared with baseline (1.7 +/- 0.5 mmol/L; P < 0.0001). Compared with baseline levels, PCSK9 levels were lower at day 2 but not at day 1 or 3 after CR. Conclusion: BPD-DS is associated with acute increases in PCSK9 levels that do not appear to be explained by CR but may be due to an acute response following surgery. BPD-DS induces chronic reductions in both PCSK9 and LDL-C levels.