Does high-density lipoprotein influence the development of saphenous vein graft disease after coronary bypass surgery?: exploratory analysis from the CASCADE trial

Background: Low levels of high-density lipoprotein (HDL) purportedly increase the risk after coronary bypass surgery. This may relate to the development of saphenous vein graft (SVG) disease early postoperatively, but this premise has never been evaluated in the context of a prospective trial. Methods: The CASCADE Trial was a multi-center study of 113 patients evaluating the use of postoperative clopidogrel. Patients received standard lipid management after surgery (96% statins). At 12 months, angiography and intravascular ultrasound was performed to assess SVG occlusion and intimal hyperplasia, respectively. In this exploratory analysis, we evaluated the influence of HDL levels on the development of SVG disease at 12 months, using the established cut-off of <40 mg/dL suggesting increased risk. Results: While HDL levels increased over the time-period of the trial (P < 0.0001), 51.1% of patients had HDL levels <40 mg/dL 12 months after surgery. Slightly more SVG occlusions occurred amongst patients with HDL levels <40 mg/dL (6.8%), compared to patients with HDL levels >40 mg/dL (4.0%, P = 0.5). With multivariate adjustment, HDL level <40 mg/dL was associated with a trend towards more SVG occlusions (odds ratio: 3.2; P = 0.12). Lower HDL level was also associated with more intimal hyperplasia on ultrasound at 12 months (P = 0.10). Patients who had HDL levels >60 mg/dL had the least amount of intimal hyperplasia, significantly less than the remainder of the cohort (P = 0.01). Conclusions: Within this population, lower HDL levels were associated with trends towards more graft occlusions and more vein intimal hyperplasia. Modulation of postoperative HDL levels may represent a valuable future strategy for the reduction of SVG disease.