Abstract 12993: Low Density Lipoprotein Aggregation is Increased and Predictive of Major Adverse Cardiovascular Events in Patients With Peripheral Artery Disease Undergoing Lower Extremity Revascularization

Patients with severe PAD undergoing lower extremity revascularization (LER) remain at increased risk for future cardiovascular events beyond the early post-operative period. Identifying those who are at elevated risk for major adverse cardiovascular events (MACE) is of critical importance. We recently showed that LDL aggregates increase MMP7 secretion from foam cells. Further, in patients with CAD, the presence of aggregation-prone LDL is predictive of future cardiovascular death independent of conventional risk factors. Whether LDL aggregation is predictive of future events in PAD is unknown. 239 patients undergoing LER were prospectively enrolled, studied preoperatively, and followed for future events. MACE were adjudicated by a blinded, independent clinical event adjudication committee. LDL was isolated from pre-operative blood samples by sequential ultracentrifugation. LDL aggregation was induced by human recombinant acidic sphingomyelinase and aggregate size was measured by dynamic light scattering for four hours. LDL aggregation was increased in PAD subjects (72.1 ? 11.1 years, 32.6% female, 62.3% white) compared to 20 age, sex and race-matched controls (p<0.001; median aggregate size at 1 hour ? 1600 and 380 nm, respectively). LDL-C did not correlate with LDL aggregation (r=-0.03). Over median follow-up of 18 months, 63/239 subjects experienced MACE. Pre-operative LDL-C did not differ in those subjects who did and did not experience MACE (71?28 vs 70?23 mg/dL), whereas LDL aggregation was increased in those experiencing MACE (p=0.01). Specifically, patients in the highest tertile of LDL aggregation experienced nearly double the event rate (38%) of the lower two tertiles (20.6%, p=0.009). Pre-operative LDL aggregation remained predictive of MACE (p=0.02) after correcting for age, sex, ethnicity, BMI, smoking, hypertension, hyperlipidemia, diabetes, CAD, prior MI, statin use, and LDL-C. Our data suggest that LDL aggregation is an independent marker of risk for MACE in patients undergoing LER. In combination with prior data in CAD patients, the potential of LDL aggregation as a useful clinical risk marker is emerging. Prospective outcome studies of interventions to reduce LDL aggregation in patients at high risk of MACE are warranted.