Abstract
BACKGROUND: The BEST-CLI (Best Endovascular Versus Best Surgical Therapy in Patients With Critical Limb Ischemia) trial tested the optimal initial revascularization strategy in patients with chronic limb-threatening ischemia. Little is known about the prognostic relevance of Lp(a) (lipoprotein[a]) and its modification by renal function in patients with chronic limb-threatening ischemia. We investigated the relationship between Lp(a) and prespecified cardiovascular outcomes. METHODS: A subgroup of patients from the BEST-CLI trial (as part of the TIDE [The Impact of Diabetes on Revascularization] study) underwent blinded, core-laboratory assessment of Lp(a) levels and were included in this analysis. The primary end point was major adverse limb events or death from any cause. Secondary end points were the components of the primary end point, major amputation, major reintervention, and major adverse cardiac events (myocardial infarction, ischemic stroke, or death from any cause). The association of Lp(a) with end points was assessed using Cox proportional hazard models adjusting for traditional risk factors and then also for renal function and statin use, which increase Lp(a) levels. RESULTS: A total of 189 patients (median [interquartile range] age 67.3 [61.6-74.1] years) were included and followed for a median of 2.1 (1.2-2.9) years. Median Lp(a) for the total study population was 27.3 (10.4-65.8) mg/dL, and 62 (32.8%) patients had elevated values (≥50 mg/dL). The 1-year event rate of the primary outcome was 33.3 (95% CI, 23.7-42.8) per 100 person-years. There was no association between Lp(a) and the primary outcome (hazard ratio [HR], 1.00 [95% CI, 0.99-1.00]; P=0.186). In secondary analyses controlling for renal function, elevated Lp(a) was associated with increased risk for all-cause death (HR, 1.03 [95% CI, 1.01-1.05]; P=0.009). Results were similar regardless of peripheral revascularization strategy. CONCLUSIONS: Elevated Lp(a) level was not associated with major adverse limb events or death but was associated with all-cause death after controlling for renal function. Lp(a) may be an important therapeutic target in the patient population with high-risk chronic limb-threatening ischemia. REGISTRATION: https://clinicaltrials.gov/study/NCT03085524; Unique identifier: NCT03085524.