Lipoprotein(a), Oxidized Phospholipids, and Progression to Symptomatic Heart Failure: The CASABLANCA Study

Abstract

Background Higher lipoprotein(a) and oxidized phospholipid concentrations are associated with increased risk for coronary artery disease and valvular heart disease. The role of lipoprotein(a) or oxidized phospholipid as a risk factor for incident heart failure (HF) or its complications remains uncertain. Methods and Results A total of 1251 individuals referred for coronary angiography in the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) study were stratified on the basis of universal definition of HF stage; those in stage A/B (N=714) were followed up for an average 3.7 years for incident stage C/D HF or the composite of HF/cardiovascular death. During follow‐up, 105 (14.7%) study participants in stage A/B progressed to symptomatic HF and 57 (8.0%) had cardiovascular death. In models adjusted for multiple HF risk factors, including severe coronary artery disease and aortic stenosis, individuals with lipoprotein(a) ≥150 nmol/L were at higher risk for progression to symptomatic HF (hazard ratio [HR], 1.90 [95% CI, 1.15–3.13]; P =0.01) or the composite of HF/cardiovascular death (HR, 1.71 [95% CI, 1.10–2.67]; P =0.02). These results remained significant after further adjustment of the model to include prior myocardial infarction (HF: HR, 1.89, P= 0.01; HF/cardiovascular death: HR, 1.68, P =0.02). Elevated oxidized phospholipid concentrations were similarly associated with risk, particularly when added to higher lipoprotein(a). In Kaplan‐Meier analyses, individuals with stage A/B HF and elevated lipoprotein(a) had shorter time to progression to stage C/D HF or HF/cardiovascular death (both log‐rank P <0.001). Conclusions Among individuals with stage A or B HF, higher lipoprotein(a) and oxidized phospholipid concentrations are independent risk factors for progression to symptomatic HF or cardiovascular death. Registration URL: https://wwwclinicaltrials.gov ; Unique identifier: NCT00842868.