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Lipoprotein(a), Oxidized Phospholipids, and Progression to Symptomatic Heart Failure: The CASABLANCA Study
James L Januzzi1,2, Roland R J van Kimmenade3, Yuxi Liu1
1Division of Cardiology Massachusetts General Hospital, Harvard Medical School Boston MA.
Insights
Higher levels of lipoprotein(a) and oxidized phospholipids increase the risk of developing symptomatic heart failure (HF) or cardiovascular death in individuals with early-stage HF. These findings highlight important risk factors for HF progression.
Area of Science:
- Cardiology
- Biomarkers
- Heart Failure Research
Background:
- Elevated lipoprotein(a) and oxidized phospholipids are linked to coronary and valvular heart disease.
- Their specific role in incident heart failure (HF) risk and complications is not fully understood.
Purpose of the Study:
- To investigate lipoprotein(a) and oxidized phospholipids as risk factors for HF progression.
- To assess their association with symptomatic HF and cardiovascular death in individuals with stage A or B HF.
Main Methods:
- Analysis of 1251 individuals from the CASABLANCA study, stratified by HF stage (A/B).
- Follow-up for incident symptomatic HF (stage C/D) or HF/cardiovascular death.
- Multivariable Cox regression models adjusted for HF risk factors and prior myocardial infarction.
Main Results:
- Individuals with lipoprotein(a) ≥150 nmol/L showed higher risk for symptomatic HF (HR, 1.90) and HF/cardiovascular death (HR, 1.71).
- Elevated oxidized phospholipids also increased risk, especially combined with high lipoprotein(a).
- Kaplan-Meier analyses revealed shorter time to HF progression in those with elevated lipoprotein(a) (log-rank P<0.001).
Conclusions:
- Higher lipoprotein(a) and oxidized phospholipid concentrations are independent risk factors for symptomatic HF progression.
- These biomarkers predict adverse cardiovascular outcomes in individuals with stage A or B HF.
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.
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