Lipoprotein(a) and oxidized phospholipids linked to increased symptomatic heart failure: CASABLANCA Study

The study, published in the Journal of the American Heart Association, revealed higher lipoprotein(a) and oxidized phospholipid concentrations to be independent risk factors for progression to symptomatic heart failure (HF) or cardiovascular death among individuals with stage A or B HF.

Heart failure remains a major public health concern globally, with substantial morbidity, mortality, and healthcare costs associated with this condition. Despite advances in treatment and management, identifying individuals at risk of developing symptomatic heart failure remains a challenge.

Higher Lp (a) and oxidized phospholipid concentrations are linked with increased coronary artery disease (CAD) and valvular heart disease risk. The role of lipoprotein(a) or oxidized phospholipid as a risk factor for incident HF or its complications remains uncertain. Considering this, James L. JanuzziJr, Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, and colleagues aimed to investigate the relationship between Lp (a), OxPLs, and the risk of progression to symptomatic stages of HF among individuals with stage A/B HF referred for coronary angiography.

The study included 1251 individuals referred for coronary angiography in the CASABLANCA study. They were stratified based on the universal definition of HF stage; those in stage A/B (N=714) were followed up for an average of 3.7 years for incident stage C/D HF or the composite of HF/cardiovascular death.

The following were the key findings of the study:

• During follow‐up, 14.7% of study participants in stage A/B progressed to symptomatic HF, and 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) or the composite of HF/cardiovascular death (HR, 1.71).
• These results remained significant after further adjustment of the model to include prior myocardial infarction (HF: HR, 1.89; HF/cardiovascular death: HR, 1.68).
• 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 a shorter time to progression to stage C/D HF or HF/cardiovascular death.

These findings suggest an independent role for lipoprotein(a) and related OxPLs in causing heart damage leading to HF.

"Whether lipoprotein(a) concentrations lowering might be expected to avert progression to symptomatic HF or its complications requires further study, including clinical trials of lipoprotein(a) lowering in trials assessing HF outcomes," the researchers concluded.

Reference:

Januzzi JL Jr, van Kimmenade RRJ, Liu Y, Hu X, Browne A, Plutzky J, Tsimikas S, Blankstein R, Natarajan P. Lipoprotein(a), Oxidized Phospholipids, and Progression to Symptomatic Heart Failure: The CASABLANCA Study. J Am Heart Assoc. 2024 Jun 11:e034774. doi: 10.1161/JAHA.124.034774. Epub ahead of print. PMID: 38860394.