Lp(a), Oxidized Phospholipids Can Predict Progression of Heart Failure, Study Finds

New research from Massachusetts General Hospital and Harvard Medical School are calling attention to the prognostic value of elevated lipoprotein(a) [Lp(a)] and oxidized phospholipids (OxPLs) among patients in the early stages of heart failure.

An analysis of data from the CASABLANCA study, results demonstrate elevated concentrations of Lp(a) and OxPLs could serve as independent risk factors for progression to new-onset heart failure or cardiovascular death among those with stage A/B heart failure.¹

“These findings suggest that there may be an important role of elevated lipoprotein(a) and related OxPLs in development of HF and its complications,” wrote investigators.¹

As heart failure specialists were busy grappling with their own onslaught of therapeutic advances and revelations in recent years, their counterparts in lipidology have been in the midst of a revolution of similar magnitude around the management of dyslipidemia. Chief among these advances have been the evolving evidence base linking Lp(a) to adverse outcomes and negative prognoses, even in the presence of well-controlled LDL-C.²

In the current study, a team led by James L. Januzzi Jr, MD, and Pradeep Natarajan, MD, MMSc, of Massachusetts General Hospital, sought to illustrate the role of Lp(a) or OxPLs as risk factors for incident heart failure and its complications. With this in mind, investigators designed their study as an analysis software data from the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) study.¹

Launch by Januzzi in 2008, CASABLANCA was a single-center, investigator-initiated, observational cohort study with the aim of assessing relationship between (novel) cardiac and renal biomarkers before and after angiography. The study enrolled 1298 individuals and hypothesized use of novel testing methods could improve prediction of complications of catheterization.^1,3

Using this as an evidence base, investigators identified 714 individuals in stage A/B heart failure for inclusion in the study. These individuals had a median follow-up of 3.7 years, a mean age of 65 (SD, 11) years, 70.9% were men, and 92.3% were White.¹

The primary outcome of interest for the investigators’ analyses was the risk for events in those with an elevated Lp(a) and in those with OxPLs greater than median concentration. For the purpose of analysis, elevated Lp(a) was defined as levels of 150 nmol/L or greater. Investigators noted median OxPL apoB‐100 and median OxPL apolipoprotein(a) were quantified via immunoassay.¹

During the follow-up period, 14.7% (n=105) study participants in stage A/B progressed to symptomatic hear failure and 8.0% (n=57) had cardiovascular death.¹

Among the 105 who progressed to symptomatic heart failure, 21% (n=22) were classified as having an elevated Lp(a). In analyses adjusted for age, sex, hypertension, diabetes, smoking, atrial fibrillation, chronic kidney disease, prevalent ASCVD at index angiogram, total cholesterol/HDL-C ratio, severe aortic valve stenosis, and hs-CRP, those with elevated Lp(a) had a 90% greater risk of new-onset symptomatic heart failure and a 71% greater risk of those composite of heart failure hospitalization and cardiovascular death. Investigators highlighted these associations remained significant even with further adjustment for prior myocardial infarction, adding LDL-C and triglycerides, or adding prevalent statin use at baseline.¹

Upon analysis, the study cohort had a median OxPL apoB‐100 was 3.63 (quartile range, 2.66 to 6.90) nmol/L and the median OxPL apolipoprotein(a) was 9.81(quartile range, 3.97–36.34) nmol/L. Investigators pointed out concentrations were above the median for OxPL apoB‐100 among 25.7% and for OxPL apolipoprotein(a) among 24.8% among those who experienced heart failure evens during the follow-up period.¹

When adding supramedian results for each OxPL to the fully adjusted model, the following results were observed for predicting risk of progression to heart failure:

• When elevated OxPL apoB‐100 added: HR, 3.97; 95% CI, 1.63 to 9.64; P = .002
• When elevated OxPL apolipoprotein(a) added: HR, 2.90; 95% CI, 1.28 to 6.54; P = .01

The following results were observed when assessing the value of adding OxPL values to full adjusted models for predicting the composite of heart failure hospitalizations or cardiovascular death:¹

• When elevated OxPL apoB‐100 added: HR, 3.03; 95% CI, 1.44 to 6.36; P = .004;
• When elevated OxPL apolipoprotein(a) added: HR, 1.92; 95% CI, 0.98 to 3.75; P = .06.

Investigators highlighted the results of a Kaplan-Meier analysis revealed those with stage A/B heart failure and elevated Lp(a) had shorter time to progression to stage C/D heart failure or the composite of heart failure and cardiovascular death.¹

“These results suggest an independent role for lipoprotein(a) and related OxPLs for causing heart damage leading to [heart failure]. Whether lowering of lipoprotein(a) concentrations might be expected to avert progression to symptomatic HF or its complications requires further study, including clinical trials of lipoprotein(a) lowering in trials evaluating [heart failure] outcomes,” investigators wrote.¹

References:

1. Januzzi JL Jr, van Kimmenade RRJ, Liu Y, et al. Lipoprotein(a), Oxidized Phospholipids, and Progression to Symptomatic Heart Failure: The CASABLANCA Study. J Am Heart Assoc. Published online June 11, 2024. doi:10.1161/JAHA.124.034774
2. Koschinsky ML, Bajaj A, Boffa MB, et al. A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice. J Clin Lipidol. Published online March 29, 2024. doi:10.1016/j.jacl.2024.03.001
3. McCarthy CP, Ibrahim NE, van Kimmenade RRJ, et al. A clinical and proteomics approach to predict the presence of obstructive peripheral arterial disease: From the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) Study. Clin Cardiol. 2018;41(7):903-909. doi:10.1002/clc.22939