Lp(a) not associated with long-term CV outcomes in secondary prevention cohorts

Analysis of observational data of 798 patients with established ASCVD showed an association of Lp(a) levels with greater plaque burden but not with 5-year risk of major adverse cardiac events or 10-year risk of all-cause mortality.

This summary is based on the publication of de Mira JVF, Vlieger S, Mulder M, et al. - Lipoprotein(a), atherosclerotic plaque burden, and long-term cardiovascular outcomes in patients with coronary artery disease. Eur J Prev Cardiol. 2026 Mar 12:zwag138 [Online ahead of print]. doi: 10.1093/eurjpc/zwag138

Introduction and methods

Background

Lp(a) is an independent risk factor for ASCVD in primary prevention settings [1-4]. Whether Lp(a) also increases the risk of adverse CV events in patients with established ASCVD on guideline-recommended lipid-lowering therapy is still unclear. Meta-analyses on secondary prevention research have produced mixed results, ranging from significant positive associations to no associations at all [5-7].

Aim of the study

The authors investigated the association of Lp(a) levels with coronary plaque characteristics and long-term CV outcomes in patients with established ASCVD.

Methods

In a pooled analysis, data of 798 patients were collected from 2 observational studies: the ATHEROREMO-IVUS (The European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis -–Intravascular Ultrasound) and IBIS-3 (Integrated Biomarker and Imaging Study 3) studies [8,9]. Participants underwent coronary angiography or PCI for stable coronary artery disease or ACS at the Erasmus Medical Center in Rotterdam, the Netherlands in the period 2008–2011. Patients received treatment according to the discretion of the treating physician, who followed the prevailing ESC guidelines (90% were on statin therapy).

To assess coronary plaque characteristics, intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) of 1 nonculprit coronary segment per patient were performed at baseline. Median follow-up time was 11.2 years (IQR: 10.9–11.5).

Outcomes

The primary endpoint was the incidence of adjudicated major adverse cardiac events, defined as a composite outcome of all-cause mortality, ACS, or unplanned coronary revascularization, at 5 years. The secondary endpoint was adjudicated all-cause mortality at 10 years.

Main results

Association between Lp(a) and coronary plaque characteristics

• Patients with Lp(a) >125 nmol/L (>~30 mg/dL) at baseline had a higher mean ± SD plaque burden as assessed with IVUS than those with ≤125 nmol/L (40.7% ± 11.5% vs. 38.6% ± 10.7%; P=0.028; adjusted estimate: 2.84; 95%CI: 0.23–5.45; P=0.03).
• After adjusting for potential confounders, there were no associations between Lp(a) levels and other IVUS-derived plaque characteristics—including necrotic core, dense calcium, and fibrous tissue fractions, minimal luminal area, and presence of a thin-cap fibroatheroma—or NIRS-derived lipid core burden indices (all P>0.05).

Association between Lp(a) and CV outcomes

• The risk of major adverse cardiac events at 5-year follow-up was not higher in participants with Lp(a) >125 nmol/L compared with those with ≤125 nmol/L (HR: 1.06; 95%CI: 0.70–1.60; P=0.78).
• When Lp(a) was analyzed as a continuous variable, the 5-year risk of major adverse cardiac events was also not increased (HR: 1.11; 95%CI: 0.99–1.24; P=0.12).
• In addition, the 10-year risk of all-cause mortality did not differ when the Lp(a) level was analyzed as a categorical variable (>125 vs. ≤125 nmol/L) (HR: 0.63; 95%CI: 0.38–1.06; P=0.08), nor when analyzed a continuous variable (HR: 0.91; 95%CI: 0.80–1.04; P=0.17).

Conclusion

This pooled analysis of the observational ATHEROREMO and IBIS-3 studies including 798 patients with established ASCVD receiving lipid-lowering therapy showed that Lp(a) levels were associated with greater atherosclerotic plaque burden but not with specific high-risk coronary plaque characteristics. Moreover, there were no associations between Lp(a) level and 5-year risk of major adverse cardiac events or 10-year risk of all-cause mortality. According to the authors, their “results suggest that Lp(a) may play a role in the progression of atherosclerotic plaque but may not be a useful prognostic marker for near-term risk in a population already receiving standard therapies for secondary prevention.”

Find this article online at Eur J Prev Cardiol.

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