Incremental prognostic value of lipoprotein(a) and oxidized LDL for long-term major adverse cardiovascular events in patients with stable coronary artery disease: A prospective cohort study

Q: What are the key findings of this study?

Concomitant elevation of Lp(a) (>50 mg/dL) and oxLDL (>78.0 U/L) independently increased MACE risk (HR 2.45, 95% CI 1.88-3.19, p<0.001) in patients with stable CAD.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Stable coronary artery disease (n=1450). Intervention: Elevated Lipoprotein(a) (>50 mg/dL) and elevated oxidized LDL (>78.0 U/L) vs. Low Lipoprotein(a) (<=50 mg/dL) and low oxidized LDL (<=78.0 U/L). Primary outcome: Major adverse cardiovascular events (MACE: composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) (HR 2.45, 95% CI 1.88-3.19, p=<0.001).

Q: What does this research mean for the field?

Concomitant elevation of lipoprotein(a) and oxidized LDL independently increases the risk of major adverse cardiovascular events in patients with stable coronary artery disease. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To determine the independent and incremental prognostic value of lipoprotein(a) and oxidized LDL for predicting major adverse cardiovascular events in patients with stable coronary artery disease.

Guofu Wang; Gaofeng Wang; Mingjing Lu; Lechang Bi; Pengchao Luo; Feilai Huang; Nan Jiang

doi:10.5937/jomb0-65069

January 1, 2026Journal of Medical BiochemistryOpen Access

Incremental prognostic value of lipoprotein(a) and oxidized LDL for long-term major adverse cardiovascular events in patients with stable coronary artery disease: A prospective cohort study

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Key result

Elevated Lp(a) and oxLDL linked to ~2.5-fold higher MACE risk in stable CAD.

HR 2.45
95% CI 1.88-3.19
P<0.001
n=1,450

Why the study?

The independent and incremental predictive value of Lp(a) and oxLDL for MACE relative to emerging biomarkers such as Galectin-3 and GDF-15 remained unclear in contemporary cohorts of patients with stable CAD.

Does the measurement of lipoprotein(a) and oxidized LDL improve the prediction of long-term major adverse cardiovascular events beyond traditional risk factors and emerging biomarkers in patients with stable coronary artery disease?

Key Points

To determine the independent and incremental prognostic value of lipoprotein(a) and oxidized LDL for predicting major adverse cardiovascular events in patients with stable coronary artery disease.
Prospective cohort study enrolling 1,450 patients with stable coronary artery disease.
Measured baseline plasma levels of Lp(a), oxLDL, Galectin-3, GDF-15, and hs-CRP.
Assessed the primary endpoint of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) using multivariable Cox proportional hazards models, C-statistics, net reclassification improvement, and integrated discrimination improvement.
During follow-up, 289 patients (19.9%) experienced a major adverse cardiovascular event.
After multivariable adjustment, Lp(a) >50 mg/dL (HR 1.68, 95% CI 1.31–2.15, p<0.001), oxLDL in the highest tertile (HR 1.55, 95% CI 1.19–2.02, p=0.001), and GDF-15 (HR per 1-SD increase 1.41, 95% CI 1.22–1.63, p<0.001) independently predicted events, whereas Galectin-3 and hs-CRP did not.
Adding both Lp(a) and oxLDL to the clinical model improved the C-statistic from 0.71 to 0.76 (p=0.01), with patients showing elevations in both markers having a substantially higher risk of events (HR 2.45, 95% CI 1.88–3.19, p<0.001).

Study Design

Type

Cohort (n=1,450)

Blinding

Blinded clinical events committee

Multicenter

No

Structured PICO

Does the measurement of lipoprotein(a) and oxidized LDL improve the prediction of long-term major adverse cardiovascular events beyond traditional risk factors and emerging biomarkers in patients with stable coronary artery disease?

P

Population

1,450 patients (mean age 64.5 years, 32% female) with stable coronary artery disease, free of recent acute coronary syndrome or stroke, enrolled between January 2024 and January 2026.

E

Exposure

Baseline plasma measurement of lipoprotein(a) [Lp(a) >50 mg/dL] and oxidized low-density lipoprotein [oxLDL in the highest tertile, >78.0 U/L], alongside emerging biomarkers Galectin-3, growth differentiation factor-15 (GDF-15), and high-sensitivity C-reactive protein (hs-CRP).

C

Comparator

Normal/lower levels of biomarkers (Lp(a) ≤50 mg/dL and oxLDL in tertiles 1-2 [≤78.0 U/L]), and comparison of incremental predictive value against a baseline multivariable clinical model (adjusted for age, sex, BMI, hypertension, diabetes, smoking status, LDL-C, HDL-C, triglycerides, eGFR, and hs-CRP).

O

Outcome

First occurrence of major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, adjudicated by a blinded clinical events committee.composite

Main Result

Hazard Ratio: 2.45 (95% CI 1.88–3.19)

Absolute Event Rate: 40% vs 12.5%

p-value: p=<0.001

In patients with stable coronary artery disease, elevated lipoprotein(a) and oxidized LDL independently and synergistically predict long-term major adverse cardiovascular events, providing incremental risk discrimination beyond traditional risk factors and emerging biomarkers.

Limitations

Single-center study limiting generalizability
Biomarkers were measured only at a single baseline time point
Potential residual confounding by unmeasured factors
Use of an isoform-insensitive Lp(a) assay
Findings in a stable, treated CAD cohort may not generalize to primary prevention or acute coronary syndrome populations
Single-centre study, which may limit generalizability
Biomarkers were measured at a single time point, which may not reflect changes over time or in response to therapy
Cannot rule out residual confounding by unmeasured factors
The Lp(a) assay used was isoform-insensitive (reported in mg/dL)
Findings in a stable, treated CAD cohort may not be generalizable to primary prevention populations or those with acute coronary syndromes

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

May refine MACE risk stratification in stable CAD; leaves open therapeutic implications pending prospective validation.

Abstract

Background: Lipoprotein(a) [Lp(a)] and oxidized lowdensity lipoprotein (oxLDL) are established risk factors for atherosclerosis, but their independent and incremental predictive value for major adverse cardiovascular events (MACE) relative to emerging biomarkers such as Galectin-3 and growth differentiation factor-15 (GDF-15) remains to be clarified in contemporary cohorts of patients with stable coronary artery disease (CAD). Methods: In this prospective cohort study, 1,450 patients with stable CAD were enrolled. Baseline plasma levels of Lp(a), oxLDL, Galectin-3, GDF-15, and high-sensitivity C-reactive protein (hs-CRP) were measured. The primary endpoint was MACE, defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Multivariable Cox proportional hazards models were used to assess the independent predictive value of each biomarker, and C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate incremental risk prediction. Median follow-up was [X] months. Results: During follow-up, 289 patients (19.9%) experienced a MACE. After adjustment for traditional risk factors, Lp(a) >50 mg/dL (HR 1.68, 95% CI 1.31-2.15, p<0.001) and oxLDL in the highest tertile (HR 1.55, 95% CI 1.19-2.02, p=0.001) remained independent predictors of MACE, as did GDF-15 (HR per 1-SD increase 1.41, 95% CI 1.22-1.63, p<0.001). Galectin-3 and hsCRP were not independently associated with MACE after full adjustment. Addition of Lp(a) and oxLDL to a baseline clinical model improved the C-statistic from 0.71 to 0.76 (p=0.01), with significant improvements in continuous NRI and IDI. Patients with elevated Lp(a) and oxLDL had a substantially higher risk than those with normal levels of both markers (HR 2.45, 95% CI 1.88-3.19, p<0.001). Conclusions: In patients with stable CAD, Lp(a) and oxLDL onclusions: are robust, independent predictors of long-term MACE and add prognostic value beyond traditional risk factors and other novel biomarkers. The combination of elevated Lp(a) and oxLDL identifies a very high-risk phenotype, suggesting a possible additive or synergistic contribution to residual cardiovascular risk.

Discussion

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Cite This Study

Wang et al. (2026) conducted a cohort in Stable coronary artery disease (n=1,450). Elevated Lipoprotein(a) (>50 mg/dL) and elevated oxidized LDL (>78.0 U/L) vs. Low Lipoprotein(a) (<=50 mg/dL) and low oxidized LDL (<=78.0 U/L) was evaluated on Major adverse cardiovascular events (MACE: composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) (HR 2.45, 95% CI 1.88-3.19, p=<0.001). Concomitant elevation of Lp(a) (>50 mg/dL) and oxLDL (>78.0 U/L) independently increased MACE risk (HR 2.45, 95% CI 1.88-3.19, p<0.001) in patients with stable CAD.

synapsesocial.com/papers/6af0dba03c845ca7837cedf9 https://doi.org/10.5937/jomb0-65069

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Incremental prognostic value of lipoprotein(a) and oxidized LDL for long-term major adverse cardiovascular events in patients with stable coronary artery disease: A prospective cohort study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Incremental prognostic value of lipoprotein(a) and oxidized LDL for long-term major adverse cardiovascular events in patients with stable coronary artery disease: A prospective cohort study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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