Activation of the complement lectin pathway is associated with long-term cardiac dysfunction and incident heart failure in acute coronary syndrome patients
International Journal of Cardiology, 2026
Zhong B., King B., Mares R., Arbanasi E., Yndigegn T., Engelbertsen D., Björkbacka H., Nilsson J., Goncalves I., Blom A., Schiopu A.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD | Patient Stratification | Plasma |  Olink Target 96 |
Abstract
Background
Myocardial injury activates the complement lectin pathway (LP) in acute coronary syndrome (ACS) and LP inhibition improved cardiac function in experimental studies, suggesting a direct pathogenic role. The clinical consequences of LP activation are insufficiently defined. We investigated how plasma levels of the LP activators mannose-binding lectin (MBL) and ficolin-2 (FCN2) relate to cardiac recovery and prognosis in ACS patients.
Methods
MBL and FCN2 were measured at baseline in a cohort of 546 ACS patients and at 6-weeks in 124 patients with available samples. Prospective associations with heart failure (HF), stroke, and major adverse cardiovascular events (MACE) during a median follow-up of 2.2 years were assessed by multivariable Cox regression. Spearman correlation was used to assess relationships between MBL and FCN2 levels, inflammatory and fibrotic mediators in plasma, and echocardiographic parameters of left ventricular (LV) remodelling and dysfunction.
Results
Baseline MBL was associated with incident HF (HR 1.50, 95% CI 1.04–2.16, p = 0.029), independently of clinical risk factors, revascularization, baseline troponin and renal function. Patients with persistently elevated MBL at baseline and follow-up had increased pro-inflammatory and pro-fibrotic mediators in plasma, dilated LV and reduced LV systolic function at 1-year post-ACS. FCN2 showed no association with the outcomes.
Conclusions
ACS patients with persistently high plasma MBL levels suffer cardiac remodelling and dysfunction, and have an increased risk for HF. Our findings provide clinical support to experimental data suggesting that the complement LP might be a potential therapeutic target to prevent post-ACS HF.