Prognostic Value of Lectin-like Oxidized Low-Density Lipoprotein Receptor-1 for Future Cardiovascular Disease Risk and Outcome: A Systematic Review and Meta-Analysis

Abstract

Cardiovascular disease (CVD) remains a leading cause of mortality globally, underscoring the need for robust predictive biomarkers to enhance risk stratification. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has emerged as a promising biomarker linked to oxidative stress and endothelial dysfunction, both critical mechanisms in atherogenesis and cardiovascular events. Objectives: This study aimed to evaluate the prognostic value of sLOX-1 in predicting major adverse cardiovascular and cerebrovascular events (MACCEs), myocardial infarction (MI), heart failure (HF), and stroke outcomes through a systematic review and meta-analysis. Methods: A systematic literature search was conducted across PubMed, Scopus, Web of Science, and Ovid databases for studies published between 2014 and October 2024. Eligible studies assessed the association between sLOX-1 levels and future CVD outcomes in adult populations. Meta-analysis pooled hazard ratios (HRs) were assessed using random- and fixed-effects models. Heterogeneity was evaluated using the I² statistic, and study quality was assessed using the Newcastle-Ottawa Scale. Results: Fourteen studies were included, encompassing diverse populations with coronary artery disease (CAD), acute coronary syndrome (ACS), or stroke, with follow-up durations ranging from 30 days to 19.5 years. The meta-analysis of three studies on CAD patients demonstrated a significant association between elevated sLOX-1 levels and increased MACCE risk (HR: 2.3, 95% CI: 0.99-5.33, p = 0.05), albeit with high heterogeneity (I² = 83%). The fixed-effects analysis yielded a more consistent HR of 1.47 (95% CI: 1.19-1.81, p < 0.01). Conclusions: sLOX-1 shows promising potential as a prognostic biomarker for CVD and is associated with an increased risk of MACCEs in CAD patients. However, the high heterogeneity among the included studies highlights the need for standardized protocols and larger, well-designed prospective studies to validate its clinical utility. The integration of sLOX-1 into risk prediction models could improve CVD management by identifying high-risk individuals for targeted interventions.

Keywords: acute coronary syndrome; cardiovascular disease; coronary artery disease; myocardial infarction; risk; soluble lectin-like oxidized LDL receptor-1; stroke.

Figure 1

Flow chart illustrating the process of selecting and screening based on PRISMA.

Figure 2

sLOX-1 as a predictor of MACCEs (random-effects model). Red box indicates the effect size for individual study which in this model, the size of the boxes are fairly similar indicating equal weight distribution across all included studies. While, the black diamond, which is the visual representation of the pooled effect sizes, is wide with its right tip touches the line of no effect denoting borderline statistical significance with wide 95% CI.

Figure 3

sLOX-1 as a predictor of MACCEs (fixed-effects). Red box indicates the effect size for individual study while the black diamond is the visual representation of the pooled effect sizes. In this model, the most weight (86.2%) is allocated to the study with the biggest red square, thus influencing the pooled effect size (black diamond).