Soluble lectin-like oxidized low-density lipoprotein receptor-1 predicts premature death in acute coronary syndromes

Abstract

Aims The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its shedding product [soluble LOX-1 (sLOX-1)] are implicated in atherosclerotic cardiovascular disease (ASCVD) pathogenesis. Herein, we examined the relationship of sLOX-1 with both fatal events and plaque progression in patients with acute coronary syndromes (ACS). Methods and results Plasma sLOX-1 was assessed at baseline in ACS and chronic coronary syndrome (CCS) patients prospectively recruited in the multicentre SPUM-ACS study, with sex- and age-matched healthy subjects serving as additional controls (n = 2924). Compared with both CCS and controls, ACS patients showed markedly elevated sLOX-1 levels (median, 2.00 and 2.00 vs. 35.08 pg/mL; P < 0.0001) which were independently associated with increased mortality risk over 30-day [tertile (T)3: adjusted hazard ratio (HR), 3.11; 95% confidence interval (CI), 1.44–10.61; P = 0.0055] and 1-year intervals (T3: adjusted HR, 2.04; 95% CI, 1.19–3.92; P = 0.0098). Results remained consistent after adjustment for GRACE 2.0 (T3: adjusted HR, 1.86; 95% CI, 1.04–3.74; P = 0.0391) and were primarily driven by the pronounced relationship of sLOX-1 with cardiovascular mortality at 30 days (T3: adjusted HR, 3.81; 95% CI, 1.62–19.62; P = 0.0036) and at 1 year (T3: adjusted HR, 2.29; 95% CI, 1.19–5.34; P = 0.0148). In ACS patients undergoing serial intracoronary imaging and statin therapy, sLOX-1 dropped significantly in those with coronary plaque regression at 1 year (ΔsLOX-1: −4.64 ± 1.80; P = 0.0057), and showed a good discrimination for predicting plaque progression (area under the curve = 0.74; 95% CI, 0.59–0.86; P = 0.0031). Conclusion Plasma sLOX-1 levels are increased during ACS and predict fatal events beyond traditional and emerging risk factors. Persistently high sLOX-1 associates with coronary plaque progression in patients with established ASCVD. Clinical Trial Registration NCT01000701.

Sex-specific evaluation and redevelopment of the GRACE score in non-ST-segment elevation acute coronary syndromes in populations from the UK and Switzerland: a multinational analysis with external cohort validation

“…Consistency of sex differences in the baseline risk profile and in the performance of the GRACE score in NSTE-ACS across independent prospective patient cohorts maximises the external validity of our findings. Despite markedly different mortality rates between the cohorts, probably due to various factors, including differences in management, [40][41][42] study design, 24,25,43 and unmeasured features of care, consistent underperformance of GRACE 2.0 in female patients with NSTE-ACS was observed. Finally, prospectively collected real-world data, as used in the current study, provides increased generalisability to the European patient population compared with clinical trial data.…”

“…In Switzerland, patient data were retrieved from the Acute Myocardial Infarction in Switzerland (AMIS) Plus national registry (NCT01305785) 24 and the Special Programme University Medicine Acute Coronary Syndrome (SPUM-ACS) cohort (NCT01000701). 25 In AMIS Plus, a prospective national registry of patients with acute coronary syndrome in Switzerland, 45 797 patients were admitted…”

“…The cohort profile and detailed inclusion and exclusion criteria of each cohort have been reported previously. 24,25…”

“…Additionally, in SPUM-ACS, the 1-year mortality endpoint was reviewed by an external endpoint adjudication committee comprising three certified expert cardiologists who were masked to patient baseline characteristics using prespecified adjudication forms. 25,26…”

tRNA-like Transcripts from the NEAT1-MALAT1 Genomic Region Critically Influence Human Innate Immunity and Macrophage Functions

“…Panel ( Ab ): Quantification and statistics of OR + vesicles in the different cell clones. Panel ( B ): The striking defect of oxLDL uptake by ΔmenRNA macrophages is paralleled by loss of scavenger receptors CD36, MCAM (CD146) [ 67 ], MSR1, and OLR1 (LOX1) [ 68 ]. In contrast, the immunoregu-latory lectin receptor CD93 [ 52 ] is ~80-fold upregulated in PMA-generated ΔmenRNA macrophages compared to controls, an effect similarly observed (~35-fold induction) in unstimulated ΔmenRNA monocytes ( Figure 8 ).…”