Prognostic role of plasma galectin-3 levels in acute coronary syndrome

Abstract

Aim: Cystatin C, neutrophil gelatinase-associated lipocalin and galectin-3 have emerged as biomarker candidates to predict cardiovascular outcomes and mortality in the general population as well as in patients with coronary artery or renal disease. However, their predictive role and clinical utility in patients with acute coronary syndromes alone or in combination beyond currently used risk scores remains to be determined. Methods and results: Cystatin C, neutrophil gelatinase-associated lipocalin, and galectin-3 were measured in plasmas of 1832 patients at the time of presentation with acute coronary syndromes requiring percutaneous coronary intervention or coronary artery bypass grafting. The primary outcomes were major adverse cardiac and cerebrovascular events (defined as the composite of all-cause mortality, cerebrovascular events, any repeat revascularization or myocardial infarction) and all-cause mortality after 1 year and occurred in 192 (10.5%) and 78 (4.3%) of patients, respectively. All three biomarkers were increased in those with major adverse cardiac and cerebrovascular events compared with those without (p<0.001). However, only galectin-3 (all-cause mortality: hazard ratio=1.027 (95% confidence interval (1.011–1.043); p=0.001), major adverse cardiac and cerebrovascular events: hazard ratio=1.025 (95% confidence interval (1.012–1.037); p<0.001)) but not cystatin C nor neutrophil gelatinase-associated lipocalin emerged as independent predictors of both major adverse cardiac and cerebrovascular events and death. The risks were particularly high in the highest quartile of galectin-3. The integration of galectin-3 into the global registry of acute coronary events (GRACE) score improved the prediction of major adverse cardiac and cerebrovascular events and all-cause mortality significantly. The areas under the receiver operator characteristics curves increased from 0.6701 to 0.6932 for major adverse cardiac and cerebrovascular events (p=0.0474) and from 0.804 to 0.8199 for all-cause mortality (p=0.0197). Finally, we applied net reclassification improvement index using different cut-offs for major adverse cardiac and cerebrovascular events which showed negative results (for the cut-offs of 5% and 15%, net reclassification improvement index 0.028, p=0.586, for the cut-offs of 10% and 20%, net reclassification improvement index 0.072, p=0.1132 and for the cut-offs of 10% and 30% the net reclassification improvement index is 0.0843, p=0.077). Conclusion: In acute coronary syndromes patients, galectin-3 has moderate prognostic accuracy, provides statistically significant incremental value in some, but not all models, and that the magnitude of any improvement would seem of questionable clinical value.

Unraveling the Cardiac Matrix: From Diabetes to Heart Failure, Exploring Pathways and Potential Medications

“…Elevated Gal-3 expression has a strong correlation with the onset and progression of CV disorders, making it closely linked to the adverse remodeling of the heart and MACEs [ 34 ]. MACE remains the leading cause of morbidity and mortality in patients with AMI, and several studies suggest that Gal-3 plays a significant role in predicting adverse events post-AMI [ 34 , 35 , 36 , 37 , 38 , 39 ]. According to research by Grandin E. and colleagues, patients with elevated levels of both BNP and Gal-3 have the highest likelihood of developing HF, suggesting that Gal-3 may provide additional value in assessing HF risk after acute coronary syndrome (ACS) [ 40 ].…”

Neutrophil-Enriched Biomarkers and Long-Term Prognosis in Acute Coronary Syndrome: a Systematic Review and Meta-analysis

“…To account for this, four of the 11 studies (36%) excluded patients with severe renal impairment as indicated by chronic renal disease, serum creatinine > 1.4 mg/dL, and/or requirement for haemodialysis [44,[47][48][49]. Though comparable exclusion criteria were not described in the remaining seven NGAL studies, five studies reported levels of serum creatinine (range 0.81-1.37 mg/dL) and eGFR (median range 65-117 mL/min/1.73 m 2 ) within normal ranges [35,40,[50][51][52], and only a small proportion of patients were reported as requiring dialysis in three studies (range 0.3-2.0%) [35,50,53]. In contrast, Barbarash et al did not state whether the moderate proportion of patients in this study (29%) with marked renal impairment (eGFR < 60 mL/min/1.73 m 2 ) were accounted for in the analysis [54].…”

“…Of the 11 studies investigating circulating NGAL levels, risk ratio data from 7 studies (64%) was extracted and pooled in a random effects model [44,[48][49][50][51][52][53]. Within these studies, a total of 1384 MACE events were recorded for 5488 patients with ACS.…”

“…Four studies were excluded from meta-analysis due to incomplete study data. Composite MACE [49,50,53] and all-cause mortality endpoints were each assessed in three studies [44,51,52], while CV mortality was assessed in one study [48]. Meta-analysis demonstrates that, when dichotomized by high or low baseline NGAL levels, high levels were associated with a 51.6% increased risk of MACE (unadjusted RR 1.52, 95% CI 1.16-2.06, p = 0.016) compared to low levels (used as the reference) (Fig.…”

Galectin-3 as a Novel Biomarker of Predicting Prognosis in Patients with Coronary Artery Disease

“…Obeid et al 2 reported that galectin-3 was an independent predictor of both major adverse cardiac and cerebrovascular events and death in patients with acute coronary syndrome. Similarly, Lorenzo-Almorós et al 3 showed that the galectin-3 is associated with increased risk of cardiovascular events in diabetic patients with stable coronary artery disease (CAD).…”