High Gal-3 levels are associated with the presence of significant carotid plaques, independent of sex, age, LDL levels, or previous myocardial infarction [13, 14]. A recent study by Li et al. indicated that serum Gal-3 levels were significantly higher in patients with angiographically proven coronary artery disease than in patients without CAD; as well as in patients with acute coronary syndrome (ACS) compared to patients without ACS [15]. Gal-3 could be an independent predictor of CAD, possibly associated with Syntax score complexity, and in the one-year follow-up, the increased risk of MACE [16, 17]. However, data on Gal-3 in patients with stable CAD are scarce and there are no studies investigating Gal-3 as a biomarker for MACE risk stratification in that subset of patients.

Our results support previous findings [17,18,19] confirming the association of Gal-3 levels and the presence of significant atherosclerotic epicardial stenosis, indicating that it may serve as a biomarker of a major atherosclerotic process. However, there was no difference between PCI and CABG groups in Gal-3 levels. This can be explained by the fact that the decision on the treatment modality is quite subjective, depending on the skill of the operator or invasive cardiologist as well as the available equipment. Therefore, a difference between these two groups could not be presumed because a patient undergoing PCI may have at least equally severe CAD as one undergoing CABG. In the clinical setting, the exact role of Gal-3 is not fully elucidated when it comes to coronary heart disease, but the results of other authors confirm our results [15, 20]. Furthermore, we have demonstrated the correlation between serum levels of Gal-3 and Ss I. The strongest association of Ss I with Gal-3 was observed in the group of subjects with the most complex lesions, Ss > 33. Similar results were demonstrated by Aksan et al. [21], but after adjustment for other risk factors, Ss did not prove to be an independent risk factor for the severity of lesions. On the other hand, we have avoided possible confounding factors by including a specific population without major risk factors and with no in-between group differences. Turan et al., along with other authors, have shown that Gal-3 was independently associated with Ss [22, 23]. Similar results were obtained when comparing serum Gal-3 levels with the number of vascular lesions. The highest level of Gal-3 was found in three-vessel disease, just as in the Ss > 33 group of subjects. As patients with reduced LV fraction, and significant renal impairment, were excluded from the study, it was expected that patients with lower Ss and fewer affected vessels would have lower Gal-3 values. Our findings support results from other studies reporting that patients with three-vessel disease had higher levels of Gal-3 than patients with 1- or 2-vessel disease [17, 18].

Patients with chronic coronary syndrome often develop acute coronary syndrome and other adverse events (occurrence of atrial fibrillation or heart failure) despite optimal drug therapy and nonpharmacological measures. It is necessary to identify patients from this group with the highest risk of MACE requiring invasive procedures (PCI or CABG) in addition to optimal drug therapy. In one study including patients with heart failure, the cut-off value of Gal-3 was 17.8 ng/mL, with values < 17.8 ng/mL, 17.8–23.9 ng/mL, and > 23.9 ng/mL set as low, moderate, and high risk, respectively, for MACE [12]. In our study, the arithmetic means of Syntax I was highest at high-risk Gal-3 levels. In addition, a significant correlation between Ss I and Gal-3 levels was also confirmed. Therefore, we could speculate that Gal-3 levels in combination with Ss could serve as a predictor of MACE in this subset of patients and influence therapeutic decisions.

The role of galectin-3 as a macrophage/endothelial derivative in the atherosclerotic-inflammatory process remains to be seen. Still, based on present knowledge, elevated Gal-3 levels increase the risk of plaque destabilization and the occurrence of ACS [15, 23]. Thus, patients with stable CAD, such as those included in our study, with high Gal-3 levels in addition to optimal drug therapy including statins, could be classified as high-risk patients. It should be pointed out that we did not observe any significant difference in serum lipid levels between PCI/CABG group and the control group, probably due to study exclusion criteria as well as statin subdosing of our patients. The observed association between Gal-3 and Syntax score suggests that patients with more complex and multiple lesions are at higher risk for adverse events. Other authors reported similar findings [15].

Presently, in order to prove the importance of coronary disease in our patients with angina pectoris, i.e. chronic coronary syndrome, in addition to conventional coronary angiography, we also perform additional functional tests fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), diastolic hyperemia-free ratio (dFR), resting full-cycle ratio (rFR) or additional imaging methods intravascular ultrasound (IVUS) and optical coherence tomography (OCT). In this way, we confirm the hemodynamic or pathoanatomical significance of certain lesions and thereby make a decision on possible revascularization (PCI or CABG) or continuation of OMT. These are extremely expensive tests making conventional coronary angiography more costly. Identifying a valuable biomarker such as Gal-3 would be more convenient method because it is simpler, cheaper, and more practical.

We have included highly selected group of patients diagnosed with CAD only, without additional factors that might have an impact on serum Gal-3 levels. Patients in daily clinical practice are more complex and often have CAD, arterial hypertension, heart failure, diabetes, and CKD, so elevated Gal-3 levels may have an even greater significance in this group of patients for the prediction of significant coronary disease as well as adverse cardiovascular events. Determination of Gal-3 in patients with suspected coronary disease not only indicates the significance of the present coronary disease, but also stratifies them as a high-risk patients. Many patients, despite adequate revascularization and DE stents of new generations, still end up on the recoronarography, which increases the costs of the healthcare system. Such patients, in addition to having a significant coronary disease, experience MACE in the form of heart attack, stroke, TLR (target lesion revascularisation), not to mention the risk of developing heart failure, primarily with preserved but also reduced EF, which reduces the survival rate, increases hospitalization costs and impairs quality and life expectancy. Therefore, adequate stratification would help in the detection of such patients who not only need to treat coronary disease but also need to prevent potential heart failure. In addition to the importance of Gal-3 as a diagnostic and prognostic biomarker for atherosclerotic disease and heart failure, Gal-3 may also be a potential target for pharmacological treatment to inhibit inflammatory and fibrotic tissue processes.

The main limitation of this study is the relatively small number of subjects since this was a single-center cross-sectional study. Further prospective studies including a larger sample size monitoring the outcomes should be conducted to explore the prognostic value of Gal-3 in patients with stable CAD. In addition, it would be interesting to include subjects with non-obstructive coronary heart disease and coronary artery stenosis < 50, and assess the association between Gal-3 and other biomarkers such as troponin, CRP and NT-proBNP to further elucidate the underlying pathophysiological mechanism involved in CAD. However, one of the main strengths of our study is the recruitment of a patient population with “pure” CAD and no other significant comorbidities that could affect Gal-3 levels. Moreover, there were no significant differences in baseline characteristics between the groups thus avoiding potential confounding factors.