Predictive Value of Selected Plasma Biomarkers in the Assessment of the Occurrence and Severity of Coronary Artery Disease
Abstract
1. Introduction
2. Results
2.1. Baseline Characteristics
2.2. Circulatory Biomarkers
3. Discussion
Limitations of the Study
4. Materials and Methods
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristic | CAD (n = 20) | Non-CAD (n = 20) | p Value |
---|---|---|---|
Male, n (%) | 15 (75%) | 12 (60%) | ns |
Age, years (SD) | 69 ± 1.75 | 67 ± 2.11 | ns |
Obesity, n (%) | 7 (35%) | 8 (40%) | ns |
BMI, mean (SD) | 28.72 ± 5.32 | 29.73 ± 5.76 | ns |
Diabetes mellitus, n (%) | 5 (25%) | 9 (45%) | ns |
Kidney disease, n (%) | 2 (10%) | 0 | ns |
Hypertension, n (%) | 11 (55) | 13 (65%) | ns |
Smoking, n (%) | 5 (25%) | 12 (60%) | 0.03 |
Atrial fibrillation, n (%) | 2 (10%) | 5 (25%) | ns |
Statin treatment, n (%) | 5 (25%) | 11 (55%) | ns |
Total Gensini Score, median (IQR) | 21 (7.5–42) | 0 (0–0.25) | <0.0001 |
Marker | Results |
---|---|
IL-8 | IL-8 levels were higher in patients with stable CAD in comparison with healthy subjects. Additionally IL-8 appeared to be a useful clinical predictor of unstable CAD [7] |
None of the 10 cytokine levels, namely IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon-γ (IFN-γ), were correlated with the severity of CAD; however, IL-8 was the only cytokine that predicted long-term cardiovascular outcomes independently of the other cytokines and hs-CRP [9] | |
IL-6, IL-8, hypercholesterolemia, diabetes mellitus, and hs-CRP independently predict restenosis risk in CAD patients who underwent percutaneous coronary intervention with drug-eluting stents [33] | |
Patients with atherosclerosis exhibited higher serum levels of IL-8 than healthy controls [32] | |
IL-8 serum level did not change significantly between severe and non-severe CAD patients. IL-12p70 and IL-17, HDL-C, gender and diabetes were the independent predictors of severe CAD [10] | |
The lack of association between IL-8 plasma levels and plaque progression in CCTA over a 12-month period in stable CAD patients [34] | |
sVCAM-1 | Premature CAD (PCAD) patients had significantly higher circulating values of sVCAM-1 that healthy controls; also, older CAD patients showed higher levels of sVCAM-1, CRP, and IL-2 when compared to their age-matched controls. However, after adjusting for multiple parameters, only CRP remained significant for PCAD and IL-2 remained significant for CAD [50] |
A significant elevation of serum levels of sVCAM-1 along with sICAM-1, E-selectin, ox-LDL and 8-iso-PGF2α in obese with atherosclerosis compared with obese without atherosclerosis or control groups [51] | |
Compared with controls, metabolic syndrome (MetS) patients had higher prevalence of carotid plaques, which was associated with a remarkable increase in circulating sICAM-1, sVCAM-1 and PAI-1. The increase in sICAM-1, sVCAM-1 and PAI-1, together with decreases in omentin-1, pointed to the presence of subclinical atherosclerosis and improved CVD risk stratification in non-smoking patients at early stage MetS beyond the traditional scores [52] | |
The lack of association between VCAM-1 plasma levels and plaque progression in CCTA over a 12-month period in stable CAD patients [34] | |
ET-1 | An association of circulating ET-1 levels with higher risk for all-cause mortality, cardiovascular death, non-cardiovascular death and sudden cardiac death in patients with stable CAD (prognostic value) [53] |
Baseline high ET-1 levels were independently associated with long-term all-cause death in prediabetes and diabetes patients with CAD undergoing PCI, suggesting that ET-1 may be a valuable marker in patients with impaired glucose metabolism [41] | |
ET-1 level was significantly higher in CAD patients than in controls. Increased ET-1 level was significantly associated with diabetes mellitus and dyslipidemia in patients with CAD [42] | |
Increased plasma ET-1 was independently associated with a higher risk of adverse cardiovascular prognosis in patients with in-stent restenosis and diabetes (a predictive biomarker). However, high ET-1 was not significantly associated with the risk of major adverse cardiovascular events in patients without diabetes [54] | |
ET-1 plasma level was significantly higher in the group of hypertensive patients with atherosclerosis in comparison with the other groups, especially hypertensive patients without atherosclerosis [43] | |
ET-1 could be an independent predictor for the presence of noncalcified and mixed plaques, which are considered as the high-risk coronary plaques [55] | |
Plasma ET-1 levels correlated with the severity and progression of CAD and associated with the need for revascularization in DM patients [56] | |
IL-6 | Higher levels of IL-32, IL-36, TNF-α and IL-6 in the CAD group compared to control [57] |
Concentrations of hs-cTn and IL-6 were associated with CAD characteristics and MACEs. | |
hs-cTn was associated with high-risk plaque and IL-6 with significant stenosis. In participants with nonobstructive CAD (stenosis 1–69%), the presence of both hs-cTn and IL-6 above median was strongly associated with MACEs [58] | |
No association between IL-6 and the severity of CAD [10] | |
There was a significant positive correlation between IL-6 and the severity of CAD assessed by Gensini score [59] | |
IL-4, IL-6, and HDL-C levels were strongly associated with chronic total occlusion, and IL-6 was also linked to procedural outcomes of CTO [60] | |
IL-6 levels positively correlated with the advancement of coronary artery disease and long-term survival [61] | |
Circulating levels of IL-6 along with sICAM-1, sVCAM-1, E-selectin, ox-LDL and 8-iso-PGF2α are sensitive markers for early prediction of atherosclerosis in obese subjects [50] | |
CAD patients, especially those with diabetes, have higher levels of IL-6 as compared with controls [62] | |
After adjusting for age, sex, LVEF, ischemia severity and confirmed multivessel CAD with ≥70% stenosis, each IQR increase in IL-6, hsTnT, GDF-15, NT-proBNP, or sCD40L was individually associated with the primary and secondary outcome [63] | |
IL-6 levels were higher in CAD patients than in the control group. Moreover, IL-6 levels were positively related to Gensini scores [36] | |
Serum levels of IL-6 showed higher levels in the CAD group (8.67 ± 3.66 pg/mL) compared to the control group (5.39 ± 1.82 pg/mL; p < 0.001) [64] | |
Serum TNF-α, and IL-6 levels significantly elevated in CAD group compared to the control group [65] | |
The blood levels of IL-6 did not differ between patients with atherosclerosis and healthy controls [32] | |
Serum IL-6 was found to be higher in the CAD group than in the control group [66] | |
The concentrations of serum IL-25, IL-6 and TNF-α positively correlated with the Gensini Score [67] | |
IP10, IL-6, and TNF-α levels in CAD patients were significantly higher than those in controls. Concerning positive relationship between miRNA 296-a gene expression level and serum concentrations of IL-6 and TNF-α in CAD patients, it is proposed that IL-6 and TNF-α inhibitor could be the main targets of miRNA 296a and, thereby, the IL-6 and TNF-α levels were increased; however, further study is needed [68] | |
Serum concentration of IL-6 and TNF-a are significantly increased in the patients with CAD than the healthy controls [69] | |
Unstable angina pectoris patients had lower serum IGF-1, IGFBP-4, and STC2 and higher serum inflammatory cytokine (hs-CRP, TNF-α, and IL-6) levels than the healthy controls [70] | |
IL-6 levels were associated with the severity of CAD assessed by the GS. Moreover, based on the highest levels of IL-6 measured in patients with STEMI, the study strongly suggests that IL-6 could be a powerful marker in evaluating myocardial necrosis [71] | |
In intermediate risk patients referred for coronary angiography, a serum IL-6 level above 1 pg/mL is predictive of significant CAD. IL-6 determination may be useful to reclassify CAD intermediate risk patients into higher risk categories [72] | |
Plasma IL-6 levels are significantly associated with increased total and noncalcified short-term plaque progression in patients with stable coronary artery disease [34] | |
None of the 10 cytokine levels, namely: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α, granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon-γ (IFN-γ), were correlated with the severity of CAD [9]. | |
IL-6 serum level did not change significantly between severe and non-severe CAD patients. IL-12p70 and IL-17, HDL-C, gender and diabetes were the independent predictors of severe CAD [10] |
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Wojciechowska, M.; Nizio, M.; Wróbel, K.; Momot, K.; Czarzasta, K.; Flis, K.; Zarębiński, M. Predictive Value of Selected Plasma Biomarkers in the Assessment of the Occurrence and Severity of Coronary Artery Disease. Int. J. Mol. Sci. 2025, 26, 537. https://doi.org/10.3390/ijms26020537
Wojciechowska M, Nizio M, Wróbel K, Momot K, Czarzasta K, Flis K, Zarębiński M. Predictive Value of Selected Plasma Biomarkers in the Assessment of the Occurrence and Severity of Coronary Artery Disease. International Journal of Molecular Sciences. 2025; 26(2):537. https://doi.org/10.3390/ijms26020537
Chicago/Turabian StyleWojciechowska, Małgorzata, Michał Nizio, Katarzyna Wróbel, Karol Momot, Katarzyna Czarzasta, Krzysztof Flis, and Maciej Zarębiński. 2025. "Predictive Value of Selected Plasma Biomarkers in the Assessment of the Occurrence and Severity of Coronary Artery Disease" International Journal of Molecular Sciences 26, no. 2: 537. https://doi.org/10.3390/ijms26020537
APA StyleWojciechowska, M., Nizio, M., Wróbel, K., Momot, K., Czarzasta, K., Flis, K., & Zarębiński, M. (2025). Predictive Value of Selected Plasma Biomarkers in the Assessment of the Occurrence and Severity of Coronary Artery Disease. International Journal of Molecular Sciences, 26(2), 537. https://doi.org/10.3390/ijms26020537