Table 2.
Studies on potential biomarkers regarding ACS.
| Biomarker | Study | Type | Population | Results | Concentrations |
|---|---|---|---|---|---|
| Cystatin C (CysC) | Brankovic et al., 2020 [67] | BIOMArCS prospective multicenter study | Case cohort of 844 patients after ACS for 1 year follow-up | CysC independent of GRACE score and associated with mortality, non-fatal MI & revascularization due to angina | CysC at any time associated with endpoint (HR [95% CI]: per 1SD increase of 2logCysC: 1.79 [1.21–2.63], p = 0.006) |
| Correa et al., 2018 [68] | Double- blind clinical trial | 4965 random, hospitalized for ACS patients from SOLID-TIMI 52 trial | Strong correlation with Creatinine & eGFR Elevated CysC- 89% higher risk of CVD, HF hospitalization, 44% of MACE, 28% of MI Q4: x5 risk of CVD or HF, >x2 MACE |
Quartiles of CysC: Q1 < 0.78, Q2 = 0.78–0.88, Q3 = 0.88–1.03, Q4 > 1.03 mg/mL |
|
| Sun et al., 2021 [69] | Meta-analysis | 10 studies | Significant correlation of high level CysC with all-cause mortality & MACE but not significant with recurrent MI | High Q4 and low Q1 quartiles from each study | |
| Chen et al., 2022 [70] | Meta-analysis | 8 studies with 7394 patients after PCI or CABG | ↑cystatin significant relation with MACE & mortality after PCI Non-significant after CABG |
- | |
| hFABP | Young et al., 2016 [71] | Feasibility study | 1079 patients, 248 with MI | hFABP + hs-cTn can identify up to 40% patients as low risk at presentation | hFABP < 4.3 ng/mL + hs-cTn I < 10.0 ng/L + (-) ECG (>99% sensitivity) |
| Van Hise et al., 2018 [72] | Cohort study | 1230 patients, 112 with MI | h-FABP, hs-cTn and ECG has high accuracy and can rule out more patients | hFABP + hs-cTn T (100% sensitivity + 32.4% specificity) hFABP and hs-cTn I (99.1% sensitivity + 43.4% specificity) hs-cTn I alone higher specificity 68.1% |
|
| Collinson et al., 2013 [73] | Randomized controlled trial | 850 patients with chest pain + (-) ECG sampled on admission + 90 min | Hs-cTn best single marker, further info on hFABP required | H-FABP + cTn T/ cTn I (sensitivity 0.78–0.92) at 2.5 μg/L cut-off (single troponin at 2 samples 0.78–0.95) | |
| Dupuy et al., 2015 [74] | Prospective cohort study | 181 patients, 47 with MI (31 NSTEMI) within 12 h | HFABP + hs-cTn T increased sensitivity (+13%) and NPV (+3%) for NSTEMI hFABP lower diagnostic accuracy than hs-cTn T |
5.8 ng/mL cutoff (sensitivity of 97% + NPV of 99%) | |
| Endocan | Ziaee et al., 2019 [75] | Cross- sectional and prospective | 320 patients with ACS: 160 with STEMI and 160 with UA/NSTEMI | Significant positive correlation between endocan levels and TIMI risk score and MACE. | Optimal cutoff values to predict clinical end points: 3.45 ng/mL in STEMI (80% sensitivity and 72% specificity) and 2.85 ng/mL in NSTEMI/UA (74% sensitivity and 67% specificity) |
| Kundi et al., 2017 [76] | Cross- sectional | 133 patients: 88 patients with STEMI and 45 patients with normal coronary arteries | Elevated in STEMI and positively correlated with hs-CRP and SYNTAX score | Cutoff value to predict STEMI: 1.7 ng/mL (76.1% sensitivity 73.6% specificity) | |
| Dogdus et al., 2021 [77] | Cross- sectional | 137 STEMI patients undergoing PCI: 45 NRP (+) & 92 NRP (-) | Endocan, initial troponin I, Triglyceride and high-grade thrombus burden were independent predictors of NRP |
Cutoff value to predict NRP: >2.7 ng/mL (89.6% sensitivity and 74.2% specificity) |
|
| Cimen et al., 2019 [78] | Cross-sectional | 35 ACS patients undergoing CABG | Significant decrease in serum hs-CRP and endocan levels (372.8 ng/mL vs. 320.2) after CABG (p < 0.05) |
- | |
| Qiu et al., 2016 [79] | Cross-sectional | 216 patients with ACS and 60 controls | Endocan significantly increased in ACS group. STEMI vs NSTEMI: (38.2 [14.4, 78.5] vs 10.5 [2.7, 32.6] ng/mL) |
- | |
| Galectin | Tian et al., 2019 [80] | Meta-analysis | 2809 patients (10 studies) | Significant negative correlation between galectin & LVEF Non-significant correlation between gal-3 & infarct size Galectin associated with high mortality |
- |
| Asleh et al., 2019 [81] | Population based cohort study | 1342 patients at time of MI | Tertile 2 & 3: 1.3 & 2.4 increased risk of death 1.4 & 2.3 risk of HF |
Gal-3 cut-offs in 3 tertiles: 1: <15.1 ng/mL 2: 15.1–22.4 ng/mL 3: >22.4 ng/ml |
|
| Gagno et al., 2019 [82] | Prospective cohort study | 469 patients with MI (60% STEMI) with 12 month follow up | Galectin associated with all-cause mortality. Gal-3bp correlated with risk of angina/MI |
Median Gal-3bp: 9.1 μg/mL Median Galectin: 9.8 ng/mL |
|
| Święcki et al., 2020 [83] | Controlled pilot study | 110 MI patients (66 STEMI & 44 NSTEMI) vs control | Galectin↓ at follow up if endpoint occurrence. Galectin > 9.2 ng/mL at discharge→x9 increase of risk of endpoint occurrence |
Galectin cut-off ≥9.2 ng/mL (91% specificity & 50% sensitivity) for MACE at follow-up | |
| Mitić et al., 2022 [84] | Cohort study | 89 patients undergoing PCI | Early galectin correlates with atherosclerosis. Day 30 galectin correlates with diastolic dysfunction and LV remodeling. |
- | |
| sST2 | Jenkins et al., 2017 [85] | Prospective longitudinal cohort | 1401 subjects with MI | Mortality increases at 5 yrs: 11.8%, 25.5% & 52% HF at 5 yrs: 11.4%, 23.6% & 44.8% in respective tertiles |
3 tertiles: T1: <37, T2: 37–72.3, T3: <72.3 ng/mL ST2 |
| Hartopo et al., 2018 [86] | Cohort study | 95 STEMI patients & 10 controls | Supramedian sST2 levels in STEMI patients 38.3% versus 12.5% higher incidence of MACE | STEMI vs controls: 152.1 ng/mL vs. 28.5 ng/mL, p < 0.01 | |
| Zhang et al., 2020 [87] | Meta-analysis | 16 studies | 3 groups:1. ischemic heart disease, 2. MI & 3 HF → No statistical significance between control and groups 1 & 2, significant only in 3. |
- | |
| D-dimers | Reihani et al., 2018 [60] | Cross- sectional study | 75 patients (34 with MI, 41 with UA) | Differentiation of MI (>548) from UA | Cut-off: 548 ng/mL (91.2% sensitivity & 63.4% specificity, p < 0.001) |
| Koch et al., 2022 [62] | Retrospective study | 435 patients with UA, 420 with NSTEMI, 22 NSTEMI, 2680 non coronary cause | PPV for final ACS diagnosis ↑ with d-dimer ↑ Unable to discriminate STEMI from non-coronary cause & UA. ↑d-dimer→↑risk of recurrent MI (esp. Q4) & all-cause mortality |
D-dimer concentrations (mg/L): 0.19–0.50 (Q1), 0.51–1.00 (Q2), 1.01–5.00 (Q3), and 5.01–35.00 (Q4). | |
| GDf-15 | Bonaca et al., 2010 [88] | Randomized control trial | 4162 patients with ACS, follow up for 2 years | significantly higher risk of death and MI | >1362 ng/L, higher rate of death or MI |
| Fibrinogen | Cetin et al., 2020 [65] | Observational study | 261 patients treated with PCI for ACS | FAR predictive of MACE | - |
| miR-483-5p | Zhao et al., 2023 [89] | Observational study | 118 patients with ACS and 75 healthy controls | Serum miR-483-5p levels were higher in ACS patients, high diagnostic value | Cut-off value of 1.292, demonstrated a feasible diagnostic value |
ACS: Acute Coronary Syndrome; CABG: Coronary Artery Bypass Grafting; CVD: Cardiac Vascular Disease; eGFR: estimated Glomerular Filtration Rate FAR: fibrinogen-to-albumin ratio; Gal-3bp: Galectin binding protein, GDF-15: Growth Differentiation Factor-15; HF: Heart Failure; LVEF: Left Ventricular Ejection Fraction; MACE: Major adverse cardiac events; MI: Myocardial Infarction; NRP: No-Reflow Phenomenon; MI: Myocardial Infarction; NPV: Negative Predictive Value; PCI: percutaneous coronary intervention; PPV: Positive Predictive Value; TIMI: Thrombolysis in Myocardial Infarction risk score.