Table 1.
Summary of the characteristics of the 27 studies included in the systematic review
| Study (year), country | Marker | Sample size (MACE, %) | Age, years | Male, % | Sampling time from symptom onset | Inclusion criteria | Major exclusion criteria | Clinical endpoint | Follow-up |
|---|---|---|---|---|---|---|---|---|---|
| Akcay (2012), Turkey [50]a | NGAL | 300 (19.8) | 51.4 ± 6.1 (53 patients with NGAL > 46 ng/mL) | 73.58 | 5 ± 2.2 hrs, before angiography | STEMI + PCI | Culprit lesion ≥ 50% stenosis‡, CABG, chronic inflammatory disease, infection or cancer | All-cause mortality and MACE† (mortality, MI, HF, revascularisation) | 1 year |
| Alfakry (2012), Finland [43]a | MPO | 141 (29.1) | 65.2 (IQR 10.2) | 65.2 | ≤ 48 hrs, angiography NR | NSTEMI and UA ± PCI | Thrombolysis ≤ 48 hrs, coronary angioplasty ≤ 6 or CABG ≤ 3 months, chronic renal or hepatic disease or chronic antibiotic use | MACE† (CV mortality, MI, UA, stroke) | Median 519 (138–924) days |
| Avci (2020), Turkey [47]a | NGAL | 68 (20.6) | 61.5 ± 14.7 | 82.4 | 4.6 ± 3 hrs, before angiography | STEMI ± PCI | Culprit lesion ≥ 50% stenosis‡, CABG or MI, LVEF < 55%, creatinine > 1.4 mg/dL, inflammatory disease, infection or cancer | CV death† | 6 months |
| Baldus (2003), multicentre [68]a | MPO | 547 (11.7) | 61.7 ± 10.4 | 61 | 8.7 ± 4.9 hrs, before angiography | ACS with significant culprit lesion + PTCA | Prior MI, persistent ischemia, culprit lesion > 50% stenosis‡; recent surgery, GI bleeding ≤ 6 weeks; anticoagulant or thrombolytic agent; autoimmune disease or platelet count < 100 × 109/L | All-cause mortality and MACE† (CV mortality, MI, UA, stroke) | 6 months |
| Barbarash (2017), Russia [54]a | NGAL | 318 (88.4) | 61.3 (95% CI 59.5–62.6) | 72.3 | 12–14 days, before angiography | STEMI ± PCI | Prior PCI or CABG, autoimmune disease or cancer | MACE† (CV mortality, MI, UA, stroke, acute HF) | 3 years |
| Brügger-Andersen (2008), Norway [102]a | MPO | 298 (27.8) | 64 ± 13 | 79.3 | 4–6 days, after angiography | MI ± PCI | Severe HF (NYHA class IV), life expectancy < 2 years, late-stage cancer, GI bleeding, hepatic disease, thrombocytopenia or platelet count < 100 × 109/L | MACE† (CV mortality, ACS) | Median 45 months |
| Cavusoglu (2007), USA [69]a | MPO | 182 (18.1) | 64.8 ± 10 | 100 | ≥ 12 hrs from admission, before angiography | ACS ± PCI | GI bleeding | MACE† (mortality, MI) | 2 years |
| Hally (2021), New Zealand [41]b | MPO-DNA, NE-DNA, CitH3 | 300 (33) | 68 (57–75) | 67.7 | 3 (2–4) days, before angiography | MI ± PCI | Cardiac arrest, CHF, eGFR < 30, fibrinolytic agent ≤ 24 hrs, inflammatory disease, platelet function disorder or count < 100 × 109/L | MACE† (CV mortality, MI, stroke) | 1 year |
| Helanova (2015), Czech Republic [51]a | NGAL | 673 (6.4) | 61 (46–78) | 76.52 | ≤ 24 hrs, before angiography | STEMI + PCI | Cardiac arrest, inflammatory or connective tissue disease, cancer, life expectancy < 12 months or culprit lesion stenosis < 50%‡ | All-cause mortality† | Median 2.7 years |
| Helseth (2019), Norway [37]a | dsDNA, MPO-DNA | 251 (7.3) | 60 (53–67) | 82 | Median 21.4 hrs, before angiography | STEMI + PCI | Prior MI, renal failure, contraindications to CMR or clinical instability | MACE† (mortality, MI, stroke, HF, revascularisation) | 1 year |
| Jensen (2010), Denmark [36]b | Calprotectin | 141 (9.2) | 68.6 ± 13.4 (13 patients who died at follow-up) | 73.6 | 12.5 days (9.2–31.6) and 14.2 (IQR 9.6–21.5)§§, before angiography | STEMI with LAD occlusion + PCI | Lack of acute LAD occlusion, prior MI, HF, infection or inflammatory disease | All-cause mortality† | 1 year |
| Kaya (2012), Turkey [70]b | MPO | 73 (21.9) | 56.5 ± 11.9 | 76.71 | ≤ 6 hrs, angiography NR | STEMI ± PCI | Valvular heart disease, chronic renal or hepatic disease inflammatory disease or cancer | MACE† (mortality, MI, CHF, revascularisation, cerebrovascular event) | Mean 25 ± 16 months |
| Langseth (2020), Norway [38]a | dsDNA, MPO-DNA, CitH3 | 959 (19.9) | 60.8 (range 24–94) | 80 | Median 24 hrs, after angiography | STEMI + PCI | Oral anticoagulant use | All-cause mortality or MACE† (mortality, MI, revascularisation, HF, stroke) | Median 4.6 years |
| Lindberg (2012), Denmark [35]a | NGAL | 584 (19) | 66 ± 13; > 170.1 μg/L | 73 | 3.2 (2.2–5.2) hrs, before angiography | STEMI + PCI | Troponin I increase ≤ 0.5g/L or no angiographic stenoses | All-cause mortality and MACE† (CV mortality, MI, HF) | Median 23 (20-24) months |
| Liu (2021), China [48]a | NGAL | 633 (6.5) | 72.1 (68.2–79.2); ≥ 102.6 ng/L | 52.92 | ≤ 24 hrs from admission, angiography NR | MI and stable angina ± PCI | Chronic renal or hepatic disease, severe aortic stenosis, cardiomyopathy, significant anaemia or cancer | CV death† | 10 years |
| McCann (2009), multi (UK) [103]a | MPO | 550 (9.8) | 62 ± 13 | 70 | 6 (3.4–12.4) hrs, before angiography | Suspected ACS with chest pain ± PCI | Thrombolytic or anticoagulant use | All-cause mortality, non-fatal MI or MACE† (mortality, MI) | 1 year |
| Mocatta (2007), New Zealand [39]a | MPO | 507 (15.4) | 61.7 ± 11 | 80 | 24–96 hrs from admission, after angiography | MI ± PCI | Cardiogenic shock or in-hospital death ≤ 24 hours after onset | All-cause mortality† | 5 years |
| Morrow (2008), multi [66]b | MPO | 1524 (15.3) | 61 (52–70) | 66.99 | ≤ 24 hrs, before angiography | ACS with survival ≥180 days + tirofiban ± PCI | Prior PCI or CABG ≤ 6 months, persistent STE, LBBB, severe CHF, cardiogenic shock, systemic disease or creatinine > 2.5 mg/dL | Non-fatal ACS† | 6 months |
| Ng (2011), UK [42]a | MPO, PR3 | 900 (22.8) | 64.6 ± 12.4 | 70 | 2–5 days, after angiography | MI ± PCI | Cancer or recent surgery ≤ 1 month | All-cause mortality or hospitalisation with HF† | Mean 347 days |
| Nguyen (2019), France [44]a | NGAL | 701 (11.5) | 62.8 ± 14.4; without CI-AKI (88%) | 74.61 | On admission, before angiography | STEMI + PCI | Chronic haemodialysis or peritoneal dialysis | All-cause mortality | 1 year |
| Nymo (2018), Sweden [52]a | NGAL | 1121 (54.4) | 69 (60–74); > 403 μg/L | 70 | Median 3 days, before angiography | MI ± PCI | Life expectancy < 1 year | All-cause mortality† | Median 167 months |
| Obeid (2020), multi (Switzerland ) [53]a | NGAL | 1832 (10.5) | NR | 79.15 | ≤ 72 hrs (91.3%), before angiography | MI ± PCI | No informed consent | All-cause mortality and MACE† (mortality, MI, revascularisation, cerebrovascular events) | 1 year |
| Peng (2019), China [49]a | NGAL | 422 (32.2) | 61 ± 13.1 | 74.17 | ≤ 24 hrs and 7 days, before angiography | NSTEMI with CTO + PCI | Rescue PCI or CABG, valvular heart disease or cardiomyopathy, CTO < 1 or > 1, life expectancy < 1 year, dialysis or contraindication to antiplatelet or anticoagulation therapy | MACE† (CV mortality, stroke, revascularisation, cardiogenic shock) | 2 years |
| Scirica (2010), multi [71]a | MPO | 352 (6.8) | Mean 64 | 64.9 | Median 22.4 hrs, before angiography | NSTEMI and UA ± PCI | Revascularisation, persistent STE, pulmonary oedema, systolic BP < 90 mmHg, cardiogenic shock, LBBB, LV hypertrophy, chronic hepatic disease, dialysis or life expectancy < 1 year | CV death, MI, HF | Mean 343 days |
| Wang (2018), China [55]a | dsDNA | 142 (18.3) | 59 (range, 28–88) | 79.5 | Mean 6.3 hrs, before angiography | STEMI + PCI | Valvular heart disease or cardiomyopathy, AF, chronic hepatic or renal disease, inflammatory or autoimmune disease or cancer | MACE† (mortality, revascularisation, ACS, stroke) | Mean 24.5-25.71 months§ |
| Wang (2019), China [56]a | Calprotectin | 273 (17.2) | 63.4 ± 8.5 | 62.4 | On admission, before angiography | ACS with diabetes + PCI | Unsuccessful PCI (≤ TIMI grade 3), prior MI or CABG, infection or inflammatory disease, chronic hepatic or renal disease, long-term antiplatelet or anticoagulant use | MACE† (CV mortality, MI, revascularisation) | 1 year |
| Yndestad (2009), multi (Europe) [40]a | NGAL | 236 (13.6) | 67.4 ± 9.8 | 71.2 | 3 (1–7) days, angiography NR | MI with acute HF ± PCI | Planned revascularisation, systolic BP < 100 mmHg, ACEi or Ang II antagonist, UA, valvular heart disease | MACE† (CV mortality, MI, stroke) | Median 2.7 years |
Abbreviations: ACEi, angiotensin-converting enzyme inhibitors; ACS, acute coronary syndrome; AF, atrial fibrillation; Ang II, angiotensin II; AP, angina pectoris; BP, blood pressure; CHF, congestive heart failure; CTO, complete total occlusion; CV, cardiovascular; GI, gastrointestinal; HF, heart failure; LAD, left anterior descending artery; LBBB, left bundle-branch block; LV, left ventricular; MI, myocardial infraction; NR, not reported; PTCA, percutaneous transluminal coronary angioplasty, may also refer to PCI; STE, ST-segment elevation; TIMI, Thrombolysis In Myocardial Infarction (risk score for NSTEMI and UA); UA, unstable angina; UK, United Kingdom; USA, United States of America. aRepresents a cohort study; brepresents a case-control study; †indicates the primary study endpoint; ‡refers to the percentage reduction of the intraluminal diameter of coronary arteries with stenosis; §denotes the mean follow-up period in months for low and high dsDNA groups, respectively; §§denotes the median time from symptom onset to sampling for patients who died and who survived at follow-up, respectively