Table 2 Diagnostic biomarker studies of Apelin-13 in thromboembolic disorders

Selimoglu et al.

2016 [152]

⁃ Case: 53 patients with PE (median 57 y)

⁃ Control: 35 healthy volunteers (median 53 y)

The serum level of Apelin-13 in the PE group (76.94 ± 10.70 ng/mL) was reported to be significantly higher than the control group (50.01 ± 7.13 ng/mL; P < 0.001)

Apelin-13 levels are elevated in patients with PE.

Apelin may be a new biomarker and a possible potential therapeutic target in patients with acute PE.

Karataş et al.

2018 [151]

⁃ Case: 82 patients with PTE (age: 71.0 ± 14.9)

(22 with DVT, 60 without DVT)

⁃ Control: 60 (age: 66.2 ± 8.1)

Serum Apelin level:

⁃ PTE group: 2219.4 +/- 65.2 ng/mL

DVT (+) group: 2495.8 +/- 738.0 ng/mL

DVT (-) group: 2118.0 +/- 496.8 ng/ml

⁃ Control group: 1234.7 +/- 35.5 ng/mL

The amount of serum Apelin-13 increased in patients with acute PTE and DVT.

Apelin-13 can potentially be a novel biomarker in patients with acute PTE and DVT.

Wang, X., et al.

2020 [164]

⁃ Before propensity score matching:

Case: 244 AIS patients (age: 60.55 ± 11.86)

Control: 167 healthy (age: 59.66 ± 6.74)

⁃ After propensity score matching:

Case: 110 AIS patients (age: 60.59 ± 12.65)

Control: 110 healthy (age: 59.27 ± 6.89)

Serum Apelin-13 levels were significantly decreased in patients with PTE versus healthy controls.

⁃ Follow-up:

A 3-month follow-up indicated a significant link between apelin-13 and mortality or major disability.

At 1-year follow-up, patients with high apelin-13 levels demonstrated a lower incidence of stroke and combined events.

Low serum apelin-13 levels were associated with increased severity, higher risk of death or major disability at 3 months, and a higher incidence of recurrent stroke and combined events at 1 year in acute ischemic stroke patients, highlighting its potential as a prognostic biomarker.

Goidescu, C.M., et al. 2021 [154]

⁃ Case: 53 with HF (age: 67.94)

⁃ Control: 13 (age: 55.38)

14 patients (24.52%) exhibited adverse clinical progression.

I: ACE2 levels exceeding 4000.75 pg/mL II: apelin-13 levels below 402.5 pg/mL correlated with poor clinical outcomes.

II: only ACE2, Apelin-13, NT-proBNP, and hsCRP presented statistically significant values, indicating that they can predict evolution.

Elevated ACE2 levels (> 4000.75 pg/mL) and low apelin-13 levels (< 402.5 pg/mL) were identified as independent predictive biomarkers of poor clinical outcomes in patients with reduced ejection fraction heart failure, highlighting their prognostic significance in disease progression.

Gergics, M., et al. 2023 [165]

124 critically ill patients (64 men, 60 women, median age: 70 (59–78) years)

Serum apelin-13 levels were lower in non-survivors compared to survivors. Notable positive correlations existed between apelin-13 and CRH, significantly elevated in surviving non-septic patients (p < 0.05 for both).

Higher serum apelin-13 levels were strongly correlated with survival in critically ill patients, serving as an independent prognostic marker alongside free cortisol, particularly in non-septic cases.

Baykal et al. 2024 [150]

⁃ Case: 94 patients with PE (mean age: 68 y)

⁃ Control: 30 (mean age: 61.5 y)

Patients with PE showed elevated HIF-1 alpha levels compared to controls, with significantly higher levels in the high-mortality risk group, while NGAL levels were also elevated in high-mortality risk patients; however, Apelin-13 levels showed no significant differences across groups.

Apelin-13 was ineffective as a biomarker for differentiating PE patients from healthy controls.

Mehrban et al. 2024 [5]

52 individuals suspected of PE (22 men and 29 women, mean age 63.67 ± 10.00)

⁃ Case: 22 patients with PE

⁃ Control: 30 patients without PE

The D-dimer cutoff point was 500 ng/ml, with 95.5% sensitivity and 43.3% specificity.

The Apelin-13 cut-off point was 58.50 ng/ml, with 90.9% sensitivity and 90% specificity.

The mean level of Apelin-13 was significantly higher in patients with PE (49.8 to 73.11 ng/L) (p < 0.001)

Serum Apelin-13 and D-dimer levels significantly increased in patients with PE,

(Apelin-13 showing promising sensitivity and specificity at a threshold of 58.50 ng/ml)