Major Adverse Cardiovascular Events and Mortality Prediction by Circulating GDF-15 in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Sources and Search Strategy
2.2. Eligibility Criteria
2.3. Definition of Study Endpoints
2.4. Data Extraction
2.5. Data Harmonization and Statistical Analysis
2.6. Assessment of Publication Bias and Study Quality
3. Results
3.1. Characteristics of the Included Prospective Studies
3.2. Elevated GDF-15 and Risks of Future MACE
3.3. Elevated GDF-15 and Hazard of All-Cause Mortality
3.4. Ascertainment of Quality of Study and Publicaiton Bias
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study, Year of Publication, Reference no. | Carlsson et al. 2020 [14] | Cavusoglu et al. 2015 [23] | Frimodt-Møller et al. 2018 [13] | Gerstein et al. 2015 [24] | Pavo et al. 2016 [25] | Resl et al. 2016 [26] | Sen et al. 2021 [20] | Sharma et al. 2020 [27] |
---|---|---|---|---|---|---|---|---|
Country | Sweden | USA | Denmark | Canada | Austria | Austria | Int’l | Int’l |
Sample size, n | 231 | 154 | 200 | 8401 | 919 | 746 | 3549 | 5154 |
Study type | Prospective | Prospective | Prospective | Prospective | Prospective | Prospective | Prospective | Prospective |
Statistical adjustment (Cox) | Multivariate | Multivariate | Multivariate | Multivariate | Univariate | Multivariate | Multivariate | Multivariate |
Median follow-up time, y | 7.9 | 5.0 | 6.1 | 6.2 | 5.0 | 5.0 | 6.1 | 1.5 |
Age, y | 68 | – | 59 | 63.2 | 62 † | – | 62.8 | 61 † |
Male, n (%) | 169 (73.0) | – | 152 (76.0) | 5928 (70.6) | 511 (55.6) | 420 (56.3) | 2374 (66.9) | 3491(67.7) |
BMI, kg/m2 | 30 | – | – | – | 28.1 † | – | 32.7 † | 29.5 |
Smoking, n (%) | 123 (15.0) | – | 59 (29.5) | 1050 (12.5) | 358 (39.0) | – | – | – |
Hypertension, n (%) | – | – | – | 6638 (79.0) | 614 (66.9) | 508 (68.0) | – | 4291 (83.3) |
Heart failure, n (%) | – | 46 (29.9) | – | – | 0 (0) | – | 473 (13.3) | 1442 (28.0) |
Atrial fibrillation, n (%) | – | 7 (4.5) | – | – | 14 (1.6) | – | – | – |
Coronary artery disease, n (%) | – | 130 (84.4) | – | – | 105 (11.5) | – | – | – |
Myocardial infarction, n (%) | – | 54 (35.1) | – | – | – | – | 4534 (88.0) | – |
Duration of diabetes, y | – | – | 14.7 | 5.3 † | – | 12.0† | 13.5 † | – |
HbA1c, % | 7.0 | – | – | – | 7.1 † | – | 8.2 † | 8.0 |
eGFR, mL/min/1.73 m² | 70.0 | – | 91.1 | – | 73.3 † | 72.7 † | 77.0 † | 70.9 |
hsTnT †, ng/L | – | – | – | – | 8 | 0.0008 | – | 9 |
NT-proBNP †, pg/mL | – | – | – | – | 62 | 67 | – | 422 |
GDF-15 †, pg/mL | – | – | 1533 | – | 1391 | 1474 | 1774 | 1246 |
Medications: | ||||||||
Aspirin, n (%) | – | 129 (83.8) | 193 (91.5) | – | 292 (32.0) | – | – | 4683 (90.9) |
Statin, n (%) | 415 (51.0) | 98 (63.6) | 189 (95.0) | 6638 (79.0) | 371 (40.4) | 317 (42.5) | – | 4672 (90.6) |
ACEI/ARB, n (%) | – | 110 (71.4) | – | 5793 (69.0) | – | 408 (54.7) | – | 4247 (82.4) |
Beta-blocker, n (%) | – | 116 (75.3) | – | 4526 (53.9) | – | 203 (27.2) | – | 4240 (82.3) |
Any OHA, n (%) | 152 (65.8) | 104 (67.5) | 170 (85.0) | – | 484 (52.7) | – | – | – |
Metformin, n (%) | – | 55 (35.7) | – | 2317 (27.6) | 412 (44.8) | 339 (45.4) | – | 3412 (66.2) |
Sulfonylurea, n (%) | – | – | – | – | 226 (24.8) | 196 (26.3) | – | 2393 (46.4) |
Insulin, n (%) | 209 (26.0) | 42 (27.3) | 124 (62.0) | – | 597 (65.0) | 508 (68.0) | – | 1540 (29.9) |
Study (Year) | Endpoint | Definition of MACE | Adjusted Confounders | Ref. |
---|---|---|---|---|
Carlsson et al. (2020) | MACE |
| Age, sex, frailty, microalbuminuria, renal function, CVD at baseline, smoking, LDL, and SBP | [14] |
All-cause death | – | – | ||
Cavusoglu et al. (2015) | MACE | – | – | [23] |
All-cause death | – | Age, HF or MI at presentation, extent of angiographic CAD, eGFR, metformin use, TZD use, and ST2 | ||
Frimodt-Møller et al. (2018) | MACE |
| Age, sex, smoking status, systolic BP, LDL, HbA1c, plasma creatinine, and urinary albumin excretion rate | [13] |
All-cause death | – | Age, sex, smoking status, systolic BP, LDL, HbA1c, plasma creatinine, and urinary albumin excretion rate | ||
Gerstein et al. (2015) | MACE |
| Age, sex, smoking status, prior DM, HT and CV events, LDL/HDL, albuminuria, and levels of serum creatinine, NT-proBNP, chromogranin A, Ang-2, GSTA, apolipoprotein B and tissue inhibitor of metalloproteinase 1 | [24] |
All-cause death | – | Age, sex, smoking status, prior DM, HT and CV event, LDL/HDL, albuminuria, and levels of serum creatinine, NT-proBNP, chromogranin A, Ang-2, GSTA, trefoil factor 3, α-2-macroglobulin, tenascin, selenoprotein P, macrophage derived chemokine, YKL-40 and IGF binding protein 2 | ||
Pavo et al. (2016) | MACE |
| – | [25] |
All-cause death | – | – | ||
Resl et al. (2016) | MACE |
| Age, sex, and log-transformed duration of DM, BP, eGFR, LDL, total cholesterol, HbA1c, urinary albumin excretion and NT-proBNP | [26] |
All-cause death | – | – | ||
Sen et al. (2021) | MACE |
| Age, sex, race, and randomized treatment assignment (canagliflozin or placebo) *, history of CVD, HbA1c, systolic and diastolic BP, BMI, LDL cholesterol, eGFR and UACR | [20] |
All-cause death | – | Age, sex, treatment assignment, UACR, eGFR, and CVD history | ||
Sharma et al. (2020) | MACE |
| Age, sex, smoking status, systolic BP, history of HF, duration of DM, prior MI, HT, hyperlipidemia, and eGFR | [27] |
All-cause death | – | – |
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Xie, S.; Li, Q.; Luk, A.O.Y.; Lan, H.-Y.; Chan, P.K.S.; Bayés-Genís, A.; Chan, F.K.L.; Fung, E. Major Adverse Cardiovascular Events and Mortality Prediction by Circulating GDF-15 in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. Biomolecules 2022, 12, 934. https://doi.org/10.3390/biom12070934
Xie S, Li Q, Luk AOY, Lan H-Y, Chan PKS, Bayés-Genís A, Chan FKL, Fung E. Major Adverse Cardiovascular Events and Mortality Prediction by Circulating GDF-15 in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. Biomolecules. 2022; 12(7):934. https://doi.org/10.3390/biom12070934
Chicago/Turabian StyleXie, Suyi, Qi Li, Andrea O. Y. Luk, Hui-Yao Lan, Paul K. S. Chan, Antoni Bayés-Genís, Francis K. L. Chan, and Erik Fung. 2022. "Major Adverse Cardiovascular Events and Mortality Prediction by Circulating GDF-15 in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis" Biomolecules 12, no. 7: 934. https://doi.org/10.3390/biom12070934