Association of Growth Differentiation Factor 15 with Arterial Stiffness and Endothelial Function in Subpopulations of Patients with Coronary Artery Disease: A Proof-of-Concept Study.
Coronary artery disease
FMD
GDF-15
PWV
acute coronary syndrome
arterial stiffness
augmentation index
endothelial dysfunction
inflammation.
non-obstructive CAD
Journal
Recent advances in inflammation & allergy drug discovery
ISSN: 2772-2716
Titre abrégé: Recent Adv Inflamm Allergy Drug Discov
Pays: Netherlands
ID NLM: 101776469
Informations de publication
Date de publication:
2022
2022
Historique:
received:
19
02
2022
revised:
24
07
2022
accepted:
11
09
2022
pubmed:
7
11
2022
medline:
20
1
2023
entrez:
6
11
2022
Statut:
ppublish
Résumé
Growth-differentiation factor-15 (GDF-15) is a biomarker belonging to the transforming growth factor-beta cytokine superfamily, which is linked to many pathological conditions, including inflammation and myocardial injury. Pulse wave velocity (cfPWV) and augmentation index (AIx) are indices of arterial stiffness, which are associated with the severity of coronary artery disease (CAD). Flow-mediated dilatation (FMD) is a well-studied surrogate marker of endothelial-dependent dysfunction and systemic inflammation. In this proof-of-concept study, we aimed to investigate the relationship between circulating GDF-15, endothelial dysfunction, and indices of arterial stiffness in different settings of coronary artery disease and myocardial injury. In this cross-sectional single-center study, we enrolled patients (n = 22) after interventional treatment for acute myocardial infarction (AMI), patients (n = 11) admitted with chest pain and elevated cardiac enzymes but without evidence of obstructing CAD (MI-NOCAD) in percutaneous coronary angiography (CAG), and patients (n = 20) who underwent CAG according to indications without evident obstructive CAD in CAG (NOCAD). FMD was assessed at the brachial artery. AIx of the central aortic pressure and cfPWV were estimated by applanation tonometry at the radial and carotid-femoral site, respectively, with a validated acquisition system (Sphygmo- Cor, AtCor Medical, Sydney (NSW), Australia). ELISA was used to determine circulating GDF- 15 serum levels (R&D Systems, Minneapolis, MN). Clinical and demographic data and values of routine biochemical biomarkers were obtained. The highest high-sensitive cardiac Troponin I (hsTpnI) value during hospitalization was also recorded. Left ventricular ejection fraction (LVEF) was assessed with a transthoracic echocardiogram. Patients with AMI were older, had worse LVEF, higher values of hsTpnI and increased circulating GDF-15 levels. Importantly, AMI patients had increased cfPWV values, deteriorated AIx values, blunted FMD and worse serum creatinine levels compared to MI-NOCAD and NOCAD patients, respectively, whereas MI-NOCAD and NOCAD did not differ from each other significantly on these biomarkers. Both AMI and MI-NOCAD patients presented a higher but comparable white blood cell count than NOCAD patients. A strong linear correlation between GDF-15 and cfPWV, hsTpnI, AIx, white blood cell count and creatinine but not with FMD was demonstrated in the general study population. This proof-of-concept study showed that higher circulating levels of GDF-15, an inflammatory biomarker, were associated significantly with increased arterial stiffness only in AMI patients, whereas elevated GDF-15 demonstrated a linear relationship with the severity of the myocardial injury.
Sections du résumé
BACKGROUND
BACKGROUND
Growth-differentiation factor-15 (GDF-15) is a biomarker belonging to the transforming growth factor-beta cytokine superfamily, which is linked to many pathological conditions, including inflammation and myocardial injury. Pulse wave velocity (cfPWV) and augmentation index (AIx) are indices of arterial stiffness, which are associated with the severity of coronary artery disease (CAD). Flow-mediated dilatation (FMD) is a well-studied surrogate marker of endothelial-dependent dysfunction and systemic inflammation.
OBJECTIVE
OBJECTIVE
In this proof-of-concept study, we aimed to investigate the relationship between circulating GDF-15, endothelial dysfunction, and indices of arterial stiffness in different settings of coronary artery disease and myocardial injury.
METHODS
METHODS
In this cross-sectional single-center study, we enrolled patients (n = 22) after interventional treatment for acute myocardial infarction (AMI), patients (n = 11) admitted with chest pain and elevated cardiac enzymes but without evidence of obstructing CAD (MI-NOCAD) in percutaneous coronary angiography (CAG), and patients (n = 20) who underwent CAG according to indications without evident obstructive CAD in CAG (NOCAD). FMD was assessed at the brachial artery. AIx of the central aortic pressure and cfPWV were estimated by applanation tonometry at the radial and carotid-femoral site, respectively, with a validated acquisition system (Sphygmo- Cor, AtCor Medical, Sydney (NSW), Australia). ELISA was used to determine circulating GDF- 15 serum levels (R&D Systems, Minneapolis, MN). Clinical and demographic data and values of routine biochemical biomarkers were obtained. The highest high-sensitive cardiac Troponin I (hsTpnI) value during hospitalization was also recorded. Left ventricular ejection fraction (LVEF) was assessed with a transthoracic echocardiogram.
RESULTS
RESULTS
Patients with AMI were older, had worse LVEF, higher values of hsTpnI and increased circulating GDF-15 levels. Importantly, AMI patients had increased cfPWV values, deteriorated AIx values, blunted FMD and worse serum creatinine levels compared to MI-NOCAD and NOCAD patients, respectively, whereas MI-NOCAD and NOCAD did not differ from each other significantly on these biomarkers. Both AMI and MI-NOCAD patients presented a higher but comparable white blood cell count than NOCAD patients. A strong linear correlation between GDF-15 and cfPWV, hsTpnI, AIx, white blood cell count and creatinine but not with FMD was demonstrated in the general study population.
CONCLUSION
CONCLUSIONS
This proof-of-concept study showed that higher circulating levels of GDF-15, an inflammatory biomarker, were associated significantly with increased arterial stiffness only in AMI patients, whereas elevated GDF-15 demonstrated a linear relationship with the severity of the myocardial injury.
Identifiants
pubmed: 36336806
pii: RAIAD-EPUB-127403
doi: 10.2174/2772270817666221104120923
doi:
Substances chimiques
Biomarkers
0
Growth Differentiation Factor 15
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
107-115Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Références
Huang H.; Chen Z.; Li Y.; GDF-15 Suppresses Atherosclerosis by Inhibiting oxLDL-Induced Lipid Accumulation and Inflammation in Macrophages. Evid Based Complement Alternat Med 2021,2021,1-13
doi: 10.1155/2021/6497568
pubmed: 34539804
Chan M.M.Y.; Santhanakrishnan R.; Chong J.P.C.; Growth differentiation factor 15 in heart failure with preserved vs. reduced ejection fraction. Eur J Heart Fail 2016,18(1),81-88
doi: 10.1002/ejhf.431
pubmed: 26497848
Hassanzadeh Daloee S.; Nakhaei N.; Hassanzadeh Daloee M.; Mahmoodi M.; Barzegar-Amini M.; Evaluation of growth differentiation factor-15 in patients with or without coronary artery disease. Acta Biomed 2021,92(2),e2021051
pubmed: 33988174
Wang Y.; Zhen C.; Wang R.; Wang G.; Growth-differentiation factor-15 predicts adverse cardiac events in patients with acute coronary syndrome: A meta-analysis. Am J Emerg Med 2019,37(7),1346-1352
doi: 10.1016/j.ajem.2019.04.035
pubmed: 31029521
Kosum P; Mattanapojanat N; Kongruttanachok N; Ariyachaipanich A.; GDF-15: a novel biomarker of heart failure predicts 30-day allcause mortality and 30-day HF rehospitalization in patients with acute heart failure syndrome. Eur Heart J 2022,43(Supplement_1)
Alfaddagh A.; Martin S.S.; Leucker T.M.; Inflammation and cardiovascular disease: From mechanisms to therapeutics. Am J Prev Cardiol 2020,4100130
doi: 10.1016/j.ajpc.2020.100130
pubmed: 34327481
Oikonomou E.; Siasos G.; Tsigkou V.; Coronary artery disease and endothelial dysfunction: novel diagnostic and therapeutic approaches. Curr Med Chem 2020,27(7),1052-1080
doi: 10.2174/0929867326666190830103219
pubmed: 31470773
Theofilis P.; Sagris M.; Oikonomou E.; Inflammatory mechanisms contributing to endothelial dysfunction. Biomedicines 2021,9(7),781
doi: 10.3390/biomedicines9070781
pubmed: 34356845
Maruhashi T.; Soga J.; Fujimura N.; Increased arterial stiffness and cardiovascular risk prediction in controlled hypertensive patients with coronary artery disease: post hoc analysis of FMD-J (Flow-mediated Dilation Japan) Study A. Hypertens Res 2020,43(8),781-790
doi: 10.1038/s41440-020-0420-6
pubmed: 32152482
Georgiopoulos G.; Papaioannou T.G.; Magkas N.; Age-dependent association of pulse wave velocity with coronary artery disease and myocardial aging in high-risk patients. J Cardiovasc Med (Hagerstown) 2019,20(4),201-209
doi: 10.2459/JCM.0000000000000769
pubmed: 30676495
Dieden A.; Malan L.; Mels C.M.C.; Exploring biomarkers associated with deteriorating vascular health using a targeted proteomics chip. Medicine (Baltimore) 2021,100(20),e25936
doi: 10.1097/MD.0000000000025936
pubmed: 34011069
Vermeulen B.; Schutte A.E.; Gafane-Matemane L.F.; Kruger R.; Growth differentiating factor-15 and its association with traditional cardiovascular risk factors: The African-PREDICT study. Nutr Metab Cardiovasc Dis 2020,30(6),925-931
doi: 10.1016/j.numecd.2020.03.001
pubmed: 32278609
Andersson C.; Enserro D.; Sullivan L.; Relations of circulating GDF-15, soluble ST2, and troponin-I concentrations with vascular function in the community: The Framingham Heart Study. Atherosclerosis 2016,248,245-251
doi: 10.1016/j.atherosclerosis.2016.02.013
pubmed: 26972631
Siasos G.; Athanasiou D.; Terzis G.; Acute effects of different types of aerobic exercise on endothelial function and arterial stiffness. Eur J Prev Cardiol 2016,23(14),1565-1572
doi: 10.1177/2047487316647185
pubmed: 27121699
McEniery C.M.; Yasmin I.R.; Hall I.R.; Qasem A.; Wilkinson I.B.; Cockcroft J.R.; Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo-Cardiff Collaborative Trial (ACCT). J Am Coll Cardiol 2005,46(9),1753-1760
doi: 10.1016/j.jacc.2005.07.037
pubmed: 16256881
Thijssen D.H.J.; Black M.A.; Pyke K.E.; Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol 2011,300(1),H2-H12
doi: 10.1152/ajpheart.00471.2010
pubmed: 20952670
Buljubasic N.; Vroegindewey M.M.; Oemrawsingh R.M.; Temporal pattern of growth differentiation factor-15 protein after acute coronary syndrome (From the BIOMArCS Study). Am J Cardiol 2019,124(1),8-13
doi: 10.1016/j.amjcard.2019.03.049
pubmed: 31047655
Rueda F.; Lupón J.; García-García C.; Acute-phase dynamics and prognostic value of growth differentiation factor-15 in ST-elevation myocardial infarction. Clin Chem Lab Med (CCLM) 2019,57(7),1093-1101
doi: 10.1515/cclm-2018-1189
pubmed: 30707681
Tzikas S.; Palapies L.; Bakogiannis C.; GDF-15 predicts cardiovascular events in acute chest pain patients. PLoS One 2017,12(8),e0182314
doi: 10.1371/journal.pone.0182314
pubmed: 28771550
Dominguez-Rodriguez A.; Abreu-Gonzalez P.; Avanzas P.; Relation of growth-differentiation factor 15 to left ventricular remodeling in ST-segment elevation myocardial infarction. Am J Cardiol 2011,108(7),955-958
doi: 10.1016/j.amjcard.2011.05.028
pubmed: 21784389
Patsalos A.; Halasz L.; Medina-Serpas M.A.; A growth factor–expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15. J Exp Med 2022,219(1),e20210420
doi: 10.1084/jem.20210420
pubmed: 34846534
Kempf T.; Zarbock A.; Widera C.; GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat Med 2011,17(5),581-588
doi: 10.1038/nm.2354
pubmed: 21516086
Agewall S.; Beltrame J.F.; Reynolds H.R.; ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J 2017,38(3),143-153
pubmed: 28158518
Ben Ahmed H.; Allouche E.; Chetoui A.; Relationship between arterial stiffness and the severity of coronary artery disease in acute coronary syndrome. Ann Cardiol Angeiol (Paris) 2021,70(1),33-40
doi: 10.1016/j.ancard.2020.11.006
pubmed: 33256951
Muroya T.; Kawano H.; Koga S.; Ikeda S.; Yamamoto F.; Maemura K.; Aortic stiffness is associated with coronary microvascular dysfunction in patients with non-obstructive coronary artery disease. Intern Med 2020,59(23),2981-2987
doi: 10.2169/internalmedicine.5401-20
pubmed: 33268696
Nichols W.W.; Denardo S.J.; Davidson J.B.; Huo T.; Bairey Merz C.N.; Pepine C.J.; Association of aortic stiffness and wave reflections with coronary flow reserve in women without obstructive coronary artery disease: An ancillary study from the National Heart, Lung, and Blood Institute–sponsored Women’s Ischemia Syndrome Evaluation (WISE). Am Heart J 2015,170(6),1243-1254
doi: 10.1016/j.ahj.2015.08.019
pubmed: 26678647
Mourouzis K.; Siasos G.; Oikonomou E.; Lipoprotein-associated phospholipase A2 levels, endothelial dysfunction and arterial stiffness in patients with stable coronary artery disease. Lipids Health Dis 2021,20(1),12
doi: 10.1186/s12944-021-01438-4
pubmed: 33583415
Tanrıkulu O, Sarıyıldız MA, Batmaz İ, et al. Serum GDF-15 level in rheumatoid arthritis: relationship with disease activity and subclinical atherosclerosis. Acta Reumatol Port 2017,42(1),66-72
pubmed: 27679935
Bao X.; Xu B.; Borné Y.; Growth differentiation factor-15 and incident chronic kidney disease: a population-based cohort study. BMC Nephrol 2021,22(1),351
doi: 10.1186/s12882-021-02558-w
pubmed: 34706669
Wang K.; Zelnick L.R.; Anderson A.; Cardiac biomarkers and risk of mortality in CKD (the CRIC Study). Kidney Int Rep 2020,5(11),2002-2012
doi: 10.1016/j.ekir.2020.08.028
pubmed: 33163721