Determinants of growth differentiation factor 15 plasma levels in outpatients with peripheral arterial disease
Keywords:
Atherosclerosis, biomarker, GDF-15, peripheral arterial disease, diabetes
Abstract
Background: Growth differentiation factor 15 (GDF-15) is a robust prognostic biomarker in patients with cardiovascular (CV) disease, and a better understanding of its clinical determinants is desirable. We aimed to study the associations between GDF-15 levels and traditional CV risk factors, indicators of atherosclerotic burden, and cardiac geometry and dysfunction in outpatients with peripheral arterial disease (PAD).
Methods: An explorative cross-sectional study (Study of Atherosclerosis in Vastmanland, Västerås, Sweden) included 439 outpatients with carotid or lower extremity PAD. The mean age was 70 years (standard deviation [SD] 7), and 59% of the patients were men. Plasma levels of GDF-15 were obtained along with potential determinants, including medical history, biochemical data, echocardiographic measures of cardiac geometry and function, ankle-brachial index (ABI), and carotid ultrasonographic data on intima-media thickness (IMT) and occurrence of carotid stenosis. The relations between GDF-15 concentrations (transformed with the natural logarithm) and the different determinants were evaluated using uni- and multivariable linear regression models. All pre-specified variables were included in the multivariable models.
Results: The multivariable analysis identified independent relations of GDF-15 with several of the included variables (adjusted R2 = 0.48). Diabetes (beta coefficient [β] of 0.37, 95% confidence interval [95% CI] 0.25 to 0.50), low-density lipoprotein (LDL) cholesterol (β = −0.22, 95% confidence interval [CI]: −0.34 to −0.09), and physical activity (β = −0.16, 95% CI: −0.25 to −0.06) had the strongest associations. In contrast, no significant independent associations with GDF-15 level were observed for cardiac geometry and function, ABI, IMT, or carotid stenosis.
Conclusions: Circulating GDF-15 is more strongly associated with traditional CV risk factors, especially diabetes, LDL cholesterol, and physical activity than with specific indicators of atherosclerotic burden or cardiac dysfunction. To better understand the pathophysiological role of GDF-15 and its link to clinical outcomes in patients with PAD, future studies should focus on the metabolic processes involved in atherosclerotic disease.
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References
1. Wesseling M, de Poel JHC, de Jager SCA. Growth differentiation factor 15 in adverse cardiac remodelling: from biomarker to causal player. ESC Heart Fail. 2020;7:1488–501. doi: 10.1002/ehf2.12728
2. Wollert KC, Kempf T, Peter T, Olofsson S, James S, Johnston N, et al. Prognostic value of growth-differentiation factor-15 in patients with non–ST-elevation acute coronary syndrome. Circulation. 2007;115:962–71. doi: 10.1161/CIRCULATIONAHA.106.650846
3. Skau E, Henriksen E, Wagner P, Hedberg P, Siegbahn A, Leppert J. GDF-15 and TRAIL-R2 are powerful predictors of long-term mortality in patients with acute myocardial infarction. Eur J Prev Cardiol. 2017;24:1576–83. doi: 10.1177/2047487317725017
4. Skau E, Henriksen E, Leppert J, Wagner P, Ärnlöv J, Hedberg P. Targeted multiplex proteomics for prediction of all-cause mortality during long-term follow-up in outpatients with peripheral arterial disease. Atherosclerosis. 2020;311:143–9. doi: 10.1016/j.atherosclerosis.2020.06.015
5. Wallentin L, Zethelius B, Berglund L, Eggers KM, Lind L, Lindahl B, et al. GDF-15 for prognostication of cardiovascular and cancer morbidity and mortality in men. PLoS One. 2013;8:e78797. doi: 10.1371/journal.pone.0078797
6. Wang J, Wei L, Yang X, Zhong J. Roles of growth differentiation factor 15 in atherosclerosis and coronary artery disease. J Am Heart Assoc. 2019;8:e012826. doi: 10.1161/JAHA.119.012826
7. De Haan JJ, Haitjema S, den Ruijter HM, Pasterkamp G, de Borst GJ, Teraa M, et al. Growth differentiation factor 15 is associated with major amputation and mortality in patients with peripheral artery disease. J Am Heart Assoc. 2017;6:e006225. doi: 10.1161/JAHA.117.006225
8. Hedberg P, Hammar C, Selmeryd J, Viklund J, Leppert J, Hellberg A, et al. Left ventricular systolic dysfunction in outpatients with peripheral atherosclerotic vascular disease: prevalence and association with location of arterial disease. Eur J Heart Fail. 2014;16:625–32. doi: 10.1002/ejhf.95
9. Vermeersch SJ, Rietzschel ER, De Buyzere ML, Van Bortel LM, D’Asseler Y, Gillebert TC, et al. Validation of a new automated IMT measurement algorithm. J Hum Hypertens. 2007;21:976–8. doi: 10.1038/sj.jhh.1002251
10. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16:233–71. doi: 10.1093/ehjci/jev014
11. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12. doi: 10.7326/0003-4819-150-9-200905050-00006
12. Hoelzel W, Weykamp C, Jeppsson J-O, Miedema K, Barr JR, Goodall I, et al. IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study. Clin Chem. 2004;50:166–74. doi: 10.1373/clinchem.2003.024802
13. Nordin G. Accuracy of HbA1c as monitored by external quality assessment and compared with patient mean values. J Diabetes Sci Technol. 2018;12:771–9. doi: 10.1177/1932296818785622
14. Wollert KC, Kempf T, Giannitsis E, Bertsch T, Braun SL, Maier H, et al. An automated assay for growth differentiation factor 15. J Appl Lab Med. 2017;1:510–21. doi: 10.1373/jalm.2016.022376
15. White IR, Royston P, Wood AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med. 2011;30:377–99. doi: 10.1002/sim.4067
16. Rubin DB. Multiple imputation after 18+ years. J Am Stat Assoc. 1996;91:473. doi: 10.2307/2291635
17. Lind L, Wallentin L, Kempf T, Tapken H, Quint A, Lindahl B, et al. Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction and disease in the elderly: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eur Heart J. 2009;30:2346–53. doi: 10.1093/eurheartj/ehp261
18. Kempf T, von Haehling S, Peter T, Allhoff T, Cicoira M, Doehner W, et al. Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure. J Am Coll Cardiol. 2007;50:1054–60. doi: 10.1016/j.jacc.2007.04.091
19. Welsh P, Kimenai DM, Marioni RE, Hayward C, Campbell A, Porteous D, et al. Reference ranges for GDF-15, and risk factors associated with GDF-15, in a large general population cohort. Clin Chem Lab Med. 2022;60:1820–9. doi: 10.1515/cclm-2022-0135
20. Wallentin L, Hijazi Z, Andersson U, Alexander JH, De Caterina R, Hanna M, et al. Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation. Circulation. 2014;130:1847–58. doi: 10.1161/CIRCULATIONAHA.114.011204
21. Bao X, Borné Y, Muhammad IF, Nilsson J, Lind L, Melander O, et al. Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus: the Malmö Diet and Cancer–Cardiovascular Cohort. Diabetologia. 2019;62:78–86. doi: 10.1007/s00125-018-4751-7
22. Eddy AC, Trask AJ. Growth differentiation factor-15 and its role in diabetes and cardiovascular disease. Cytokine Growth Factor Rev. 2021;57:11–18. doi: 10.1016/j.cytogfr.2020.11.002
23. Gerstein HC, Pare G, Hess S, Ford RJ, Sjaarda J, Raman K, et al. Growth differentiation factor 15 as a novel biomarker for metformin. Diabetes Care. 2017;40:280–3. doi: 10.2337/dc16-1682
24. Coll AP, Chen M, Taskar P, Rimmington D, Patel S, Tadross JA, et al. GDF15 mediates the effects of metformin on body weight and energy balance. Nature. 2020;578:444–48. doi: 10.1038/s41586-019-1911-y
25. Li J, Yang L, Qin W, Zhang G, Yuan J, Wang F. Adaptive induction of growth differentiation factor 15 attenuates endothelial cell apoptosis in response to high glucose stimulus. PLoS One. 2013;8:e65549. doi: 10.1371/journal.pone.0065549
26. Poznyak A V., Nikiforov NG, Markin AM, Kashirskikh DA, Myasoedova VA, Gerasimova E V., et al. Overview of OxLDL and its impact on cardiovascular health: focus on atherosclerosis. Front Pharmacol. 2021;11: 613780. doi: 10.3389/fphar.2020.613780
27. Schlittenhardt D, Schober A, Strelau J, Bonaterra GA, Schmiedt W, Unsicker K, et al. Involvement of growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in oxLDL-induced apoptosis of human macrophages in vitro and in arteriosclerotic lesions. Cell Tissue Res. 2004;318:325–33. doi: 10.1007/s00441-004-0986-3
28. Liu Y, Coresh J, Eustace JA, Longenecker JC, Jaar B, Fink NE, et al. Association between cholesterol level and mortality in dialysis patients. JAMA. 2004;291:451. doi: 10.1001/jama.291.4.451
29. Witte KKA, Clark AL. Nutritional abnormalities contributing to cachexia in chronic illness. Int J Cardiol. 2002;85:23–31. doi: 10.1016/S0167-5273(02)00231-0
30. Ahmed DS, Isnard S, Lin J, Routy B, Routy J-P. GDF15/GFRAL pathway as a metabolic signature for cachexia in patients with cancer. J Cancer. 2021;12:1125–32. doi: 10.7150/jca.50376
31. Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med. 1999;340:115–26. doi: 10.1056/NEJM199901143400207
32. Kim Y, Noren Hooten N, Evans MK. CRP stimulates GDF15 expression in endothelial cells through p53. Mediators Inflamm. 2018;2018:1–9. doi: 10.1155/2018/8278039
33. Gohar A, Gonçalves I, Vrijenhoek J, Haitjema S, van Koeverden I, Nilsson J, et al. Circulating GDF-15 levels predict future secondary manifestations of cardiovascular disease explicitly in women but not men with atherosclerosis. Int J Cardiol. 2017;241:430–6. doi: 10.1016/j.ijcard.2017.03.101
34. Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY, et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily. Proc Natl Acad Sci. 1997;94:11514–9. doi: 10.1073/pnas.94.21.11514
35. Valdivielso JM, Rodríguez-Puyol D, Pascual J, Barrios C, Bermúdez-López M, Sánchez-Niño MD, et al. Atherosclerosis in chronic kidney disease. Arterioscler Thromb Vasc Biol. 2019;39:1938–66. doi: 10.1161/ATVBAHA.119.312705
36. Lajer M, Jorsal A, Tarnow L, Parving H-H, Rossing P. Plasma growth differentiation factor-15 independently predicts all-cause and cardiovascular mortality as well as deterioration of kidney function in type 1 diabetic patients with nephropathy. Diabetes Care. 2010;33:1567–72. doi: 10.2337/dc09-2174
37. Ho JE, Hwang S-J, Wollert KC, Larson MG, Cheng S, Kempf T, et al. Biomarkers of cardiovascular stress and incident chronic kidney disease. Clin Chem. 2013;59:1613–20. doi: 10.1373/clinchem.2013.205716
38. Akchurin OM, Kaskel F. Update on inflammation in chronic kidney disease. Blood Purif. 2015;39:84–92. doi: 10.1159/000368940
39. Doerstling S, Hedberg P, Öhrvik J, Leppert J, Henriksen E. Growth differentiation factor 15 in a community-based sample: age-dependent reference limits and prognostic impact. Upsala J Med Sci. 2018;123:86–93. doi: 10.1080/03009734.2018.1460427
40. Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease. J Am Coll Cardiol. 2004;43:1731–7. doi: 10.1016/j.jacc.2003.12.047
41. Kraus WE, Powell KE, Haskell WL, Janz KF, Campbell WW, Jakicic JM, et al. Physical activity, all-cause and cardiovascular mortality, and cardiovascular disease. Med Sci Sports Exerc. 2019;51:1270–81. doi: 10.1249/MSS.0000000000001939
42. Enarsson M, Feldreich T, Byberg L, Nowak C, Lind L, Ärnlöv J. Association between cardiorespiratory fitness and circulating proteins in 50-year-old Swedish men and women: a cross-sectional study. Sports Med Open. 2021;7:52. doi: 10.1186/s40798-021-00343-5
43. Bonithon-Kopp C, Touboul P-J, Berr C, Leroux C, Mainard F, Courbon D, et al. Relation of intima-media thickness to atherosclerotic plaques in carotid arteries. Arterioscler Thromb Vasc Biol. 1996;16:310–6. doi: 10.1161/01.ATV.16.2.310
44. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness. Circulation. 2007;115:459–67. doi: 10.1161/CIRCULATIONAHA.106.628875
45. O’Hare AM, Katz R, Shlipak MG, Cushman M, Newman AB. Mortality and cardiovascular risk across the ankle-arm index spectrum. Circulation. 2006;113:388–93. doi: 10.1161/CIRCULATIONAHA.105.570903
46. de Jager SCA, Bermúdez B, Bot I, Koenen RR, Bot M, Kavelaars A, et al. Growth differentiation factor 15 deficiency protects against atherosclerosis by attenuating CCR2-mediated macrophage chemotaxis. J Exp Med. 2011;208:217–25. doi: 10.1084/jem.20100370
47. Wang TJ, Wollert KC, Larson MG, Coglianese E, McCabe EL, Cheng S, et al. Prognostic utility of novel biomarkers of cardiovascular stress. Circulation. 2012;126:1596–604. doi: 10.1161/CIRCULATIONAHA.112.129437
48. Kempf T, Horn-Wichmann R, Brabant G, Peter T, Allhoff T, Klein G, et al. Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Clin Chem. 2007;53:284–91. doi: 10.1373/clinchem.2006.076828
49. Unsicker K, Spittau B, Krieglstein K. The multiple facets of the TGF-β family cytokine growth/differentiation factor-15/macrophage inhibitory cytokine-1. Cytokine Growth Factor Rev. 2013;24:373–84. doi: 10.1016/j.cytogfr.2013.05.003
2. Wollert KC, Kempf T, Peter T, Olofsson S, James S, Johnston N, et al. Prognostic value of growth-differentiation factor-15 in patients with non–ST-elevation acute coronary syndrome. Circulation. 2007;115:962–71. doi: 10.1161/CIRCULATIONAHA.106.650846
3. Skau E, Henriksen E, Wagner P, Hedberg P, Siegbahn A, Leppert J. GDF-15 and TRAIL-R2 are powerful predictors of long-term mortality in patients with acute myocardial infarction. Eur J Prev Cardiol. 2017;24:1576–83. doi: 10.1177/2047487317725017
4. Skau E, Henriksen E, Leppert J, Wagner P, Ärnlöv J, Hedberg P. Targeted multiplex proteomics for prediction of all-cause mortality during long-term follow-up in outpatients with peripheral arterial disease. Atherosclerosis. 2020;311:143–9. doi: 10.1016/j.atherosclerosis.2020.06.015
5. Wallentin L, Zethelius B, Berglund L, Eggers KM, Lind L, Lindahl B, et al. GDF-15 for prognostication of cardiovascular and cancer morbidity and mortality in men. PLoS One. 2013;8:e78797. doi: 10.1371/journal.pone.0078797
6. Wang J, Wei L, Yang X, Zhong J. Roles of growth differentiation factor 15 in atherosclerosis and coronary artery disease. J Am Heart Assoc. 2019;8:e012826. doi: 10.1161/JAHA.119.012826
7. De Haan JJ, Haitjema S, den Ruijter HM, Pasterkamp G, de Borst GJ, Teraa M, et al. Growth differentiation factor 15 is associated with major amputation and mortality in patients with peripheral artery disease. J Am Heart Assoc. 2017;6:e006225. doi: 10.1161/JAHA.117.006225
8. Hedberg P, Hammar C, Selmeryd J, Viklund J, Leppert J, Hellberg A, et al. Left ventricular systolic dysfunction in outpatients with peripheral atherosclerotic vascular disease: prevalence and association with location of arterial disease. Eur J Heart Fail. 2014;16:625–32. doi: 10.1002/ejhf.95
9. Vermeersch SJ, Rietzschel ER, De Buyzere ML, Van Bortel LM, D’Asseler Y, Gillebert TC, et al. Validation of a new automated IMT measurement algorithm. J Hum Hypertens. 2007;21:976–8. doi: 10.1038/sj.jhh.1002251
10. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16:233–71. doi: 10.1093/ehjci/jev014
11. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12. doi: 10.7326/0003-4819-150-9-200905050-00006
12. Hoelzel W, Weykamp C, Jeppsson J-O, Miedema K, Barr JR, Goodall I, et al. IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study. Clin Chem. 2004;50:166–74. doi: 10.1373/clinchem.2003.024802
13. Nordin G. Accuracy of HbA1c as monitored by external quality assessment and compared with patient mean values. J Diabetes Sci Technol. 2018;12:771–9. doi: 10.1177/1932296818785622
14. Wollert KC, Kempf T, Giannitsis E, Bertsch T, Braun SL, Maier H, et al. An automated assay for growth differentiation factor 15. J Appl Lab Med. 2017;1:510–21. doi: 10.1373/jalm.2016.022376
15. White IR, Royston P, Wood AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med. 2011;30:377–99. doi: 10.1002/sim.4067
16. Rubin DB. Multiple imputation after 18+ years. J Am Stat Assoc. 1996;91:473. doi: 10.2307/2291635
17. Lind L, Wallentin L, Kempf T, Tapken H, Quint A, Lindahl B, et al. Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction and disease in the elderly: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eur Heart J. 2009;30:2346–53. doi: 10.1093/eurheartj/ehp261
18. Kempf T, von Haehling S, Peter T, Allhoff T, Cicoira M, Doehner W, et al. Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure. J Am Coll Cardiol. 2007;50:1054–60. doi: 10.1016/j.jacc.2007.04.091
19. Welsh P, Kimenai DM, Marioni RE, Hayward C, Campbell A, Porteous D, et al. Reference ranges for GDF-15, and risk factors associated with GDF-15, in a large general population cohort. Clin Chem Lab Med. 2022;60:1820–9. doi: 10.1515/cclm-2022-0135
20. Wallentin L, Hijazi Z, Andersson U, Alexander JH, De Caterina R, Hanna M, et al. Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation. Circulation. 2014;130:1847–58. doi: 10.1161/CIRCULATIONAHA.114.011204
21. Bao X, Borné Y, Muhammad IF, Nilsson J, Lind L, Melander O, et al. Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus: the Malmö Diet and Cancer–Cardiovascular Cohort. Diabetologia. 2019;62:78–86. doi: 10.1007/s00125-018-4751-7
22. Eddy AC, Trask AJ. Growth differentiation factor-15 and its role in diabetes and cardiovascular disease. Cytokine Growth Factor Rev. 2021;57:11–18. doi: 10.1016/j.cytogfr.2020.11.002
23. Gerstein HC, Pare G, Hess S, Ford RJ, Sjaarda J, Raman K, et al. Growth differentiation factor 15 as a novel biomarker for metformin. Diabetes Care. 2017;40:280–3. doi: 10.2337/dc16-1682
24. Coll AP, Chen M, Taskar P, Rimmington D, Patel S, Tadross JA, et al. GDF15 mediates the effects of metformin on body weight and energy balance. Nature. 2020;578:444–48. doi: 10.1038/s41586-019-1911-y
25. Li J, Yang L, Qin W, Zhang G, Yuan J, Wang F. Adaptive induction of growth differentiation factor 15 attenuates endothelial cell apoptosis in response to high glucose stimulus. PLoS One. 2013;8:e65549. doi: 10.1371/journal.pone.0065549
26. Poznyak A V., Nikiforov NG, Markin AM, Kashirskikh DA, Myasoedova VA, Gerasimova E V., et al. Overview of OxLDL and its impact on cardiovascular health: focus on atherosclerosis. Front Pharmacol. 2021;11: 613780. doi: 10.3389/fphar.2020.613780
27. Schlittenhardt D, Schober A, Strelau J, Bonaterra GA, Schmiedt W, Unsicker K, et al. Involvement of growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in oxLDL-induced apoptosis of human macrophages in vitro and in arteriosclerotic lesions. Cell Tissue Res. 2004;318:325–33. doi: 10.1007/s00441-004-0986-3
28. Liu Y, Coresh J, Eustace JA, Longenecker JC, Jaar B, Fink NE, et al. Association between cholesterol level and mortality in dialysis patients. JAMA. 2004;291:451. doi: 10.1001/jama.291.4.451
29. Witte KKA, Clark AL. Nutritional abnormalities contributing to cachexia in chronic illness. Int J Cardiol. 2002;85:23–31. doi: 10.1016/S0167-5273(02)00231-0
30. Ahmed DS, Isnard S, Lin J, Routy B, Routy J-P. GDF15/GFRAL pathway as a metabolic signature for cachexia in patients with cancer. J Cancer. 2021;12:1125–32. doi: 10.7150/jca.50376
31. Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med. 1999;340:115–26. doi: 10.1056/NEJM199901143400207
32. Kim Y, Noren Hooten N, Evans MK. CRP stimulates GDF15 expression in endothelial cells through p53. Mediators Inflamm. 2018;2018:1–9. doi: 10.1155/2018/8278039
33. Gohar A, Gonçalves I, Vrijenhoek J, Haitjema S, van Koeverden I, Nilsson J, et al. Circulating GDF-15 levels predict future secondary manifestations of cardiovascular disease explicitly in women but not men with atherosclerosis. Int J Cardiol. 2017;241:430–6. doi: 10.1016/j.ijcard.2017.03.101
34. Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY, et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily. Proc Natl Acad Sci. 1997;94:11514–9. doi: 10.1073/pnas.94.21.11514
35. Valdivielso JM, Rodríguez-Puyol D, Pascual J, Barrios C, Bermúdez-López M, Sánchez-Niño MD, et al. Atherosclerosis in chronic kidney disease. Arterioscler Thromb Vasc Biol. 2019;39:1938–66. doi: 10.1161/ATVBAHA.119.312705
36. Lajer M, Jorsal A, Tarnow L, Parving H-H, Rossing P. Plasma growth differentiation factor-15 independently predicts all-cause and cardiovascular mortality as well as deterioration of kidney function in type 1 diabetic patients with nephropathy. Diabetes Care. 2010;33:1567–72. doi: 10.2337/dc09-2174
37. Ho JE, Hwang S-J, Wollert KC, Larson MG, Cheng S, Kempf T, et al. Biomarkers of cardiovascular stress and incident chronic kidney disease. Clin Chem. 2013;59:1613–20. doi: 10.1373/clinchem.2013.205716
38. Akchurin OM, Kaskel F. Update on inflammation in chronic kidney disease. Blood Purif. 2015;39:84–92. doi: 10.1159/000368940
39. Doerstling S, Hedberg P, Öhrvik J, Leppert J, Henriksen E. Growth differentiation factor 15 in a community-based sample: age-dependent reference limits and prognostic impact. Upsala J Med Sci. 2018;123:86–93. doi: 10.1080/03009734.2018.1460427
40. Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease. J Am Coll Cardiol. 2004;43:1731–7. doi: 10.1016/j.jacc.2003.12.047
41. Kraus WE, Powell KE, Haskell WL, Janz KF, Campbell WW, Jakicic JM, et al. Physical activity, all-cause and cardiovascular mortality, and cardiovascular disease. Med Sci Sports Exerc. 2019;51:1270–81. doi: 10.1249/MSS.0000000000001939
42. Enarsson M, Feldreich T, Byberg L, Nowak C, Lind L, Ärnlöv J. Association between cardiorespiratory fitness and circulating proteins in 50-year-old Swedish men and women: a cross-sectional study. Sports Med Open. 2021;7:52. doi: 10.1186/s40798-021-00343-5
43. Bonithon-Kopp C, Touboul P-J, Berr C, Leroux C, Mainard F, Courbon D, et al. Relation of intima-media thickness to atherosclerotic plaques in carotid arteries. Arterioscler Thromb Vasc Biol. 1996;16:310–6. doi: 10.1161/01.ATV.16.2.310
44. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness. Circulation. 2007;115:459–67. doi: 10.1161/CIRCULATIONAHA.106.628875
45. O’Hare AM, Katz R, Shlipak MG, Cushman M, Newman AB. Mortality and cardiovascular risk across the ankle-arm index spectrum. Circulation. 2006;113:388–93. doi: 10.1161/CIRCULATIONAHA.105.570903
46. de Jager SCA, Bermúdez B, Bot I, Koenen RR, Bot M, Kavelaars A, et al. Growth differentiation factor 15 deficiency protects against atherosclerosis by attenuating CCR2-mediated macrophage chemotaxis. J Exp Med. 2011;208:217–25. doi: 10.1084/jem.20100370
47. Wang TJ, Wollert KC, Larson MG, Coglianese E, McCabe EL, Cheng S, et al. Prognostic utility of novel biomarkers of cardiovascular stress. Circulation. 2012;126:1596–604. doi: 10.1161/CIRCULATIONAHA.112.129437
48. Kempf T, Horn-Wichmann R, Brabant G, Peter T, Allhoff T, Klein G, et al. Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Clin Chem. 2007;53:284–91. doi: 10.1373/clinchem.2006.076828
49. Unsicker K, Spittau B, Krieglstein K. The multiple facets of the TGF-β family cytokine growth/differentiation factor-15/macrophage inhibitory cytokine-1. Cytokine Growth Factor Rev. 2013;24:373–84. doi: 10.1016/j.cytogfr.2013.05.003
Published
2024-12-27
How to Cite
Skau E., Wagner P., Leppert J., Ärnlöv J., & Hedberg P. (2024). Determinants of growth differentiation factor 15 plasma levels in outpatients with peripheral arterial disease. Upsala Journal of Medical Sciences, 129. https://doi.org/10.48101/ujms.v129.11001
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