Predictive value of calculated plasma osmolality and atherogenic index of plasma for chronic limb-threatening ischemia in lower extremity artery disease

Objectives: Chronic limb-threatening ischemia (CLTI) is the end-stage form of lower extremity artery disease (LEAD) whose main reason is atherosclerosis. Plasma osmolality (PO) and plasma lipid levels affect the development and progression of atherosclerosis directly. The purpose of this study was to investigate the predictive effect of PO and atherogenic index of plasma (AIP) for the development of CLTI. Methods: A total of 324 patients who were diagnosed with LEAD were analyzed retrospectively. The clinical stage of the disease was evaluated according to the Rutherford classification, and patients without CLTI were defined as “Group 1” and patients with CLTI as “Group 2”. Results: There were 248 patients (mean age 64.44 ± 9.05 years and 73.4% male) in Group 1, and 76 patients (mean age 66.62 ± 8.22 years and 76.3% male) in Group 2. In the multivariate regression analysis, CAD, PO, CRP and AIP were defined as independent predictive factors for the development of CLTI (p = 0.015, p < 0.001, p = 0.007, p < 0.001; respectively). ROC curve analysis showed that, PO cut-off value for CLTI development was 293.28 mOsm/kg (AUC: 0.821, p < 0.001) with 75% sensitivity and 74.2% specificity, and AIP cut-off value was 0.23 (AUC: 0.740, p < 0.001) with 67.1% sensitivity and 68.5% specificity. Conclusions: The PO and AIP values in LEAD patients may be used as the new biomarkers of atherosclerosis progression, and therefore as predictive factors for the development of CLTI.

___

  • 1. Conte MS, Bradbury AW, Kolh P, White JV, Dick F, Fitridge R, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. J Vasc Surg. 2019;69(6S):3S-125S.e40. Erratum in: J Vasc Surg 2019;70:662.
  • 2. Yavuz Ş, Özsin KK, Sanrı US, Toktaş F. Peripheral artery disease in women. Eur Res J 2020;6:178-86.
  • 3. Aboyans V, Ricco JB, Bartelink MEL, Björck M, Brodmann M, Cohnert T, et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. Eur Heart J 2018;39:763-816.
  • 4. Rasouli M, Kiasari AM, Arab S. Indicators of dehydration and haemoconcentration are associated with the prevalence and severity of coronary artery disease. Clin Exp Pharmacol Physiol 2008;35:889-94.
  • 5. Kanat S, Demirci H, Üstündağ Y, Can FE, Aydın U, Ocakoğlu G. Effect of serum osmolality on 6-year survival rates in patients with acute myocardial infarction. Turk J Clin Lab 2020;1:24-32.
  • 6. Beckman JA, Paneni F, Cosentino F, Creager MA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II. Eur Heart J 2013;34:2444-52.
  • 7. Bae MH, Kim JH, Jang SY, Park SH, Lee JH, Yang DH, et al. Hyponatremia at discharge as a predictor of 12-month clinical outcomes in hospital survivors after acute myocardial infarction. Heart Vessels 2017;32:126-133.
  • 8. Gary T, Pichler M, Schilcher G, Hafner F, Hackl G, Rief P, et al. Elevated blood urea nitrogen is associated with critical limb ischemia in peripheral arterial disease patients. Medicine (Baltimore) 2015;94:e948.
  • 9. Aday AW, Everett BM. Dyslipidemia profiles in patients with peripheral artery disease. Curr Cardiol Rep 2019;21:42.
  • 10. Murabito JM, Evans JC, Nieto K, Larson MG, Levy D, Wilson PW. Prevalence and clinical correlates of peripheral arterial disease in the Framingham Offspring Study. Am Heart J 2002;143:961-5.
  • 11. Shen S, Lu Y, Qi H, Li F, Shen Z, Wu L, et al. Association between ideal cardiovascular health and the atherogenic index of plasma. Medicine (Baltimore) 2016;95:e3866. Erratum in: Medicine (Baltimore) 2016;95:e5074.
  • 12. Crawford F, Welch K, Andras A, Chappell FM. Ankle brachial index for the diagnosis of lower limb peripheral arterial disease. Cochrane Database Syst Rev 2016;9:CD010680.
  • 13. Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997;26:517-38. Erratum in: J Vasc Surg 2001;33:805.
  • 14. Fazekas AS, Funk GC, Klobassa DS, Rüther H, Ziegler I, Zander R, et al. Evaluation of 36 formulas for calculating plasma osmolality. Intens Care Med 2013;39:302-8.
  • 15. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007;45 Suppl S:S5-67.
  • 16. Guetl K, Raggam RB, Muster V, Gressenberger P, Vujic J, Avian A, et al. The white blood cell count to mean platelet volume ratio for the prediction of chronic limb-threatening ischemia in lower extremity artery disease. J Clin Med 2019;8:1593.
  • 17. Teperman J, Carruthers D, Guo Y, Barnett MP, Harris AA, Sedlis SP, et al. Relationship between neutrophil-lymphocyte ratio and severity of lower extremity peripheral artery disease. Int J Cardiol 2017;228:201-4.
  • 18. Mathur RK. The role of hyperosmolal food in the development of atherosclerosis. Med Hypotheses 2005;64:579-81.
  • 19. Moriya J. Critical roles of inflammation in atherosclerosis. J Cardiol. 2019;73:22-7.
  • 20. Tatlisu MA, Kaya A, Keskin M, Uzman O, Borklu EB, Cinier G, et al. Can we use plasma hyperosmolality as a predictor of mortality for ST-segment elevation myocardial infarction? Coron Artery Dis 2017;28:70-6.
  • 21. Valdivielso JM, Rodríguez-Puyol D, Pascual J, Barrios C, Bermúdez-López M, Sánchez-Niño MD, et al. Atherosclerosis in chronic kidney disease: more, less, or just different? Arterioscler Thromb Vasc Biol 2019;39:1938-66.
  • 22. Martinez-Aguilar E, Orbe J, Fernández-Montero A, Fernández-Alonso S, Rodríguez JA, Fernández-Alonso L, et al. Reduced high-density lipoprotein cholesterol: A valuable, independent prognostic marker in peripheral arterial disease. J Vasc Surg 2017;66:1527-33.e1.
  • 23. Barter PJ, Nicholls S, Rye KA, Anantharamaiah GM, Navab M, Fogelman AM. Antiinflammatory properties of HDL. Circ Res 2004;95:764-72.
  • 24. Peng J, Luo F, Ruan G, Peng R, Li X. Hypertriglyceridemia and atherosclerosis. Lipids Health Dis 2017;16:233.
  • 25. Sayın S, Kutlu R, Koçak A. The relationship between atherogenic index of plasma and major risk factors of cardiovascular disease in obese and nonobese individuals. Eur Res J 2019;5:678-85.
  • 26. Onat A, Can G, Kaya H, Hergenç G. "Atherogenic index of plasma" (log10 triglyceride/high-density lipoprotein-cholesterol) predicts high blood pressure, diabetes, and vascular events. J Clin Lipidol 2010;4:89-98.
  • 27. Wu TT, Gao Y, Zheng YY, Ma YT, Xie X. Atherogenic index of plasma (AIP): a novel predictive indicator for the coronary artery disease in postmenopausal women. Lipids Health Dis 2018;17:197.
  • 28. Dobiásová M. [AIP--atherogenic index of plasma as a significant predictor of cardiovascular risk: from research to practice]. Vnitr Lek 2006;52:64-71. [Article in Czech]
  • 29. Swastini DA, Wiryanthini IAD, Ariastuti NLP, Muliantara A. Atherosclerosis prediction with high sensitivity C-reactive protein (hs-CRP) and related risk factor in patient with dyslipidemia. Open Access Maced J Med Sci 2019;7:3887-90.
  • 30. Barani J, Nilsson JA, Mattiasson I, Lindblad B, Gottsäter A. Inflammatory mediators are associated with 1-year mortality in critical limb ischemia. J Vasc Surg 2005;42:75-80.
  • 31. Hur DJ, Kizilgul M, Aung WW, Roussillon KC, Keeley EC. Frequency of coronary artery disease in patients undergoing peripheral artery disease surgery. Am J Cardiol 2012;110:736-40.
  • 32. Chen DC, Singh GD, Armstrong EJ, Waldo SW, Laird JR, Amsterdam EA. Long-term comparative outcomes of patients with peripheral artery disease with and without concomitant coronary artery disease. Am J Cardiol 2017;119:1146-52.
  • 33. Sigvant B, Lundin F, Wahlberg E. The risk of disease progression in peripheral arterial disease is higher than expected: a meta-analysis of mortality and disease progression in peripheral arterial disease. Eur J Vasc Endovasc Surg 2016;51:395-403.