Plasma Protein Oxidation as a Determinant of Impaired Fibrinolysis in Type 2 Diabetes

Agata H. Bryk; Malgorzata Konieczynska; Pawel Rostoff; Elzbieta Broniatowska; Jerzy Hohendorff; Maciej T. Malecki; Anetta Undas

doi:10.1055/s-0038-1676609

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2019; 119(02): 213-222
DOI: 10.1055/s-0038-1676609

Coagulation and Fibrinolysis

Georg Thieme Verlag KG Stuttgart · New York

Plasma Protein Oxidation as a Determinant of Impaired Fibrinolysis in Type 2 Diabetes

Agata H. Bryk

¹Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland

²Department for Diagnosis, John Paul II Hospital, Krakow, Poland

,

Malgorzata Konieczynska

²Department for Diagnosis, John Paul II Hospital, Krakow, Poland

,

Pawel Rostoff

¹Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland

³Department of Coronary Disease and Heart Failure, John Paul II Hospital, Krakow, Poland

,

Elzbieta Broniatowska

⁴Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Poland

,

Jerzy Hohendorff

⁵Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland

⁶Department of Metabolic Diseases, University Hospital, Krakow, Poland

,

Maciej T. Malecki

⁵Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland

⁶Department of Metabolic Diseases, University Hospital, Krakow, Poland

,

Anetta Undas

¹Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland

⁷Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland

⁸Faculty of Medicine and Health Sciences, Jan Kochanowski University, Kielce, Poland

› Institutsangaben

Abstract

Objective We investigated clinical and laboratory determinants of plasma protein oxidation and its associations with clot fibrinolysis in type 2 diabetes patients.

Materials and Methods Our cross-sectional study consisted of 246 type 2 diabetic patients, 143 (58%) with concomitant cardiovascular disease (CVD), including 41 (17%) with previous myocardial infarction (MI). We measured total protein carbonylation (PC), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) along with clot lysis time (CLT) and clot permeation (K_s ), fibrinogen, plasminogen, α-2-antiplasmin, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI) and thrombomodulin.

Results Total PC correlated positively, while TAC correlated inversely with glycated haemoglobin and diabetes duration (all p < 0.05). Diabetic patients with CVD had higher total PC, TBARS and lower TAC compared with the remainder (all p < 0.001). Among correlations of total PC with K_s , PAI-1, thrombomodulin and TAFI, the strongest was with CLT (r = 0.687, all p < 0.01). High total PC, defined as ≥ 3.45 nmol/mg, was predicted by time since diabetes diagnosis ≥ 5 years (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.36–6.63) and previous MI (OR: 11.31, 95% CI: 4.37–29.32). After adjustment for potential confounders, total PC accounted for 34.9% of the total variance in CLT. Total PC at a cut-off of 3.44 nmol/mg showed high discriminatory power for identifying patients with prolonged CLT (area under the curve: 0.845, 95% CI: 0.792–0.898, p < 0.001).

Conclusion Elevated plasma PC, largely driven by a long history of diabetes and concomitant CVD, is an important determinant of hypofibrinolysis in type 2 diabetes.

Keywords

type 2 diabetes - fibrinolysis - oxidation - carbonylation - cardiovascular disease

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Referenzen

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