Τίτλος:
β-Amyloid and mitochondrial-derived peptide-c are additive predictors of adverse outcome to high-on-treatment platelet reactivity in type 2 diabetics with revascularized coronary artery disease
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background and aims: Increased β-amyloid and decreased mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization. Patients and methods: In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: (a) maximum platelet aggregation to adenosine diphosphate (ADP) by light transmission aggregometry (LTAmax), (b) malondialdehyde (MDA), as oxidative stress marker, (c) MOTS-c, (d) β-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up. Results: Out of 121 patients, 32 showed HPR (LTAmax > 48%,). At baseline, HPR was associated with β-amyloid > 51 pg/ml (p = 0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, β-amyloid > 51 pg/ml and MOTS-c < 167 ng/ml were predictors of MACE (relative risk 3.1, 3.5 and 3.8 respectively, p < 0.05) after adjusting for confounders and medication. There was significant interaction between HPR and β-amyloid or MOTS-c for the prediction of MACE (p < 0.05). Patients with HPR and β-amyloid > 51 mg/dl or HPR and MOTS-c concentration < 167 ng/ml had a fourfold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p < 0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD. Conclusions: Increased β-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow-up. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT04027712. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Συγγραφείς:
Ikonomidis, I.
Katogiannis, K.
Kyriakou, E.
Taichert, M.
Katsimaglis, G.
Tsoumani, M.
Andreadou, I.
Maratou, E.
Lambadiari, V.
Kousathana, F.
Papadopoulou, A.
Varlamos, C.
Plotas, P.
Parissis, J.
Stamatelopoulos, K.
Alexopoulos, D.
Dimitriadis, G.
Tsantes, A.E.
Περιοδικό:
Journal of Thrombosis and Thrombolysis
Λέξεις-κλειδιά:
acetylsalicylic acid; adenosine diphosphate; amyloid beta protein; antidiabetic agent; beta adrenergic receptor blocking agent; calcium channel blocking agent; clopidogrel; dipeptidyl carboxypeptidase inhibitor; hemoglobin A1c; hydroxymethylglutaryl coenzyme A reductase inhibitor; insulin; malonaldehyde; mitochondrial derived peptide C; mitochondrial protein; oral antidiabetic agent; unclassified drug; amyloid beta protein; clopidogrel; malonaldehyde; mitochondrial protein; MOTS-c peptide, human, acute coronary syndrome; adverse outcome; aged; amyloid beta protein blood level; analytic method; Article; cohort analysis; controlled study; coronary artery disease; coronary artery recanalization; diagnostic test accuracy study; external validity; female; follow up; heart death; high risk patient; human; human cell; light transmission aggregometry; major clinical study; male; non insulin dependent diabetes mellitus; outcome assessment; oxidative stress; platelet reactivity; prediction; predictive value; priority journal; protein blood level; reference value; retrospective study; thrombocyte aggregation; validation study; blood; clinical trial; coronary artery disease; drug effect; heart muscle revascularization; middle aged; multicenter study; non insulin dependent diabetes mellitus; risk factor; thrombocyte; thrombocyte activation, Aged; Amyloid beta-Peptides; Blood Platelets; Clopidogrel; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Male; Malondialdehyde; Middle Aged; Mitochondrial Proteins; Myocardial Revascularization; Platelet Activation; Risk Factors
DOI:
10.1007/s11239-020-02060-4
