TY - JOUR
TI - 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
AU - Ikonomidis, I.
AU - Katogiannis, K.
AU - Kyriakou, E.
AU - Taichert, M.
AU - Katsimaglis, G.
AU - Tsoumani, M.
AU - Andreadou, I.
AU - Maratou, E.
AU - Lambadiari, V.
AU - Kousathana, F.
AU - Papadopoulou, A.
AU - Varlamos, C.
AU - Plotas, P.
AU - Parissis, J.
AU - Stamatelopoulos, K.
AU - Alexopoulos, D.
AU - Dimitriadis, G.
AU - Tsantes, A.E.
JO - Journal of Thrombosis and Thrombolysis
PY - 2020
VL - 49
TODO - 3
SP - 365-376
PB - Springer-Verlag
SN - 0929-5305
TODO - 10.1007/s11239-020-02060-4
TODO - 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
TODO - 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.
ER -