@article{3121251,
    title = "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",
    author = "Ikonomidis, I. and Katogiannis, K. and Kyriakou, E. and Taichert, M. and Katsimaglis, G. and Tsoumani, M. and Andreadou, I. and Maratou, E. and Lambadiari, V. and Kousathana, F. and Papadopoulou, A. and Varlamos, C. and Plotas, P. and Parissis, J. and Stamatelopoulos, K. and Alexopoulos, D. and Dimitriadis, G. and Tsantes, A.E.",
    journal = "Journal of Thrombosis and Thrombolysis",
    year = "2020",
    volume = "49",
    number = "3",
    pages = "365-376",
    publisher = "Springer-Verlag",
    issn = "0929-5305",
    doi = "10.1007/s11239-020-02060-4",
    keywords = "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",
    abstract = "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."
}