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Background and aims Increased b-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) b-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 &amp;gt;48%,). At baseline, HPR was associated with b-amyloid &amp;gt;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, b-amyloid &amp;gt;51 pg/ml and MOTS-c&amp;lt;167 ng/ml were predictors of MACE (relative risk 3.1, 3.5 and 3.8 respectively, p&amp;lt;0.05) after adjusting for confounders and medication. There was significant interaction between HPR and b-amyloid or MOTS-c for the prediction of MACE (p&amp;lt;0.05). Patients with HPR and b-amyloid&amp;gt;51mg/dl or HPR and MOTS-c concentration&amp;lt;167 ng/ml had a 4-fold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p&amp;lt;0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD. Conclusions Increased b-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. Funding Acknowledgement Type of funding source: None

european heart journal

Beta-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