Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction.

Antiplatelet medication is standard of care in acute myocardial infarction (AMI). However, it may have obscured beneficial properties of the activated platelet secretome. We identify platelets as major source of a sphingosine-1-phosphate (S1P) burst during AMI, and find its magnitude to favorably associate with cardiovascular mortality and infarct size in STEMI patients over 12 months. Experimentally, administration of supernatant from activated platelets reduces infarct size in murine AMI, which is blunted in platelets deficient for S1P export (Mfsd2b) or production (Sphk1) and in mice deficient for cardiomyocyte S1P receptor 1 (S1P1). Our study reveals an exploitable therapeutic window in antiplatelet therapy in AMI as the GPIIb/IIIa antagonist tirofiban preserves S1P release and cardioprotection, whereas the P2Y12 antagonist cangrelor does not. Here, we report that platelet-mediated intrinsic cardioprotection is an exciting therapeutic paradigm reaching beyond AMI, the benefits of which may need to be considered in all antiplatelet therapies.

Platelet reactivity is higher in e-cigarette vaping as compared to traditional smoking.

INTRODUCTION: Vaping emerges as alternative to standard tobacco smoking. However, there is evidence for critical cardiovascular, gastrointestinal and respiratory side effects. Nevertheless, long-term vaping effects on thrombocyte reactivity have not been investigated. Therefore, we investigated the influence of vaping on thrombocyte reactivity in comparison to standard smoking and non-smoking. METHODS: Platelet function was measured by Multiplate Impedance Aggregometry as area under the curve (AUC). Smoking habits and characteristics were assessed by questionnaire. Results were analyzed using inverse probability of treatment weighting (IPTW) and conventional t-tests to test for robustness. RESULTS: After IPTW adjustment, participants in all groups were balanced by age, gender, body height and weight. Collagen-induced aggregation was higher in vapers compared to non-smokers (non-smokers 52.55 ± 23.97 vs. vapers 66.63 ± 18.96 AUC, p = 0.002) and to smokers (vapers vs. smokers 49.50 ± 26.05 AUC, p < 0.0001). ADP-induced aggregation in vapers was higher compared to non-smokers (non-smokers 33.16 ± 16.61 vs. vapers 45.27 ± 18.67 AUC, p = 0.001) and was numerically increased compared to smokers (vapers vs. smokers 40.09 ± 19.80 AUC, p = 0.08). These findings remained robust in t-test analysis. CONCLUSION: This study provides first evidence that vaping leads to enhanced platelet reactivity compared to standard smoking and non-smoking. This suggests health effects of vaping might be more severe than previously assumed. Whether this effect translates to clinical outcome with a higher incidence of major cardiovascular events, should be evaluated in large-scaled clinical studies.

Aspirin I.V. Loading during Elective Percutaneous Coronary Intervention.

Additional loading dose of acetylsalicylic acid (ASA) during percutaneous coronary interventions (PCIs) despite permanent oral ASA medication is frequently applicated. The impact on platelet reactivity and clinical events is not known. In this pilot study, we aimed to analyze high on-treatment platelet reactivity (HTPR) to aspirin in patients undergoing elective PCI. Platelet reactivity was measured using light-transmission aggregometry in 100 patients on permanent low-dose ASA medication undergoing elective PCI. Platelet reactivity measured by arachidonic acid-induced maximum of aggregation (MoA) in patients with versus without additional peri-procedural ASA loading (500 mg i.v.) was compared. HTPR was defined as MoA >20% for ASA. Major adverse cerebro- and cardiovascular events (MACCEs) and bleeding events were evaluated during hospital course. HTPR rate was similar in both groups (HTPR to ASA: loading vs. control 6% vs. 16%, odds ratio [OR] = 0.33, 95% confidence interval [CI] 0.08-1.35, p = 0.12). In-hospital MACCEs were not different between groups (MACCE: loading vs. control: 0 vs. 0 patient, OR = 1.32, 95% CI 0.03-67.95, p = 0.89). Thrombolysis in myocardial infarction minimal bleedings were numerically higher in patients without ASA loading dose. In this pharmacodynamic pilot study, additional ASA loading did not reduce HTPR to ASA. Furthermore, ASA loading did not increase in-hospital MACCE and bleeding complications.

Risk prediction of bleeding and MACCE by PRECISE-DAPT score post-PCI.

BACKGROUND: Guidelines recommend the PRECISE-DAPT (PD) score to adapt duration of dual antiplatelet therapy due to bleeding risk. However, there is first evidence that PD predicts mortality and ischemic events as well. METHODS: We investigated PD Score in 994 patients after percutaneous coronary intervention (PCI). PD was correlated with clinically frequently used scores. Major adverse cardiac and cerebrovascular events (MACCE) and Thrombolysis in Myocardial Infarction (TIMI) bleeding were assessed during one-year follow-up. RESULTS: 524 patients had PD < 25 and 470 patients PD ≥ 25 (47%). Rate of major and minor bleeding was higher in the PD ≥ 25 group (major bleeding: Hazard ratio [HR] 2.9, 95% confidence interval [Cl] 1.01-8.16, p = 0.049; minor bleeding: HR 3.94, 95% Cl 1.36-9.19, p = 0.0096). Rate of MACCE, death and myocardial infarction were higher as well (MACCE: HR 2.0, 95% Cl 1.52-2.71, p < 0.0001; death: HR 3.9, 95% Cl 2.12-5.68, p < 0.0001; MI: HR 2.1, 95% Cl 1.26-3.43, p = 0.0041). Rate of stroke/transient ischemic attack did not differ between groups. Discriminative potency to predict major and minor bleeding, MACCE, death and MI were high with nearly equal cut-off values calculated by Youden's index (YI) (major bleeding: Area under the curve [AUC] 0.66; p = 0.026; YI 32; minor bleeding: AUC 0.72; p = 0.001; YI 28; MACCE: AUC 0.62; p < 0.0001; YI 24). CONCLUSION: In our cohort, PD score predicted bleeding moderately in post-PCI patients. In this study, ischemic events were predicted as well. Adaption of antiplatelet therapy duration by PD score is accurate. Nevertheless, it should be well-balanced with patient-related risk for ischemic events.

Targeting the human microbiome and its metabolite TMAO in cardiovascular prevention and therapy.

The human gut microbiota is the most important active part of the intestinal micro-ecosystem. Lifestyle modification, drug intake and nutrition have an impact on the composition of the gut microbiota and its metabolites. This review focuses on the effects of changes in the gut microbiota as well as the important metabolite Trimethylamine-N-oxide (TMAO). Furthermore, relevant therapeutic options to target the human microbiome in patients with cardiovascular disease are presented.