Impact of a high-fat meal on assessment of clopidogrel-induced platelet inhibition in healthy subjects.

BACKGROUND: Ideal conditions for platelet reactivity testing are critical for optimal selection of a P2Y12 inhibitor. Data are inconsistent regarding the impact of high-fat meals on test assessment. METHODS: Participants included 12 healthy subjects not taking antiplatelet drugs after a 12-hour fast. After baseline assessment, subjects were given a 600 mg dose of clopidogrel. Four hours later, maximum platelet inhibition was tested in the fasting state by light transmission aggregometry (LTA), VerifyNow P2Y12, vasodilator-stimulated phosphoprotein (VASP), and whole blood aggregometry (WBA). Subjects were then provided a high-fat meal, and platelet function was evaluated two hours later. Change in measured platelet aggregation by LTA was the primary endpoint of the study. The Wilcoxon Rank Sum test was used to compare the change in platelet reactivity between fasting and non-fasting conditions. The Spearman rho (ρ) correlation coefficient was used to evaluate the association between fasting platelet reactivity and the change following a high-fat meal. RESULTS: No significant change occurred in maximal light transmission, as assessed by LTA with 5 μM ADP (p = 0.15) and with 20 μM ADP (p = 0.07). There was a significant change in the area under the curve with 5 μM ADP (p = 0.03) but not with 20 μM ADP (p = 0.18). Although there was no significant change with the VerifyNow P2Y12 assay (p = 0.16), the change was correlated with the initial fasting value (Spearman\u27s rho p = 0.008). The VASP assay and WBA varied minimally. CONCLUSION: The high-fat meal did not significantly alter platelet function assessment of commonly used platelet function tests. Greater intra-subject variability existed for the optically-dependent compared with non-optically dependent tests. TRIAL REGISTRATION: NCT01307657

Hemostatic Assessment of Patients Undergoing lntraaortic Balloon Pump Therapy

Patients undergoing intraaortic balloon pump (IABP) therapy are at risk for developing coagulopathies due to the adverse effects of prolonged exposure of the synthetic surface of the polyurethane balloon to blood components. Hemorrhagic risk has been attributed to a number of factors including thrombocytopenia, vascular injury, and/or platelet degranulation which increase the potential of receiving autogeneic blood transfusions. The present study is a prospective evaluation of coagulation using a viscoelastic monitor (Thrombelastograph- TEG) that measures functional aspects of clot development and stabilization in patients being treated with IABP therapy. Following Institutional Review Board approval, six patients undergoing IABP therapy for hemodynamic instability were enrolled in this study. Blood samples were taken prior to balloon insertion, at 8, 16, 24, 48, 72, and 96 hours on IABP therapy, and 24 hours following the removal of the balloon when applicable. Samples were incubated with heparinase to degrade heparin and TEG profiles were subsequently determined in duplicate. Measured parameters on the TEG included Rtime, K-time, maximum amplitude, alpha angle, and lysis at 30 and 60 minutes with calculation of the TEG index. Mortality was 33% following IABP discontinuation. Transfusion of packed red blood cells occurred in 50% of the patients during their balloon pump therapy. Patients demonstrated a significant deviance in fibrinolytic potential from pre-IABP lysis (1.6% ± 1.8) at both 24 hours (18.8% ± 22.9) and 48 hours (21.9% ± 28.5) of therapy (p<0.05) which returned to baseline shortly after balloon removal. Activation of coagulation factors appeared evident by a steadily increasing alpha angle from pre-IABP data (31.1 ± 9.2) throughout the duration of therapy and 24 hour recovery (53 ± 14; p<.005), and by a steadily trending increase in the TEG index pre-IABP (.251 ± 1.4) to post-IABP (2.6 ± 1.7; p<0.05). The results indicate that IABP therapy induces an increase in fibrinolytic potential at 24 to 48 hours of balloon pump therapy with a paradoxical trend toward increased coagulability, potentially predisposing the patient to hemorrhagic risk

Unique antibody responses to malondialdehyde-acetaldehyde (MAA)-protein adducts predict coronary artery disease.

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease

MAA-Adduction and its Implications.

<p>MAA-Adduction and its Implications.</p

Serum Concentrations of IgM, IgG and IgA Antibodies 24 Hours post-AMI.

<p>A subgroup of patients (n = 10) were evaluated 24 hours post-AMI for the presence of circulating IgM, IgG and IgA anti-MAA antibody levels (Figure 3A) and the total serum IgM, IgG, and IgA concentrations (Figure 3B). Results are expressed as relative mg/L or g/L of Human IgM, IgG, and IgA using a standard curve. *P<0.01 significantly different comparing AMI and 24 hours post-AMI.</p

Light and Confocal Microscopy of MAA in the Culprit AMI Aspirated Tissue.

<p>Panel A and B illustrates a Masson’s Trichrome staining at low (20X) and high magnification (80X) with panel B as the inset box of panel A. Panel C is the rabbit IgG isotype control stain. Panel D illustrates the rabbit anti-MAA staining with Cy3 reporter (80X). Note the absence of collagen or fibrosis and the presence of cholesterol clefts in Panel A which are typical of an atheroma. Also note the localization of MAA in Panel D (white arrows) to cellular vacuolization and necrosis as noted by the arrows on the Masson’s Trichrome in Panel B (black arrows).</p

Relative Serum Concentrations of anti-MDA LDL and anti-MAA LDL IgG Antibody are not Different in Individuals with Coronary Artery Disease (CAD) and in Individuals who Present with an Acute Myocardial Infarction (AMI).

<p>CAD patients were grouped in the following categories; control patients (n = 82), patients with chest pain and CAD (Non-Obstructive CAD, n = 40), patients presenting with AMI (n = 42), and patients with significant Multi-Vessel Obstructive CAD requiring coronary bypass grafting (n = 72). Serum anti-MDA LDL (Figure 2A) and anti-MAA LDL (Figure 2B). There is no significant difference in serum antibody levels when comparing all study groups (p>0.5).</p

Relative Serum Concentrations of anti-MAA IgM, IgG and IgA Antibodies are Increased in Individuals with Coronary Artery Disease (CAD) and in Individuals who Present with an Acute Myocardial Infarction (AMI).

<p>CAD patients were grouped in the following categories; control patients (n = 82), patients with chest pain and CAD (Non-Obstructive CAD, n = 40), patients presenting with AMI (n = 42), and patients with significant Multi-Vessel Obstructive CAD requiring coronary bypass grafting (n = 72). Serum anti-MAA antibodies were evaluated for the isotypes IgM (Figure 1A), IgG (Figure 1B), and IgA (Figure 1C). *P<0.001 significantly increased compared to controls. #P<0.03 significantly increased compared to Non-Obstructive CAD. $P<0.003 significantly increased compared to Multi-Vessel Obstructive CAD.</p

Patient demographics.

a<p>P<0.01 significantly increased compared to control.</p>b<p>P<0.05 significantly increase compared to Non-Obstructive and Acute AMI.</p>c<p>P<0.001 significantly increased compared to control.</p>d<p>P<0.01 significantly increased compared to control.</p>e<p>P<0.001 significantly increased compared to control, Non-Obstructive CAD, and Obstructive Multi-Vessel CAD.</p>f<p>P = 0.03 significantly decreased compared to control, Non-Obstructive CAD, and acute.</p>g<p>P<0.02 significantly decreased compared to control, acute.</p><p>*#Control subjects reported they were healthy with no medical problems or medications.</p><p>Patient demographics.</p