Characteristics of Young Women Presenting With Acute Myocardial Infarction: The Prospective, Multicenter, Observational Young Women Presenting Acute Myocardial Infarction in France Study.

BACKGROUND: The percentage of women <50 years of age hospitalized with myocardial infarction is increasing. We describe the clinical, morphological, and biological characteristics, as well as the clinical outcomes of this population. METHODS AND RESULTS: This prospective, observational study included consecutive women <50 years of age admitted for myocardial infarction at 30 centers in France (May 2017-June 2019). The primary outcome was the composite of net adverse clinical events: all-cause death, cardiovascular death, recurrent myocardial infarction, stent thrombosis, any stroke, or major bleeding occurring during hospitalization with a 12-month follow up. Three hundred fourteen women were included. The mean age was 43.0 (±5.7) years, 60.8% presented with ST-segment-elevation myocardial infarction, 75.5% were current smokers, 31.2% had a history of complicated pregnancy, and 55.1% reported recent emotional stress. Most (91.6%) women presented with typical chest pain. Of patients on an estrogen-containing contraceptive, 86.0% had at least 1 contraindication. Of patients with ST-segment-elevation myocardial infarction, 17.8% had myocardial infarction with nonobstructive coronary arteries and 14.6% had spontaneous coronary artery dissection, whereas 29.3% presented with multivessel vessel disease. During hospitalization, 11 net adverse clinical events occurred in 9 (2.8%) women, but no deaths or stent thromboses occurred. By 12 months, 14 net adverse clinical events occurred in 10 (3.2%) women; 2 (0.6%) died (from progressive cancer) and 25 (7.9%) had an ischemia-driven repeat percutaneous coronary intervention. CONCLUSIONS: Most young women with myocardial infarction reported typical chest pain and had modifiable cardiovascular risk factors. History of adverse pregnancy outcomes and prescription of combined oral contraceptive despite a contraindication were prevalent, emphasizing the need for comprehensive cardiological and gynecological evaluation and follow-up. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03073447.

Infliximab for the Treatment of Inflammatory Labyrinthitis: A Retrospective Cohort Study.

Inflammatory labyrinthitis is defined as a fluctuant vestibulo-cochlear syndrome associated with an impairment of the blood-labyrinthine barrier (BLB) on delayed FLAIR MRI sequences. Systemic and intratympanic corticosteroids are the gold standard treatment but their effect is frequently insufficient. The objective is here to determine whether infliximab could be of value in the treatment of bilateral inflammatory labyrinthitis. A retrospective monocentric study was conducted between January 2013 and December 2021. All patients included in the study were affected with a bilateral vestibulo-cochlear syndrome associated with bilateral blood-labyrinthine barrier impairment. Patients were administered infliximab at the dose of 5 mg/kg every 6 weeks for 6 months. Audiometry, MRI with delayed FLAIR sequences on the labyrinth, and corticosteroid doses still required were assessed both before and after treatment with infliximab was completed. Pure-tone average (PTA) was the primary outcome. The secondary outcomes were the speech recognition threshold (SRT), the Dizziness Handicap Inventory (DHI) score, and the corticosteroid (CS) dose. A total of nine patients including five men and four women were enrolled in the study. Thirteen ears were analyzed. After a 6-month period of treatment, the mean PTA (54 ± 24 db versus 66 ± 22 db; p = 0.027), SRT (54 ± 37 db versus 66 ± 32 db; p = 0.041) and DHI score (27 ± 15 versus 9 ± 2; p = 0.032) significantly improved. After the 6-month treatment period, the mean CS dose decreased from 38 ± 33 to 6 ± 5 mg/day (p = 0.003). We conclude that infliximab substantially improves the vestibulo-cochlear function in patients with bilateral inflammatory labyrinthitis and could be of value in corticosteroid-dependent cases.

C-reactive protein and D-dimer in cerebral vein thrombosis: Relation to clinical and imaging characteristics as well as outcomes in a French cohort study.

Introduction: Cerebral venous sinus thrombosis (CVST) is a rare disease with highly variable clinical presentation and outcomes. Clinical studies suggest a role of inflammation and coagulation in CVST outcomes. The aim of this study was to investigate the association of inflammation and hypercoagulability biomarkers with CVST clinical manifestations and prognosis. Methods: This prospective multicenter study was conducted from July 2011 to September 2016. Consecutive patients referred to 21 French stroke units and who had a diagnosis of symptomatic CVST were included. High-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), D-dimer, and thrombin generation using calibrated automated thrombogram system were measured at different time points until 1 month after anticoagulant therapy discontinuation. Results: Two hundred thirty-one patients were included. Eight patients died, of whom 5 during hospitalization. The day 0 hs-CRP levels, NLR, and D-dimer were higher in patients with initial consciousness disturbance than in those without (hs-CRP: 10.2 mg/L [3.6-25.5] vs 23.7 mg/L [4.8-60.0], respectively; NLR: 3.51 [2.15-5.88] vs 4.78 [3.10-9.59], respectively; D-dimer: 950 µg/L [520-2075] vs 1220 µg/L [950-2445], respectively). Patients with ischemic parenchymal lesions (n = 31) had a higher endogenous thrombin potential5pM than those with hemorrhagic parenchymal lesions (n = 31): 2025 nM min (1646-2441) vs 1629 nM min (1371-2090), respectively (P = .0082). Using unadjusted logistic regression with values >75th percentile, day 0 hs-CRP levels of >29.7 mg/L (odds ratio, 10.76 [1.55-140.4]; P = .037) and day 5 D-dimer levels of >1060 mg/L (odds ratio, 14.63 [2.28-179.9]; P = .010) were associated with death occurrence. Conclusion: Two widely available biomarkers measured upon admission, especially hs-CRP, could help predict bad prognosis in CVST in addition to patient characteristics. These results need to be validated in other cohorts.

Deep phenotyping and biomarkers of various dairy fat intakes in an 8-week randomized clinical trial and 2-year swine study.

Health effects of dairy fats (DF) are difficult to evaluate, as DF intakes are hard to assess epidemiologically and DF have heterogeneous compositions that influence biological responses. We set out to find biomarkers of DF intake and assess biological response to a summer DF diet (R2), a winter DF diet (R3), and a R3 supplemented with calcium (R4) compared to a plant-fat-based diet (R1) in a randomized clinical trial (n=173) and a 2-year study in mildly metabolically disturbed downsized pigs (n=32). Conventional clinical measures were completed by LC/MS plasma metabolomics/lipidomics. The measured effects were modeled as biological functions to facilitate interpretation. DF intakes in pigs specifically induced a U-shaped metabolic trajectory, reprogramming metabolism to close to its initial status after a one-year turnaround. Twelve lipid species repeatably predicted DF intakes in both pigs and humans (6.6% errors). More broadly, in pigs, quality of DF modulated the time-related biological response (R2: 30 regulated functions, primarily at 6 months; R3: 26 regulated functions, mostly at 6-12 months; R4: 43 regulated functions, mostly at 18 months). Despite this heterogeneity, 9 functions overlapped under all 3 DF diets in both studies, related to a restricted area of amino acids metabolism, cofactors, nucleotides and xenobiotic pathways and the microbiota. In conclusion, over the long-term, DF reprograms metabolism to close to its initial biological status in metabolically-disrupted pigs. Quality of the DF modulates its metabolic influence, although some effects were common to all DF. A resilient signature of DF consumption found in pigs was validated in humans.

Cerebral Venous Thrombosis: Clinical, Radiological, Biological, and Etiological Characteristics of a French Prospective Cohort (FPCCVT)-Comparison With ISCVT Cohort.

Introduction: Cerebral venous thrombosis (CVT) is a rare disease with highly variable clinical presentation and outcome. Etiological assessment may be negative. The clinical and radiological presentation and evolution can be highly variable. The mechanisms involved in this variability remain unknown. Objective: The aim of this multicenter French study registered on ClinicalTrials.gov (NCT02013635) was therefore to prospectively recruit a cohort of patients with cerebral venous thrombosis (FPCCVT) in order to study thrombin generation and clot degradation, and to evaluate their influence on clinical radiological characteristics. The first part of the study was to compare our cohort with a reference cohort. Methods: This prospective, multicenter, French study was conducted from July 2011 to September 2016. Consecutive patients (aged >15 years) referred to the stroke units of 21 French centers and who had a diagnosis of symptomatic CVT were included. All patients gave their written informed consent. The diagnosis of CVT had to be confirmed by imaging. Clinical, radiological, biological, and etiological characteristics were recorded at baseline, at acute phase, at 3 months and at last follow-up visit. Thrombophilia screening and the choice of treatment were performed by the attending physician. All data were compared with data from the International Study on CVT published by Ferro et al. Results: Two hundred thirty-one patients were included: 117 (50.6%) had isolated intracranial hypertension, 96 (41.5%) had focal syndrome. During hospitalization, 229 (99.1%) patients received anticoagulant treatment. Median length of hospital stay was 10 days. Five patients died during hospitalization (2.2%). At 3 months, 216 patients (97.0%) had follow-up with neurological data based on an outpatient visit. The mean duration of antithrombotic treatment was 9 months, and the mean time to last follow-up was 10.5 months. At the end of follow-up, eight patients had died, and 26 patients were lost to follow-up. At least one risk factor was identified in 200 patients. Conclusions: We demonstrated that the FPCCVT cohort had radiological, biological, and etiological characteristics similar to the historical ISCVT cohort. Nevertheless, the initial clinical presentation was less severe in our study probably due to an improvement in diagnostic methods between the two studies.

Is platelet function testing at the acute phase under P2Y12 inhibitors helpful in predicting bleeding in real-life patients with acute coronary syndrome? The AVALANCHE study.

BACKGROUND: In patients with acute coronary syndrome (ACS), current international guidelines recommend newer potent and predictable P2Y12 inhibitors as first-line treatment despite a greater bleeding risk compared with clopidogrel. AIM: To determine if platelet function testing can predict bleeding in real-life patients with ACS treated with newer P2Y12 inhibitors. METHODS: In this retrospective study, all consecutive adults admitted to the Lariboisière University Hospital for ACS, whatever the P2Y12 inhibitor prescribed, who had platelet function testing (vasodilator-stimulated phosphoprotein phosphorylation [VASP] index and aggregation tests) during the initial hospital stay were included. Follow-up was performed to record bleeding events according to the Bleeding Academic Research Consortium (BARC) classification. RESULTS: A total of 364 patients were included, treated with ticagrelor (n=123), prasugrel (n=105) or clopidogrel (n=136); 42.3% after an ST-segment elevation myocardial infarction, 27.1% after a non-ST-segment elevation myocardial infarction and 30.6% with unstable angina. Mean age was 64±11 years. Median VASP index was significantly lower with the newer P2Y12 inhibitors (14% under ticagrelor, 14% under prasugrel) than with clopidogrel (42%). Despite these differences in the degree of platelet inhibition, the occurrence of bleeding (BARC 2-5) during follow-up was 7.7% overall, and was similar for all P2Y12 inhibitors (ticagrelor 8.9%; prasugrel 6.6%; clopidogrel 7.4%). For each P2Y12 inhibitor, it was impossible to determine a VASP index threshold under which bleeding was significantly greater during follow-up. Similarly, ADP-induced aggregation was more profoundly inhibited by ticagrelor and prasugrel than by clopidogrel, but this did not allow a threshold to be set for increased haemorrhagic risk. CONCLUSIONS: Despite the substantial occurrence of bleeding in patients with ACS during follow-up, neither the VASP index nor platelet aggregation test results measured at the acute phase were helpful in predicting bleeding risk. Whether platelet function testing could be helpful later in the course of treatment remains to be evaluated.

[GFHT proposals for management of discordance between the International normalized ratio measured in the laboratory and by self-testing]. / Propositions du GFHT pour la gestion des discordances entre l'International normalized ratio mesuré au laboratoire et en automesure.

The lack of quality control for patient point-of-care (POC) INR devices is an issue that has led the French health authorities to make recommendations: a laboratory INR (lab INR) has to be performed at the same time as the POC INR every 6 months. However, the differences observed between the two INRs, POC and lab INRs, are not necessarily due to a failure of the POC INR device. We present here a review of the different causes of discrepancies between INR results, which are the basis of the proposals of the Groupe français d'études sur l'hémostase et la thrombose (GFHT) on the management of lab and POC INR discrepancies. Pre-analytical conditions may account for discrepancies (sampling, transport and storage conditions), as well as analytical factors (mainly the nature of the thromboplastin used) and the clinical context (inflammatory or autoimmune diseases, polycythaemia...). The interpretation of INR discrepancies is not always easy and these proposals aim at standardizing the procedure to be followed in order to make the most appropriate decision for the patient.

Giant intrahepatic venous malformation with localized intravascular coagulopathy. Follow-up and treatment during pregnancy.

Intrahepatic lesions in adults, commonly named hepatic hemangioma, should be called Intrahepatic Venous Malformations (IHVM), or Giant Intrahepatic Venous Malformations (GIHVM) when larger than 10 cm according to the ISSVA classification (International society study group for vascular anomalies). Localized coagulation disorders (LIC) in patients with venous malformations are quite commonly associated in venous malformations, they result in decreased fibrinogen (< 2g/l) and elevated d-dimers (> 1500 ng/ml) and might be responsible of intralesional thrombotic, pain or bleeding episodes.We report a case report of a 41 y/o patient that presented with right hypochondrium pain episodes discovering an unknown GIHVM on ultrasound imaging with a prior history of uterine bleeding episodes and multiples miscarriages.On laboratory work up the patient presented an associated localized Intravascular Coagulation (LIC) with the GIHVM. As the patient desire to become pregnant was important our multidisciplinary clinic allowed a pregnancy with close clinical, biological and imaging monitoring and follow up. Early initiation of low molecular weighted heparin (LMWH) successfully allowed an uncomplicated term pregnancy and delivery. Intrahepatic lesion stability was achieved and prevented progression from LIC to diffuse intravascular coagulation disorder (DIC)..

Plasma Serotonin is Elevated in Adult Patients with Sudden Sensorineural Hearing Loss.

BACKGROUND: The roles of thrombophilia and cardiovascular risk factors in sudden sensorineural hearing loss (SSNHL) remain controversial. Cochlear microthrombosis and vasospasm have been hypothesized as possible pathogenic mechanisms of SSNHL. This article investigates the circulating serotonin and homocysteine levels besides thrombophilia screening in patients with idiopathic SSNHL. METHODS: A total of 133 SSNHL patients and age- and sex-matched controls were investigated (discovery cohort). Measurement included common inherited natural coagulation inhibitors, factor VIII, von Willebrand factor (VWF), antiphospholipid antibodies, homocysteine, and serotonin (whole blood, platelet, and plasma) levels, along with frequent relevant genetic variants. A validation cohort (128 SSNHL patients) was studied for homocysteine and serotonin levels. RESULTS AND CONCLUSION: In the discovery cohort, 58.6% of patients exhibited thrombophilia, of which most had a low to moderate titers of antiphospholipid antibodies and high levels of factor VIII/VWF. Twenty-seven patients (20%) had mild-to-moderate hyperhomocysteinemia or were homozygous for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Regarding serotonin, SSNHL patients had elevated whole blood levels that remained within the normal range and normal platelet content. However, approximately 90% patients of both cohorts had elevated plasma serotonin. Elevated plasma serotoninemia was accompanied by serotonylation of platelet rhoA protein. This study shows that increased plasma serotonin appears as a biomarker of SSNHL (specificity: ∼96%, sensitivity: ∼90%) and could participate in the pathophysiology of SSNHL.

Kawasaki-like diseases and thrombotic coagulopathy in COVID-19: delayed over-activation of the STING pathway?

We previously made the hypothesis that STING contributes to COVID-19. The present review detail new arguments for over-activation of STING pathways in COVID-19, following the description of hyper-coagulability and Kawasaki-like diseases in children. Indeed, Kawasaki disease is induced by overreaction of innate cells following exposition to various viruses, including herpes viruses which trigger STING. It predisposes to diffuse vasculitis and aneurysms, whereas STING is over-expressed in arterial aneurisms. The redness at the inoculation site of bacillus Calmette-Guérin, a specific feature of Kawasaki disease, is reproduced by activation of the STING pathway, which is inhibited upstream by aspirin, intravenous immunoglobulins, and Vitamin-D. SARS-CoV2 binding to ACE2 can lead to excessive angiotensin II signaling, which activates the STING pathway in mice. Over-activation of the STING-pathway promotes hyper-coagulability through release of interferon-ß and tissue factor by monocytes-macrophages. Aspirin and dipyridamole, besides their anti-platelet activity, also reduce tissue factor procoagulant activity, and aspirin inhibits the STING pathway upstream of STING. Aspirin and dipyridamole may be used, in combination with drugs blocking downstream the activation of the STING pathway, like inhibitors of IL-6R and JAK/STAT pathways. The risk of bleeding should be low as bleeding has not been reported in severe COVID-19 patients.

Educational Impact on Apixaban Adherence in Atrial Fibrillation (the AEGEAN STUDY): A Randomized Clinical Trial.

INTRODUCTION: Adherence to non-vitamin-K oral anticoagulants (NOACs) may be lower than to vitamin K antagonists because NOACs do not require routine monitoring. OBJECTIVE: We assessed the impact of an educational program on adherence and persistence with apixaban in patients with non-valvular atrial fibrillation (NVAF). METHODS: Patients with NVAF eligible for NOACs with one or more stroke risk factor (prior stroke/transient ischemic attack, age ≥ 75 years, hypertension, diabetes, or symptomatic heart failure) were randomized (1:1) to standard of care (SOC) or SOC with additional educational (information booklet, reminder tools, virtual clinic access). The primary outcome was adherence to apixaban (2.5 or 5 mg twice daily) at 24 weeks. Patients receiving the educational program were re-randomized (1:1) to continue the program for 24 further weeks or to switch to secondary SOC. Implementation adherence and persistence were reassessed at 48 weeks. RESULTS: In total, 1162 patients were randomized (SOC, 583; educational program, 579). Mean implementation adherence ± standard deviation (SD) at 24 weeks was 91.6% ± 17.1 for SOC and 91.9% ± 16.1 for the educational program arm; results did not differ significantly between groups at any time-point. At 48 weeks, implementation adherence was 90.4% ± 18.0, 90.1% ± 18.6, and 89.3% ± 18.1 for continued educational program, SOC, and secondary SOC, respectively; and corresponding persistence was 86.1% (95% confidence interval [CI] 81.3-89.7), 85.2% (95% CI 81.5-88.2), and 87.8% (95% CI 83.4-91.1). Serious adverse events were similar across groups. CONCLUSION: High implementation adherence and persistence with apixaban were observed in patients with NVAF receiving apixaban. The educational program did not show additional benefits. CLINICAL TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov [NCT01884350].

Effect of milk fat on LDL cholesterol and other cardiovascular risk markers in healthy humans: the INNOVALAIT project.

BACKGROUND: Milk has a specific saturated fatty acid profile and its calcium content may change the kinetics of fat absorption. OBJECTIVE: The goal of this study was to compare the effect on LDL Cholesterol and other risk markers of four isolipidic diets differing by their fat food source, vegetable fat, spring milk fat, winter milk fat or winter milk fat supplemented with calcium, in healthy moderately hypercholesterolemic humans. INDIVIDUALS AND METHODS: This double-blind, randomized trial with four parallel arms included 172 healthy adults with plasma LDL cholesterol (LDL-C) from 130 to 220 mg/dL and triglycerides below 300 mg/dL. Individual meal plans ensured a stable energy intake. In the three diets containing milk fat, milk fat provided 38% of energy. Vegetable fat and spring milk fat diets provided the same amount of saturated fatty acids while the winter milk fat diets were slightly richer in saturated fatty acids. Vegetable fat diet and winter milk fat diets provided the same amount of palmitic acid (7.0% EI), while the spring milk fat diet was slightly poorer in this fatty acid (5.1% EI). Cardiovascular risk markers were analyzed after 8 weeks of dietary intervention. RESULTS: There was no significant difference in LDL-C and other markers, except total cholesterol (TC), apo C3 and CRP. TC was significantly higher with spring milk fat than with vegetable fat. CONCLUSIONS: In this trial, the chosen vegetable fat did not have a significant beneficial effect on LDL-C compared to dairy fat. However, sub-group analysis showed differences in TC, apo C3 and CRP. These results need confirmation and long-term studies aiming at cardiovascular endpoints are warranted.

Variation in Coronary Atherosclerosis Severity Related to a Distinct LDL (Low-Density Lipoprotein) Profile: Findings From a Familial Hypercholesterolemia Pig Model.

OBJECTIVE: In an adult porcine model of familial hypercholesterolemia (FH), coronary plaque development was characterized. To elucidate the underlying mechanisms of the observed inter-individual variation in disease severity, detailed lipoprotein profiles were determined. Approach and Results: FH pigs (3 years old, homozygous LDLR R84C mutation) received an atherogenic diet for 12 months. Coronary atherosclerosis development was monitored using serial invasive imaging and histology. A pronounced difference was observed between mildly diseased pigs which exclusively developed early lesions (maximal plaque burden, 25% [23%-34%]; n=5) and advanced-diseased pigs (n=5) which developed human-like, lumen intruding plaques (maximal plaque burden, 69% [57%-77%]) with large necrotic cores, intraplaque hemorrhage, and calcifications. Advanced-diseased pigs and mildly diseased pigs displayed no differences in conventional risk factors. Additional plasma lipoprotein profiling by size-exclusion chromatography revealed 2 different LDL (low-density lipoprotein) subtypes: regular and larger LDL. Cholesterol, sphingosine-1-phosphate, ceramide, and sphingomyelin levels were determined in these LDL-subfractions using standard laboratory techniques and high-pressure liquid chromatography mass-spectrometry analyses, respectively. At 3 months of diet, regular LDL of advanced-diseased pigs contained relatively more cholesterol (LDL-C; regular/larger LDL-C ratio 1.7 [1.3-1.9] versus 0.8 [0.6-0.9]; P=0.008) than mildly diseased pigs, while larger LDL contained more sphingosine-1-phosphate, ceramides, and sphingomyelins. Larger and regular LDL was also found in plasma of 3 patients with homozygous FH with varying LDL-C ratios. CONCLUSIONS: In our adult FH pig model, inter-individual differences in atherosclerotic disease severity were directly related to the distribution of cholesterol and sphingolipids over a distinct LDL profile with regular and larger LDL shortly after the diet start. A similar LDL profile was detected in patients with homozygous FH.

A novel experimental thrombotic myocardial infarction and primary angioplasty model in swine.

AIMS: We sought to develop a reproducible animal model for acute myocardial infarction (AMI) in adult atherosclerosis-prone pigs. METHODS AND RESULTS: A coil was placed in the right coronary artery or the left anterior descending artery in 26 downsized spontaneously hypercholesterolaemic pigs and left untreated until thrombotic occlusion. Then, we crossed the thrombotic occlusion with a guidewire, followed by predilatation, thrombus visualisation with optical coherence tomography (OCT) imaging and, finally, deployment of a stent and repeated OCT. After revascularisation, we calculated the index of microcirculatory resistance (IMR). After a feasibility phase (six animals), acute thrombotic occlusion was achieved in all 20 pigs. Eighteen animals were successfully revascularised and survived until sacrifice. Thrombus formation was confirmed by OCT, measurement of thrombin-antithrombin complexes and pathology examination. Myocardial necrosis was confirmed by troponin T elevation, myocardial staining and pathology examination. Distal thrombotic embolisation and microvascular obstruction were supported by increased IMR and pathology examination. CONCLUSIONS: A porcine model of thrombotic occlusion AMI in miniaturised adult spontaneously atherosclerosis-prone pigs is feasible by percutaneous intracoronary placement of a coil. The reperfusion by angioplasty completed this model which mirrors human pathological conditions with myocardial infarction, necrosis and distal embolisation.

Platelet activation and aggregation after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Endovascular techniques have proven beneficial in the treatment of aneurysmal subarachnoid hemorrhage (aSAH), but with high risk of arterial clotting, emboli and dissection. Platelet activation and alterations in hemostasis may contribute to these complications. We investigated platelet activation and aggregation pathways in aSAH patients who underwent endovascular treatment. METHODS: Two blood samples were taken, in the early days after bleeding and during the period at risk of vasospasm. We studied platelet activation through the expression of GpIIbIIIa and P-selectin as well as aggregation rate in the presence of agonists. Platelets from aSAH patients were compared with those from orthopedic postoperative patients (POSTOP). RESULTS: Platelets in aSAH were initially spontaneously activated and remained so over time. aSAH platelets were further activated with rapid aggregation in the presence of agonists, particularly ADP, with behavior comparable to POSTOP platelets. CONCLUSIONS: aSAH platelets showed prolonged increases in activation and aggregation. Therapies targeting the ADP pathway might reduce the risk of clotting and ischemic events in this context among patients requiring multiple endovascular procedures. TRIAL REGISTRATION: Not applicable.

Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs.

BACKGROUND: Obesity and metabolic syndrome (MetS) are major risk factors for atherosclerotic diseases; however, a causal link remains elusive. Animal models resembling human MetS and its complications, while important, are scarce. We aimed at developing a porcine model of human MetS. METHODS: Forty pigs with familial hypercholesterolemia were fed a high fat + fructose diet for 30 weeks. Metabolic assessments and subcutaneous fat biopsies were obtained at 18 and 30 weeks, and fat distribution was assessed by CT-scans. Postmortem, macrophage density, and phenotype in fat tissues were quantified along with atherosclerotic burden. RESULTS: During the experiment, we observed a >4-fold in body weight, a significant but small increase in fasting glucose (4.1 mmol/L), insulin (3.1 mU/L), triglycerides (0.5 mmol/L), and HDL cholesterol (2.6 mmol/L). Subcutaneous fat correlated with insulin resistance, but intra-abdominal fat correlated inversely with insulin resistance and LDL cholesterol. More inflammatory macrophages were found in visceral versus subcutaneous fat, and inflammation decreased in subcutaneous fat over time. CONCLUSIONS: MetS based on human criteria was not achieved. Surprisingly, visceral fat seemed part of a healthier metabolic and inflammatory profile. These results differ from human findings, and further research is needed to understand the relationship between obesity and MetS in porcine models.