Effect of different initial anticoagulant strategies on short-term outcome of patients with symptomatic DVT in China.

PURPOSE: In ambulant patients with lower limb DVT managed with Warfarin, there is a need for initial treatment and short time "bridging" with a rapidly acting anticoagulant until there is a stable therapeutic INR. In this study, results from bridging with subcutaneous low molecular weight heparin (LMWH) or oral Rivaroxaban were compared. METHODS: One hundred and twenty-four patients received LMWH and 98 patients received Rivaroxaban, both in addition to Warfarin. Patients were assessed at 1 and 4 weeks after treatment initiation for thrombus progression, bleeding, clinic attendance and INR. FINDINGS: The treatment groups were well matched. There were no significant differences between the treatment groups for any of the end-points at either 1 week or 4 weeks. IMPLICATIONS: In ambulant patients with DVT treated with Warfarin both Rivaroxaban and LMWH are suitable for use in the early phase of Warfarin treatment until therapeutic INR is achieved. Rivaroxaban is a suitable alternative to LMWH for patients who prefer not to have injections.

Trends and predictors of recurrent acute coronary syndrome hospitalizations and unplanned revascularization after index acute myocardial infarction treated with percutaneous coronary intervention.

BACKGROUND: Repeat hospitalizations for recurrent acute coronary syndrome (ACS) or unplanned revascularization after acute myocardial infarction (MI) are common, costly and potentially preventable. We aim to describe 10-year trends and identify independent risk factors of these repeat hospitalizations. METHODS: We analyzed data from 9615 patients from the Melbourne Interventional Group registry (2005-2014) who underwent percutaneous coronary intervention (PCI) for their index MI and survived to discharge. Patients with ≥1 hospitalization for recurrent ACS events and/or unplanned revascularization in the year after discharge were included in the recurrent coronary hospitalization group. We assessed yearly trends of recurrent coronary events and identified independent predictors using multivariate analysis. RESULTS: Recurrent coronary hospitalization occurred in 1175 (12.2%) patients. There was a significant decrease in the rate of recurrent ACS hospitalization (15.3%-7.6%, P for trend <.001) and unplanned revascularization (4.2%-2.1%, P for trend = .01), but not in all-cause re-hospitalizations (P for trend = .28). On multivariate analysis, female gender, diabetes mellitus, previous coronary bypass surgery, previous PCI, reduced ejection fraction, heart failure, multi-vessel coronary disease and obstructive sleep apnea were independent predictors of recurrent coronary hospitalizations (all P < .05). CONCLUSIONS: Recurrent hospitalization for ACS or unplanned revascularization has decreased significantly over the past decade. Risk factors for such events are numerous and largely non-modifiable, however they identify a cohort of patients in whom non-culprit vessel PCI in multi-vessel disease, optimization of left ventricular dysfunction and diabetes management may improve outcomes.

Preoperative biomarker evaluation for the prediction of cardiovascular events after major vascular surgery.

OBJECTIVE: The cause of perioperative myocardial infarction (PMI) is postulated to involve hemodynamic stress or coronary plaque destabilization. We aimed to evaluate perioperative factors in patients with peripheral artery disease (PAD) undergoing major vascular surgery to determine the likely mechanisms and predictors of PMI. METHODS: This was a prospective cohort study of 133 patients undergoing major vascular surgery including open abdominal aortic aneurysm (AAA) repair (n = 40) and major suprainguinal or infrainguinal arterial bypasses (non-AAA; n = 93). Preoperative assessment with history, physical examination, and peripheral artery tonometry was performed in addition to plasma sampling of biomarkers associated with inflammation and coronary plaque instability. The primary outcome was occurrence of a 30-day cardiovascular event (CVE; composite of PMI [troponin I elevation >99th percentile reference of ≥0.1 µg/L], stroke, or death). RESULTS: Of 133 patients, 36 patients (27%) developed a 30-day CVE after vascular surgery, and all were PMI. Patients with 30-day CVE were older (75 ± 8 years vs 69 ± 10 years, mean ± standard deviation; P = .001), had higher prevalence of hypertension (94% vs 79%; P = .01) and preoperative beta-blocker therapy (50% vs 29%; P = .02), and had longer duration of surgery (5.1 ± 1.8 hours vs 4.0 ± 1.1 hours; P < .0001). Significant elevations in cystatin C, N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin I, high-sensitivity troponin T, matrix metalloproteinase 3, and osteoprotegerin occurred in those who developed 30-day CVE (all P < .05). Multivariate binary logistic regression identified AAA surgery and log-transformed NT-proBNP to be independent preoperative predictors of 30-day CVE (area under the receiver operating characteristic curve = 0.81). CONCLUSIONS: In patients with peripheral artery disease undergoing major vascular surgery, the likely mechanism of PMI appears to be the hemodynamic stress related to the type and duration of surgery. NT-proBNP was a useful independent predictor of CVE and thus may serve as an important biomarker of cardiovascular fitness for surgery.

Upregulated galectin-3 is not a critical disease mediator of cardiomyopathy induced by ß2-adrenoceptor overexpression.

Preclinical studies have demonstrated that anti-galectin-3 (Gal-3) interventions are effective in attenuating cardiac remodeling, fibrosis, and dysfunction. We determined, in a transgenic (TG) mouse model of fibrotic cardiomyopathy, whether Gal-3 expression was elevated and whether Gal-3 played a critical role in disease development. We studied mice with fibrotic cardiomyopathy attributable to cardiac overexpression of human ß2-adrenoceptors (ß2-TG). Cardiac expression levels of Gal-3 and fibrotic or inflammatory genes were determined. The effect of Gal-3 inhibition in ß2-TG mice was studied by treatment with Gal-3 inhibitors ( N-acetyllactosamine and modified citrus pectin) or by deletion of Gal-3 through crossing ß2-TG and Gal-3 knockout mice. Changes in cardiomyopathy phenotypes were assessed by echocardiography and biochemical assays. In ß2-TG mice at 3, 6, and 9 mo of age, upregulation of Gal-3 expression was observed at mRNA (~6- to 15-fold) and protein (~4- to 8-fold) levels. Treatment of ß2-TG mice with N-acetyllactosamine (3 wk) or modified citrus pectin (3 mo) did not reverse cardiac fibrosis, inflammation, and cardiomyopathy. Similarly, Gal-3 gene deletion in ß2-TG mice aged 3 and 9 mo did not rescue the cardiomyopathy phenotype. In conclusion, the ß2-TG model of cardiomyopathy showed a robust upregulation of Gal-3 that correlated with disease severity, but Gal-3 inhibitors or Gal-3 gene deletion had no effect in halting myocardial fibrosis, remodeling, and dysfunction. Gal-3 may not be critical for cardiac fibrogenesis and remodeling in this cardiomyopathy model. NEW & NOTEWORTHY We showed a robust upregulation of cardiac galectin-3 (Gal-3) expression in a mouse model of cardiomyopathy attributable to cardiomyocyte-restricted transgenic activation of ß2-adrenoceptors. However, pharmacological and genetic inhibition of Gal-3 did not confer benefit in this model, implying that Gal-3 may not be a critical disease mediator of cardiac remodeling in this model.

The relationship between maternal anxiety and cortisol during pregnancy and birth weight of chinese neonates.

BACKGROUND: To determine the relationship between maternal anxiety and cortisol values and birth weight at various stages of pregnancy. METHODS: Two hundred sixteen pregnant Chinese women were assessed for anxiety and depression and had measurement of morning fasting serum cortisol. Women were assessed either in the first (71), second (72) or third (73) trimester. Birth weights of all children were recorded. RESULTS: There were significant negative correlations between anxiety level and birth weight of - 0.507 (p < 0.01) and - 0.275 (p < 0.05) in trimesters 1and 2. In trimester 3 the negative relation between anxiety and birth weight of -.209 failed to reach significance (p = 0.070). There was no relation between depression and birth weight in any trimester (p > 0.5 for all). Maternal cortisol was significantly inversely related to birth weight in trimester 1 (r = - 0.322) and with borderline significance in trimester 2 (r = - 0.229). Anxiety score and maternal cortisol were significantly correlated in each trimester (r = 0.551, 0.650, 0.537). When both anxiety score and maternal cortisol were simultaneously included in multiple regression analyses only anxiety score remained significant. CONCLUSION: Whilst both maternal anxiety score and maternal cortisol are inversely related to birth weight the associations with anxiety score were more robust perhaps indicating the importance of mechanisms other than, or in addition to, maternal cortisol in mediating the effects of anxiety. The findings indicate the importance of measures to reduce maternal anxiety, particularly of a severe degree, at all stages of pregnancy. TRIAL REGISTRATION: The study was approved by the Ethics Committee of the 1st Affiliated Hospital of Xi'an Jiaotong University.

Inhibition of the Renin-Angiotensin System Post Myocardial Infarction Prevents Inflammation-Associated Acute Cardiac Rupture.

PURPOSE: Inhibition of the renin-angiotensin system (RAS) is beneficial in patient management after myocardial infarction (MI). However, whether RAS inhibition also provides cardiac protection in the acute phase of MI is unclear. METHODS: Male 129sv mice underwent coronary artery occlusion to induce MI, followed by treatment with losartan (L, 20 and 60 mg/kg), perindopril (P, 2 and 6 mg/kg), amlodipine (20 mg/kg as a BP-lowering agent) or vehicle as control. Drug effects on hemodynamics were examined. Effects of treatments on incidence of cardiac rupture, haematological profile, monocyte and neutrophil population in the spleen and the heart, cardiac leukocyte density, expression of inflammatory genes and activity of MMPs were studied after MI. RESULTS: Incidence of cardiac rupture within 2 weeks was significantly and similarly reduced by both losartan (L) and perindopril (P) in a dose-dependent manner [75% (27/36) in vehicle, 40-45% in low-dose (L 10/22, P 8/20) and 16-20% (L 5/32, P 4/20) in high-dose groups, all P < 0.05]. This action was independent of their BP-lowering action, as amlodipine reduced BP to a similar degree without effect on rupture (70%, 21/30). Compared to the control group, high dose losartan and perindopril decreased counts of white blood cells, neutrophils and lymphocytes (all P < 0.05), and inhibited splenic monocyte and neutrophil release into the circulation. Consequently, monocyte, neutrophil and leukocyte infiltration, inflammatory gene expressions (IL-1ß, IL-6, MMP9, MCP-1, TNF-α and TGFß1) and activity of MMP2 and MMP9 in the infarct tissue were attenuated by losartan and/or perindopril treatment (all P < 0.05). CONCLUSIONS: RAS inhibition by losartan or perindopril prevented cardiac rupture at the acute phase of MI through blockade of splenic release of monocytes and neutrophils and consequently attenuation of systemic and regional inflammatory responses.

Splenic release of platelets contributes to increased circulating platelet size and inflammation after myocardial infarction.

Acute myocardial infarction (AMI) is characterized by a rapid increase in circulating platelet size but the mechanism for this is unclear. Large platelets are hyperactive and associated with adverse clinical outcomes. We determined mean platelet volume (MPV) and platelet-monocyte conjugation (PMC) using blood samples from patients, and blood and the spleen from mice with AMI. We further measured changes in platelet size, PMC, cardiac and splenic contents of platelets and leucocyte infiltration into the mouse heart. In AMI patients, circulating MPV and PMC increased at 1-3 h post-MI and MPV returned to reference levels within 24 h after admission. In mice with MI, increases in platelet size and PMC became evident within 12 h and were sustained up to 72 h. Splenic platelets are bigger than circulating platelets in normal or infarct mice. At 24 h post-MI, splenic platelet storage was halved whereas cardiac platelets increased by 4-fold. Splenectomy attenuated all changes observed in the blood, reduced leucocyte and platelet accumulation in the infarct myocardium, limited infarct size and alleviated cardiac dilatation and dysfunction. AMI-induced elevated circulating levels of adenosine diphosphate and catecholamines in both human and the mouse, which may trigger splenic platelet release. Pharmacological inhibition of angiotensin-converting enzyme, ß1-adrenergic receptor or platelet P2Y12 receptor reduced platelet abundance in the murine infarct myocardium albeit having diverse effects on platelet size and PMC. In conclusion, AMI evokes release of splenic platelets, which contributes to the increase in platelet size and PMC and facilitates myocardial accumulation of platelets and leucocytes, thereby promoting post-infarct inflammation.

Effects of Maternal Cortisol during Pregnancy on Children's Blood Pressure Responses.

BACKGROUND: It is well established that birth weight has an effect on subsequent blood pressure. Predominantly experimental studies have also reported effects of altered corticosteroid levels on subsequent cardiovascular responses. In the current study, we have examined the effects of both birth weight and maternal cortisol levels in a cohort of mothers and their pre-adolescent children. PROCEDURE: A total of 216 women and their 7- to 9-year-old children comprised the cohort. The women had been assessed for plasma cortisol during the first (n = 71), second (n = 72) and third (n = 73) trimester. Maternal cortisol had been measured on a fasting sample taken between 9 and 11 a.m. The children's blood pressure and heart rate were recorded in the resting state, in response to a 10-min video game stress challenge and during recovery. Resting values, incremental responses to stress and recovery were evaluated. OBSERVATION: Maternal cortisol levels increased with duration of pregnancy. There were inverse correlations between birth weight and all haemodynamic measures. The positive associations between maternal cortisol and children's haemodynamic measures were most evident in the first and second trimesters. Birth weight was inversely related to maternal cortisol. In multiple regression analyses, the effects of maternal cortisol were more consistent than those of birth weight. CONCLUSION: Both birth weight and maternal cortisol are predictive of children's resting and stress-modulated haemodynamic measures. The effects of birth weight may partly mediate the effects of maternal cortisol.

Circulating microRNAs as biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy.

BACKGROUND: Circulating microRNAs may represent novel markers for cardiovascular diseases. We evaluated whether circulating miRNAs served as potential biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM). METHODS: Cardiac magnetic resonance imaging with postcontrast T1 mapping was performed to non-invasively quantify diffuse myocardial fibrosis in HCM patients who were classified into two groups (T1 < 470 ms or T1 ≥ 470 ms, as likely or unlikely to have diffuse fibrosis, respectively). First, we screened 84 miRNAs using human serum/plasma miRNA array on plasma of 8 HCM patients (4/group based on T1 time) and 4 healthy controls. From the results of this initial array, 16 miRNAs were selected based on their fold changes and relevance to myocardial fibrosis for further validation by Taqman real-time PCR in 55 HCM patients. RESULTS: Among the 16 miRNAs, the expression of miR-96-5p and miR-373-3p was low. The remaining 14 (miR-18a-5p, miR-146a-5p, miR-30d-5p, miR-17-5p, miR-200a-3p, miR-19b-3p, miR-21-5p, miR-193-5p, miR-10b-5p, miR-15a-5p, miR-192-5p, miR-296-5p, miR-29a-3p, and miR-133a-3p) were upregulated in HCM patients with T1 < 470 ms compared with those with T1 ≥ 470 ms, and 11 (except miR-192-5p, miR-296-5p and miR-133a-3p) were significantly inversely correlated with postcontrast T1 values. Individual miRNA had moderate diagnostic value for diffuse myocardial fibrosis (AUC: 0.663-0.742), but the diagnostic value was greatly improved (AUC: 0.87) for a combination of 8 miRNAs. In comparison, circulating markers of collagen turnover did not have predictive values for diffuse myocardial fibrosis. CONCLUSIONS: These findings suggest that circulating miRNAs provide attractive candidates as putative biomarkers for diffuse myocardial fibrosis in HCM.

Differential roles of cardiac and leukocyte derived macrophage migration inhibitory factor in inflammatory responses and cardiac remodelling post myocardial infarction.

Myocardial infarction (MI) provokes regional inflammation which facilitates the healing, whereas excessive inflammation leads to adverse cardiac remodelling. Our aim was to determine the role of macrophage migration inhibitory factor (MIF) in inflammation and cardiac remodelling following MI. Wild type (WT) or global MIF deficient (MIFKO) mice were subjected to coronary artery occlusion. Compared to WT mice, MIFKO mice had a significantly lower incidence of post-MI cardiac rupture (27% vs. 53%) and amelioration of cardiac remodelling. These were associated with suppressed myocardial leukocyte infiltration, inflammatory mediators' expression, and reduced activity of MMP-2, MMP-9, p38 and JNK MAPK. Infarct myocardium-derived or exogenous MIF mediated macrophage chemotaxis in vitro that was suppressed by inhibition of p38 MAPK or NF-κB. To further dissect the role of MIF derived from different cellular sources in post-MI cardiac remodelling, we generated chimeric mice with MIF deficiency either in bone marrow derived-cells (WT(KO)) or in somatic-cells (KO(WT)). Compared to WT and KO(WT) mice, WT(KO) mice had reduced rupture risk and ameliorated cardiac remodelling, associated with attenuated regional leukocyte infiltration and expression of inflammatory mediators. In contrast, KO(WT) mice had delayed healing and enhanced expression of M1 macrophage markers, but diminished expression of M2 markers during the early healing phase. In conclusion, global MIF deletion protects the heart from post-infarct cardiac rupture and remodelling through suppression of leukocyte infiltration and inflammation. Leukocyte-derived MIF promotes inflammatory responses after MI, whereas cardiac-derived MIF affects early but not ultimate healing process.

Associations between surface markers on blood monocytes and carotid atherosclerosis in HIV-positive individuals.

Chronic HIV infection is associated with increased risk of cardiovascular disease (CVD), including in patients with virological suppression. Persistent innate immune activation may contribute to the development of CVD via activation of monocytes in these patients. We investigated whether changes in monocyte phenotype predict subclinical atherosclerosis in virologically suppressed HIV-positive individuals with low cardiovascular risk. We enroled 51 virologically suppressed HIV-positive individuals not receiving protease inhibitors or statins and 49 age-matched uninfected controls in this study. Carotid artery intima-media thickness (cIMT) was used as a surrogate marker for CVD, and traditional risk factors, including Framingham risk scores, were recorded. Markers of monocyte activation (CD14, CD16, CCR2, CX3CR1, CD38, HLA-DR and CD11b) were measured in whole-blood samples by flow cytometry. Associations were assessed using univariate and multivariate median regressions. Median cIMT was similar between HIV-positive and HIV-negative participants (P=0.3), although HIV-positive patients had significantly higher Framingham risk score (P=0.009) and systemic inflammation. Expression of two monocyte markers, CD11b and CX3CR1, independently predicted carotid artery thickness in HIV-positive individuals after controlling for Framingham risk score (P=0.025 and 0.015, respectively). These markers were not predictive of carotid artery thickening in controls. Our study indicates that monocyte surface markers may serve as novel predictors of CVD in HIV-positive individuals and is consistent with an important role for monocyte activation in the progression of HIV-related cardiovascular pathology.

Role of MIF in myocardial ischaemia and infarction: insight from recent clinical and experimental findings.

First discovered in 1966 as an inflammatory cytokine, MIF (macrophage migration inhibitory factor) has been extensively studied for its pivotal role in a variety of inflammatory diseases, including rheumatoid arthritis and atherosclerosis. Although initial studies over a decade ago reported increases in circulating MIF levels following acute MI (myocardial infarction), the dynamic changes in MIF and its pathophysiological significance following MI have been unknown until recently. In the present review, we summarize recent experimental and clinical studies examining the diverse functions of MIF across the spectrum of acute MI from brief ischaemia to post-infarct healing. Following an acute ischaemic insult, MIF is rapidly released from jeopardized cardiomyocytes, followed by a persistent MIF production and release from activated immune cells, resulting in a sustained increase in circulating levels of MIF. Recent studies have documented two distinct actions of MIF following acute MI. In the supra-acute phase of ischaemia, MIF mediates cardioprotection via several distinct mechanisms, including metabolic activation, apoptosis suppression and antioxidative stress. In prolonged myocardial ischaemia, however, MIF promotes inflammatory responses with largely detrimental effects on cardiac function and remodelling. The pro-inflammatory properties of MIF are complex and involve MIF derived from cardiac and immune cells contributing sequentially to the innate immune response evoked by MI. Emerging evidence on the role of MIF in myocardial ischaemia and infarction highlights a significant potential for the clinical use of MIF agonists or antagonists and as a unique cardiac biomarker.

Diverse regulation of cardiac expression of relaxin receptor by α1- and ß1-adrenoceptors.

PURPOSE: Relaxin, a new drug for heart failure therapy, exerts its cardiac actions through relaxin family peptide receptor 1 (RXFP1). Factors regulating RXFP1 expression remain unknown. We have investigated effects of activation of adrenoceptors (AR), an important modulator in the development and prognosis of heart failure, on expression of RXFP1 in rat cardiomyocytes and mouse left ventricles (LV). METHODS: Expression of RXFP1 at mRNA (real-time PCR) and protein levels (immunoblotting) was measured in cardiomyocytes treated with α- and ß-AR agonists or antagonists. RXFP1 expression was also determined in the LV of transgenic mouse strains with cardiac-restricted overexpression of α1A-, α1B- or ß2-AR. Specific inhibitors were used to explore signal pathways involved in α1-AR mediated regulation of RXFP1 in cardiomyocytes. RESULTS: In cultured cardiomyocytes, α1-AR stimulation resulted in 2-3 fold increase in RXFP1 mRNA (P < 0.001), which was blocked by specific inhibitors for protein kinase C (PKC) or mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK). Activation of ß1-, but not ß2-AR, significantly inhibited RXFP1 expression (P < 0.001). Relative to respective wild-type controls, RXFP1 mRNA levels in the LV of mice overexpressing α1A- or α1B-AR were increased by 3- or 10-fold, respectively, but unchanged in ß2-AR transgenic hearts. Upregulation by α1-AR stimulation RXFP1 expression was confirmed at protein levels both in vitro and in vivo. CONCLUSIONS: Expression of RXFP1 was up-regulated by α1-AR but suppressed by ß-AR, mainly ß1-AR subtype, in cardiomyocytes. Future studies are warranted to characterize the functional significance of such regulation, especially in the setting of heart failure.

Haemodynamic and metabolic adaptations in coronary microvascular disease.

OBJECTIVE: We aimed to evaluate the microcirculatory resistance (MR) and myocardial metabolic adaptations at rest and in response to increased cardiac workload in patients with suspected coronary microvascular dysfunction (CMD). METHODS: Patients with objective ischaemia and/or myocardial injury and non-obstructive coronary artery disease underwent thermodilution-derived microcirculatory assessment and transcardiac blood sampling during graded exercise with adenosine-mediated hyperaemia. We measured MR at rest and following supine cycle ergometry. Patients (n=24) were stratified by the resting index of MR (IMR) into normal-IMR (IMR<22U, n=12) and high-IMR groups (IMR≥22U, n=12). RESULTS: The mean age was 57 years; 67% were males and 38% had hypertension. The normal-IMR group had increased IMR response to exercise (16±5 vs 23±12U, p=0.03) compared with the high-IMR group, who had persistently elevated IMR at rest and following exercise (38±19 vs 33±15U, p=0.39) despite similar exercise duration and rate-pressure product between the groups, both p>0.05. The normal-IMR group had augmented oxygen extraction ratio following exercise (53±18 vs 64±11%, p=0.03) compared with the high-IMR group (65±14 vs 59±11%, p=0.26). The postexercise lactate uptake was greater in the high-IMR (0.04±0.05 vs 0.11±0.07 mmol/L, p=0.004) compared with normal-IMR group (0.08±0.06 vs 0.09±0.09 mmol/L, p=0.67). The high-IMR group demonstrated greater troponin release following exercise compared with the normal-IMR group (0.13±0.12 vs 0.001±0.05 ng/L, p=0.03). CONCLUSIONS: Patients with suspected CMD appear to have distinctive microcirculatory resistive and myocardial metabolic profiles at rest and in response to exercise. These differences in phenotypes may permit individualised therapies targeting microvascular responsiveness (normal-IMR group) and/or myocardial metabolic adaptations (normal-IMR and high-IMR groups).

Influence of atrial fibrillation on microRNA expression profiles in left and right atria from patients with valvular heart disease.

Chronic atrial fibrillation (AF) is a complication associated with the dilated atria of patients with valvular heart disease and contributes to worsened pathology. We examined microRNA (miRNA) expression profiles in right and left atrial appendage tissue from valvular heart disease (VHD) patients. Right atrial (RA) appendage from patients undergoing coronary artery bypass grafting and left atrial (LA) appendage from healthy hearts, not used for transplant, were used as controls. There was no detectable effect of chronic AF on miRNA expression in LA tissue, but miRNA expression in RA was strongly influenced by AF, with 47 miRNAs (15 higher, 32 lower) showing differential expression between the AF and control sinus rhythm groups. VHD induced different changes in miRNA expression in LA compared with RA. Fifty-three (12 higher, 41 lower) miRNAs were altered by VHD in LA, compared with 5 (4 higher, 1 lower) in RA tissue. miRNA profiles also differed between VHD-LA and VHD-RA (13 higher, 26 lower). We conclude that VHD and AF influence miRNA expression patterns in LA and RA, but these are affected differently by disease progression and by the development of AF. These findings provide new insights into the progression of VHD.

Novel role of platelets in mediating inflammatory responses and ventricular rupture or remodeling following myocardial infarction.

OBJECTIVE: The goal of this study was to investigate the role of platelets in systemic and cardiac inflammatory responses and the development of postinfarct ventricular complications, as well as the efficacy of antiplatelet interventions. METHODS AND RESULTS: Using a mouse myocardial infarction (MI) model, we determined platelet accumulation and severity of inflammation within the infarcted myocardium by immunohistochemistry and biochemical assays, analyzed peripheral blood platelet-leukocyte conjugation using flow cytometry, and tested antiplatelet interventions, including thienopyridines and platelet depletion. Platelets accumulated within the infarcted region early post-MI and colocalized with inflammatory cells. MI evoked early increase in circulating platelet-leukocyte conjugation mediated by P-selectin/P-selectin glycoprotein ligand-1. Antiplatelet interventions inhibited platelet-leukocyte conjugation in peripheral blood, inflammatory infiltration, content of matrix metalloproteinases or plasminogen activation, and expression of inflammatory mediators in the infarcted myocardium (all P<0.05) and lowered rupture incidence (P<0.01). Clopidogrel therapy alleviated the extent of chronic ventricular dilatation by serial echocardiography. CONCLUSIONS: Platelets play a pivotal role in promoting systemic and cardiac inflammatory responses post-MI. Platelets accumulate within the infarcted myocardium, contributing to regional inflammation, ventricular remodeling, and rupture. Antiplatelet therapy reduces the severity of inflammation and risk of post-MI complications, demonstrating a previously unrecognized protective action.

Plasma lipidomic analysis of stable and unstable coronary artery disease.

OBJECTIVE: Traditional risk factors for coronary artery disease (CAD) fail to adequately distinguish patients who have atherosclerotic plaques susceptible to instability from those who have more benign forms. Using plasma lipid profiling, this study aimed to provide insight into disease pathogenesis and evaluate the potential of lipid profiles to assess risk of future plaque instability. METHODS AND RESULTS: Plasma lipid profiles containing 305 lipids were measured on 220 individuals (matched healthy controls, n=80; stable angina, n=60; unstable coronary syndrome, n=80) using electrospray-ionisation tandem mass spectrometry. ReliefF feature selection coupled with an L2-regularized logistic regression based classifier was used to create multivariate classification models which were verified via 3-fold cross-validation (1000 repeats). Models incorporating both lipids and traditional risk factors provided improved classification of unstable CAD from stable CAD (C-statistic=0.875, 95% CI 0.874-0.877) compared with models containing only traditional risk factors (C-statistic=0.796, 95% CI 0.795-0.798). Many of the lipids identified as discriminatory for unstable CAD displayed an association with disease acuity (severity), suggesting that they are antecedents to the onset of acute coronary syndrome. CONCLUSION: Plasma lipid profiling may contribute to a new approach to risk stratification for unstable CAD.

Effect of altering dietary n-6:n-3 PUFA ratio on cardiovascular risk measures in patients treated with statins: a pilot study.

Increasing dietary n-3 PUFA decreases the risk of CHD. Since n-6 PUFA compete with n-3 PUFA for common metabolic enzymes, the n-6:n-3 ratio intake rather than the n-3 PUFA intake levels per se may be critical. We aimed to examine whether altering the n-6:n-3 ratio affects cardiovascular risk factors in hypercholesterolaemic patients on lipid management with statins. Adhering to a randomised, crossover study design, patients on statins (n 11) were placed on one of two dietary interventions (Diet high-ratio (HR) - n-6:n-3 = 30:1 or Diet low-ratio (LR) - n-6:n-3 = 1·7:1) for 4 weeks followed after an 8-week washout period by the alternate diet. Foods enriched with n-3 or n-6 PUFA were delivered to each patient, who were given clear guidance on consumption expectations for the study. Measures of lipid profile, blood pressure and vascular function were determined. Diet LR significantly reduced body weight, LDL-cholesterol, high-sensitivity C-reactive protein, blood pressure and the apoA-1:apoB ratio. While Diet HR trended towards a similar cardioprotective profile, most of the parameters examined did not reach statistical significance. A direct comparison between diets demonstrated no significant superiority of Diet LR over Diet HR. These results suggest that a dietary intervention focused on n-6 and n-3 fatty acids may improve cardiovascular risk factors in patients over and above standard lipid management, but there is no significant advantage of a low n-6:n-3 ratio diet when compared to a high-ratio diet.

An Effective Protocol for Management of International Arrivals at Risk in COVID-19 Pandemic: Experience From the Pre-Hospital Covid-19 Response Teams at Xi'an, China.

Background: The coronavirus disease 2019 (COVID-19) outbreak within China has been well controlled and stabilized since early April 2020. Therefore, the current major focus in China is to prevent the introduction of COVID into China from international arrivals. To achieve this, pre-Hospital COVID-19 Response Teams (pHCRTs) have been established. Context: The pHRCTs were established in Xi'an, China in early 2020. During the 12 months covered in this report, there were 356 international flight arrivals with over 5,000 COVID-19 Nucleic Acid Test (NAT) positive people, 500 of them with symptomatic COVID-19 and requiring admission to special hospitals. All other arrivals were managed in dedicated facilities by pHRCTs. The outcome measure of this report was the number of positive cases among the pHRCT members. Details: Four hundred forty-two staff worked in the pHCRTs during the reporting period. Despite multiple throat swab PCR tests during their pHRCTs tour of duty, and the subsequent mandatory 14-day quarantine required before return to the general community, no staff became NAT positive. Conclusion: The prevention of community transmission from imported cases is a vital part of the strategy to maintain the low numbers of cases in countries which have achieved control, or suppression of local internal cases. The program of pHCRTs described in this article gives successful protocols for transportation of patients who are infectious based on the minimal transmission of virus and staff safety. The strategies employed may prove useful in future pandemics.