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INTRODUCTION Early-onset peritonitis (EOP) is a risk factor for mortality in peritoneal dialysis (PD) patients. This study investigates the clinical features and outcomes of EOP in elderly patients. METHODS This multicenter retrospective study evaluated 433 elderly PD patients with end-stage renal disease. The cohort was divided into nonperitonitis group (n = 239), EOP group (≤12 months, n = 109) and late-onset peritonitis (LOP) group (>12 months, n = 85). Clinical data, treatment results, and outcomes were compared between the groups. RESULTS Compared with LOP group, there were no significant intergroup differences in the rate of primary recovery, complete cure, relapse, catheter removal, or death from PDAP (p >0.05) in the most recent PDAP episode. However, Kaplan-Meier analysis showed that patients in the EOP group were likely to have multiple episodes of PD-associated peritonitis (PDAP), technique failure, all-cause death, and composite endpoint in the long-term prognostic outcomes (p

Objective: Niacin therapy fails to reduce cardiovascular events in statin-treated subjects even though it increases plasma HDL-C (HDL [high-density lipoprotein] cholesterol) and decreases LDL-C (LDL [low-density lipoprotein] cholesterol) and triglyceride levels. To investigate potential mechanisms for this lack of cardioprotection, we quantified the HDL proteome of subjects in 2 niacin clinical trials: the CPC study (Carotid Plaque Composition) and the HDL Proteomics substudy of the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides). Approach and Results: Using targeted proteomics, we quantified levels of 31 HDL proteins from 124 CPC subjects and 120 AIM-HIGH subjects. The samples were obtained at baseline and after 1 year of statin monotherapy or niacin-statin combination therapy. Compared with statin monotherapy, niacin-statin combination therapy did not reduce HDL-associated apolipoproteins APOC1, APOC2, APOC3, and APOC4, despite significantly lowering triglycerides. In contrast, niacin markedly elevated HDL-associated PLTP (phospholipid transfer protein), CLU (clusterin), and HP/HPR (haptoglobin/haptoglobin-related proteins; P ≤0.0001 for each) in both the CPC and AIM-HIGH cohorts. Conclusions: The addition of niacin to statin therapy resulted in elevated levels of multiple HDL proteins linked to increased atherosclerotic risk, which might have compromised the cardioprotective effects associated with higher HDL-C levels and lower levels of LDL-C and triglycerides. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00715273; NCT00880178; NCT00120289.

PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events. The clinical benefits presumably result from favorable effects on atherosclerotic plaques. Lipid-core and plaque inflammation have been recognized as main determinants of risk for plaque rupture and cardiovascular events. Both can be noninvasively assessed with carotid MRI. We studied if PCSK9 inhibition with alirocumab induces regression in lipid-core or plaque inflammation within 6 months as measured by MRI. Patients with non-calcified carotid plaque(s) and baseline LDL-C ≥ 70 mg/dl, who were statin-intolerant or taking a low-dose statin (≤ 10 mg per day of atorvastatin or an equivalent), received subcutaneous alirocumab 150 mg every 2 weeks. Carotid MRI was performed at baseline and 6 months after treatment, including pre- and post-contrast images for measuring percent lipid-core volume (%LC) and dynamic contrast-enhanced images for measuring microvessel leakiness (Ktrans), a marker of inflammation. Twenty-eight patients completed the study (69 ± 9 years; 64% male). Alirocumab led to significant changes in LDL-C (p

Objective To investigate the relationship between admission SBP and subsequent cardiovascular and all-cause mortality in older patients hospitalized for acute coronary syndrome (ACS). Methods This is a retrospective observational study. Data from the CBD Bank (Cardiovascular Center Beijing Friendship Hospital Database Bank) were used to analyze the cardiovascular and all-cause mortality during hospitalization and over the follow-up period in relation to admission SBP among patients aged at least 65 years admitted for ACS from December 2012 through July 2019. Results were presented according to SBP quartiles: Q1, less than 120 mmHg; Q2, from 120 to 129 mmHg; Q3, from 130 to 143 mmHg; and Q4, at or above 144 mmHg. Results A total of 6785 patients were included in this cohort study. Mean (SD) patient age was 74.0 (6.5) years, and 47.6% were women. Mean (SD) follow-up time was 2.54 (1.82) years. A nonlinear relation was observed between SBP at admission and cardiovascular and all-cause mortality during hospitalization and over the follow-up period using restricted cubic splines. After adjustment for potential confounders, patients in Q1 had higher risk for 2-year cardiovascular death by Cox proportional hazard model compared with patients in Q2 [hazard ratio, 1.58; 95% confidence interval (CI), 1.12-2.21, P = 0.009], whereas patients in Q3 or Q4 exhibited a trend towards increased risk for 2-year cardiovascular death (hazard ratio, 1.33, 95% CI, 0.95-1.86, P = 0.094, for Q3 vs. Q2; and hazard ratio, 1.28, 95% CI, 0.91-1.82, P = 0.160, for Q4 vs. Q2). Meanwhile, when compared with patients in Q1, patients in Q2 had lower risk for 2-year cardiovascular death (hazard ratio, 0.64; 95% CI, 0.45-0.89, P = 0.009) whereas patients in Q3 or Q4 had similar risk for cardiovascular death (hazard ratio, 0.85, 95% CI, 0.63-1.14, P = 0.272, for Q3 vs. Q1; and hazard ratio, 0.82, 95% CI, 0.59-1.13, P = 0.221, for Q4 vs. Q1). However, low-admission SBP was not an independent predictor of 2-year all-cause mortality in this population. Conclusion Among patients aged at least 65 years admitted for ACS, there is a J-curve relationship between supine admission SBP and risk for 2-year cardiovascular death, with a nadir at 120-129 mmHg.

Increased body mass index (BMI) is a well-established risk factor for cardiovascular disease; however, patients with elevated BMI, in comparison to those with low BMI, seem to have better survival, a phenomenon reported as "obesity paradox," which remains controversial. We investigated the effect of BMI on cardiac mortality post acute myocardial infarction (AMI).In this analysis, 3562 AMI patients were included and classified into four groups based on BMI values. The primary endpoint was cardiac death. Compared to normoweight group, overweight and obese group subjects were younger, mostly men, and more likely to receive percutaneous coronary intervention (PCI) and had higher levels of glucose and lipids, but lower level of NTproBNP. Subjects in the underweight group were older, were mostly women, had lower Barthel index (BI), were less likely to receive PCI, and had lower levels of glucose and lipids, but higher level of N-terminal pro-brain natriuretic peptide (NTproBNP) and higher rates of left ventricular ejection fraction (LVEF) < 50%. During a median follow-up period of 1.9 years, cardiac death occurred significantly more in the underweight group (30.0%, 10.6%, 7.0%, and 5.0% among the four groups from underweight to obese; P < 0.001 for trend). The Cox analysis revealed that underweight was an independent predictor of subsequent cardiac death (odds ratio (OR), 1.86; 95% confidence interval (CI), 1.07-3.25) and identified that older age, BI < 60, higher levels of cardiac troponin I (cTnI), LVEF < 50%, and not receiving PCI were independently associated with increased risk of cardiac death.Patients who were underweight were at greater risk of cardiac death post AMI. In addition, older age, frail, higher levels of cTnI, LVEF < 50%, and not receiving PCI also independently predicted cardiac mortality post AMI.

To detect whether Danlou Tablet (丹蒌片, DLT) regulates the hypoxia-induced factor (HIF)-1 α-angiopoietin-like 4 (Angptl4) mRNA signaling pathway and explore the role of DLT in treating chronic intermittent hypoxia (CIH)-induced dyslipidemia and arteriosclerosis. The mature adipocytes were obtained from 3T3-L1 cell culturation and allocated into 8 groups including control groups (Groups 1 and 5, 0.1 mL of cell culture grade water); DLT groups (Groups 2 and 6, 0.1 mL of 1,000 µg/mL DLT submicron powder solution); dimethyloxalylglycine (DMOG) groups (Groups 3 and 7, DMOG and 0.1 mL of cell culture grade water); DMOG plus DLT groups (Groups 4 and 8, DMOG and 0.1 mL of 1,000 µg/mL DLT submicron powder solution). Groups 1–4 used mature adipocytes and groups 5–8 used HIF-1 α-siRNA lentivirus-transfected mature adipocytes. After 24-h treatment, real-time polymerase chain reaction and Western blot were employed to determine the mRNA and protein expression levels of HIF-1 α and Angptl4. In animal experiments, the CIH model in ApoE−/− mice was established. Sixteen mice were complete randomly divided into 4 groups including sham group, CIH model group [intermittent hypoxia and normal saline (2 mL/time) gavage once a day]; Angptl4 Ab group [intermittent hypoxia and Angptl4 antibody (30 mg/kg) intraperitoneally injected every week]; DLT group [intermittent hypoxia and DLT (250 mg/kg) once a day], 4 mice in each group. After 4-week treatment, enzyme linked immunosorbent assay was used to detect the expression levels of serum total cholesterol (TC) and triglyceride (TG). Hematoxylin-eosin and CD68 staining were used to observe the morphological properties of arterial plaques. Angptl4 expression was dependent on HIF-1 α, with a reduction in mRNA expression and no response in protein level to DMOG or DLT treatment in relation to siHIF-1 α -transfected cells. DLT inhibited HIF-1 α and Angptl4 mRNA expression (P

Background: Inflammation plays an important role in diabetes mellitus (DM)-related acute ischemic stroke (AIS). The mechanisms of un-resolved inflammation in DM-related AIS are not fully understood. Specialized pro-resolving mediators (SPMs) are key regulators that promote resolution of inflammation. We aimed to examine resolution function in patients with AIS complicated with DM, and explore potential treatment effects of one of the SPMs, resolvin D2 (RvD2) ex vivo and in vivo. Methods: Cultured human macrophages, which were derived from peripheral blood mononuclear cells of AIS and none-AIS patients with or without DM, were stimulated with oxidized-low density lipoprotein (ox-LDL). Levels of SPMs and inflammatory markers were analyzed and RvD2 treatment effects were evaluated in these cells. For experiments in vivo, challenges with high fat diet and low-dose streptozotocin (STZ) were used to induce DM in C57BL/6J mice. AIS model was established by permanent middle cerebral artery occlusion (pMCAO) followed by intra-cerebroventricular injection of RvD2. Results: Compared with macrophages of AIS patients without DM, the ratios of SPMs to leukotriene B4 (LTB4) were decreased in AIS patients with DM, accompanied by reduced expression of SPM synthesis enzyme, 15-lipoxygenase-1. Moreover, the levels of pro-inflammatory pathway markers were increased and the macrophages were skewed to M1 polarization in AIS patients with DM. In mice, treatment with RvD2 ameliorated pMCAO-induced brain injury, neurological dysfunction, and inflammatory response. Furthermore, RvD2 rescued resolution of inflammation by promoting macrophage /microglia polarization to pro-resolving M2 phenotype ex vivo and in vivo. Conclusions: Our data demonstrate resolution of inflammation is impaired by DM in AIS patients, implicating a novel mechanism of un-resolved inflammation in DM-related AIS. Furthermore, RvD2 promotes inflammation resolution in macrophages/microglia and protects DM-related AIS, and may thus serve as a novel therapeutic target.

ObjectivesSerum calcium levels (sCa) were reported to be associated with risk of cardiovascular diseases. The aim of this study was to analyse the association between sCa and long-term mortality in patients with acute coronary syndrome (ACS).DesignA retrospective observational cohort study.SettingSingle-centre study with participants recruited from the local area.ParticipantsA total of consecutive 13 772 patients with ACS were included in this analysis. Patients were divided based on their sCa profile (≤2.1 mmol/L, 2.1–2.2 mmol/L, 2.2–2.3 mmol/L, 2.3–2.4 mmol/L, 2.4–2.5 mmol/L,>2.5 mmol/L) and followed up for a median of 2.96 years (IQR 1.01–4.07).Primary outcomeLong-term all-cause mortality.ResultsDuring a median follow-up period of 2.96 years, patients with sCa ≤2.1 mmol/L had the highest cumulative incidences of all-cause mortality (16.7%), whereas those with sCa 2.4–2.5 mmol/L had the lowest cumulative incidences of all-cause mortality (3.5%). After adjusting for potentially confounding variables, the Cox analysis revealed that compared with the reference group (sCa 2.4–2.5 mmol/L), all the other groups had higher mortality except for the sCa 2.3–2.4 mmol/L group (HR, 1.32, 95% CI 0.93 to 1.87). Restricted cubic splines showed that the relationship between sCa and all-cause mortality seemed to be U shaped. The optimal sCa cut-off point, 2.35 mmol/L, was determined based on the shape of restricted cubic splines.ConclusionsAltered serum calcium homeostasis at admission independently predicts all-cause mortality in patients with ACS. In addition, a U-shaped relationship between sCa and all-cause mortality exists, and maintaining sCa at approximately 2.35 mmol/L may minimise the risk of mortality.

Objective To investigate the relationship between admission diastolic blood pressure (DBP) and subsequent cardiovascular and all-cause mortality in elderly patients with acute coronary syndrome (ACS). Methods This is a retrospective observational study. Consecutive patients ≥65 years of age admitted for ACS at a 2,300-bed tertiary hospital from December 2012 to July 2019 were included. The association between admission DBP and cardiovascular and all-cause mortality during hospitalization and over the follow-up period among this population were analyzed using multivariate COX regression model. Results were presented according to DBP quartiles: Q1, less than 67 mm Hg; Q2, from 67 to 72 mm Hg; Q3, from 73 to 80 mm Hg; and Q4, above 80 mm Hg. Results A total of 6 785 patients were included in this cohort study. Mean (SD) patient age was 74.0 (6.5) years, and 47.6% were women. Mean (SD) follow-up time was 2.54 (1.82) years. A non-linear relation was observed between DBP at admission and cardiovascular and all-cause mortality during hospitalization and over the follow-up period using restricted cubic splines. After adjustment for potential confounders, patients in Q3 or Q2 had lower risk for 2-year cardiovascular death by Cox proportional hazard model compared with patients in Q4 (hazard ratio [HR] 0.66; 95% confidence interval [CI], 0.48–0.90, P=0.010, for Q3 vs Q4; and HR 0.72; 95% CI, 0.53–0.99, P=0.041, for Q2vs Q4), while patients in Q1 had similar risk for cardiovascular death with that of patients in Q4. Meanwhile, when compared with patients in Q1, patients in Q3 had lower risk for 2-year cardiovascular death (HR, 0.72; 95% CI, 0.53–0.97, P=0.033). However, lower or higher admission DBP was not an independent predictor of 2-year all-cause mortality in this population. Conclusion Among patients aged ≥65 years admitted for ACS, there is a J-curve relationship between supine admission DBP and risk for 2-year cardiovascular death, with a nadir at 73–80 mm Hg. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support Study population and selectionAdjusted multivariate COX regression

This study investigated whether a novel index of stress hyperglycemia might have a better prognostic value compared to admission glycemia alone in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). The acute-to-chronic glycemic ratio was expressed as admission blood glucose (ABG) devided by the estimated average glucose (eAG), and eAG was derived from the glycated hemoglobin (HbA1c). A total of 1300 consecutive patients with STEMI treated with PCI were included. Baseline data and outcomes were analyzed. The study end point was a composite of in-hospital all-cause death, cardiogenic shock, and acute pulmonary edema. Accuracy was defined with area under the curve (AUC) by a receiver–operating characteristic (ROC) curve analysis. After multivariate adjustment, both ABG/eAG and ABG were closely associated with an increased risk of the composite end point in nondiabetic patients. However, only ABG/eAG (odds ratio = 2.45, 95% confidence interval: 1.24-4.82, P = .010), instead of ABG, was associated with the outcomes in diabetic patients. Compared to ABG, ABG/eAG had an equivalent predictive value in nondiabetic patients but a superior discriminatory ability in diabetic patients (AUC improved from 0.52-0.63, P < .001). Taken together, ABG/eAG provides more significant in-hospital prognostic information than ABG in diabetic patients with STEMI after PCI.

The prognostic value of the CHA2DS2-VASc score in acute coronary syndrome (ACS) patients without atrial fibrillation (AF) who underwent percutaneous coronary intervention remains uncertain. We examine the association of the CHA2DS2-VASc score and major adverse cardiovascular events (MACE) in this population and compared its risk prediction with 2 other commonly used risk scores (Global Registry of Acute Coronary Events [GRACE] and thrombolysis in myocardial infarction [TIMI]). A total of 3,745 consecutive ACS patients without AF who underwent percutaneous coronary intervention during 2013 to 2017 were classified into 4 groups according to the CHA2DS2-VASc score: low (0 to 1), moderate (2 to 3), high (4 to 5), and very high (>5). Incidences of MACE including cardiovascular death, nonfatal myocardial infarction, or stroke in-hospital and during a median follow-up of 33 months were compared among the 4 groups. Receiver-operating characteristic curves were generated to compare CHA2DS2-VASc with GRACE and TIMI for risk prediction. The incidences of in-hospital MACE (3.5%, 6.6%, 7.6%, and 9.1%, p

Severe haemorrhagic transformation (HT), a common complication of recombinant tissue plasminogen activator (rtPA) treatment, predicts poor clinical outcomes in acute ischaemic stroke. The search for agents to mitigate this effect includes investigating biomolecules involved in neovascularization. This study examines the role of Cathepsin K (Ctsk) in rtPA-induced HT after focal cerebral ischaemia in mice. After knockout of Ctsk, the gene encoding Ctsk, the outcomes of Ctsk+/+ and Ctsk−/− mice were compared 24 h after rtPA-treated cerebral ischaemia with respect to HT severity, neurological deficits, brain oedema, infarct volume, number of apoptotic neurons and activated microglia/macrophage, blood–brain barrier integrity, vascular endothelial growth factor (VEGF) expression and Akt-mTOR pathway activation. We observed that haemoglobin levels, brain oedema and infarct volume were significantly greater and resulted in more severe neurological deficits in Ctsk−/− than in Ctsk+/+ mice. Consistent with our hypothesis, the number of NeuN-positive neurons was lower and the number of TUNEL-positive apoptotic neurons and activated microglia/macrophage was higher in Ctsk−/− than in Ctsk+/+ mice. Ctsk knockout mice exhibited more severe blood–brain barrier (BBB) disruption, with microvascular endothelial cells exhibiting greater VEGF expression and lower ratios of phospo-Akt/Akt and phospo-mTOR/mTOR than in Ctsk+/+ mice. This study is the first to provide molecular insights into Ctsk-regulated HT after cerebral ischaemia, suggesting that Ctsk deficiency may disrupt the BBB via Akt/mTOR/VEGF signalling, resulting in neurological deficits and neuron apoptosis. Ctsk administration has the potential as a novel modality for improving the safety of rtPA treatment following stroke.

Background: Inflammation plays an important role in diabetes mellitus (DM) and its related complications, including atherosclerosis and acute ischemic stroke (AIS). The mechanisms of excessive inflammation in DM are not fully understood. Specialized pro-resolving mediators (SPMs) are key regulators that promote resolution of inflammation. Unbalance of pro-resolving and pro-inflammatory signals may be the key pathogenesis in DM and DM-related diseases. We examined the resolution function in macrophages of DM patients with AIS.Methods: Macrophages were derived from peripheral blood mononuclear cells of AIS and none-AIS patients with or without DM. The cultured macrophages were treated with oxidized low-density lipoprotein. Resolution and inflammatory pathway markers were analyzed in the culture medium and cells. Results: In AIS patients, the ratios of SPMs to leukotriene B4 (LTB4) released by macrophages were decreased in those with DM compared to those without DM. Oxidized low-density lipoprotein treatment further reduced the ratios of SPMs/LTB4 in DM patients with AIS, but such a reduction was not observed in none-DM AIS patients. Analysis of M2/M1 polarization and MAPK/NFkB pathway markers also demonstrated un-resolved inflammation in macrophages of AIS patients with DM. Treatment with one of the SPMs, resolvin D2, rescued the resolution function and ameliorated inflammation in macrophages from these patients.Conclusions: Our data demonstrated that resolution of inflammation is disturbed by DM in macrophages of AIS patients, implicating a novel mechanism of un-resolved inflammation in DM-related vascular disorder. Exogenous SPMs treatment can rescue resolution and downregulate inflammatory signals, and may thus be beneficial in DM-related AIS.

Introduction: Medically underserved (US) populations have an increased level of atherosclerotic cardiovascular disease (ASCVD) risk, however, few studies investigated ASCVD risk reduction in US. Methods: Of 217 subjects with ApoB ≥120 mg/dL and carotid atherosclerosis (≥15% stenosis by ultrasound) enrolled in the Carotid Plaque Composition by MRI (CPC) study between 2005 and 2011, US (n=33) was defined as those without adequate healthcare insurance, while AS (n=184) included those with adequate healthcare coverage. All subjects received atorvastatin-based lipid therapies and lifestyle intervention for 2 years. Metabolic and inflammatory risk factors were compared between AS and US. Results: At baseline, compared to AS, US displayed higher levels of metabolic and inflammatory risk including systolic blood pressure (140±27 vs. 131±18 mmHg, p=0.04), fasting glucose (125±59 vs. 102±22 mg/dL, p=0.03) and fasting insulin (39±33 vs. 28±20 µU/dL, p=0.03) which resulted in higher insulin resistance (HOMA-IR 2.2±0.4 vs. 1.3±0.1, p=0.03), and hsCRP (5.6±1.5 vs. 2.8±0.2 mg/L, p=0.03). Over 2 years of intervention, US and AS showed similar reductions in LDL-C (-10.7% vs. -16% per year, p=0.2), triglycerides (-16.7% vs. -15.9% per year, p=0.4), and hsCRP (-0.11% vs. -0.04% per year, p=0.1). However, US continued to show significantly higher levels of fasting blood glucose (115±6.0 vs. 101±2.0 mg/dL, p=0.03) and HOMA-IR (1.9±0.2 vs. 1.5±0.1, p=0.047), and hsCRP (3.9±0.7 vs. 1.9±0.2 mg/L, p

AIM To evaluate the prognostic value of triglyceride-glucose (TyG) index in nondiabetic patients with acute coronary syndrome (ACS) with low-density lipoprotein cholesterol (LDL-C) below 1.8 mmol/L. METHODS A total of 1655 nondiabetic patients with ACS with LDL-C below 1.8 mmol/L were included in the analysis. Patients were stratified into two groups. The incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, and major adverse cardiac and cerebral event during a median of 35.6-month follow-up were determined and compared between the two groups. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL)×fasting plasma glucose (mg/dL)/2]. RESULTS Compared with the TyG index ＜8.33 group, the TyG index ≥ 8.33 group had a significantly higher incidence of AMI (21.2% vs. 15.2%, p=0.014) and larger infarct size in patients with AMI [the peak value of troponin I: 10.4 vs. 4.8 ng/ml, p=0.003; the peak value of Creatine kinase MB: 52.8 vs. 22.0 ng/ml, p=0.006; the peak value of myoglobin: 73.7 vs. 46.0 ng/ml, p=0.038]. Although there was no significant difference in mortality between the two groups, the incidence of revascularization of the TyG index ≥ 8.33 group was significantly higher than that of the TyG index ＜8.33 group (8.9% vs. 5.0%, p=0.035). A multivariable Cox regression revealed that the TyG index was positively associated with revascularization [hazard ratio, 1.67; 95% confidence interval, 1.02-2.75; p=0.043]. CONCLUSIONS In nondiabetic patients with ACS with LDL-C below 1.8 mmol/L, a high TyG index level was associated with higher incidence of AMI, larger infarct size, and higher incidence of revascularization. A high TyG index level might be a valid predictor of subsequent revascularization.

Background Triglyceride glucose (TyG) index is considered a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular (CV) outcomes. However, the prognostic value of TyG index in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI) remains unclear. Methods A total of 1932 consecutive patients with T2DM and AMI were enrolled in this study. Patients were divided into tertiles according to their TyG index levels. The incidence of major adverse cardiac and cerebral events (MACCEs) was recorded. The TyG index was calculated as the ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. Results Competing risk regression revealed that the TyG index was positively associated with CV death [2.71(1.92 to 3.83), p p = 0.001], cardiac rehospitalization [2.42(1.81 to 3.24), p p p p p Conclusions The TyG index was significantly associated with MACCEs, suggesting that the TyG index may be a valid marker for risk stratification and prognosis in patients with T2DM and AMI. Trial registration Retrospectively registered.

Background Serum calcium levels were reported to be associated with risk of cardiovascular diseases. The aim of this study was to analyze the association between serum calcium levels and all-cause mortality in patients with acute myocardial infarction (AMI). Methods A total of consecutive 3886 AMI patients with serum calcium data available were included in this analysis. The baseline characteristics, including clinical and laboratory parameters were collected. Patients were classified into 4 equally-sized groups based on serum calcium values (≤2.15, 2.16–2.23, 2.24–2.31, ≥2.32 mmol/L). Serum calcium tests were finished within 12 hours after admission. Patients were followed up for a median of 2.0 years (interquartile range 0.6–4.0). The primary endpoint was all-cause mortality. Results Compared to upper quartiles of serum calcium groups, subjects in the lowest quartile group (≤2.15 mmol/L) were older, lower body mass index (BMI), had lower levels of LDL-C and albumin, but higher level of NTproBNP. During a median follow-up period of 2.0 years, all-cause death occurred significantly more in the lowest quartile group (19.8%, 11.9%, 8.0% and 9.2% among the 4 groups from lowest to highest quartile, p Conclusion Low serum calcium levels on admission independently predict mortality in patients with AMI. Further studies are required to determine whether calcium supplementation could improve outcomes in AMI patients with hypocalcemia. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Beijing Natural Science Foundation (no. 7194253);Scientific Research Common Program of Beijing Municipal Commission of Education (KM201910025017)

Background Whether elderly women over 80 years old with acute coronary syndrome (ACS) should actively receive PCI treatment is still controversial. Purpose We assessed the effectiveness and long-term clinical outcomes of PCI in very elderly women patients, and detected predictive factors which contributed to the major adverse cardiovascular and cerebrovascular events (MACCE). Methods Female ACS patients aged ≥80 years were continuously enrolled from the hospital database bank (n=729, a mean age of 83.6±3.1 years). All patients were followed up for MACCE: non-fatal MI, stroke, heart failure (HF) re-hospitalization, cardiovascular (CV) death, and the composite of them. Before and after Propensity Score (PS) Matching (1:1), the incidences of MACCE were compared between female PCI group (n=232) and medical group (n=497). Clinical and coronary artery characteristics were analyzed in PCI treatment patients with (n=56) and without MACCE (n=176). Multivariate Cox regression analysis was performed to identify risk factors which independently associated with MACCE in female PCI patients. Results A total of 31.8% women (n=232) received PCI treatment in the retrospective study.Compared to medical group, PCI treatment significantly reduced the incidences of non-fatal MI (6.2%, 20.2%, p Conclusion In very elderly women with ACS, PCI treatment significantly decreased the risks of MACCE and improves the long-term clinical outcomes.STEMI and elevated NT-proBNP value were independently associated with the increase of the composite MACCE after PCI in this population. Funding Acknowledgement Type of funding source: None

Background To explore the relevant factors for early liver transplantation (LT) after Kasai portoenterostomy (KP). Methods Retrospective analysis was performed for 200 children with biliary atresia, who underwent LT with hepatic failure after KP. According to the interval between KP and LT, they were divided into three groups: G1 (≤6-month), G2 (6-month~ 2-year) and G3 (> 2-year). Gender, age of Kasai portoenterostomy, jaundice-clearance, cholangitis after KP and liver function indexes before LT were compared among the three groups. Results The proportion of patients with age of KP (≤90-day) in G1 was lower than that in G3 (P = 0.003). Jaundice-clearance occurred in 6 (7.6%), 26(28.6%) and 26 (86.7%) patients after KP in G1, G2 and G3 respectively (P P = 0.035, 90-day was lower than that of children at operation age ≤ 90-day (P = 0.002). The NLS rate of the children with jaundice-clearance after KP was significantly better than that of the children without jaundice-clearance (P P = 0.026). The NLS rate of patients of G2 and G3 with cholangitis after KP was lower than that in children without cholangitis (P = 0.017). Multiple logistic regression analysis showed uncleared jaundice after KP was a risk factor for the NLS time in patients. Conclusion The age of KP (> 90-day), jaundice-unclear and early cholangitis could reduce the NLS time after KP, which were related to early liver transplantation. Jaundice-unclear was a risk factor for early liver transplantation.

Introduction: The impact of early-onset peritonitis (EOP) on patients with diabetes undergoing peritoneal dialysis (PD) has not been adequately addressed. We therefore sought to investigate the effects of EOP on the therapeutic response to management and long-term prognostic outcomes in patients with diabetes undergoing PD. Methods: For this retrospective cohort study, we analyzed the data for patients with end-stage renal disease, who were also suffering from diabetes mellitus and had undergone PD between January 1, 2013, and December 31, 2018. EOP was defined as the first episode of peritoneal dialysis-related peritonitis (PDAP) occurring within 12 months of PD initiation. All patients were divided into an EOP group and a later-onset peritonitis (LOP) group. Clinical data, treatment results, and outcomes were compared between groups. Results: Ultimately, 202 patients were enrolled for the analysis. Compared to the EOP group, the LOP group had more Streptococcus (p = 0.033) and Pseudomonas (p = 0.048). Patients with diabetes in the EOP group were less likely to have PDAP-related death (OR 0.13, CI: 0.02–0.82, p = 0.030). Patients with diabetes in the EOP group were more likely to have multiple episodes of PDAP and had higher rates of technical failure and poorer patient survival than those in the LOP group, as indicated by Kaplan-Meier analysis (p = 0.019, p = 0.004, and p < 0.001). In the multivariate Cox proportional hazards model, EOP was a significant predictor for multiple PDAP (HR 4.20, CI: 1.48–11.96, p = 0.007), technical failure (HR 6.37, CI: 2.21–18.38, p = 0.001), and poorer patient survival (HR 3.09, CI: 1.45–6.58, p = 0.003). Conclusions: The occurrence of EOP is significantly associated with lower rates of PDAP-related death and poorer clinical outcomes in patients with diabetes undergoing PD.

Background Triglyceride glucose (TyG) index is considered a new marker for metabolic disorders. Although recent studies have found an association between TyG index level and vascular disease development, the prognostic value of TyG index in patients with acute myocardial infarction (AMI) remains unclear. Methods A total of 3181 patients with AMI, who underwent coronary angiography, were identified from the Cardiovascular Center of Beijing Friendship Hospital Database Bank and included in the analysis. Patients were stratified into 2 groups according to their baseline TyG index levels: the TyG index 2, smoker, diabetes mellitus, estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2, high-density lipoprotein cholesterol ≥ 1.01 mmol/L and left ventricular ejection fraction (LVEF) ≥ 0.50. The results also revealed that diabetes mellitus, previous AMI, eGFR, LVEF, and multi-vessel/left main coronary artery lesions were independent predictors of MACEs in patients with AMI (all P

Background Current guidelines recommend angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) as a first-line therapy in diabetic hypertensive patients and for secondary prevention in patients with obstructive coronary artery disease (OCAD). However, the effects of using ACEI/ARB before the initial diagnosis of OCAD on major adverse cardiac and cerebral event (MACCE) in diabetic hypertensive patients remain unclear. This study investigated whether using ACEI/ARB before the initial diagnosis of OCAD could be associated with improved clinical outcomes in diabetic hypertensive patients. Methods A total of 2501 patients with hypertension and diabetes, who were first diagnosed with OCAD by coronary angiography, were included in the analysis. Of the 2501 patients, 1300 did not used ACEI/ARB before the initial diagnosis of OCAD [the ACEI/ARB(-) group]; 1201 did [the ACEI/ARB(+) group]. Propensity score matching at 1:1 was performed to select 1050 patients from each group. Incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, heart function, and subsequent MACCE during a median of 25.4-month follow-up were determined and compared between the 2 groups. Results Compared with the ACEI/ARB(-) group, the ACEI/ARB(+) group had significantly lower incidence of AMI (22.5% vs. 28.4%, p Conclusions In diabetic hypertensive patients, treatment with ACEI/ARB before the initial diagnosis with OCAD was associated with decreased incidence of AMI, smaller infarct size, improved heart function, and lower incidences of non-fatal stroke and composite MACCE. Trial registration Retrospectively registered

BACKGROUND Low triiodothyronine (T3) syndrome (LT3S) is frequently seen in patients with acute myocardial infarction (AMI). We examined the association between LT3S and severity of myocardial injury and determined whether LT3S adds predictive value over thrombolysis in myocardial infarction (TIMI) risk score for in-hospital cardiovascular (CV) death. METHODS Of 2459 AMI patients, 529 pairs of euthyroid and LT3S individuals with similar baseline characteristics were identified using 1:1 propensity score matching. LT3S was defined as free T3 (fT3)

Niacin (nicotinic acid) has been used for primary and secondary coronary heart disease prevention for over 40 years. Until recently clinical trials incorporating niacin as part of an intervention strategy consistently demonstrated reduction in clinical events and lesion improvement, including ≥6% absolute mortality reduction. Two large clinical event trials in 2011 (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) and 2014 (Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events) concluded that niacin added to statin therapy did not provide clinical event benefit over statin alone. This has prompted some individuals to call for an end to the use of niacin in statin-treated patients and the US Food and Drug Administration to halt marketing of statin/niacin combination tablets. There are significant differences between the earlier clinical trials that revealed cardiovascular benefit of niacin and the 2 trials that failed to demonstrate a benefit. These differences include dyslipidemia types, niacin formulation, dosing, and timing. In general, the patient population that benefits the most from incorporating niacin in their treatment regimen can be defined by elevations in low-density lipoprotein cholesterol and triglycerides, and reduced high-density lipoprotein cholesterol. The niacin formulation and dose should be capable of achieving adequate lipoprotein change. Mealtime dosing of niacin, as opposed to bedtime dosing, may avoid a counter-regulatory hormone response, including catecholamines, because of altered fuel supply potentially leading to unexpected cardiovascular outcomes.

Objectives: The aim of this study was to investigate whether and what carotid plaque characteristics predict systemic cardiovascular outcomes in patients with clinically established atheros...

Background Increased body mass index (BMI) is a well-established risk factor for cardiovascular disease, however, patients with elevated BMI comparing to low BMI seem to have better survival, a phenomenon reported as “obesity paradox” which remains as a controversy. We investigated the effect of BMI, including underweight, normoweight, overweight and obese, on cardiac mortality post acute myocardial infarction (AMI). Methods This analysis included 3562 AMI patients with documented BMI. The baseline characteristics including clinical and laboratory parameters were collected at hospital admission for AMI. Patients were classified into 4 groups based on BMI values: underweight (BMI Results Of 3562, 110 (3%) were underweight, 1579 (44%) were normoweight, 1493 (42%) were overweight, and 380 (11%) were obese. Compared to the normoweight group, subjects in overweight and obese groups were younger, more men, more hypertension, more likely to receive percutaneous coronary intervention (PCI), and had higher levels of glucose and lipids, but, lower level of N-terminal pro-brain natriuretic peptide (NTproBNP). Subjects in underweight group were older, more women, fewer diabetes, less likely to receive PCI, lower levels of glucose and lipids, but, higher level of NTproBNP and higher rates of left ventricular ejection fraction (LVEF) Conclusions Patients who were underweight were at greater risk of cardiac death post AMI. In addition, older age, higher levels of cTnI, LVEF Acknowledgement/Funding Beijing Natural Science Foundation (No. 7194253);Scientific Research Common Program of Beijing Municipal Commission of Education (KM201910025017)

Supplemental Digital Content is available in the text., Background: This study investigated whether the age, creatinine, and ejection fraction (ACEF) score [age (years) /ejection fraction (%) +1 (if creatinine>176μmol/L)] could predict 1-year outcomes following ST-segment elevation myocardial infarction after percutaneous coronary intervention, and whether accuracy could be improved by establishing novel ACEF-derived risk models. Methods: A total of 1146 patients were included. The study endpoint was 1-year major adverse cardio-cerebrovascular events, including all-cause death, nonfatal myocardial infarction, unplanned revascularization, and nonfatal stroke. Accuracy was defined with area under the curve by receiver-operating characteristic curve analysis. Results: The incidence of 1-year major adverse cardio-cerebrovascular event increased with the rising age, creatinine, and ejection fraction score tertiles (4.8%, 8.4%, and 15.2%, P < 0.001 for all). Higher ACEF score was significantly associated with an increased risk of the endpoint in overall (odds ratio = 3.75, 95% confidence interval, 2.44–5.77, P < 0.001) and in subgroups (all P < 0.05). The accuracy of the ACEF score was equivalent to the other complex risk scores. The combination of ACEF, and diabetes (ACEF-diabetes score) yielded a superior discriminatory ability than the original ACEF score (increase in C-statistic from 0.67 to 0.71, P = 0.048; continuous net reclassification improvement = 51.9%, 95% confidence interval, 33.4–70.5%, P < 0.001; integrated discrimination improvement = 0.020, 95% confidence interval, 0.011–0.030, P < 0.001). Conclusions: The simplified ACEF score performed well in predicting 1-year outcomes in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention. The novel ACEF-diabetes score provided a better predictive value and thus may help stratify high-risk patients and potentially facilitate decision making.

Background Patients with acute myocardial infarction (AMI) often accompanied by admission hyperglycemia, which usually predicts a poor clinical outcomes for non-diabetes mellitus. Appropriate cut-point to identify high risk individuals in these patients remains controversial. Methods One thousand six hundred ninety-eight non-diabetes AMI patients in this retrospective study were divided into 3 groups according to admission glucose levels (euglycemia group≤140 mg/dL, moderate hyperglycemia group 141–179 mg/dL, severe hyperglycemia group≥180 mg/dL). The primary endpoint of this study was all-cause in-hospital mortality rate. In-hospital motality related risk factors was analyzed by multivariate binary logistic regression analyses. Results All myocardial necrosis markers and Log NT-proBNP in severe hyperglycemia group were significantly higher than those in the other 2 groups. Logistic regression showed that independent predictors of the in-hospital mortality rate in non-diabetic patients with AMI were age (OR = 1.057, 95% CI 1.024–1.091, P

Background: Exacerbated blood-brain barrier (BBB) damage is related with tissue plasminogen activator (tPA)-induced brain hemorrhage after stroke. Platelets have long been recognized as the cellular orchestrators of primary haemostasis. Recent studies have demonstrated further that platelets are required for supporting intact mature blood vessels and play a crucial role in maintaining vascular integrity during inflammation. Therefore, we sought to investigate whether platelets could reduce tPA-induced deterioration of cerebrovascular integrity and lead to less hemorrhagic transformation. Methods: Mice were subjected to models of collagenase-induced intracerebral hemorrhage (ICH) and transient middle cerebral artery (MCA) occlusion. After 2 hours of MCA occlusion, tPA (10 mg/kg) was administered as an intravenous bolus injection of 1 mg/kg followed by a 9 mg/kg infusion for 30 minutes. Immediately after tPA treatment, mice were transfused with platelets. Hemorrhagic volume, infarct size, neurological deficit, tight junction and basal membrane damages, endothelial cell apoptosis, and extravascular accumulation of circulating dextran and IgG, and Evans blue were quantified at 24 hours. Results: Platelet transfusion resulted in a significant decrease in hematoma volume after ICH. In mice after ischemia, tPA administration increased brain hemorrhage transformation and this was reversed by resting but not activated platelets. Consistent with this, we observed that tPA-induced brain hemorrhage was dramatically exacerbated in thrombocytopenic mice. Transfusion of resting platelets ameliorated tPA-induced loss of cerebrovascular integrity and reduced extravascular accumulation of circulating serum proteins and Evans blue, associated with improved neurological functions after ischemia. No changes were found for infarct volume. Inhibition of platelet receptor glycoprotein VI (GPVI) blunted the ability of platelets to attenuate tPA-induced BBB disruption and hemorrhage after ischemia. Conclusions: Our findings demonstrate the importance of platelets in safeguarding BBB integrity and suggest that transfusion of resting platelets may be useful to improve the safety of tPA thrombolysis in ischemic stroke.

Previous studies demonstrated that men were more likely to have plaque rupture and are at greater risk for myocardial infarction and stroke than women. We evaluated differences in carotid plaque characteristics by MRI between men and women with mild-moderate atherosclerosis and elevated ApoB levels. One hundred eighty-two subjects (104 men and 78 women) with CAD or carotid stenosis (≥ 15% by ultrasound), ApoB ≥ 120 mg/dL and carotid MRI scan were included. Percent wall volume (%WV) was calculated as (wall volume/total vessel volume) × 100%. Three major plaque compositions, fibrous tissue (FT), calcification (CA) and lipid rich necrotic core (LRNC), were identified and quantified using published MRI criteria. Adventitial and plaque neovascularization as fractional plasma volume (Vp) and permeability as transfer constant (Ktrans) were analyzed using kinetic modeling. These characteristics were compared between men and women. Men, compared to women, were younger (54 ± 8 vs. 58 ± 8 years, p = 0.01), had higher rate of previous MI (46 vs. 26%, p = 0.005) but lower proportions of metabolic syndrome (37 vs. 59%, p = 0.003). After adjusting for between-gender differences, men were significantly more likely to have LRNC (OR 2.22, 95% CI 1.04–4.89, p = 0.04) and showed significantly larger %LRNC than women (diff = 4.3%, 95% CI 1.6–6.9%, p = 0.002), while %WV, FT, and CA were similar between men and women. There were no statistically significant differences in adventitial and plaque Vp or Ktrans. Men were significantly more likely to have LRNC and had larger LRNC than women. However, men and women showed relatively similar levels of adventitial and plaque neovascularization and permeability. Trial registration: NCT00715273 at ClinicalTrials.gov. Registered 15 July 2008, retrospectively registered.

Background Statin therapy can improve plaque stability. However, the time course of effects of statin on adventitial angiogenesis and plaque neovascularization has not been studied. Objective The objective of the study was to investigate whether statin therapy reduces plaque neovascularization, associated with adventitial angiogenesis, over 24 months as assessed by using carotid dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods Forty-three lipid treatment–naive subjects with asymptomatic carotid atherosclerosis received rosuvastatin (5–20 mg/d) to lower low-density lipoprotein cholesterol to Results Adventitia Vp and adventitia Ktrans were significantly correlated with plaque Vp and plaque Ktrans at baseline. Rosuvastatin significantly reduced both adventitial and plaque Vp significantly at 3 months from 0.121 ± 0.064 to 0.085 ± 0.049 (P = .008) and from 0.096 ± 0.052 to 0.067 ± 0.043 (P = .013). Adventitial and plaque Vp continued to decrease by 43% and 34% at 12 months and by 49% and 45% at 24 months. However, the continued reductions from 3 to 12 months and from 12 to 24 months were not statistically significant. Adventitial and plaque Ktrans showed similar trends, but nonstatistically significant decreases during the 24 months of treatment. Conclusions Rosuvastatin therapy rapidly and significantly decreased adventitial and plaque neovascularization at 3 months followed by continued, but nonstatistically significant, decreases at 12 and 24 months.

Contains fulltext : 215333.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, pinteraction=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p

The cerebral accumulation of amyloid beta (Aβ) is one of the key pathological hallmarks of Alzheimer's disease (AD). Aβ is also found in bodily fluids such as the cerebrospinal fluid (CSF) and plasma. However, the significance of Aβ accumulation in the brain and different bodily pools, as well as its correlation with aging and cerebral amyloid pathology, is not completely understood. To better understand this question, we selected the rhesus monkey, which is phylogenetically and physiologically highly similar to the human, as a model to study. We quantified the levels of the two main Aβ isoforms (Aβ42 and Aβ40) in different sections of the brain (frontal cortex, temporal cortex, and hippocampus) and bodily fluids (CSF and plasma) of rhesus monkeys at different developmental phases (young, 5-9 years of age; mature, 10-19 years of age; and old, 21-24 years of age). We found that the levels of neuronal and insoluble Aβ42 increased significantly in the brain with aging, suggesting that this specific isoform might be directly involved in aging and AD-like pathophysiology. There was no significant change in the Aβ40 level in the brain with aging. In addition, the Aβ42 level, but not the Aβ40 level, in both the CSF and plasma increased with aging. We also identified a positive correlation between Aβ42 in the CSF and plasma and Aβ42 in the brain. Taken collectively, our results indicate that there is an association between Aβ accumulation and age. These results support the increased incidence of AD with aging.

BackgroundCardiovascular disease (CVD) begins early in life and is associated with both the number of risk factors present and length of exposure to these risk factors including hyperlipidemia.ObjectivesThe clinical benefit of intensive lipid therapy over 25years was investigated in the Familial Atherosclerosis Treatment Study-Observational Study.MethodsOf 175 coronary artery disease subjects with mean low-density lipoprotein cholesterol (LDL-C) of 191mg/dL and mean age of 50years, who completed the randomized and placebo-controlled Familial Atherosclerosis Treatment Study, 100 chose receiving lipid management by their physicians (usual care [UC]) and 75 elected to receive an intensive treatment [IT] for lipid management with lovastatin (40mg/d), niacin (2.5g/d), and colestipol (20g/d) from 1989 to 2004, followed by double therapy with simvastatin (40-80mg/d) and niacin from 2005 to 2006 and by triple therapy of ezetimibe 10mg and simvastatin 40 to 80mg/d plus niacin during 2007 to 2012. Deaths from CVD, non-CVD, and any cause were compared between UC and IT using Cox proportional hazards model.ResultsUC and IT groups were similar in risk factors with the exception that IT had more severe coronary artery disease. Mean LDL-C levels were 167mg/dL from 1988 to 2004, 97 from 2005 to 2006, and 96 from 2007 to 2012 in surviving subjects receiving UC. IT lowered LDL-C to 119, 97, and 83 mg/dL in the 3 periods, respectively. Compared with UC, IT significantly reduced total mortality (11.1 vs 26.3 per 1000 person years [PY], hazard ratio [HR]=0.45, 95% confidence interval [CI]: 0.26-0.77, P=.003) and CVD mortality (10.6 vs 27.7 per 1000 PY, HR=0.34, 95% CI: 0.15-0.80, P=.009). The non-CVD mortality was also reduced but was not of statistical significance (6.8 vs 12.7 per 1000 PY, HR=0.55, 95% CI: 0.27-1.14, P=.11).ConclusionsLong-term intensive lipid therapy significantly reduced total and cardiovascular mortality in Familial Atherosclerosis Treatment Study-Observational Study. These results support the importance of lifetime risk management to improve long-term outcome.

We examined the association of N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP), a marker of cardiac remodeling, with subsequent major adverse cardiovascular and cerebral event (MACCE) in patients had successful PCI for ACS and normal left ventricular ejection fraction (LVEF). Of a total of

Background Cardiorenal syndrome type 1 ( CRS 1) as a complication of acute myocardial infarction can lead to adverse outcomes, and a method for early detection is needed. This study investigated the individual and integrated effectiveness of amino‐terminal pro–brain natriuretic peptide (Pro‐BNP), estimated glomerular filtration rate (eGFR), and high‐sensitivity C‐reactive protein (CRP) as predictive factors for CRS 1 in patients with acute myocardial infarction. Methods and Results In a retrospective analysis of 2094 patients with acute myocardial infarction, risk factors for CRS 1 were analyzed by logistic regression. Receiver operating characteristic curves were constructed to determine the predictive ability of the biomarkers individually and in combination. Overall, 177 patients (8.45%) developed CRS 1 during hospitalization. On multivariable analysis, all 3 biomarkers were independent predictors of CRS 1 with odds radios and 95% confidence intervals for a 1‐SD change of 1.792 (1.311‐2.450) for log(amino‐terminal pro–brain natriuretic peptide, 0.424 (0.310‐0.576) for estimated glomerular filtration rate, and 1.429 (1.180‐1.747) for high‐sensitivity C‐reactive peptide. After propensity score matching, the biomarkers individually and together significantly predicted CRS 1 with areas under the curve of 0.719 for amino‐terminal pro–brain natriuretic peptide, 0.843 for estimated glomerular filtration rate, 0.656 for high‐sensitivity C‐reactive peptide, and 0.863 for the 3‐marker panel (all P P CRS 1 risk correlated with the number of biomarkers showing abnormal levels. Abnormal measurements for at least 2 biomarkers indicated a greater risk of CRS 1 (odds ratio 36.19, 95% confidence interval 8.534‐153.455, P Conclusions The combination of amino‐terminal pro–brain natriuretic peptide, estimated glomerular filtration rate, and high‐sensitivity C‐reactive peptide at presentation may assist in the prediction of CRS 1 and corresponding risk stratification in patients with acute myocardial infarction.

Background: Growth differentiation factor 11 (GDF11), a member of transforming growth factor-β (TGF-β) superfamily, was shown to rejuvenate cardiac and skeletal muscle function and to improve cerebral vasculature and neurogenesis in old mice. However, recent experimental data reported that raising GDF11 levels inhibited skeletal muscle regeneration and had no effect on cardiac hypertrophy. Our aim was to investigate the effects of GDF11 on brain repair during the recovery phase after stroke. Methods: Mice were subjected to distal middle cerebral artery occlusion, and recombinant GDF11 (rGDF11) was injected intraperitoneally once a day during days 7–13 after stroke. Neuronal precursor cells (NPCs) proliferation and angiogenesis were assayed at 14 days. Neuronal regeneration was assayed at 42 days. The beam-walking test and CatWalk were used to evaluate behavioral functions. Downstream pathways of GDF11 were also investigated. Results: GDF11 was upregulated in the ipsilateral peri-infarct cortex and subventricular zone (SVZ) at 14 days after stroke. Treatment with rGDF11 enhanced the number of newborn NPCs and endothelial cells, microvascular length and area, and brain capillary perfusion. Western blots showed that rGDF11 upregulated brain-derived neurotrophic factor (BDNF) and increased the levels of proangiogenic factor angiopoietin-2 (Ang-2) and phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2). We also found that rGDF11 upregulated the transcription factors Smad2 and Smad3 phosphorylation, but these activations were blocked by a TGF-β receptor inhibitor SB431542. Moreover, rGDF11-induced angiogenic remodeling and NPCs proliferation were reversed by injection of SB431542, suggesting that GDF11 may exert its effect via the TGF-β/Smad2/3 signaling pathway. Finally, treating mice with rGDF11 resulted in a significant increase in neuronal regeneration and functional recovery. Conclusion: GDF11 promoted neurogenesis and angiogenesis and contributed to functional recovery after stroke in mice.

Objective— To assess whether Lp(a) (lipoprotein(a)) levels and other lipid levels were predictive of progression of atherosclerosis burden as assessed by carotid magnetic resonance imaging in subjects who have been treated with LDL-C (low-density lipoprotein cholesterol)–lowering therapy and participated in the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes). Approach and Results— AIM-HIGH was a randomized, double-blind study of subjects with established vascular disease, elevated triglycerides, and low HDL-C (high-density lipoprotein cholesterol). One hundred fifty-two AIM-HIGH subjects underwent both baseline and 2-year follow-up carotid artery magnetic resonance imaging. Plaque burden was measured by the percent wall volume (%WV) of the carotid artery. Associations between annualized change in %WV with baseline and on-study (1 year) lipid variables were evaluated using multivariate linear regression and the Bonferroni correction to account for multiple comparisons. Average %WV at baseline was 41.6±6.8% and annualized change in %WV over 2 years ranged from −3.2% to 3.7% per year (mean: 0.2±1.1% per year; P =0.032). Increases in %WV were significantly associated with higher baseline Lp(a) (β=0.34 per 1-SD increase of Lp(a); 95% confidence interval, 0.15–0.52; P P Conclusions— Despite intensive lipid therapy, aimed at aggressively lowering LDL-C to

Managing endovascular thrombectomy (ET) in diabetic ischemic stroke (IS) with novel anticoagulants is challenging due to putative risk of intracerebral hemorrhage. The study evaluates increased hemorrhagic transformation (HT) risk in Rivaroxaban-treated diabetic rats post ET. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 60 mg/kg streptozotocin. After 4-weeks, rats were pretreated orally with 30 mg/kg Rivaroxaban/saline; prothrombin time was monitored. IS and ET was induced after 1 h, by thread-induced transient middle cerebral artery occlusion (tMCAO) that mimicked mechanical ET for proximal MCA occlusion at 60 min. After 24 h reperfusion, infarct volumes, HT, blood-brain barrier (BBB) permeability, tight junction at peri-ischemic lesion and matrix metalloproteinase-9 (MMP-9) activity was measured. Diabetic rats seemed to exhibit increased infarct volume and HT at 24 h after ET than normal rats. Infarct volumes and functional outcomes did not differ between Rivaroxaban and diabetic control groups. A significant increase in HT volumes and BBB permeability under Rivaroxaban treatment was not detected. Compared to diabetic control group, neither the occludin expression was remarkably lower in the Rivaroxaban group nor the MMP-9 activity was higher. Together, Rivaroxaban does not increase HT after ET in diabetic rats with proximal MCA occlusion, since Rivaroxaban has fewer effects on post-ischemic BBB permeability.

Background The risk prediction of pregnancy-associated plasma protein-A (PAPP-A) for future cardiovascular (CV) events post acute coronary syndrome (ACS) in patients with type-2 diabetes mellitus (T2DM) was investigated in comparison to other risk factors. Methods PAPP-A was measured at hospital admission in 320 consecutive ACS patients (136 with T2DM and 184 without). All patients were followed for 2 years for occurrence of CV death, non-fatal MI or stroke. Effect of PAPP-A on the CV event risk was estimated using Cox regression models. Receiver operating characteristics (ROC) curves were generated to demonstrate the sensitivity and specificity of PAPP-A in predicting CV events. Results ACS patients with T2DM had higher PAPP-A (19.29 ± 16.36 vs. 13.29 ± 13.90 ng/ml, p 10(PAPP-A), 95% CI 2.11–4.18, p Conclusions Patients with T2DM had higher levels of PAPP-A and increased risk of CV events. Elevated PAPP-A compared to other risk factors was a stronger predictor for future CV events 2 years post ACS in patients with T2DM. Trial registration ISRCTN10805074. Registered on 20 January 2017, retrospectively registered.

Excessive formation of advanced glycation end products (AGEs) impairs voltage-gated potassium (Kv) channels in rat coronary artery smooth muscle cells (CSMCs), resulting in weakened Kv-mediated coronary vasodilation. We hypothesized that induction of the nuclear factor-κB (NF-κB) signaling pathway by AGEs plays a significant role in the regulation of Kv channel-mediated vasodilation in Zucker diabetic fatty (ZDF) rats. Assays of mRNA transcripts, protein expression, and intracellular localization as well as patch-clamp experiments in cultured CSMCs revealed that AGEs significantly induced activation of the NF-κB signaling pathway, reduced Kv1.2/1.5 expression, and inhibited Kv currents. In addition, silencing of the receptor for AGEs (RAGE) or p65 with siRNA and treatment with alagrebrium (ALA) or pyrrolidine dithiocarbamate (PDTC) alleviated the AGE-induced impairment of Kv channels in CSMCs. Compared with Zucker lean (ZL) rats, the amount of AGEs, RAGE protein expression, and NF-κB activity in coronary arteries were higher in ZDF rats; whereas Kv1.2/1.5 expression was significantly lower in ZDF rats. Reduced Kv1.2/1.5 expression in coronary arteries and impaired Kv-mediated coronary relaxation tested by wire myography in ZDF rats were markedly improved by treatment with aminoguanidine (AG), ALA, or PDTC. These effects were accompanied by diminished NF-κB activity, inflammation, and oxidative stress. Taken together, these results indicate that an increased interaction between AGEs and RAGE in diabetic rats leads to impaired Kv channel-mediated coronary vasodilation. Moreover, activation of the NF-κB signaling pathway and a subsequent increase of inflammation and oxidative stress may play an important role in AGE-induced impairment of coronary vasodilation in diabetes.

Objectives This study sought to examine the relationship between niacin treatment, lipoproteins, and cardiovascular (CV) outcomes in this secondary analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial. Background During a 3-year follow-up in 3,414 patients with established CV disease and low high-density lipoprotein cholesterol (HDL-C) levels, combined niacin + low-density lipoprotein cholesterol (LDL-C)–lowering therapy did not reduce CV events compared with LDL-C–lowering therapy alone. Methods Subjects taking simvastatin and/or ezetimibe were randomized to receive extended-release (ER) niacin 1,500 to 2,000 mg or minimal immediate-release niacin (≤150 mg) as placebo at bedtime. LDL-C levels in both groups were maintained from 40 to 80 mg/dl. Hazard ratios were estimated by using Cox proportional hazards models for relationships between lipoproteins and the composite endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization. Results CV outcomes were not associated with ER niacin in any baseline lipoprotein tertile. In a subset of patients in both the highest triglyceride (≥198 mg/dl) and lowest HDL-C ( Conclusions Baseline lipoprotein tertiles did not predict differential benefit or harm with ER niacin added to LDL-C–lowering therapy, but a small dyslipidemic subgroup may benefit. ER niacin attenuated expected relationships of lipoprotein risk factors with CV events, raising the possibility that nonlipoprotein actions of niacin could affect risk. (Niacin Plus Statin to Prevent Vascular Events [AIM-HIGH]; NCT00120289 )

Angiogenic response is essential for ischemic brain repair. The von Willebrand factor (VWF)-cleaving protease disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) is required for endothelial tube formation in vitro, but there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) breakdown and extravascular deposits of serum proteins in the peri-infarct cortex at 14 days after stroke. Deficiency of VWF or anti-VWF antibody treatment significantly increased microvessels, perfused capillary length, and reversed pericyte loss and BBB changes in Adamts13-/- mice. Furthermore, we observed that ADAMTS13 deficiency decreased angiopoietin-2 and galectin-3 levels in the isolated brain microvessels, whereas VWF deficiency had the opposite effect. Correlating with this, overexpression of angiopoietin-2 by adenoviruses treatment or administration of recombinant galectin-3 normalized microvascular reductions, pericyte loss, and BBB breakdown in Adamts13-/- mice. The vascular changes induced by angiopoietin-2 overexpression and recombinant galectin-3 treatment in Adamts13-/- mice were abolished by the vascular endothelial growth factor receptor-2 antagonist SU1498. Importantly, treating wild-type mice with recombinant ADAMTS13 at 7 days after stroke markedly increased neovascularization and vascular repair and improved functional recovery at 14 days. Our results suggest that ADAMTS13 controls key steps of ischemic vascular remodeling and that recombinant ADAMTS13 is a putative therapeutic avenue for promoting stroke recovery.

Background Type 2 diabetes mellitus (T2DM) has reported to be a major public health crisis in China. Objective We examined the incidence of new T2DM over 4 years for association of clinical factors and lipids with development of T2DM in a community-based population. Methods We included 923 Chinese subjects who participated in community-organized health checkout in both 2009 and 2013. Health history was collected; physical examination was performed; biochemistry, lipids, and glucose were measured. Of 923, 819 were confirmed without T2DM in 2009 and included in the analysis. Unadjusted and adjusted logistic regression models were used to estimate the effects of clinical factors and biomarkers on the risk of new T2DM. Results Of 819 subjects without T2DM in 2009, 65 were identified as T2DM in 2013, 8% over 4 years. These 65 subjects, compared with those 754 without new T2DM, were older, more likely to be male and smokers. They had higher body mass index (BMI), fasting glucose, blood pressure and triglycerides, and lower levels of high-density lipoprotein-cholesterol and apolipoprotein A1 (ApoA1). Multivariate logistic regression identified larger BMI (odds ratio [OR] = 1.7; 95% confidence interval [CI], 1.22–2.39, P = .002), higher fasting glucose levels (OR = 4.2, 95% CI, 2.90–6.19, P P = .002) were independently associated with new T2DM. Furthermore, receiver operating characteristics curves for multivariate models for new T2DM showed that area under the curve improved from 0.87 to 0.89 when adding ApoA1 to the Framingham Diabetes Risk Scoring Model and from 0.85 to 0.89 when adding ApoA1 to a 4-variable (age, BMI, glucose, and triglycerides) Chinese model. Conclusions There is a high incidence of new T2DM at 8% over 4 years among Chinese. Larger BMI, higher glucose levels, and lower levels of ApoA1 are significantly and independently associated with new T2DM. Lower ApoA1 improves the risk prediction of new type 2 diabetes when it was added to the existing risk models.

Aims: Type-2 diabetes mellitus (T2DM) has become a major public health crisis in China. We examined the incidence of new T2DM over 4 years for association of clinical factors and lipids with development of T2DM in a community-based population. Methods: We included 923 Chinese subjects who participated in community-organized health checkout in both 2009 and 2013. Health history was collected; physical examination was performed; biochemistry, lipids and glucose were measured. Of 923, 819 were confirmed without T2DM in 2009 and included in the analysis. Results: Sixty-five subjects without T2DM in 2009 were identified as having new T2DM in 2013, 8% (65/819) over 4 years. These 65 subjects, compared to those 754 without new T2DM, were older, more likely to be male and smokers. They had higher BMI, fasting glucose, blood pressure and triglycerides, and lower levels of HDL-C and ApoA1. Multivariate logistic regression identified larger BMI (OR=1.7, 95%CI 1.22-2.39, p=0.002), higher fasting glucose (OR=4.2, 95%CI 2.90-6.19, p

Objectives The purpose of this study was to test the lipid depletion hypothesis and to establish the time course of change in carotid plaque morphology and composition during lipid therapy using high-resolution magnetic resonance imaging (MRI). Background Lipid therapy is thought to improve plaque stability and reduce cardiovascular events by targeting the plaque rupture risk features such as large lipid core, thin fibrous cap, and high level of inflammatory infiltrates. However, the plaque stabilizing process during lipid therapy has not been clearly demonstrated in humans and in vivo. Methods Subjects with coronary or carotid artery disease, apolipoprotein B ≥120 mg/dl, and lipid treatment history Results After 3 years of lipid therapy, the 33 subjects with measurable lipid-rich necrotic core (LRNC) at baseline had a significant reduction in plaque lipid content: LRNC volume decreased from 60.4 ± 59.5 mm3 to 37.4 ± 69.5 mm3 (p Conclusions Intensive lipid therapy significantly depletes carotid plaque lipid. Statistically significant plaque lipid depletion is observed after 1 year of treatment and continues in the second year, and precedes plaque regression. (Using Magnetic Resonance Imaging to Evaluate Carotid Artery Plaque Composition in People Receiving Cholesterol-Lowering Medications [The CPC Study]; NCT00715273 ).