Current problems in renal denervation and a hope to break the stage.

Renal denervation (RDN) is currently confronted with the considerable heterogeneity of different post-procedural blood pressure responses. The challenges predominantly arise from not only the lack of selection of appropriate responders but also the absence of detection for the successful endpoints of intervention. In this paper, we summarize the significant characteristics of potentially appropriate hypertensive patients and propose a hopeful way to improve the accuracy of RDN, that is, the application of three-dimensional reconstruction technology combined with electrical renal nerve stimulation to guide the radiofrequency catheter ablation, which may promote the development of selective and accurate RDN in real-world clinical practice. This paper focuses on two current critical concerns of renal denervation (RDN): appropriate patient selection and the improvement in the accuracy of selective RDN. A hopeful way of accurate RDN may be the combination of 3D electroanatomic mapping systems for the renal artery with modified renal nerve stimulation (RNS) techniques and technology for appropriate hypertensive candidates.

Renal nerve stimulation identifies renal innervation and optimizes the strategy for renal denervation in canine.

BACKGROUND: Renal denervation (RDN) was still performed without any intra-procedural method for nerve mapping. Whether renal nerve stimulation (RNS) is an efficient way to identify renal autonomic innervation and optimize the strategy for RDN remain to be worthy for further exploration. METHODS: The characteristics of renal autonomic innervation at the sites with different blood pressure (BP) responses to RNS were explored. Then, dogs anatomically eligible for RDN were randomly assigned into elevated BP response ablation group, reduced BP response ablation group, and RNS-control group. The postoperative outcomes were measured at baseline and after 4 weeks follow-up. RESULTS: The proportion of afferent sensory nerve was higher at elevated BP response sites (ERS) than reduced BP response sites (RRS) and non-response sites (NRS) (P = 0.012 and P = 0.004). Conversely, the proportion of parasympathetic nerve at RRS was the highest (RRS vs. ERS, P = 0.017; RRS vs. NRS, P = 0.023). More importantly, there was a significant correlation between systolic blood pressure changes and the area ratios of afferent sensory and parasympathetic nerve (R = 0.859; P < 0.001). In addition, ablation at BP-elevation sites can result in a significant decrease in BP and plasma norepinephrine (NE) after 4 weeks (P = 0.002; P = 0.008), while ablation at BP-reduction sites can lead to significant increases in BP and plasma NE (P = 0.016; P = 0.033). CONCLUSIONS: RNS is an effective method to identify renal autonomic innervation. It could not only help to identify optimal target sites, but also avoid ablation of sympathetic-inhibitory areas during RDN.

Activating transcription factor 4 regulates angiogenesis under lipid overload via methionine adenosyltransferase 2A-mediated endothelial epigenetic alteration.

Lipid overload is intimately connected with the change of endothelial epigenetic status which impacts cellular signaling activities and endothelial function. Activating transcription factor 4 (ATF4) is involved in the regulation of lipid metabolism and meanwhile an epigenetic modifier. However, the role of ATF4 in the angiogenesis under lipid overload is not well understood. Here, to induce lipid overload status, we employed high-fat diet (HFD)-induced obese mouse model in vivo and palmitic acid (PA) to stimulate endothelial cells in vitro. Compared with mice fed with normal chow diet (NCD), HFD-induced obese mice showed angiogenic defects evidenced by decline in (1) blood flow recovery after hind limb ischemia, (2) wound healing speed after skin injury, (3) capillary density in injured tissues and matrigel plugs, and (4) endothelial sprouts of aortic ring. ATF4 deficiency aggravated above angiogenic defects in mice while ATF4 overexpression improved the blunted angiogenic response. Mechanistically, lipid overload lowered the H3K4 methylation levels at the regulatory regions of NOS3 and ERK1 genes, leading to reduced angiogenic signaling activity. Methionine adenosyltransferase 2A (MAT2A) is identified as a target of ATF4 and formed complex with ATF4 to direct lysine methyltransferase 2A (MLL1) to the regulatory regions of both genes for the maintenance of the H3K4 methylation level and angiogenic signaling activity. Here, we uncovered a novel metabolic-epigenetic coupling orchestrated by the ATF4-MAT2A axis for angiogenesis. The ATF4-MAT2A axis links lipid overload milieu to altered epigenetic status of relevant angiogenic signaling in endothelial cells, suggesting a potential therapeutic target for angiogenesis impaired by lipid overload.

The bifunctional SDF-1-AnxA5 fusion protein protects cardiac function after myocardial infarction.

Stromal cell-derived factor-1 (SDF-1) is a well-characterized cytokine that protects heart from ischaemic injury. However, the beneficial effects of native SDF-1, in terms of promoting myocardial repair, are limited by its low concentration in the ischaemic myocardium. Annexin V (AnxA5) can precisely detect dead cells in vivo. As massive cardiomyocytes die after MI, we hypothesize that AnxA5 can be used as an anchor to carry SDF-1 to the ischaemic myocardium. In this study, we constructed a fusion protein consisting of SDF-1 and AnxA5 domains. The receptor competition assay revealed that SDF-1-AnxA5 had high binding affinity to SDF-1 receptor CXCR4. The treatment of SDF-1-AnxA5 could significantly promote phosphorylation of AKT and ERK and induce chemotactic response, angiogenesis and cell survival in vitro. The binding membrane assay and immunofluorescence revealed that AnxA5 domain had the ability to specifically recognize and bind to cells injured by hypoxia. Furthermore, SDF-1-AnxA5 administered via peripheral vein could accumulate at the infarcted myocardium in vivo. The treatment with SDF-1-AnxA5 attenuated cell apoptosis, enhanced angiogenesis, reduced infarcted size and improved cardiac function after mouse myocardial infarction. Our results suggest that the bifunctional SDF-1-AnxA5 can specifically bind to dead cells. The systemic administration of bifunctional SDF-1-AnxA5 effectively provides cardioprotection after myocardial infarction.

Influence of age on the effect of reduced renal function on outcomes in patients with coronary artery disease.

BACKGROUND: Ageing is a risk factor for both coronary artery disease (CAD) and reduced renal function (RRF), and it is also associated with poor prognosis in patients with CAD or RRF. However, little is known about whether the impact of RRF on clinical outcomes are different in CAD patients at different age groups. This study aimed to investigate whether ageing influences the effect of RRF on long-term risk of death in patients with CAD. METHODS: A retrospective analysis was conducted using data from a single-center cohort study. Three thousand and two consecutive patients with CAD confirmed by coronary angiography were enrolled. RRF was defined as an estimated glomerular filtration rate (eGFR) of less than 60 ml/min. The primary endpoint in this study was all-cause mortality. RESULTS: The mean follow-up time was 29.1 ± 12.5 months and death events occurred in 275 cases (all-cause mortality: 9.2%). The correlation analysis revealed a negative correlation between eGFR and age (r = - 0.386, P < 0.001). Comparing the younger group (age ≤ 59) with the elderly one (age ≥ 70), the prevalence of RRF increased from 5.9 to 27.5%. Multivariable Cox regression revealed that RRF was independently associated with all-cause mortality in all age groups, and the relative risks in older patients were lower than those in younger ones (age ≤ 59 vs. age 60-69 vs. age ≥ 70: hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.04-6.37 vs. HR 2.00, 95% CI 1.17-3.42 vs. HR 1.46, 95% CI 1.06-2.02). There was a significant trend for HRs for all-cause mortality according to the interaction terms for RRF and age group (RRF*age [≤59] vs. RRF*age [60-69] vs. RRF*age [≥70]: HR 1.00[reference] vs. HR 0.60, 95% CI 0.23-1.54 vs. HR 0.32, 95% CI 0.14-0.75; P for trend = 0.010). CONCLUSIONS: RRF may have different impacts on clinical outcomes in CAD patients at different age groups. The association of RRF with the risk of all-cause mortality was attenuated with ageing.

The triglyceride paradox in the mortality of coronary artery disease.

BACKGROUND: The role of triglyceride (TG) in secondary prevention of patients with coronary artery disease (CAD) was debated. In the present study, we assessed the association between admission TG levels and long-term mortality risk in CAD patients. METHODS: A retrospective analysis was conducted from a single registered database. 3061 consecutive patients with CAD confirmed by coronary angiography were enrolled and were grouped into 3 categories by the tertiles of admission serum TG levels. The primary end point in this study was all-cause mortality and the secondary end point was cardiovascular mortality. RESULTS: The mean follow-up time was 26.9 ± 13.6 months and death events occurred in 258 cases and cardiovascular death events occurred in 146 cases. Cumulative survival curves indicated that the risk of all-cause death decreased with increasing TG level (Tertile 1 vs. Tertile 2 vs. Tertile 3 = 10.3% vs. 8.6% vs. 6.3%, log rank test for overall p = 0.001). Cox regression analysis showed an independent correlation between TG level and risk of all-cause mortality [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.86] and cardiovascular mortality (HR 0.67, 95% CI 0.51-0.89) in total patients with CAD. Subgroup analysis found the similar results in patients with acute coronary syndrome and acute myocardial infarction. CONCLUSIONS: This study found an inverse association between TG levels and mortality risk in CAD patients, which suggests that the "TG paradox" may exist in CAD patients. TRIAL REGISTRATION: ChiCTR, ChiCTR-OOC-17010433 . Registered 17 February 2017 - Retrospectively registered.

Ovarian Cancer Cells Commonly Exhibit Defective STING Signaling Which Affects Sensitivity to Viral Oncolysis.

Ovarian cancer is the sixth most prevalent cancer in women and the most lethal of the gynecologic malignancies. Treatments have comprised the use of immunotherapeutic agents as well as oncolytic viruses, with varying results for reasons that remain to be clarified. To better understand the mechanisms that may help predict treatment outcome, we have evaluated innate immune signaling in select ovarian cancer cell lines, governed by the Stimulator of Interferon Genes (STING), which controls self or viral DNA-triggered cytokine production. Our results indicate that STING-dependent signaling is habitually defective in majority of ovarian cancer cells examined, frequently through the suppression of STING and/or the cyclic dinucleotide (CDN) enzyme Cyclic GMP-AMP synthase (cGAS) expression, by epigenetic processes. However, STING-independent, dsRNA-activated innate immune cytokine production, which require RIG-I/MDA5, were largely unaffected. Such defects enabled ovarian cancer cells to avoid DNA damage-mediated cytokine production, which would alert the immunosurveillance system. Loss of STING signaling also rendered ovarian cancer cells highly susceptible to viral oncolytic γ34.5 deleted-HSV1 (Herpes simplex virus) infection in vitro and in vivo. IMPLICATIONS: STING signaling evaluation in tumors may help predict disease outcome and possibly dictate the efficacy of oncoviral and other types of cancer therapies.

The impact of renal function on the prognostic value of N-terminal pro-B-type natriuretic peptide in patients with coronary artery disease.

BACKGROUND: The impact of renal function on the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) remains unclear in coronary artery disease (CAD). This study sought to investigate the value of using NT-proBNP level to predict prognoses of CAD patients with different estimated glomerular filtration rates (eGFRs). METHODS: A retrospective analysis was conducted from a single registered database. 2087 consecutive patients with CAD confirmed by coronary angiography were enrolled. The primary endpoint was allcause mortality. RESULTS: The mean follow-up time was 26.4 ± 11.9 months and death events occurred in 197 cases. The NT-proBNP levels increased with the deterioration of renal function, as well as the optimal cutoff values based on eGFR stratification to predict endpoint outcome (179.4 pg/mL, 1443.0 pg/mL, 3478.0 pg/mL, for eGFR ≥ 90, 60-90 and < 60 mL/min/1.73 m2, respectively). Compared with the routine cut-off value or overall optimal one, stratified optimal ones had superior predictive ability for endpoint in each eGFR group (all with the highest Youden's J statistics). And the prognostic value became weaker as eGFR level decreased (eGFR ≥ 90 vs. 60-90 vs. < 60 mL/min/1.73 m2, odds ratio [OR] 7.7; 95% confidence interval [CI] 1.7-33.9 vs. OR 4.8; 95% CI 2.7-8.5 vs. OR 3.0; 95% CI 1.5-6.2). CONCLUSIONS: This study demonstrated that NT-proBNP exhibits different predictive values for prognosis for CAD patients with different levels of renal function. Among the assessed values, the NT-proBNP cut-off value determined using renal function improve the accuracy of the prognosis prediction of CAD. Moreover, lower eGFR is associated with a higher NT-proBNP cut-off value for prognostic prediction.

Prevalence and Prognostic Significance of Right Ventricular Dysfunction in Patients With Hypertrophic Cardiomyopathy.

Few data are available regarding the prevalence and clinical significance of right ventricular systolic dysfunction (RVSD) in hypertrophic cardiomyopathy (HC) patients. This study aimed to evaluate right ventricular (RV) systolic function by cardiovascular magnetic resonance and explore the prevalence and prognostic significance of RVSD in HC patients. A total of 226 patients with HC assessed by cardiovascular magnetic resonance were included in this retrospective study. RVSD was defined by RV ejection fraction (RVEF) ≤45% and was present in 26 (11.5%) patients. Association between RVSD, clinical characteristics, and outcomes were analyzed. RVEF was significantly lower in patients with RVSD than without RVSD (36.2 ± 7.0% vs 60.5 ± 7.4%, p < 0.001). There was a positive correlation between RVEF and left ventricular ejection fraction (r = 0.45; p < 0.001). During a mean follow-up of 30.5 ± 23.9 months, there were 22 (9.7 %) all-cause mortality, including 12 (5.3%) cardiovascular death. Kaplan-Meier analysis showed a significantly higher risk for cardiovascular mortality in patients with RVSD (p = 0.026), but no significant difference in all-cause mortality (p = 0.118) and heart failure related rehospitalization (p = 0.485). On multivariate Cox regression analysis, RVSD (hazard ratio 5.36; confidence interval 1.39 to 20.77; p = 0.015) and RVEF (hazard ratio 0.94; confidence interval 0.89 to 0.98; p = 0.011) were independent predictors of cardiovascular mortality. In conclusion, RVSD is a common phenotype and a strong independent predictor of cardiovascular mortality in HC patients.

Efficacy of Different Types of Exercise-Based Cardiac Rehabilitation on Coronary Heart Disease: a Network Meta-analysis.

BACKGROUND: Exercise-based cardiac rehabilitation (CR) has been recognized as an essential component of the treatment for coronary heart disease (CHD). Determining the efficacy of modern alternative treatment methods is the key to developing exercise-based CR programs. METHODS: Studies published through June 6, 2016, were identified using MEDLINE, EMBASE, and the Cochrane Library. English-language articles regarding the efficacy of different modes of CR in patients with CHD were included in this analysis. Two investigators independently reviewed abstracts and full-text articles and extracted data from the studies. According to the categories described by prior Cochrane reviews, exercise-based CR was classified into center-based CR, home-based CR, tele-based CR, and combined CR for this analysis. Outcomes included all-cause mortality, cardiovascular death, recurrent fatal and/or nonfatal myocardial infarction, recurrent cardiac artery bypass grafting, recurrent percutaneous coronary intervention (PCI), and hospital readmissions. RESULTS: Sixty randomized clinical trials (n = 19,411) were included in the analysis. Network meta-analysis (NMA) demonstrated that only center-based CR significantly reduced all-cause mortality (center-based: RR = 0.76 [95% CI 0.64-0.90], p = 0.002) compared to usual care. Other modes of CR were not significantly different from usual care with regard to their ability to reduce mortality. Treatment ranking indicated that combined CR exhibited the highest probability (86.9%) of being the most effective mode, but this finding was not statistically significant due to the small sample size (combined: RR = 0.50 [95% CI 0.20-1.27], p = 0.146). CONCLUSIONS: Current evidence suggests that center-based CR is acceptable for patients with CHD. As home- and tele-based CR can save time, money, effort, and resources and may be preferred by patients, their efficacy should be investigated further in subsequent studies.

Extrinsic Phagocyte-Dependent STING Signaling Dictates the Immunogenicity of Dying Cells.

The ability of dying cells to activate antigen-presenting cells (APCs) is carefully controlled to avoid unwarranted inflammatory responses. Here, we show that engulfed cells containing cytosolic double-stranded DNA species (viral or synthetic) or cyclic di-nucleotides (CDNs) are able to stimulate APCs via extrinsic STING (stimulator of interferon genes) signaling, to promote antigen cross-presentation. In the absence of STING agonists, dying cells were ineffectual in the stimulation of APCs in trans. Cytosolic STING activators, including CDNs, constitute cellular danger-associated molecular patterns (DAMPs) only generated by viral infection or following DNA damage events that rendered tumor cells highly immunogenic. Our data shed insight into the molecular mechanisms that drive appropriate anti-tumor adaptive immune responses, while averting harmful autoinflammatory disease, and provide a therapeutic strategy for cancer treatment.

The impact of age on the implementation of evidence-based medications in patients with coronary artery disease and its prognostic significance: a retrospective cohort study.

BACKGROUND: Elderly patients with coronary artery disease (CAD) frequently complicated with more cardiovascular risk factors, but received fewer evidence-based medications (EBMs). This study explored the association of EBMs compliance in different age groups and the risk of long-term death. METHODS: A retrospective analysis was conducted from a single registered database. 2830 consecutive patients with CAD were enrolled and grouped into 3 categories by age. The primary end point was all-cause mortality and secondary endpoint is cardiovascular mortality. RESULTS: The mean follow-up time was 30.25 ± 11.89 months and death occurred in 270 cases,including 150 cases of cardiac death. Cumulative survival curves indicated that the incidence rates of all-cause death and cardiovascular death increased with age (older than 75 years old vs. 60 to 75 years old vs. younger than 60 years old, mortality: 18.7% vs. 9.6% vs. 4.1%, p < 0.001; cardiovascular mortality: 10.3% vs. 5.1% vs. 2.7%, p < 0.001). The percentage of elderly patients using no EBMs was significantly higher than the percentages in the other age group (7.7% vs. 4.6% vs. 2.2%,p < 0.05). Cox regression analysis revealed the benefit of combination EBMs (all-cause mortality: hazard ratio [HR] 0.15, 95% CI 0.08-0.27; cardiac mortality: HR 0.08, 95% CI 0.04-0.19) for older CAD patients. Similar trends were found about different kinds of EBMs in elderly patients. CONCLUSIONS: Elderly patients with CAD had higher risk of death but a lower degree of compliance with EBMs usage. Elderly CAD patients could receive more clinical benefits by using EBMs.

No modifying effect of nutritional status on statins therapy in relation to all-cause death in older patients with coronary artery disease.

BACKGROUND: Statins therapy in the secondary prevention of coronary artery disease (CAD) is associated with a lower risk of adverse cardiovascular events. However, little is known regarding the association of elderly patients with nutritional risk on statin therapy. AIMS: To investigate whether older patients with CAD who were at nutritional risk gain similar survival benefit from statins therapy as their counterparts without nutritional risk. METHODS: We conducted a retrospective hospital-based cohort study among 1705 patients with CAD who were older than 65 years of age, using coronary heart disease database from 2008 to 2012. Nutritional status of included patients was gauged using the geriatric nutritional risk index. After stratification by nutritional status, the hazard of all-cause death was compared between those with or without statins therapy. RESULTS: Of the 1705 patients included in the study (mean age 72 years; 73% male), all-cause death occurred in 146 (9.2%) patients with statins use and in 33 (26.2%) patients without statins use. The rate of all-cause death was higher in patients not receiving statins irrespective of nutritional status. After adjustments for potential confounders, the HR with statins use was 0.33 (95% CI 0.20-0.55) in patients without nutritional risk and 0.47 (95% CI 0.22-1.00) in patients with nutritional risk. No interaction effect was detected between nutritional status and statins use in relation to all-cause death (P value for interaction effect 0.516). CONCLUSION: Despite of the patient's nutritional status, statins therapy as a secondary prevention in elderly CAD patients was associated with decreased risk of all-cause death.

Relation of premature atrial complexes with stroke and death: Systematic review and meta-analysis.

Frequent premature atrial complexes (PACs) are universal in the general population; however, their clinical significance is unclear. We hypothesize that frequent PACs are associated with increased risk of stroke and death. The PubMed (from 1966 to April 2017) and Embase (from 1974 to April 2017) databases were searched for longitudinal studies that reported the relation of PACs with incidence of stroke and death with various etiologies. Study quality was evaluated, and the relative risks (RR) of unfavorable outcomes in subjects with frequent PACs vs those without were calculated. Eleven studies with overall high quality were eligible according to inclusion criteria. The meta-analysis demonstrated that frequent PACs were associated with an increased risk of stroke (unadjusted RR: 2.20, 95% confidence interval [CI]: 1.79-2.70; adjusted RR: 1.41, 95% CI: 1.25-1.60) and death from all causes (unadjusted RR: 2.17, 95% CI: 1.80-2.63; adjusted RR: 1.26, 95% CI: 1.13-1.41), cardiovascular diseases (unadjusted RR: 2.89, 95% CI: 2.20-3.79; adjusted RR: 1.38, 95% CI: 1.24-1.54), and coronary artery disease (unadjusted RR: 2.74, 95% CI: 1.64-4.58; adjusted RR: 1.74, 95% CI: 1.27-2.37). No significant publication bias was detected. The association was robust in sensitivity analysis, subgroup analysis, and pooled analysis of estimates adjusting for confounding factors. Frequent PACs are not benign phenomena; they are associated with higher risk of unfavorable outcomes. Further research on the optimal management of subjects with frequent PACs is urgently required.

Trends in prescribing rate of statins at discharge and modifiable factors in patients with atherosclerotic cardiovascular disease.

Tremendous effort has been invested in reducing the prevalence of atherosclerotic cardiovascular disease (ASCVD) in China. Meanwhile, accumulating evidence has emerged to show the benefits of statins in the prevention of cardiovascular disease. The present study investigated the change trends of statins prescription at discharge among patients with ASCVD in recent years, differences across subtypes of ASCVD, and associated factors. The study included 51,972 patients with a discharge diagnosis of ASCVD who were hospitalized in West China Hospital from 2008 to 2014. Trends of statins prescription rates between subtypes of ASCVD were compared and potential influential factors were explored. The overall statins prescription rate in patients with ASCVD was 58.8%. Adjusted odds ratios (ORs) of increase in prescription rate per year were 1.15 (95% CI 1.13-1.17, p < 0.001), 1.14 (95% CI 1.10-1.17, p < 0.001), 1.19 (95% CI 1.16-1.23; p < 0.001), 1.14 (95% CI 1.09-1.19; p < 0.001), and 1.13 (95% CI 1.09-1.17; p < 0.001) for ASCVD, coronary artery disease, cerebrovascular disease, peripheral arterial disease (PAD), and polyvascular disease, respectively; no significant differences in trends were detected among ASCVD subtypes. However, statins prescription rates were persistently lower in cerebrovascular disease and PAD than the other two subtypes. Discharge departments, together with other physician-related and patient-related characteristics were associated with statins utilization. In conclusion, between 2008 and 2014, statins prescription rate in patients with ASCVD was not optimal. The increasing trends in statins prescription among patients with ASCVD subtypes were similar but the differences did not decrease. Consciousness of integrated and successive medical care should be strengthened in China.

Cutting Edge: Innate Immune Augmenting Vesicular Stomatitis Virus Expressing Zika Virus Proteins Confers Protective Immunity.

Zika virus (ZIKV) has become a serious public health concern because of its link to brain damage in developing human fetuses. Recombinant vesicular stomatitis virus (rVSV) was shown to be a highly effective and safe vector for the delivery of foreign immunogens for vaccine purposes. In this study, we generated rVSVs (wild-type and attenuated VSV with mutated matrix protein [VSVm] versions) that express either the full length ZIKV envelope protein (ZENV) alone or include the ZENV precursor to the membrane protein upstream of the envelope protein, and our rVSV-ZIKV constructs showed efficient immunogenicity in murine models. We also demonstrated maternal protective immunity in challenged newborn mice born to female mice vaccinated with VSVm-ZENV containing the transmembrane domain. Our data indicate that rVSVm may be a suitable strategy for the design of effective vaccines against ZIKV.

Body Composition and Mortality in Coronary Artery Disease With Mild Renal Insufficiency in Chinese Patients.

OBJECTIVE: Obesity is a risk factor for both coronary artery disease (CAD) and chronic renal insufficiency (RI); patients with CAD are prone to obesity and RI. In this study, we try to analyze the effect of body composition on death in CAD patients with mild RI. DESIGN: Retrospective cohort study. SUBJECTS: A total of 1,591 consecutive CAD patients confirmed by coronary angiography were enrolled and met the mild RI criteria by estimated glomerular filtration rate: 60-90 mL/min. MAIN OUTCOME MEASUREMENTS: The influence of body composition on mortality of CAD was detected in different body compositions, including body mass index (BMI), body fat (BF), and lean mass index (LMI). The end points were all-cause mortality. Cox models were used to evaluate the relationship of quintiles of body compositions with all-cause mortality. RESULTS: A survival curve showed that the risk of death was higher in the low BMI group than in the high BMI group (log-rank for overall P = .002); LMI was inversely correlated with risk of death, such that a lower LMI was associated with a higher risk of death (log-rank for overall P < .001). No significant correlation was observed between BF and risk of death. Multifactorial correction show that LMI was still inversely correlated with risk of death (quintile 1: reference; quintile 2: hazard ratio [HR]: 0.49, 95% confidence interval [CI]: 0.26-0.92; quintile 3: HR: 0.35, 95% CI: 0.17-0.70; quintile 4: HR: 0.41, 95% CI: 0.20-0.85; quintile 5: HR: 0.28, 95% CI: 0.12-0.67). CONCLUSION: For CAD patients with mild RI, BMI or BF was unrelated to risk of death, while LMI was inversely correlated with risk of death. A weak "obesity paradox" was observed in this study.

Fibrinogen is related to long-term mortality in Chinese patients with acute coronary syndrome but failed to enhance the prognostic value of the GRACE score.

Fibrinogen (Fib) is considered to be a potential risk factor for the prognosis of patients with acute coronary syndrome (ACS), but it is unclear whether Fib level have synergistic effects to enhance the prognostic value of the GRACE score in patients with ACS. A retrospective analysis was conducted from a single registered database. 2253 consecutive patients with ACS confirmed by coronary angiography were enrolled and were grouped into 3 categories by the tertiles of admission plasma Fib levels. The end points were all-cause mortality and cardiac mortality. The mean follow-up time was 27.2 ± 13.1 months and death events occurred in 223 cases and cardiac death events occurred in 130 cases. Cumulative survival curves indicated that the risk of all-cause death increased with increasing Fib level (mortality rates for Tertile 1 vs. Tertile 2 vs. Tertile 3 = 6.6% vs. 10.8 %vs. 12.3%, p < 0.001). Cox multivariate regression analysis indicated that compared with other traditional risk factors, plasma Fib level is independently correlated with all-cause death (HR 1.33, 95% CI 1.04-1.70). However, incorporating elevated Fib level into the GRACE model did not significantly increase the predictive value of the GRACE score; for instance, AUC only increased from 0.703 to 0.713 (p = 0.765). In conclusion, Fib level at admission was independently associated with death risk among Chinese patients with ACS. However, the incorporation of Fib level at admission into the GRACE score did not improve this score's predictive value for death risk among these patients.

CHADS2, CHA2DS2-VASc and R2CHADS2 scores predict mortality in patients with coronary artery disease.

Few studies to date address the predictive ability of CHA2DS2-VASc and R2CHADS2 in CAD patients. Our aim is to investigate the prognostic performance of CHADS2, CHA2DS2-VASc and R2CHADS2 scores in patients with coronary artery disease (CAD). Angiographically obstructive CAD patients were enrolled. The prognostic performance of the three risk scores was evaluated using Cox hazards models. In addition, we compared their predictive values by calculating C statistics, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). The endpoints are death from any cause and cardiovascular death. Of 3295 subjects with CAD, the mean CHADS2, CHA2DS2-VASc and R2CHADS2 scores are 1.2 ± 1.0, 2.4 ± 1.4, and 1.6 ± 1.4, respectively. The CHADS2-guided risk classification is markedly distinct from CHA2DS-2-VASc- and R2CHADS2-guided ones. Over a median follow-up of 24 months, a total of 290 (rate 4.00/100 person-year) deaths occurred, and 163 (rate 2.2/100 person-year) were attributed to cardiovascular deaths. Event rates increase by CHADS2, CHA2DS2-VASc and R2CHADS2 (P for trend <0.001). The multivariate analyses show 60, 111 and 82% higher risk of mortality per unit increase of CHADS2, CHA2DS2-VASc and R2CHADS2 scores, respectively. Comparing with CHADS2 score (c-statistic = 0.61), CHA2DS2-VASc (c-statistic 0.65, NRI 0.52 and IDI 0.06, P for all <0.05) and R2CHADS2 (c-statistic 0.66, NRI 0.43 and IDI 0.09, P for all <0.05) scores provide better discrimination and reclassification for mortality. Also, CHA2DS2-VASc and R2CHADS2 have comparable predictive ability of mortality to the GRACE score. The CHADS2, CHA2DS2-VASc and R2CHADS2 scores are simple yet robust prognostic tools in CAD patients.

The influence of metabolic syndrome and diabetes mellitus on the N-terminal pro-B-type natriuretic peptide level and its prognostic performance in patients with coronary artery disease.

OBJECTIVES: Our aim was to investigate whether the presence of metabolic syndrome (MetS) and diabetes mellitus (DM) influenced the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and its prognostic performance in coronary artery disease (CAD). PATIENTS AND METHODS: The present study enrolled a total of 1638 CAD patients. Multivariate regression analyses were carried out to relate NT-proBNP to metabolic components, nondiabetic MetS, DM, and MetS score. Furthermore, we examined the prognostic performance of NT-proBNP in patients with non-MetS, nondiabetic MetS, and DM. RESULTS: NT-proBNP levels correlated inversely with BMI (ß=-0.11, P=0.003) and correlated positively with fasting glucose (ß=0.12, P=0.001). There were no significant relationships of NT-proBNP with other metabolic parameters. Compared with non-MetS, the presence of DM significantly increased NT-proBNP levels (P=0.004), whereas nondiabetic MetS did not influence NT-proBNP levels (P=0.954). During the median follow-up of 21 months, 109 all-cause deaths occurred. NT-proBNP levels independently predicted all-cause deaths irrespective of the presence of nondiabetic MetS and DM (Pinteraction=0.43). CONCLUSION: DM, but not nondiabetic MetS, is associated with higher NT-proBNP levels. NT-proBNP can still predict death in patients with CAD, even with the confounding effect of MetS and diabetes.