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.

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.

The influence of body composition on the N-terminal pro-B-type natriuretic peptide level and its prognostic performance in patients with acute coronary syndrome: a cohort study.

BACKGROUND: Whether body composition is associated with the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and its prognostic performance in acute coronary syndrome (ACS) remains unknown. We aimed to investigate the influence of body composition on the NT-proBNP level and its prognostic performance among ACS patients. METHODS: In total, 1623 ACS patients with NT-proBNP data were enrolled. Percent body fat and lean mass index were estimated using the Clínica Universidad de Navarra-Body Adiposity Estimator equation. Patients were divided into three groups according to the tertiles of sex-specific body mass index, percent body fat, or lean mass index. The endpoints were death from any cause and cardiovascular death. RESULTS: Body mass index was inversely correlated with NT-proBNP levels (ß = -0.036, P = 0.003). Lean mass index, but not percent body fat, was inversely associated with NT-proBNP levels (ß of lean mass index = -0.692, P = 0.002). During a median follow-up of 23 months, 161 all-cause deaths occurred, and of these, 93 (57.8 %) were attributed to cardiovascular causes. Multivariate Cox analysis showed that the NT-proBNP level independently predicted all-cause mortality or cardiovascular death in the lower body mass index, lean mass index, and percent body fat groups. However, the prognostic performance of NT-proBNP was attenuated in patients with high body mass index, lean mass index, and percent body fat. In the subgroup of patients with diabetes, inverse associations between NT-proBNP levels and body mass index or body composition were not observed. In addition, the negative influence of high body mass index and body composition on the prognostic performance of the NT-proBNP level appeared to be attenuated. CONCLUSIONS: Body mass index and lean mass index, but not percent body fat, are inversely associated with NT-proBNP levels. The prognostic performance of this biomarker may be compromised in patients with high body mass index, percent body fat, or lean mass index. Additionally, the influence of body composition on the NT-proBNP level and its prognostic performance might be attenuated in diabetic patients with ACS.

The influence of body composition on renal function in patients with coronary artery disease and its prognostic significance: a retrospective cohort study.

OBJECTIVE: We try to analyse the effect of renal functions on death in CAD patients with different body compositions. METHODS: A retrospective analysis was conducted in 2989 consecutive patients with CAD confirmed by coronary angiography were enrolled and were grouped into two categories: basically preserved renal function (PRF) (eGFR ≥60 ml/min) and obviously reduced renal function (RRF) (eGFR <60 ml/min). The influence of renal insufficiency on mortality of CAD was detected in every tertile of body composition, including body mass index (BMI), body fat (BF) and lean mass index (LMI). The end points were all-cause mortality. RESULTS: The mean follow-up time was 29.1 ± 12.5 months and death events occurred in 271 cases. The percentage of patients with RRF was positively correlated with BF and inversely correlated with the LMI, but no relationship to BMI. The survival curves showed that the risk of death was significantly higher in the RRF patients in all subgroups stratified using BMI, BF, or LMI (log rank test, all p < 0.001). The COX multivariate regression analysis showed that the risk of death was significantly higher in the RRF patients with high BF (HR 1.95, CI 1.25-3.05) and low LMI (HR 1.82, CI 1.19-2.79). Meanwhile, risk of death was significantly higher in RRF patients with a high BMI (HR 2.08, CI 1.22-3.55) or low BMI (HR 1.98, CI 1.28-3.08) but this risk was not significant in patients with a medium BMI (HR 1.12, 0.65-1.94). The subgroup analysis of patients with acute coronary syndrome (ACS) showed similar results. CONCLUSIONS: For patients with CAD, renal insufficiency was positively correlated with BF, inversely correlated with LMI, and unrelated to BMI. The effect of renal insufficiency on the risk of death of CAD was related to body composition.

Association Between Bisphosphonates Therapy and Incident Myocardial Infarction: Meta-analysis and Trial Sequential Analysis.

BACKGROUND: Bisphosphonates have shown potential to inhibit atherosclerosis in animal experiments; however, whether bisphosphonates therapy lowers the risk of incidence of myocardial infarction (MI) is debated. We performed the meta-analysis and trial sequential analysis (TSA) to investigate the relation between bisphosphonates therapy and incident MI. METHODS: Pubmed and Embase databases were systematically searched in April 2015 to identify studies, which compared the incidence of MI in subjects receiving bisphosphonates with that in subjects not receiving the agents. Meta-analysis was conducted using random effects model in consideration of statistical heterogeneity between studies. Reliability of the results from meta-analysis was examined using TSA. RESULTS: Six observational studies (n = 440261) and 3 randomized control trials (RCTs, n = 11,024) met the eligible criteria. In the pooled analysis of observational studies, bisphosphonates therapy was not associated with reduced risk of MI either using unadjusted estimates (relative risk 0.93, 95% confidence interval (CI), 0.75-1.15) or estimates adjusted for confounding factors (hazard ratio 1.01, 95% CI, 0.84-1.21). Furthermore, hazard of incident MI did not differ between alendronate users and nonusers. TSA showed that evidence from observational studies firmly precluded the association between bisphosphonates and incident MI. Pooled analysis of RCTs also suggested no benefits of decrease in incident MI associated with bisphosphonates therapy (relative risk 1.05, 95% CI, 0.53-2.09). However, TSA demonstrated that evidence from RCTs was insufficient to draw a conclusion. CONCLUSIONS: Despite the encouraging findings from animal studies, bisphosphonates therapy is not associated with reduced risk of MI.

EDIL3 deficiency ameliorates adverse cardiac remodelling by neutrophil extracellular traps (NET)-mediated macrophage polarization.

AIMS: After myocardial infarction (MI), injured cardiomyocytes recruit neutrophils and monocytes/macrophages to myocardium, which in turn initiates inflammatory and reparative cascades, respectively. Either insufficient or excessive inflammation impairs cardiac healing. As an endogenous inhibitor of neutrophil adhesion, EDIL3 plays a crucial role in inflammatory regulation. However, the role of EDIL3 in MI remains obscure. We aimed to define the role of EDIL3 in cardiac remodelling after MI. METHODS AND RESULTS: Serum EDIL3 levels in MI patients were negatively associated with MI biomarkers. Consistently, WT mice after MI showed low levels of cardiac EDIL3. Compared with WT mice, Edil3-/- mice showed improvement of post-MI adverse remodelling, as they exhibited lower mortality, better cardiac function, shorter scar length, and smaller LV cavity. Accordingly, infarcted hearts of Edil3-/- mice contained fewer cellular debris and lower amounts of fibrosis content, with decreased collagen I/III expression and the percentage of α-smooth muscle actin myofibroblasts. Mechanistically, EDIL3 deficiency did not affect the recruitment of monocytes or T cells, but enhanced neutrophil recruitment and following expansion of pro-inflammatory Mertk-MHC-IIlo-int (myeloid-epithelial-reproductive tyrosine kinase/major histocompatibility complex II) macrophages. The injection of neutrophil-specific C-X-C motif chemokine receptor 2 antagonist eliminated the differences in macrophage polarization and cardiac function between WT and Edil3-/- mice after MI. Neutrophil extracellular traps (NETs), which were more abundant in the hearts of Edil3-/- mice, contributed to Mertk-MHC-IIlo-int polarization via Toll-like receptor 9 pathway. The inhibition of NET formation by treatment of neutrophil elastase inhibitor or DNase I impaired macrophage polarization, increased cellular debris and aggravated cardiac adverse remodelling, thus removed the differences of cardiac function between WT and Edil3-/- mice. Totally, EDIL3 plays an important role in NET-primed macrophage polarization and cardiac remodelling during MI. CONCLUSION: We not only reveal that EDIL3 deficiency ameliorates adverse cardiac healing via NET-mediated pro-inflammatory macrophage polarization but also discover a new crosstalk between neutrophil and macrophage after MI.

Interleukin-37 promotes colitis-associated carcinogenesis via SIGIRR-mediated cytotoxic T cells dysfunction.

Interleukin-37b (hereafter called IL-37) was identified as fundamental inhibitor of natural and acquired immunity. The molecular mechanism and function of IL-37 in colorectal cancer (CRC) has been elusive. Here, we found that IL-37 transgenic (IL-37tg) mice were highly susceptible to colitis-associated colorectal cancer (CAC) and suffered from dramatically increased tumor burdens in colon. Nevertheless, IL-37 is dispensable for intestinal mutagenesis, and CRC cell proliferation, apoptosis, and migration. Notably, IL-37 dampened protective cytotoxic T cell-mediated immunity in CAC and B16-OVA models. CD8+ T cell dysfunction is defined by reduced retention and activation as well as failure to proliferate and produce cytotoxic cytokines in IL-37tg mice, enabling tumor evasion of immune surveillance. The dysfunction led by IL-37 antagonizes IL-18-induced proliferation and effector function of CD8+ T cells, which was dependent on SIGIRR (single immunoglobulin interleukin-1 receptor-related protein). Finally, we observed that IL-37 levels were significantly increased in CRC patients, and positively correlated with serum CRC biomarker CEA levels, but negatively correlated with the CD8+ T cell infiltration in CRC patients. Our findings highlight the role of IL-37 in harnessing antitumor immunity by inactivation of cytotoxic T cells and establish a new defined inhibitory factor IL-37/SIGIRR in cancer-immunity cycle as therapeutic targets in CRC.

Autophagy-based unconventional secretion of HMGB1 by keratinocytes plays a pivotal role in psoriatic skin inflammation.

The precise mechanism through which macroautophagy/autophagy affects psoriasis is poorly understood. Here, we found that keratinocyte (KC) autophagy, which was positively correlated with psoriatic severity in patients and mouse models and could be inhibited by mitogen-activated protein kinase (MAPK) family inactivation. The impairment of autophagic flux alleviated psoriasisform inflammation. We also found that an autophagy-based unconventional secretory pathway (autosecretion) dependent on ATG5 (autophagy related 5) and GORASP2 (golgi reassembly stacking protein 2) promoted psoriasiform KC inflammation. Moreover, the alarmin HMGB1 (high mobility group box 1) was more effective than other autosecretory proteins in regulating psoriasiform cutaneous inflammation. HMGB1 neutralization in autophagy-efficient KCs eliminated the differences in psoriasiform inflammation between Krt14+/+-Atg5f/f KCs and Krt14Cre/+-atg5f/f KCs, and conversely, recombinant HMGB1 almost completely restored psoriasiform inflammation in Krt14Cre/+-atg5f/f KCs in vivo. These results suggest that HMGB1-associated autosecretion plays a pivotal role in cutaneous inflammation. Finally, we demonstrated that Krt14Cre/+-hmgb1f/f mice displayed attenuated psoriatic inflammation due to the essential crosstalk between KC-specific HMGB1-associated autosecretion and γδT cells. Thus, this study uncovered a novel autophagy mechanism in psoriasis pathogenesis, and the findings imply the clinical significance of investigating and treating psoriasis.Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; AGER: advanced glycosylation end-product specific receptor; Anti-HMGB1: anti-HMGB1 neutralizing antibody; Anti-IL18: anti-IL18 neutralizing antibody; Anti-IL1B: anti-IL1B neutralizing antibody; ATG5: autophagy related 5; BAF: bafilomycin A1; BECN1: beclin 1; CASP1: caspase 1; CCL: C-C motif chemokine ligand; CsA: cyclosporine A; ctrl shRNA: lentivirus harboring shRNA against control; CXCL: C-X-C motif chemokine ligand; DCs: dendritic cells; DMEM: dulbecco's modified Eagle's medium; ELISA: enzyme-linked immunosorbent assay; EM: electron microscopy; FBS: fetal bovine serum; GORASP2 shRNA: lentivirus harboring shRNA against GORASP2; GORASP2/GRASP55: golgi reassembly stacking protein 2; GR1: a composite epitope between LY6 (lymphocyte antigen 6 complex) locus C1 and LY6 locus G6D antigens; H&E: hematoxylin and eosin; HMGB1: high mobility group box 1; HMGB1 shRNA: lentivirus harboring shRNA against HMGB1; IFNG/IFN-γ: interferon gamma; IL17A: interleukin 17A; IL18: interleukin 18; IL1A/IL-1α: interleukin 1 alpha; IL1B/IL-1ß: interleukin 1 beta; IL22/IL-22: interleukin 22; IL23A: interleukin 23 subunit alpha; IL23R: interleukin 23 receptor; IMQ: imiquimod; ITGAM/CD11B: integrin subunit alpha M; ITGAX/CD11C: integrin subunit alpha X; IVL: involucrin; KC: keratinocyte; KD: knockdown; KO: knockout; Krt14+/+-Atg5f/f mice: mice bearing an Atg5 flox allele, in which exon 3 of the Atg5 gene is flanked by two loxP sites; Krt14+/+-Hmgb1f/f: mice bearing an Hmgb1 flox allele, in which exon 2 to 4 of the Hmgb1 gene is flanked by two loxP sites; Krt14Cre/+-atg5f/f mice: keratinocyte-specific atg5 knockout mice generated by mating Atg5-floxed mice with mice expressing Cre recombinase under the control of the promoter of Krt4; Krt14Cre/+-hmgb1f/f mice: keratinocyte-specific hmgb1 knockout mice generated by mating Hmgb1-floxed mice with mice expressing Cre recombinase under the control of the promoter of Krt14; Krt14-Vegfa mice: mice expressing 164-amino acid Vegfa splice variant recombinase under the control of promoter of Krt14; LAMP1: lysosomal associated membrane protein 1; LDH: lactate dehydrogenase; LORICRIN: loricrin cornified envelope precursor protein; M5: TNF, IL1A, IL17A, IL22 and OSM in combination; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MKI67: marker of proliferation Ki-67; MTT: thiazolyl blue tetrazolium bromide; NFKB/NF-κB: nuclear factor kappa B; NHEKs: primary normal human epidermal keratinocytes; NS: not significant; OSM: oncostatin M; PASI: psoriasis area and severity index; PtdIns3K: class III phosphatidylinositol 3-kinase; qRT-PCR: quantitative RT-PCR; RELA/p65: RELA proto-oncogene, NF-kB subunit; rHMGB1: recombinant HMGB1; rIL18: recombinant interleukin 18; rIL1B: recombinant interleukin 1 beta; S100A: S100 calcium binding protein A; SQSTM1/p62: sequestosome 1; T17: IL17A-producing T; TCR: T-cell receptor; tcrd KO mice: tcrd (T cell receptor delta chain) knockout mice, which show deficient receptor expression in all adult lymphoid and epithelial organs; TLR: toll-like receptor; TNF/TNF-α: tumor necrosis factor; WOR: wortmannin; WT: wild-type; γδT17 cells: IL17A-producing γδ T cells.

The impact of renal function on efficacy and safety of new oral anticoagulant in atrial fibrillation patients: A systemic review and meta-analysis.

BACKGROUND AND OBJECTIVES: This meta-analysis was to investigate the efficacy and safety of new oral anticoagulant (NOAC) in atrial fibrillation (AF) patients with renal function insufficiency, and to explore whether renal decline occurs in AF patients with NOAC and its impact on outcomes. METHODS AND RESULTS: In AF patients with mild renal insufficiency, the NOAC was associated with significantly lower rates of stroke (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.67-0.91; P < .05). Lower rates of bleeding were significantly observed in NOAC group (OR, 0.85; 95% CI, 0.75-0.97; P < .05). In AF patients with moderate renal impairment, similar results were revealed (OR for stroke or systemic embolism, 0.80; 95% CI, 0.67-0.95, P < .05; OR for major bleeding, 0.78; 95% CI, 0.59-1.03; P = .07). During the follow-up, pooled data revealed that NOAC showed a less renal toxicity, but the difference did not reach statistical significance (creatinine clearance decline: -0.12 mL/min [-0.84, 0.61 mL/min]). We have revealed that the NOACs were associated with significantly lower rates of stroke or systemic embolism (hazard ratio [HR], 0.66; 95% CI, 0.42-0.89; P < .05) and lower rates of bleeding (HR, 0.93; 95% CI, 0.70-1.16; P = .153) in AF patients with worsening renal function. CONCLUSIONS: NOAC may have the potentiality to be at least as effective as warfarin and may equal safety outcomes in AF patients with renal impairment. Renal decline during therapeutics may be less likely happened in NOAC than warfarin dose. NOAC may reveal good efficacy and safety outcomes in these scenarios. Further detailed research is needed to gain more clear profile on this new anticoagulant.

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.

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.

The correlation between serum total bilirubin and outcomes in patients with different subtypes of coronary artery disease.

BACKGROUNDS: The relation between serum total bilirubin (TBi) and mortality in patients with established coronary artery disease (CAD) remains undefined. We try to investigate the role of the subtypes of CAD in the association. METHODS: A total of 3013 patients with angiographically obstructive CAD were enrolled. A retrospective analysis was conducted. Patients were divided into 3 groups as follows: stable CAD (SCAD), unstable angina pectoris (UAP) and acute myocardial infarction (AMI). The predictive values of TBi for 30-day and long-term mortality were assessed using logistic and Cox regression, respectively. RESULTS: Higher initial serum TBi levels were significantly associated with increased risk of short-term mortality (OR 2.35, 95% CI 1.15-4.77) in AMI group. However, the association was absent among patients with SCAD and UAP. Serum TBi was able to independently predict the long-term mortality in SCAD (HR 0.34, 95% CI 0.16-0.70) and UAP (HR 0.49, 95% CI 0.31-0.78) groups. However, there was no significant relation between TBi and long-term mortality in AMI groups. CONCLUSION: The different subtypes of CAD affected the relation between serum TBi and clinical prognosis. Initial serum TBi was positively correlated with short-term mortality of AMI patients, and negatively correlated with long-term mortality in SCAD or UAP 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 effect of activated clotting time values for patients undergoing percutaneous coronary intervention: A systematic review and meta-analysis.

Our aim was to illustrate the effect of higher activated clotting time (ACT) values versus lower ACT values on thrombotic or hemorrhagic events in coronary atherosclerotic heart disease (CHD) patients undergoing percutaneous coronary intervention (PCI). PubMed, Embase, Web of Science, and Cochrane Library were searched. Observational studies assessing ACT related major adverse cardiac event (MACE) and major bleeding were included. Studies were allocated into three groups. Group 1 included studies with low percentage of participants prescribed with glycoprotein IIb/IIIa inhibitors ([GPI] ≤30%), Group 2 with high percentage of participants prescribed with GPI (>30%), and Group 3 with routine direct thrombin inhibitors (DTI) prescription. The cutoff is designed as 300s (290-310s) for Group 1, and 250s (240-260s) for Group 2. With regard to MACE and major bleeding in Group 1, there was no significant difference between higher ACT values and lower ACT values (risk ratio [RR] for MACE, 1.16, 95% confidence interval [CI], 0.65-2.05, p=0.62, I(2)=94%, RR for major bleeding, 0.96, 95% CI, 0.66-1.40, p=0.83, I(2)=0%). Likewise, no significant difference was found in Group 2 between higher ACT values and lower ACT values (RR for MACE, 1.15, 95% CI, 0.97-1.35, p=0.10, I(2)=0%, RR for major bleeding, 0.85, 95% CI, 0.45-1.60, p=0.61, I(2)=83%). In conclusion, ACT may not have a substantial effect on thrombotic or hemorrhagic complications. Under current clinical practice, target ACT may be higher than what is necessary to prevent thrombotic events. We may achieve a relative low ACT level to preserve efficacy and enhance safety.

Gender Disparity in the Safety and Efficacy of Radial and Femoral Access for Coronary Intervention: A Systematic Review and Meta-Analysis.

Our aim was to investigate the gender disparity in the safety and efficacy of transradial percutaneous coronary intervention (PCI; TRI) and transfemoral PCI (TFI) by a meta-analysis. MEDLINE, Embase, and CENTRAL were searched to identify studies on vascular access with sex-specific events available or studies on sex difference with the events reported by vascular access. Fifteen studies involving 3 921 848 participants were included. Transradial PCI significantly reduced the risk of bleeding complications in both sexes (TRI-versus-TFI odds ratio [OR]: 0.37 in females vs 0.47 in males) and major adverse cardiac events (MACE) in females (OR: 0.70, P < .001) but not in males (OR: 0.83, P = .15) compared to TFI. Transradial PCI diminished the sex difference in the incidence of bleeding complications (female-versus-male OR: 1.82 with TRI vs 2.39 with TFI; interaction P = .01) and MACE (female-versus-male OR: 1.21 with TRI vs 1.41 with TFI; interaction P = .003) compared to TFI. Females were associated with higher crossover rate in the TRI subgroup but not in the TFI subgroup (interaction P = .05). In conclusion, TRI may improve the safety and efficacy of outcomes in both sexes and be an effective means to cut down the gender difference in prognosis.

The Prognosis of Patients With Nonobstructive Coronary Artery Disease Versus Normal Arteries Determined by Invasive Coronary Angiography or Computed Tomography Coronary Angiography: A Systematic Review.

Limited data exist regarding the outcomes of patients with nonobstructive coronary artery disease (CAD) detected by computed tomography coronary angiography (CTCA) or invasive coronary angiography (ICA). Our aim was to compare the prognosis of patients with nonobstructive coronary artery plaques with that of patients with entirely normal arteries. The MEDLINE, Cochrane Library, and Embase databases were searched. Studies comparing the prognosis of individuals with nonobstructive CAD versus normal coronary arteries detected by CTCA or ICA were included. The primary outcome was major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, hospitalization due to unstable angina or revascularization. A fixed effects model was chosen to pool the estimates of odds ratios (ORs). Forty-eight studies with 64,905 individuals met the inclusion criteria. Patients in the nonobstructive CAD arm had a significantly higher risk of MACE compared to their counterparts in the normal artery arm (pooled OR, 3.17, 95% confidence interval, 2.77-3.63). When excluding revascularization as an endpoint, hard cardiac composite outcomes were also more frequent among patients with nonobstructive CAD (pooled OR, 2.10; 95%CI, 1.79-2.45). All subgroups (age, sex, follow-up duration, different outcomes, diagnostic modality, and CAD risk factor) consistently showed a poorer prognosis with nonobstructive CAD than with normal arteries. When dividing the studies into a CTCA and ICA group for further analysis based on the indications for diagnostic tests, we also found nonobstructive CAD to be associated with a higher risk of MACE in both stable and acute chest pain. Patients with nonobstructive CAD had a poorer prognosis compared with their counterparts with normal arteries.

The influence of age on the clinical implications of N-terminal pro-B-type natriuretic peptide in acute coronary syndrome.

Currently, there are no studies addressing the influence of age on the prognostic information of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in Asian population with acute coronary syndrome (ACS). The purpose of this study was to investigate the prognostic performance of NT-proBNP in Chinese patients with ACS across different age groups. A total of 1512 ACS patients with venous blood NT-proBNP measured were enrolled. Patients were divided into tertiles based on their ages (<61, 61-71, ≥72 years). The median NT-proBNP concentrations in the three groups (T1-T3) were 406, 573, and 1288 pg/ml (p < 0.001), respectively. During a median follow-up of 23 months, 150 all-cause deaths occurred, and 88 (58.7 %) were attributed to cardiovascular cause. NT-proBNP levels are independently associated with mortality in each age group [1st group: HR 2.19 95 % CI (1.17-4.10); 2nd group: HR 1.82 95 % CI (1.04-3.20); 3rd group: HR 1.48 95 % CI (1.09-2.01), P interaction = 0.062]. NT-proBNP improves discrimination and reclassification for mortality beyond thrombolysis in myocardial infarction score in patients of all ages. The optimal NT-proBNP cutoff points for predicting mortality in three age groups are 1511, 2340, and 2883 pg/ml, respectively. In conclusion, NT-proBNP is a valuable biomarker in predicting long-term mortality and provides an improvement in discrimination and reclassification for prognosis in ACS patients of all ages.

Understanding the controversy surrounding the correlation between fibrinogen level and prognosis of coronary artery disease-The role of the subtypes of coronary artery disease.

BACKGROUND: There is a controversy surrounding the correlation between fibrinogen (Fib) level and prognosis of coronary artery disease (CAD). We try to investigate the role of the subtypes of CAD in this controversy. METHODS: A retrospective analysis was conducted from a single center CAD registered database. 3020 consecutive patients with CAD confirmed by coronary angiography were enrolled. The end points were all-cause mortality. RESULTS: The mean follow-up time was 27.2±13.1months and death events occurred in 258 cases. Mortality rates for patients with CAD and those in the stable coronary artery disease (SCAD) and unstable angina pectoris (UAP) groups exhibited an overall rising trend as Fib levels increased (log rank test, all p<0.05). However, similar trends were not detected in patients with acute myocardial infarction (AMI). The results of a Cox proportional-hazards regression analysis showed that Fib level was independently correlated with the risk of death in patients with CAD as well as those in the SCAD and UAP groups (CAD, HR 1.40, CI 1.16-1.68; SCAD, HR 1.86, CI 1.24-2.79; UAP, HR 1.42, CI 1.06-1.90). In the AMI group, however, no independent correlation was observed between Fib level and mortality. CONCLUSION: The different proportions of subtypes of CAD affected the correlation between Fib level and the clinical prognosis of patients with CAD. This is maybe a clue to explain the controversy.

The efficacy and safety of prehospital therapeutic hypothermia in patients with out-of-hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: The benefit of therapeutic hypothermia (TH) to patients suffering out-of-hospital cardiac arrest (OHCA) has been well established. However, the effect of prehospital cooling remains unclear. We aimed to investigate the efficacy and safety of prehospital TH for OHCA patients by conducting a systematic review of randomised controlled trials (RCTs). METHODS: The MEDLINE, EMbase and CENTRAL databases were searched for publications from inception to April 2015. RCTs that compared cooling with no cooling in a prehospital setting among adults with OHCA were eligible for inclusion. Random- and fixed-effect models were used depending on inter-study heterogeneity. RESULTS: Eight trials that recruited 2379 participants met the inclusion criteria. Prehospital TH was significantly associated with a lower temperature at admission (mean difference (MD) -0.94; 95% confidence interval (CI) -1.06 to -0.82). However, survival upon admission (Risk ratio (RR) 1.01, 95%CI 0.98-1.04), survival at discharge (RR 1.02, 95%CI 0.91-1.14), in-hospital survival (RR 1.05, 95%CI 0.92-1.19) and good neurological function recovery (RR 1.06, 95% CI 0.91-1.23) did not differ between the TH-treated and non-treated groups. Prehospital cooling increased the incidence of recurrent arrest (RR 1.23, 95%CI 1.02-1.48) and decreased the PH at admission (MD -0.04, 95%CI -0.07 to -0.02). Pulmonary oedema did not differ between the arms (RR 1.02, 95%CI 0.67-1.57). None of the potentially controversial issues (cooling methods, time of inducing TH, the proportion of continuing cooling in hospital, actual prehospital infusion volume and primary cardiac rhythms) affected the efficacy. CONCLUSION: Evidence does not support the administration of prehospital TH to patients with OHCA.

Meta-Analysis of Relation Between Oral ß-Blocker Therapy and Outcomes in Patients With Acute Myocardial Infarction Who Underwent Percutaneous Coronary Intervention.

The aim of the present review was to investigate the association between the use of oral ß-blockers and prognosis in patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) treatment. A systematic literature search was conducted in Pubmed (from inception to September 27, 2014) and Embase (Ovid SP, from 1974 to September 29, 2014) to identify studies that compared the outcome of patients with AMI taking oral ß-blockers with that of patients not taking after PCI. Systematic review and meta-analysis were performed with random-effects model or fixed-effects model. Ten observational studies with a total of 40,873 patients were included. Use of ß-blockers was associated with a reduced risk of all-cause death (unadjusted relative risk 0.58, 95% confidential interval 0.48 to 0.71; adjusted hazard ratio 0.76, 95% confidential interval 0.62 to 0.94). The potential benefit of ß-blockers in preventing all-cause death was not similar in all population but was restricted to those with reduced ejection fraction, with low use proportion of other secondary prevention drugs or with non-ST-segment elevation myocardial infarction. The association between the use of ß-blockers and improved survival rate was significant in ≤1-year follow-up duration. Rates of cardiac death, myocardial infarction, and heart failure readmission in patients using ß-blockers were not significantly different from those in patients without ß-blocker therapy. In conclusion, there is lack of evidence to support routine use of ß-blockers in all patients with AMI who underwent PCI. Further trials are urgently needed to address the issue.