The Simplified Thrombo-Inflammatory Score as a Novel Predictor of All-Cause Mortality in Patients with Heart Failure: A Retrospective Cohort Study.

Background: The simplified thrombo-inflammatory score (sTIPS) has recently emerged as a novel prognostic score. Hence, we investigated the prognostic value of sTIPS for predicting long-term mortality in patients with heart failure (HF). Methods: A total of 3741 patients were analyzed in this study. The sTIPS was calculated based on the white blood cell count (WBC) and the mean platelet volume to platelet count (MPV/PC) ratio at admission. The mean follow-up time was 22.75 months. Multivariable Cox regression analyses were used to investigate the associations between the sTIPS and all-cause mortality (ACM). Results: In the whole study population, multivariate Cox regression analysis showed that patients in both the sTIPS 2 and sTIPS 1 groups had significantly increased risk of ACM as compared with patients in the sTIPS 0 group (hazard ratio [HR]=1.706, 95% confidence interval [CI]: 1.405-2.072, P<0.001 and HR = 1.431, 95% CI 1.270-1.612, P<0.001). The same significant trend was observed in heart failure with preserved ejection fraction (HFpEF) patients (sTIPS1 vs sTIPS0: HR = 1.366, 95% CI 1.100-1.697, P = 0.005; sTIPS2 vs sTIPS0: HR = 1.995, 95% CI 1.460-2.725, P<0.001). However, only sTIPS 1 group had a significantly increased the risk of ACM compared to the sTIPS 0 group among patients with HFmrEF (sTIPS1 vs sTIPS0: HR = 1.648, 95% CI 1.238-2.194, P = 0.001) and HFrEF (sTIPS1 vs sTIPS0: HR = 1.322, 95% CI 1.021-1.712, P = 0.035). Conclusion: sTIPS is useful in predicting risk for long-term mortality in patients with HF.

Regulation of calcium pump through Notch/Jagged/Hes signaling pathway in canine model of chronic atrial fibrillation.

OBJECTIVE: Using a canine model of atrial fibrillation (AF) induced by chronic pacing of left atrial fibrillation, the present study aimed to investigate the protein expression and content change of Notch-1 and its downstream target genes including Hes1, Jagged1, and SERCA2a in the atrial myocardium of canines with chronic AF. Furthermore, the correlation between Notch-1/Hes1/Jagged1 and the SERCA2a calcium pump was also analyzed. METHODS: Ten healthy Beagle dogs including both males and females, aged 7-9 years were randomly divided into a sham group (n = 5) and AF group (n = 5). The AF group underwent minimally invasive surgery with implantation of a pacemaker into the left atrial appendage for induction of AF. After 8 weeks of pacemaker implantation, animals were euthanized and specimens from the right and left atrial free walls were excised for histologic and biochemical analyses. RESULTS: After 8 weeks' pacemaker implantation, immunohistochemical expression of Notch-1, Hes1, Jagget1 and SERCA2a in the sham group was positive. Compared with the sham operation group, the intensity of Notch-1, Hes1 and Jagget1 in AF group was stronger with a significant increasing trend in the intensity of the color, respectively. The expression of SERCA2a was weak; the intensity decreased significantly (P < 0.05). Pearson correlation analysis revealed that in the AF group, Notch-1 was negatively correlated with SERCA2a (r = -0.77, P = 0.028), and was positively correlated with Hes1 and Jagged1 (r = 0.92, P = 0.014; r = 0.73, P = 0.030) proteins, respectively. CONCLUSION: The activation of the Notch signaling pathway was associated with a decrease in SERCA2a protein expression and contributes to the development and maintenance of electrical remodeling in AF through modulation of calcium pump function and calcium homeostasis.

Changes in microRNAs expression are involved in age-related atrial structural remodeling and atrial fibrillation.

BACKGROUND: Small noncoding microRNAs regulate gene expression in cardiac development and disease and have been implicated in the aging process and in the regulation of extracellular matrix proteins. However, their role in age-related cardiac remodeling and atrial fibrillation (AF) was not well understood. The present study was designed to decipher molecular mechanisms underlying age-related atrial structural remodeling and AF. METHODS: Three groups of dogs were studied: adult and aged dogs in sinus rhythm and with persistent AF induced by rapid atrial pacing. The expressions of microRNAs were measured by quantitative real-time polymerase chain reaction. Pathohistological and ultrastructural changes were tested by light and electron microscopy. Apoptosis index of myocytes was detected by TUNEL. RESULTS: Samples of atrial tissue showed the abnormal pathohistological and ultrastructural changes, the accelerated fibrosis, and apoptosis with aging and/or in AF dogs. Compared to the adult group, the expressions of microRNAs-21 and -29 were significantly increased, whereas the expressions of microRNAs-1 and -133 showed obvious downregulation tendency in the aged group. Compared to the aged group, the expressions of microRNAs-1, -21, and -29 was significantly increased in the old group in AF; contrastingly, the expressions of microRNA-133 showed obvious downregulation tendency. CONCLUSION: These multiple aberrantly expressed microRNAs may be responsible for modulating the transition from adaptation to pathological atrial remodeling with aging and/or in AF.

Association of interleukin-6 and C-reactive protein genetic polymorphisms levels with venous thromboembolism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Increased levels of interleukin-6 (IL-6) and C-reactive protein (CRP) have been reported in patients with venous thromboembolisms (VTE). However, prospective studies did not confirm an association between IL-6, CRP and their polymorphism with the risk of VTE.</p><p><b>METHODS</b>One hundred and forty patients (including 66 males and 74 females, mean age (55.55 ± 17.11) years) and one hundred and sixty controls (including 74 males and 86 females, mean age (56.58 ± 12.24) years) were involved. An enzyme linked immunosorbent assay (ELISA) method was used for detecting the serum levels of inflammatory factors IL-6 and CRP in both groups. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for analyzing the distribution of polymorphisms at the -572C/G and -597G/A sites of the promoter of the IL-6 gene and at 1059G/C of the CRP gene.</p><p><b>RESULTS</b>Serum levels of IL-6 and CRP were significantly higher in the VTE group than in the control group (P < 0.05). The frequencies of -572C/G promoter polymorphisms CC, CG, and GG in the IL-6 gene were found to be 34%, 48%, and 18%, respectively, and the derived allele frequencies for the C and G alleles were 58% and 42%. There was a significant difference in the -572C/G promoter polymorphisms between the VTE group and control group (P < 0.05). For the -597G/A polymorphism, individuals all carried the GG and GA type; AA genotypes were not detected. The frequency of the GG, GC, and CC genotypes at the CRP1059G/C promoter was 87.57%, 7.86% and 3.57% in VTE group, while 86.25%, 10%, and 3.75% in control group, respectively. The frequency of G and C alleles at CRP 1059G/C was 91.43% and 8.57% in VTE group and 91.56% and 8.44% in the control group. The results showed that there was no statistically significant difference of 1059G/C genotype and mutation frequency of the allele between the VTE group and control group (P > 0.05). Multiple Logistic regression analysis showed CC homozygotes of the IL-6 -572G/C, body mass index (BMI), and CRP, IL-6, and high-density lipoprotein cholesterol (HDL-C) were independent risk factors for VTE (P < 0.05).</p><p><b>CONCLUSIONS</b>We found that VTE was associated with IL-6 and CRP levels, and there was an association of IL-6 and its promoter polymorphism at -572G/C with the risk of VTE. Thus far, a causal relationship between inflammation and VTE remains to be clarified and more prospective data are required.</p>

Association between gene polymorphisms of methylenetetrahydrofolate reductase and plasma homocysteine in Uygur patients with venous thromboembolism / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and plasma homocysteine (Hcy) levels in Uygur patients with venous thromboembolism (VTE) in Xinjiang.</p><p><b>METHODS</b>A total of 222 VTE patients including 74 Uygur and 148 Han ethnic patients were examined, and 86 Uygur ethnic and Han 134 ethnic healthy people were included as controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to detect MTHFR gene C677T polymorphism and plasma Hcy levels were measured by fluorescence polarization immunoassay.</p><p><b>RESULTS</b>The MTHFR gene C677T genotypes distribution in Uygur VTE patients and control groups were: TT [28.38% (35/86) vs. 12.79% (11/86), P < 0.05], CT [41.89% (31/74) vs. 52.33% (45/86), P > 0.05]and CC [29.73% (22/74) vs. 34.88% (30/86), P > 0.05], respectively; and in Han VTE patients and control groups were: TT[27.03% (40/148) vs. 14.92% (20/134), P < 0.05], CT [44.59% (66/148) vs. 52.99% (71/134), P > 0.05] and CC [28.38% (42/148) vs. 32.09% (43/134), P > 0.05], respectively. SNP genotyping distribution frequency in Uygur and Han ethnic population was similar between controls and between VTE patients (P > 0.05). Plasma levels of Hcy in MTHFR gene TT genotype were statistically higher than CT and CC genotype (P < 0.05). After adjusting for age, gender, smoking history, hyperlipidemia, hypertension, diabetes, and MTHFR genotype, multifactor logistic regression analysis showed that plasma Hcy level (OR = 1.025, 95%CI 1.003 - 1.046, P = 0.024) and obesity (OR = 4.660, 95%CI 1.417 - 15.324, P = 0.011) were independent risk factors for Uygur ethnic patients with VTE while plasma Hcy level (OR = 1.020, 95%CI 1.006 - 1.034, P = 0.004) and smoking (OR = 2.867, 95%CI 1.062 - 6.586, P = 0.024) were independent risk factors for Han ethnic patients with VTE.</p><p><b>CONCLUSION</b>MTHFR C677T polymorphism (TT genotype carrier) and increased plasma levels of Hcy are risk factors for Uygur and Han ethnic patients with VTE in Xinjiang.</p>

[Outcome and factors affecting left atrial remodeling after percutaneous balloon mitral valvuloplasty in patients with mitral valve stenosis].

OBJECTIVE: To observe the outcome and assess related factors affecting left atrial remodeling after percutaneous balloon mitral valvuloplasty (PBMV) in patients with mitral valve stenosis. METHODS: From March 1998 to June 2002, there were 96 mitral valve stenosis patients who underwent PBMV in our hospital. Echocardiographic, 12 leads united electrocardiogram and other clinical datas were collected at preoperation, 1 week after operation, and 4 - 6 years after operation to retrospective analysis. Multiple stepwise regression analysis was used to assess controllable factors of left atrial remodeling. RESULTS: Left atrial diameter reduced from (44.6 +/- 6.6) cm before PBMV to (42.8 +/- 6.5) cm (P > 0.05) 1 week after PBMV and enlarged to (47.2 +/- 5.7)cm (all P < 0.05) at the end of 4 - 6 years follow up post operation. The mitral valve area (MVA) increased from (1.06 +/- 0.32) cm2 before PBMV to (2.02 +/- 0.43) cm2 1 week after PBMV and (1.98 +/- 0.36) cm2 4 - 6 years post operation (all P < 0.05). Heart function assessed by NYHA classification improved significantly at 1 week and 4 - 6 years after surgery compared with pre-operation (P < 0.01). Multiple stepwise regression analysis showed that systolic blood pressure at 4 - 6 years after operation, MVA at 1 week after operation, preoperative atrial fibrillation, Wilkins score < or = 8, preoperative left atrial diameter were the independent predictive factors of left atrial remodeling at 4 - 6 years after PBMV. CONCLUSIONS: PBMV was an effective therapy option for patients with mitral valve stenosis. Systolic blood pressure at 4 - 6 years after operation, MVA at 1 week after operation, preoperative atrial fibrillation, Wilkins < or = 8, preoperative left atrial diameter are the predictive factors of left atrial remodeling after PBMV.

Early local intracoronary platelet activation after drug-eluting stent placement / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Early local platelet activation after coronary intervention identifies patients at increased risk of acute stent thrombosis (AST). However, early changes in platelet activation in coronary circulation following drug-eluting stent (DES) implantation have never been reported.</p><p><b>METHODS</b>In a prospective study of 26 consecutive elective stable angina patients, platelet activation was analyzed by measuring soluble glycoprotein V (sGPV) and P-selectin (CD62P) before and after implantation of either DES or bare metal stent (BMS). All patients were pretreated with clopidogrel (300 mg loading dose) and aspirin (75 mg orally) the day before the procedure. Blood samples were drawn from the coronary ostium and 10 - 20 mm distal to the lesion site.</p><p><b>RESULTS</b>Consistent with the lower baseline clinical risk, the levels of CD62P and sGPV were within normal reference range, both in the coronary ostium and distal to the lesion before percutaneous coronary intervention (PCI) procedure. The levels of CD62P and sGPV did not change significantly (CD62P: (31.1 +/- 9.86) ng/ml vs (29.5 +/- 9.02) ng/ml, P = 0.319 and sGPV: (52.4 +/- 13.5) ng/ml vs (51.8 +/- 11.7) ng/ml, P = 0.674, respectively) after stent implantation when compared with baseline. Changes in these platelet activation markers did not differ between stent types.</p><p><b>CONCLUSIONS</b>Intracoronary local platelet activation does not occur in stable angina patients before and immediately following DES implantation when dual anti-platelet is administered.</p>