Activation of the CaR-CSE/H2S pathway confers cardioprotection against ischemia-reperfusion injury.

Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H2O2, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury.

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.

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.

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.

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 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.