B-type natriuretic peptide predicts new-onset atrial fibrillation in patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention

The predictive value of B-type natriuretic peptide (BNP) with respect to the occurrence of new-onset atrial fibrillation (AF) in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) is unknown. The aim of this study was to evaluate whether BNP has a predictive value for the occurrence of new-onset AF in patients with STEMI treated by primary PCI. In 180 patients with STEMI treated by primary PCI, BNP concentrations were measured 24h after chest pain onset. The Receiver Operating Characteristic analysis was performed to identify the most useful BNP cut-off level for the prediction of AF. The patients were divided into the two groups according to calculated cut-off level: high BNP group (BNP≥720 pg/mL, n=33) and low BNP group (BNP<720 pg/mL, n=147). The incidence of AF was 5.0%, and occurred more frequently in high BNP group (7/33, 21.2%) than in low BNP group (2/147, 1.4%), (p<0.001). Patients with high BNP were older (p=0.017), had more often anterior wall infarction (p=0.015), higher Killip class on admission (p=0.038), higher peak troponin I (p=0.002), lower left ventricular ejection fraction (p=0.029) than patients with low BNP. After multivariate adjustment, BNP was an independent predictor of AF (OR 3.70, 95% CI 1.40-9.77, p=0.008). BNP independently predicts the occurrence of new-onset AF in STEMI patients treated by primary PCI.     

C - 反应蛋白在不同程度急性心梗患者中的相关性研究

目的:探讨C-反应蛋白(CRP)在急性心肌梗死患者中的变化及与心功能之间的关系。方法:选取121例急性心肌梗死(AMI)患者和50例健康对照者,酶联免疫吸附法(ELISA)检测血清C-反应蛋白(CRP)和B型钠尿肽(BNP)。结果:AMI患者血清CRP显著高于健康对照,AMI伴心功能III,IV级者血清BNP、CRP显著高于AMI伴心功能I,II级者。结论:血清CRP对于急性心肌梗死患者的心功能重要参考指标。     

C-反应蛋白在不同程度急性心梗患者中的相关性研究

目的：探讨C-反应蛋白（CRP）在急性心肌梗死患者中的变化及与心功能之间的关系。方法：选取121例急性心肌梗死（AMI）患者和50例健康对照者,酶联免疫吸附法（ELISA）检测血清C-反应蛋白（CRP）和B型钠尿肽（BNP）。结果：AMI患者血清CRP显著高于健康对照,AMI伴心功能III,IV级者血清BNP、CRP显著高于AMI伴心功能I,II级者。结论：血清CRP对于急性心肌梗死患者的心功能重要参考指标。     

Head-to-head comparison of BNP and IL-6 as markers of clinical and experimental heart failure: Superiority of BNP

Activation of BNP and IL-6 are hallmarks of left ventricular (LV) dysfunction and congestive heart failure (CHF). To assess the relative activation of BNP and IL-6 in clinical and experimental heart failure, we performed a human study in which plasma N-terminal proBNP (NT-proBNP) and IL-6 were measured in a large group of patients in the chronic phase after myocardial infarction (MI) and an animal study in which LV gene expression of BNP and IL-6 was assessed in rapid ventricular pacing-induced heart failure. In the human study, NT-proBNP and IL-6 were measured by non-extracted, enzyme-linked immunoassay in 845 subjects (n=468 outpatients after MI, MONICA MI register Augsburg; and 377 siblings without MI, control). NT-proBNP (295+/-23pg/mL vs. CTRL 84+/-8, P<0.05) and IL-6 (2.7+/-0.1pg/mL vs. CTRL 2.1+/-0.1, P<0.05) were both elevated in subjects with MI. These increases were particularly pronounced in the presence of concomitant CHF (both P<0.01 vs. CTRL) and LV dysfunction (EF<45%, both P<0.05 vs. CTRL). However, NT-proBNP was significantly correlated with several cardiac structural and functional parameters (EF, LVMI, history of MI, CHF symptoms; all P<0.05) upon regression analysis whereas IL-6 was only correlated with history of MI (P<0.001). Accordingly, MI subjects with symptomatic LV dysfunction were detected by NT-proBNP with a greater sensitivity, specificity, and ROC-area (85%, 88%, and 0.87, respectively) as compared to IL-6 (69%, 53%, and 0.67, respectively). In the animal study, IL-6 and BNP expression were both significantly elevated in CHF (both P<0.05) but with a much greater absolute activation of BNP. In addition, BNP mRNA expression displayed a stronger inverse correlation with LV function (r=-0.74; P<0.001) than IL-6 (r=-0.53; P=0.001) and was a markedly more sensitive and specific molecular marker of LV dysfunction (sensitivity 91%, specificity 100%, ROC-area 0.94) than IL-6 (sensitivity 74%, specificity 83%, ROC-area 0.87). Our animal study provides evidence that IL-6 expression is activated in heart failure but to a significantly lesser degree than that of BNP. Both the stronger expression of BNP and the better correlation with LV function provide the molecular basis for a diagnostic superiority of NT-proBNP in clinical LV dysfunction and heart failure.     

G-CSF Predicts Cardiovascular Events in Patients with Stable Coronary Artery Disease

Granulocyte-colony-stimulating-factor (G-CSF) induces mobilization of progenitor cells but may also exert pro-inflammatory and pro-thrombotic effects. Treatment with recombinant G-CSF after acute myocardial infarction is currently under examination and has been associated with in-stent restenosis. However, it is not known whether plasma levels of endogenous G-CSF are also associated with an increased cardiovascular risk. Therefore we included 280 patients with angiographically proven stable coronary artery disease. G-CSF was measured by specific ELISA and patients were followed for a median of 30 months for the occurrence of major adverse cardiovascular events (MACE: death, myocardial infarction, re-hospitalization). Those with cardiac events during follow-up showed significant higher G-CSF levels (32.3 pg/mL IQR 21.4–40.5 pg/mL vs. 24.6 pg/mL IQR 16.4–34.9 pg/mL; p<0.05) at baseline. Patients with G-CSF plasma levels above the median had a 2-fold increased risk for MACE (p<0.05). This was independent from established cardiovascular risk factors. In addition, G-CSF above the median was a predictor of clinical in-stent restenosis after implantation of bare-metal stents (6.6% vs. 19.4%; p<0.05) but not of drug-eluting stents (7.7% vs. 7.6%; p = 0.98). This data suggests that endogenous plasma levels of G-CSF predict cardiovascular events independently from established cardiac risk factors and are associated with increased in-stent restenosis rates after implantation of bare metal stents.     

Plasma profiles of circulating granulocyte-macrophage colony-stimulating factor and soluble cellular adhesion molecules in acute myocardial infarction. Contribution to post-infarction left ventricular dysfunction

No in vivo data exist about the relationship of circulating granulocyte-macrophage colony stimulating factor (GM-CSF) and soluble adhesion molecules ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) to the severity of acute myocardial infarction (AMI) and the pathophysiological events of post-infarction left ventricular dysfunction. We investigated the kinetics of these inflammatory mediators in the plasma of patients with AMI, and correlated the findings with the clinical severity of the disease during the first week of hospitalization as well as the degree of left ventricular dysfunction one month after the AMI. Plasma levels of inflammatory markers were determined in 41 AMI patients (all received thrombolytic treatment) by ELISA assays, serially during the first week of hospitalization and one month after hospital admission. Patients (n = 20) with uncomplicated AMI (Killip class I) were classified as group A, patients (n = 21) with AMI complicated by heart failure manifestations (Killip classes II and III) were classified as group B, while 20 age- and sex-matched volunteers were used as healthy controls. A sustained increase in GM-CSF, sICAM-1 and sVCAM-1 plasma concentrations was observed only in group B during the first week of the study. Patients from group B exhibited significantly higher levels of GM-CSF (P < 0.01), sICAM-1 (P < 0.05) and sVCAM-1 (P < 0.01) than patients from group A and the healthy controls (P < 0.001). In group B patients, significant correlations were observed between the peak of GM-CSF levels and the peak of serum creatine kinase-MB (r = 0.42; P < 0.05), white blood cell counts (r = 0.67; P < 0.001) and LVEF (r =- 0.51; P < 0.01). At one month follow-up, patients (n = 17) with severe post-infarction left ventricular dysfunction (LVEF 35%). Significant correlations were observed between GM-CSF levels and left ventricular end-diastolic volume index (r = 0.55; P < 0.001) or left ventricular end-systolic volume index (r = 0.49; P = 0.001). We have found a significant elevation of plasma GM-CSF and soluble adhesion molecules during the course of AMI, with the highest values in patients with AMI complicated by heart failure manifestations and severe left ventricular dysfunction. These monocyte-related inflammatory mediators may actively contribute to the pathophysiology of the disease and post-infarction cardiac dysfunction.     

Can serum amyloid A or macrophage colony stimulating factor serve as marker of amyloid formation process?

Amyloid formation depends on amyloid precursor production and is influenced by the activity of the underlying disorder and mediated by some proinflammatory cytokines. In this pilot study we tried to find some specific markers that could establish the activity of the disease. We investigated 45 samples of sera and 38 samples of urine from patients (pts) with secondary amyloidosis (AA), primary amyloidosis (AL), systemic autoimmune diseases with renal impairment (Vasc) and healthy controls (Co). Pts with AA had increased plasma levels of TNF alpha (9.97 +/- 4.22 vs. 2.63 +/- 1.34 pg/mL, p < 0.001) and SAA (43.14 +/- 16.0 vs. 3.42 +/- 0.7 ng/mL, p < 0.05) in comparison with Co. Plasma levels of M-CSF in the AA group were significantly increased in comparison with Co (1077.34 +/- 238.6 vs. 137.71 +/- 19.6, pg/mL, p < 0.001) and also in comparison with Vasc (482.24 +/- 86.7 pg/mL, p < 0.05). Urinary excretions of TNF alpha (8.92 +/- 8.1 vs. 0.17 +/- 0.11 microgram/mol creatinine, p < 0.01), sIL-6R (1.39 +/- 1.14 vs. 0.07 +/- 0.05 g/mol creatinine, p < 0.01) and M-CSF (650.2 +/- 153.7 vs. 33.3 +/- 8.6 micrograms/mol creatinine, p < 0.01) in AA were significantly increased in comparison with Co. Pts with AL had increased plasma levels of M-CSF (819.83 +/- 264.2 vs. 137.71 +/- 19.6 pg/mL, p < 0.05) and urinary excretion of M-CSF (865.0 +/- 188.4 vs. 33.3 +/- 8.6 micrograms/mol creatinine, p < 0.01) in comparison with Co. SAA has a low specificity for amyloidosis but is a sensitive acute phase reactant. TNF alpha, a proinflammatory cytokine, may reflect the activity of the underlying diseases in secondary amyloidosis. M-CSF was increased both in plasma and urine in amyloidosis groups and seems to be the most promising (possibly specific) marker of amyloidosis.     

Left Ventricular Dysfunction and CXCR3 Ligands in Hypertension: From Animal Experiments to a Population-Based Pilot Study

Detecting left ventricular (LV) dysfunction at an early stage is key in addressing the heart failure epidemic. In proteome profiling experiments in mice subjected either to aortic banding or sham, the circulating CXCR3 ligands monokine induced by interferon-γ (MIG) and interferon-γ inducible protein 10 (IP10) were 5 to 40 fold up-regulated at eight weeks. We assessed the diagnostic value of circulating NT-pro BNP and CXCR3 ligands (MIG, IP10, Interferon-inducible T-cell alpha chemo-attractant [I–TAC]) in patients with hypertension (≥140/90 mm Hg) associated with subclinical (n = 19) or symptomatic (n = 16) diastolic LV dysfunction on echocardiography and healthy controls. NT–pro BNP, MIG, IP10, I–TAC all increased (p ≤ 0.014) across the categories of worsening left ventricular dysfunction. In patients with symptomatic disease, MIG, IP10, and I–TAC increased 210% (p = 0.015), 140% (p = 0.007) and 120% (p = 0.035) more than NT-pro BNP. The optimal discrimination limits, obtained by maximizing Youden’s index were 246 pmol/L, 65 pg/mL, 93 pg/mL, and 24 pg/mL, respectively. The odds ratios associated with the four biomarkers were significant (p ≤ 0.010), ranging from 4.00 for IP10 to 9.69 for MIG. With adjustment for NT–pro BNP, the CXCR3 ligands retained significance (p ≤ 0.028). Adding optimized thresholds for the CXCR3 ligands to NT–pro BNP enhanced (p ≤ 0.014) the integrated discrimination improvement and the net reclassification improvement. In conclusion, congruent with the concept that inflammation plays a key role in the pathogenesis of LV dysfunction, MIG, IP10 and I–TAC add diagnostic accuracy over and beyond NT–pro BNP.     

B-type natriuretic peptide and wall stress in dilated human heart

Background Although B-type natriuretic peptide (BNP) is used as complimentary diagnostic tool in patients with unknown thoracic disorders, many other factors appear to trigger its release. In particular, it remains unresolved to what extent cellular stretch or wall stress of the whole heart contributes to enhanced serum BNP concentration. Wall stress cannot be determined directly, but has to be calculated from wall volume, cavity volume and intraventricular pressure of the heart. The hypothesis was, therefore, addressed that wall stress as determined by cardiac magnetic resonance imaging (CMR) is the major determinant of serum BNP in patients with a varying degree of left ventricular dilatation or dysfunction (LVD). Methods A thick-walled sphere model based on volumetric analysis of the LV using CMR was compared with an echocardiography-based approach to calculate LV wall stress in 39 patients with LVD and 21 controls. Serum BNP was used as in vivo marker of a putatively raised wall stress. Nomograms of isostress lines were established to assess the extent of load reduction that is necessary to restore normal wall stress and related biochemical events. Results Both enddiastolic and endsystolic LV wall stress were correlated with the enddiastolic LV volume (r = 0.54, P < 0.001; r = 0.81, P < 0.001). LV enddiastolic wall stress was related to pulmonary pressure (capillary: r = 0.69, P < 0.001; artery: r = 0.67, P < 0.001). Although LV growth was correlated with the enddiastolic and endsystolic volume (r = 0.73, P < 0.001; r = 0.70, P < 0.001), patients with LVD exhibited increased LV wall stress indicating an inadequately enhanced LV growth. Both enddiastolic (P < 0.05) and endsystolic (P < 0.01) wall stress were increased in patients with increased BNP. In turn, BNP concentration was elevated in individuals with increased enddiastolic wall stress (>8 kPa: 587 +/- 648 pg/ml, P < 0.05; >12 kPa: 715 +/- 661 pg/ml, P < 0.001; normal < or =4 kPa: 124 +/- 203 pg/ml). Analysis of variance revealed LV enddiastolic wall stress as the only independent hemodynamic parameter influencing BNP (P < 0.01). Using nomograms with "isostress" curves, the extent of load reduction required for restoring normal LV wall stress was assessed. Compared with the CMR-based volumetric analysis for wall stress calculation, the echocardiography based approach underestimated LV wall stress particularly of dilated hearts. Conclusions In patients with LVD, serum BNP was increased over the whole range of stress values which were the only hemodynamic predictors. Cellular stretch appears to be a major trigger for BNP release. Biochemical mechanisms need to be explored which appear to operate over this wide range of wall stress values. It is concluded that the diagnostic use of BNP should primarily be directed to assess ventricular wall stress rather than the extent of functional ventricular impairment in LVD.     

Diagnostic utility of C-reactive Protein combined with brain natriuretic peptide in acute pulmonary edema: a cross sectional study

Introduction Discriminating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) from cardiogenic pulmonary edema (CPE) using the plasma level of brain natriuretic peptide (BNP) alone remains controversial. The aim of this study was to determine the diagnostic utility of combination measurements of BNP and C-reactive protein (CRP) in critically ill patients with pulmonary edema.

Methods

This was a cross-sectional study. BNP and CRP data from 147 patients who presented to the emergency department due to acute respiratory failure with bilateral pulmonary infiltrates were analyzed.

Results

There were 53 patients with ALI/ARDS, 71 with CPE, and 23 with mixed edema. Median BNP and CRP levels were 202 (interquartile range 95-439) pg/mL and 119 (62-165) mg/L in ALI/ARDS, and 691 (416-1,194) pg/mL (p < 0.001) and 8 (2-42) mg/L (p < 0.001) in CPE. BNP or CRP alone offered good discriminatory performance (C-statistics 0.831 and 0.887), but the combination offered greater one [C-statistics 0.931 (p < 0.001 versus BNP) (p = 0.030 versus CRP)]. In multiple logistic-regression, BNP and CRP were independent predictors for the diagnosis after adjusting for other variables.

Conclusions

Measurement of CRP is useful as well as that of BNP for distinguishing ALI/ARDS from CPE. Furthermore, a combination of BNP and CRP can provide higher accuracy for the diagnosis.     

The Radiation Issue in Cardiology: the time for action is now

Background

The study was designed to evaluate whether the preserved coronary flow reserve (CFR) 72 hours after reperfused acute myocardial infarction (AMI) is associated with less microvascular dysfunction and is predictive of left ventricular (LV) functional recovery and the final infarct size at follow-up.

Methods

In our study, CFR was assessed by transthoracic Doppler echocardiography (TDE) in 44 patients after the successful percutaneous coronary intervention during the acute AMI phase. CFR was correlated with contractile reserve assessed by low-dose dobutamine echocardiography and with the total perfusion defect measured by single-photon emission computed tomography 72 hours after reperfusion and at 5 months follow-up. The ROC analysis was performed to determine test sensitivity and specificity based on CFR. Categorical data were compared by an χ² analysis, continuous variables were analysed with the independent Student's t test. In order to analyse correlation between CFR and the parameters of LV function and perfusion, the Pearson correlation analysis was conducted. The linear regression analysis was used to assess the relationship between CFR and myocardial contractility as well as the final infarct size.

Results

We estimated the CFR cut-off value of 1.75 as providing the maximal accuracy to distinguish between patients with preserved and impaired CFR during the acute AMI phase (sensitivity 91.7%, specificity 75%). Wall motion score index was better in the subgroup with preserved CFR as compared to the subgroup with reduced CFR: 1.74 (0.29) vs. 1.89 (0.17) (p < 0.001) during the acute phase and 1.47 (0.30) vs. 1.81 (0.20) (p < 0.001) at follow-up, respectively. LV ejection fraction was 47.78% (8.99) in preserved CFR group vs. 40.79% (7.25) in impaired CFR group (p = 0.007) 72 hours after reperfusion and 49.78% (8.70) vs. 40.36% (7.90) (p = 0.001) after 5 months at follow-up, respectively. The final infarct size was smaller in patients with preserved as compared to patients with reduced CFR: 5.26% (6.14) vs. 23.28% (12.19) (p < 0.001) at follow-up.

Conclusion

The early measurement of CFR by TDE can be of high value for the assessment of successful reperfusion in AMI and can be used to predict LV functional recovery, myocardial viability and the final infarct size.     

Different contribution of extent of myocardial injury to left ventricular systolic and diastolic function in early reperfused acute myocardial infarction

Background

We sought to investigate the influence of the extent of myocardial injury on left ventricular (LV) systolic and diastolic function in patients after reperfused acute myocardial infarction (AMI).

Methods

Thirty-eight reperfused AMI patients underwent cardiac magnetic resonance (CMR) imaging after percutaneous coronary revascularization. The extent of myocardial edema and scarring were assessed by T2 weighted imaging and late gadolinium enhancement (LGE) imaging, respectively. Within a day of CMR, echocardiography was done. Using 2D speckle tracking analysis, LV longitudinal, circumferential strain, and twist were measured.

Results

Extent of LGE were significantly correlated with LV systolic functional indices such as ejection fraction (r?=?-0.57, p?<?0.001), regional wall motion score index (r?=?0.52, p?=?0.001), and global longitudinal strain (r?=?0.56, p?<?0.001). The diastolic functional indices significantly correlated with age (r?=?-0.64, p?<?0.001), LV twist (r?=?-0.39, p?=?0.02), average non-infarcted myocardial circumferential strain (r?=?-0.52, p?=?0.001), and LV end-diastolic wall stress index (r?=?-0.47, p?=?0.003 with e’) but not or weakly with extent of LGE. In multivariate analysis, age and non-infarcted myocardial circumferential strain independently correlated with diastolic functional indices rather than extent of injury.

Conclusions

In patients with timely reperfused AMI, not only extent of myocardial injury but also age and non-infarcted myocardial function were more significantly related to LV chamber diastolic function.     

Evidence for the Role of Epstein Barr Virus Infections in the Pathogenesis of Acute Coronary Events

Background

The role of viral infections in the pathogenesis of atherosclerosis remains controversial largely due to inconsistent detection of the virus in atherosclerotic lesions. However, viral infections elicit a pro-inflammatory cascade known to be atherogenic and to precipitate acute ischemic events. We have published in vitro data that provide the foundation for a mechanism that reconciles these conflicting observations. To determine the relation between an early viral protein, deoxyuridine triphosphate nucleotidohydrolase (dUTPase), produced following reactivation of Epstein Barr Virus (EBV) to circulating pro-inflammatory cytokines, intercellular adhesion molecule-1 (ICAM-1) and acute coronary events.

Methodology/Principal Findings

Blood samples were obtained from 299 patients undergoing percutaneous coronary intervention for stable angina (SA), unstable angina (UA), or acute myocardial infarction (AMI). Plasma concentrations of pro-inflammatory cytokines and neutralizing antibody against EBV-encoded dUTPase were compared in the three patient groups. AMI was associated with the highest measures of interleukin-6 (ANOVA p<0.05; 4.6±2.6 pg/mL in patients with AMI vs. 3.2±2.3 pg/mL in SA). ICAM-1 was significantly higher in patients with AMI (ANOVA p<0.05; 304±116 pg/mL in AMI vs. 265±86 pg/mL SA). The highest values of ICAM-1 were found in patients having an AMI and who were antibody positive for dUTPase (ANOVA p = 0.008; 369±183 pg/mL in AMI and positive for dUTPase vs. 249±70 pg/mL in SA negative for dUTPase antibody).

Conclusions/Significance

These clinical data support a model, based on in vitro studies, by which EBV may precipitate AMI even under conditions of low viral load through the pro-inflammatory action of the early protein dUTPase that is produced even during incomplete viral replication. They further support the putative role of viral infections in the pathogenesis of atherosclerosis and coronary artery events.     

Procalcitonin as a prognostic marker in patients with acute myocardial infarction

Background: Procalcitonin is involved in the inflammatory response and is associated with adverse prognosis in certain conditions.

Aims: To investigate the association between procalcitonin and major adverse cardiac events (MACE), left ventricular (LV) function and remodelling following acute myocardial infarction (AMI).

Methods: Plasma procalcitonin was measured in 977 patients with AMI. Subjects were followed for MACE (median 671 days). A subgroup underwent echocardiography at discharge and follow-up LV function and volume assessment.

Results: Procalcitonin was associated with MACE on uni- and multivariable analysis. Kaplan–Meier assessment revealed an adverse outcome in subjects with procalcitonin above the median. Procalcitonin was related to markers of LV dysfunction and remodelling.

Conclusion: Procalcitonin is associated with MACE, LV dysfunction and remodelling post-AMI.     

Prognostic prediction in acute heart failure patients with extreme BNP values

Background: Some patients have good prognosis despite elevated B-type natriuretic peptide (BNP), while others have ominous outcome with low BNP. We aimed at characterising these groups of patients.

Methods: We analysed patients prospectively included in an acute HF registry. Vital status within 1-year post discharge was ascertained. A receiver–operating characteristic curve was used to define discharge BNP cut-offs for 1-year death prediction. Among survivors, we compared patients with low and not-low BNP (cut-off 400?pg/mL); and among non-survivors those with high vs not-high BNP (cut-off 2000?pg/mL). In the specific subgroups of patients with low and high BNP, mortality predictors were assessed with multivariate Cox-regression analysis.

Results: We studied 584 patients, median age 78 years, 62.5% had HF with reduced ejection fraction; and 199 (34.1%) died during the first year. Non-survivors were very homogeneous irrespective of BNP, survivors were substantially different. In patients discharged with BNP <400?pg/mL, increasing age independently predicted death; when BNP ≥2000?pg/mL death predictors were higher NYHA class, and non-use of evidence-based therapy. BNP was outcome associated in both groups.

Conclusions: Different prognostic predictors may play a role in different BNP levels. We suggest that risk stratification in HF would probably be more accurate if made on top of BNP knowledge.     

急性缺血性脑卒中患者入院时血浆BNP水平与梗死部位关系

目的：分析急性缺血性脑卒中患者入院时血浆脑钠肽（BNP）水平与缺血性脑卒中梗死部位的关系。方法：随机入选88例急性缺血性脑卒中患者,按梗死部位,将其分为前循环病灶组（66名）和后循环病灶组（22名）两组进行比较。测定入院时血浆脑钠肽（BNP）水平进行比较。两组脑卒中病人的危险因素血糖、糖化血红蛋白、血脂全套,肝肾功能分析对比,并将急性缺血性脑卒中患者梗死部位相关的多个变量采用单因素logistic回归分析。结果：前循环病灶组血浆脑利钠肽水平的中位数是225.90 pg/mL,四分位数间距为596.00 pg/mL;后循环病灶组的中位数是750.95 pg/mL,四分位数间距为907.00 pg/mL。后循环病灶组血浆脑利钠肽水平要显著高于前循环病灶组血浆脑利钠肽水平,两个部位间入院时的脑利钠肽水平有统计学差异（P=0.004）。通过入院时脑利钠肽水平与缺血性脑卒中梗死部位的关系的ROC曲线,得出截点299.50 pg/mL。入院时血浆脑利钠肽水平≥299.50 pg/mL可以作为后循环病灶组的预测指标,其敏感性72.72%,特异性62.12%。结论：急性缺血性脑卒中患者入院时血浆BNP水平可作为急性期区别前后循环脑梗死的预测因子。     

Impact of Obstructive Sleep Apnea on the Levels of Placental Growth Factor (PlGF) and Their Value for Predicting Short-Term Adverse Outcomes in Patients with Acute Coronary Syndrome

Background

Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA.

Methods

A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay.

Results

Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6–24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7–22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment.

Conclusions

The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01335087","term_id":"NCT01335087"}}NCT01335087     

Lipids and carotid plaque in the Northern Manhattan Study (NOMAS)

Background

Heterogeneity in B-type natriuretic peptide (BNP) levels, especially among individuals with acute heart failure with normal left ventricular ejection fraction (HFNEF), can cause confusion in interpreting results. We investigated the characteristics of cases of acute HFNEF with only modestly elevated BNP.

Methods

One hundred forty-two patients with acute or acute exacerbation of chronic HFNEF were divided into two groups by BNP level: BNP < 100 pg/ml (NB group, n = 45) and BNP ≥ 100 pg/ml (B group, n = 97). We compared clinical findings, echocardiography results, and neurohormonal factors between these two groups.

Results

In the NB group, a history of open-heart surgery (OHS) was more frequent (71% vs. 22%, p < 0.0001) and hypertension was less frequent (p = 0.0005). Left atrial diameter (LAd) was higher (p = 0.0026), while interventricular septal thickness, posterior wall thickness, relative wall thickness, left ventricular mass index were lower (p = 0.0005, p = 0.0225, p = 0.0114, p = 0.0051, respectively) in the NB group. In patients with HFNEF, a history of OHS remained an independent predictor of BNP level (< 100 pg/ml) after adjustment for hypertension, age, LAd, and interventricular septal thickness (odds ratio 3.6, p = 0.0252).

Conclusion

We found associations between acute HFNEF with less elevated BNP and a history of OHS. In a patient suspected of HFNEF, a history of OHS is considered diagnostic evidence of presence of diastolic heart failure when plasma levels of BNP are less elevated.     

B-type natriuretic peptide, vascular endothelial growth factor, endothelin-1, and nitric oxide synthase in chronic mountain sickness

The pathogenesis of chronic mountain sickness (CMS) may involve vasoactive peptides. The aim of this study was to investigate associations between CMS and levels of B-type natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and endothelial nitric oxide synthase (eNOS). A total of 24 patients with CMS and 50 control subjects residing at 4,300 m participated in this study. Mean pulmonary arterial pressure (mPAP) was measured by echocardiography. Serum BNP, VEGF, ET-1, and eNOS were measured. Receiver operator characteristic curves to assess the balance of sensitivity and specificity for CMS were constructed. As a result, patients with CMS had significantly greater mPAP compared with controls and had lower arterial O(2) saturation (Sa(O(2))). Both BNP and ET-1 correlated positively with mPAP and negatively with Sa(O(2)), whereas serum VEGF levels were inversely correlated with Sa(O(2)); eNOS correlated negatively with mPAP and positively with Sa(O(2)). Median concentrations of BNP were greater in patients with CMS compared with those without CMS: 369 pg/ml [interquartile range (IQR) = 336-431] vs. 243 pg/ml (IQR = 216-279); P < 0.001. Similarly, concentrations of VEGF [543 pg/ml (IQR = 446-546) vs. 243 pg/ml (IQR = 216-279); P < 0.001] and ET-1 [14.7 pg/ml (IQR = 12.5-17.9) vs. 11.1 pg/ml (IQR = 8.7-13.9); P = 0.05] were higher in those with CMS compared with those without, whereas eNOS levels were lower in those with CMS [8.90 pg/ml (IQR 7.59-10.8) vs. 11.2 pg/ml (9.13-13.1); P < 0.001]. The areas under the receiver operator characteristic curves for diagnosis of CMS were 0.91, 0.93, 0.77, and 0.74 for BNP, VEGF, ET-1, and eNOS, respectively. In age- and biomarker-adjusted logistic regression, BNP and VEGF were positively predictive of CMS, whereas eNOS was inversely predictive. In conclusion, severe chronic hypoxemia and consequent pulmonary hypertension in patients with CMS may stimulate release of natriuretic peptides and angiogenic cytokines. These vasoactive peptides may play an important role in the pathogenesis and clinical expression of CMS and may indicate potential prognostic factors in CMS that could serve as targets for therapeutic trials or clinical decision making.     

急性心肌梗死伴新发束支传导阻滞的临床意义

目的:观察急性心肌梗死伴新发左、右束支传导阻滞的临床特点,评价束支阻滞对急性心肌梗死预后的影响。方法:对上海交通大学附属第一人民医院心内科重症监护室2010年1月1日到12月31日收治的197例急性心肌梗死患者的病历资料进行回顾性分析,根据束支传导阻滞有无及类型分为左束支传导阻滞组(12例),右束支传导阻滞组(19例)和对照组(无束支传导阻滞的急性心梗,166例)。分析和比较三组患者的基线资料,心梗部位、Killip分级、恶性室性心律失常、左室射血分数LVEF、病变血管数量、梗死相关冠脉、住院天数及病死率、实验室检查(BNP,心肌损伤标志物峰值)。结果:LBBB组AMI患者的恶性心律失常发生率明显高于对照组(P=0.007),LVEF明显低于RBBB组和对照组(P值分别为0.020、0.045),梗死相关动脉以LAD多见。结论:急性心梗伴束支传导阻滞往往提示病情严重,预后不良,急性心梗合并左束支阻滞较合并右束支阻滞病情更严重。