Admission glycemia: a predictor of death after acute coronary syndrome in non-diabetic patients?

BACKGROUND: Previous studies have demonstrated that acute phase hyperglycemia is associated with increased in-hospital mortality in diabetic patients admitted with acute coronary syndrome (ACS), but this has not been clearly demonstrated in non-diabetic patients. The present study was designed to determine whether admission hyperglycemia (AG) is an independent predictor of in-hospital and six-month mortality after ACS in non-diabetic patients. METHODS: This was a retrospective cohort study of 426 non-diabetic patients consecutively admitted with ACS. The patients were stratified into quartile groups according to AG, which was also analyzed as a continuous variable. Vital status was obtained at six-month follow-up in 96.8% of the patients surviving hospitalization. Logistic regression analysis was used to identify independent predictors of in-hospital and six-month death. RESULTS: Of the 426 patients included in the study (age 62.6 years+/-13.1, 77% male), 22 (5.4%) patients died during hospitalization and 20 (5.2% of the patients surviving hospitalization) within six months of ACS. Mean AG was 134.89 mg/dl+/-51.95. The higher the AG, the more probable was presentation with ST-segment elevation ACS (STEMI), anterior STEMI, higher heart rate, Killip class higher than one (KK >1), higher serum creatinine and greater risk of in-hospital and six-month death. In multivariate analysis, only age (OR=1.10; 95% CI 1.04-1.17), STEMI (OR=3.02; 95% CI 1.07-8.50), AG (OR=1.073; 95% CI 1.004-1.146), serum creatinine (OR=1.10; 95% CI 1.009-1.204) and KK >1 on admission (OR=4.65; 95% CI 1.59-13.52) were independently associated with in-hospital death. Age (OR=1.07; 95% CI 1.03-1.12), serum creatinine (OR=1.09; 95% CI 1.01-1.18) and in-hospital development of heart failure (OR=2.34; 95% CI 1.07-5.10) were independently associated with higher risk of death within six months of ACS. CONCLUSIONS: AG is an independent predictive factor of in-hospital death after ACS in non-diabetic patients. Although it did not show an independent association with higher risk of six-month death, AG appears to contribute to it, since the risk is greater the higher the AG. Its predictive value may have been blunted by the insufficient power of the sample and/or by the time interval between acquisition of AG and the evaluated endpoint.     

The effect of pre-hospital glycoprotein IIb-IIIa inhibitors on angiographic outcome in STEMI patients who are candidates for primary PCI

Objectives : Aim of this study was to assess the effect of early initiation of high bolus dose tirofiban on top of dual antiplatelet therapy on angiographic outcome before and after primary percutaneous coronary intervention (PCI) in ST‐elevation myocardial infraction patients. Background : Glycoprotein IIb/IIIa inhibitors are effective inhibitors of platelet aggregation, and have shown to reduce thrombotic complications in patients undergoing PCI. Methods : This is a pre‐specified angiographic analysis of the On‐TIME 2 trial (N = 984) and its open label run‐in phase (N = 414). All angiographic parameters, including quantitative coronary angiography (QCA) were performed in an independent angiographic core lab. Results : Of the 1,398 patients, 709 patients (50.7%) were randomized to pre‐hospital tirofiban. An open infarct related vessel (TIMI 2 or 3 flow) at initial angiography was more often present in the tirofiban group as compared to the no tirofiban group (58.3% vs. 49.7%, P = 0.002). Tirofiban also reduced initial thrombus burden (P for trend = 0.035) as well as thrombus grade 5 (46.9% vs. 54.3%, P = 0.016) and showed a trend toward a reduction in large thrombus burden (LTB) (69.4% vs. 74.5%, P = 0.055). After PCI, a trend towards a lower corrected TIMI frame count (cTFC) in the tirofiban group was found. A significant interaction was found with time of initiation of study drug, with highest efficacy of tirofiban when given within 76 min after symptom onset, with a significantly lower cTFC after PCI (21.9 ± 17.6 vs. 23.9 ± 18.5, P = 0.008, P for interaction P = 0.006). Conclusion : In patients undergoing primary PCI, pre‐hospital administration of tirofiban reduces initial thrombus burden and improves initial patency of the infarct related vessel before PCI. Initiation of tirofiban seems to be most effective when given very early after the onset of symptoms; however, this finding needs confirmation in other studies. Clinical trial registration : The On‐TIME 2 trial is registered, at http://isrctn.org , number ISRCTN06195297. © 2011 Wiley Periodicals, Inc.     

Role of inflammation in the extent of microvascular obstruction in patients undergoing primary PCI

When considering the clinical significance of admission high CRP levels in patients with acute myocardial infarction (AMI), it can be concluded that the development of poor myocardial perfusion may partially explain the relation between high CRP levels and poor clinical outcomes. We considered that poor myocardial perfusion after primary percutaneous coronary intervention (PCI) is not only related to procedural factors and clinical characteristics of the patients but may also be related with microvascular damage starting before PCI. We suggested that CRP mediated complement activation and neutrophil plugging may be the factors contributing to the development of microvascular damage in patients with AMI. Further large-scale randomized studies are needed to clarify the clinical utility of admission CRP levels in the prediction of poor myocardial perfusion after PCI in patients with ST segment elevation myocardial infarction.     

高龄急性ST段抬高型心肌梗死患者行直接经皮冠状动脉介入治疗的近期预后

目的分析高龄急性ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者行直接PCI的30d预后及其影响因素。方法选择STEMI行直接PCI的患者870例,根据年龄分为高龄组92例(≥80岁)和对照组778例(45~79岁),对比2组的临床和冠状动脉造影特点、药物治疗以及30d预后,分析30d全因死亡的预测因素。结果高龄组住院时间明显长于对照组(13dvs 10d,P=0.000),LVEF明显低于对照组(55%vs59%,P=0.007),心源性休克;急性肾损伤和30d全因死亡发生率明显高于对照组(18.5%vs 6.0%,22.8%vs8.6%,19.6%vs 5.0%,P=0.000),差异有统计学意义。多因素分析显示,年龄≥80岁是所有STEMI患者30d全因死亡的独立预测因素之一(HR=1.898,95%CI:1.030~3.497,P=0.040);而女性(HR=4.894,95%CI:1.572~15.234,P=0.006)和急性肾损伤(HR=10.155,95%CI:3.140~32.837,P=0.000)是高龄组30d全因死亡的独立预测因素。结论高龄STEMI患者即使接受了直接PCI,其30d全因死亡率仍高于年龄<80岁患者。     

Osteoprotegerin,inflammation and dyslipidemia are associated with abdominal aortic calcification in non-diabetic patients on peritoneal dialysis

Background and aimsAbdominal aortic calcification (AC) has been reported to be associated with cardiovascular disease (CVD) in hemodialysis patients but is rarely discussed in peritoneal dialysis (PD) patients. We examined the independent predictors and predictive power for survival of AC in prevalent PD patients.Methods and ResultsAC was detected by computed tomography (CT) and represented as the percentage of the total aortic cross-section area affected by AC (%AC). The predictors of %AC ≥15 were examined by multiple logistic regression analysis. Cox proportional hazard analysis was used to determine the hazard ratios associated with high %AC. A total of 183 PD patients were recruited to receive CT scans and divided into group 1 (%AC < 15, n = 97), group 2 (%AC ≥ 15, n = 41), and group 3 (diabetic patients, n = 45). Group 1 patients had lower osteoprotegerin (OPG) levels than group 2 patients (798 ± 378 vs. 1308 ± 1350 pg/mL, p < 0.05). The independent predictors for %AC ≥ 15 included the atherogenic index, OPG, and C-reactive protein (CRP). The age-adjusted hazard ratios associated with %AC ≥15 were 3.46 (p = 0.043) for mortality and 1.90 (p = 0.007) for hospitalization.Conclusions%AC can predict mortality and morbidity in non-diabetic PD patients, and 15% is a good cut-off value for such predictions. There are complex associations among mineral metabolism, inflammation, and dyslipidemia in the pathogenesis of AC.     

MDR1 and MRP1 gene expression are independent predictors for treatment outcome in adult acute myeloid leukaemia

Multi drug resistance (MDR) is a major obstacle for cancer therapy. The three major candidates accounting for the development of MDR in acute myeloid leukaemia (AML) are multi drug resistance gene (MDR1), multi drug resistance-related protein gene (MRP1) and lung resistance protein gene (LRP). So far, the differential impact of resistance gene expression on treatment outcome in AML is not clear. Therefore, we examined MDR1, MRP1 and LRP gene expression at diagnosis in 331 adult AML patients in the context of other known prognostic factors, such as age, disease status, cytogenetics and FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication mutational status. Median observation time was longer than 5 years [64.1 months (40.0-87.6)]. MDR1 expression proved to be an independent prognostic factor for outcome of induction therapy (P <0.001) and overall survival (P=0.02), whereas MRP1 expression was an independent predictor for disease-free survival (P=0.01) in the multivariate analysis. This prognostic impact of both resistance genes was also found in patients with intermediate risk cytogenetics. LRP expression, however, had no impact on treatment outcome in AML. Our study shows that resistance gene expression should be considered together with age, cytogenetics and FLT3 mutational status for risk-adapted treatment strategies in AML in the future.     

Human leukocyte antigens class II and tumor necrosis factor genetic polymorphisms are independent predictors of non-Hodgkin lymphoma outcome

Tumor necrosis factor (TNF) production and non-Hodgkin lymphoma (NHL) outcome was found to be related to the TNF(-308) polymorphism. To explore whether this could be linked to neighboring polymorphisms, we genotyped the TNF(-376,-308,-238,-163), lymphotoxin alpha (LTalpha)(+252), and HLA DRB1 alleles in 204 patients with NHL and 120 controls. TNF(-308A) was the only allele associated with higher TNF and its p55 and p75 receptors' levels (P =.009, P =.03, and P =.007) and lower complete remission rates (P =.006). Freedom from progression (FFP) and overall survival (OS) were shorter in patients with TNF(-308A) (P =.009 and P =.02), null HLA DRB1*02 allele (P =.007 and P =.14), or both genetic markers (P =.004 and P =.005). Multivariate analysis incorporating International Prognostic Index (IPI) identified TNF(-308A) (P <.0001, relative risk [RR] = 1.63; P <.0001, RR = 1.51) and null HLA DRB1*02 alleles (P =.015, RR = 1.18; P <.0001, RR = 1.25) as independent factors for FFP and OS. These results indicate the existence of at least 2 inherited factors involved in NHL outcome.     

Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS

Aims To investigate the relationships between a known history of diabetes and ambient fasting plasma glucose (FPG) levels with death and morbidity rates in patients with severe acute respiratory syndrome (SARS). Methods In this retrospective analysis, the clinical and biochemical characteristics of 135 patients who had died from SARS, 385 survivors of SARS and 19 patients with non‐SARS pneumonia were compared. Results All patients were treated according to a predefined protocol. Before steroid treatment, the mean FPG level was significantly higher in the SARS group (deceased vs. survivors vs. non‐SARS pneumonia group: 9.7 ± 5.2 vs. 6.5 ± 3.0 vs. 5.1 ± 1.0 mmol/l, P < 0.01). In the SARS group, the percentage of patients with a known history of diabetes was significantly higher in the deceased patients than in the survivors (21.5% vs. 3.9%, P < 0.01). Among patients with no known history of diabetes and before commencement of steroid therapy, those who had hypoxaemia (SaO₂ < 93%) had higher FPG levels than those who did not have hypoxia in both the survivor (8.7 ± 4.9 vs. 6.3 ± 2.1 mmol/l, P < 0.001) and deceased (9.8 ± 4.8 vs. 7.2 ± 1.5 mmol/l, P < 0.001) groups. A known history of diabetes [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.4, 6.3; P = 0.005] and FPG ≥ 7.0 mmol/l before steroid treatment (OR 3.3, 95% CI 1.4, 7.7, P = 0.006) were independent predictors of death. During the course of the illness, FPG levels were negatively associated with SaO₂ (β =?0.682 ± 0.305, P = 0.025, general estimation equation model) in SARS patients. Survival analysis showed that FPG was independently associated with an increased hazard ratio (HR) of mortality (HR = 1.1, 95% CI 1.0, 1.1, P = 0.001) and hypoxia (HR = 1.1, 95% CI 1.0, 1.1, P = 0.002) after controlling for age and gender. Conclusions A known history of diabetes and ambient hyperglycaemia were independent predictors for death and morbidity in SARS patients. Metabolic control may improve the prognosis of SARS patients.     

Peripartum cardiomyopathy: inflammatory markers as predictors of outcome in 100 prospectively studied patients.

AIMS: Peripartum cardiomyopathy (PPCM) is a disorder of unknown aetiology with a course and outcome that is largely unpredictable. We evaluated the prognostic role of multiple inflammatory markers in the plasma of a large cohort of African patients with PPCM. METHODS AND RESULTS: The study of 100 patients with newly diagnosed PPCM was single-centred, prospective, and longitudinal. Clinical assessment, echocardiography, and blood analysis were done at baseline and after 6 months of standard therapy. Inflammatory markers were measured at baseline only. Fifteen patients died. Left ventricular ejection fraction (LVEF) improved from 26.2+/-8.2 to 42.9+/-13.6% at 6 months (P<0.0001). However, normalization of LVEF (>50%) was only observed in 23%. Baseline levels of C-reactive protein correlated positively with baseline LV end-diastolic (rs=0.33, P=0.0026) and end-systolic (rs=0.35, P=0.0012) diameters and inversely with LVEF (rs=-0.27, P=0.015). Patients who died presented with significantly lower mean EF and higher Fas/Apo-1 plasma values (P<0.05). Fas/Apo-1 and New York Heart Association functional class (NYHA FC) predicted mortality at baseline. CONCLUSION: Plasma markers of inflammation were significantly elevated and correlated with increased LV dimensions and lower LVEF at presentation. Baseline Fas/Apo-1 and higher NYHA FC were the only predictors of mortality. Normalization of LVEF was only observed in 23% of this African cohort.     

Metabolic syndrome and microalbuminuria predict renal outcome in non-diabetic patients with primary hypertension: the MAGIC study

Metabolic syndrome (MS) has recently been shown to be a forerunner of chronic kidney disease (CKD). Microalbuminuria (MA) is associated with both MS and CKD. This study aimed to prospectively investigate the relationship among MA, MS and renal outcome in non-diabetic patients with primary hypertension. A total of 790 hypertensive patients enrolled in the MAGIC study between 1993 and 1997 (mean age 49.3±10.7 years) were included in the analysis. Renal outcome was defined as the first hospitalization with a diagnosis of CKD. At baseline, 146 (19%) and 60 (7.6%) patients met MS and MA criteria, respectively. A total of 20 patients (2.5%) concomitantly showed MS and MA. After a median follow-up of 11.6 years (interquartile range 3.2 years), renal end point was reached in 15.8% of patients with MS and in 8.9% of those without it (P=0.0087). The incidence of renal events increased progressively starting from patients with neither MS nor MA, to patients with only one of these abnormalities and then to those with both. Significant interaction was observed between MS and MA. Patients with concomitant occurrence of MS and MA at baseline showed a greater than fivefold risk of renal outcome, as compared with patients with neither of these two risk factors (hazard ratio 5.46; 95% confidence interval 2.34-12.75). This risk became even higher when data were adjusted for potential confounders. MS and MA are independent and interactive predictors of renal outcome in non-diabetic patients with primary hypertension.     

Admission glucose and left ventricular systolic function in non-diabetic patients with acute myocardial infarction

Carbohydrate metabolism disorder in patients hospitalized due to acute ST-segment elevation myocardial infarction (STEMI) is associated with poor outcome. The association is even stronger in non-diabetic patients compared to the diabetics. Poor outcome of patients with elevated parameters of carbohydrate metabolism may be associated with negative impact of these disorders on left ventricular (LV) function. The aim of the study was to determine the impact of admission glycemia on LV systolic function in acute phase and 6 months after myocardial infarction in STEMI patients treated with primary angioplasty, without carbohydrate disorders. The study group consisted of 52 patients (9 female, 43 male) aged 35–74 years, admitted to the Department of Cardiology and Internal Medicine, Collegium Medicum in Bydgoszcz, due to the first STEMI treated with primary coronary angioplasty with stent implantation, without diabetes in anamnesis and carbohydrate metabolism disorders diagnosed during hospitalization. Echocardiography was performed in all patients in acute phase and 6 months after MI. Plasma glucose were measured at hospital admission. In the subgroup with glycemia ≥7.1 mmol/l, in comparison to patients with glycemia <7.1 mmol/l, significantly lower ejection fraction (EF) was observed in acute phase of MI (44.4 ± 5.4 vs. 47.8 ± 6.3 %, p = 0.04) and trend to lower EF 6 months after MI [47.2 ± 6.5 vs. 50.3 ± 6.3 %, p = 0.08 (ns)]. Higher admission glycemia in patients with STEMI and without carbohydrate metabolism disturbances, may be a marker of poorer prognosis resulting from lower LV ejection fraction in the acute phase and in the long-term follow-up.     

Inflammatory markers as predictors of clinical outcome in acute coronary syndromes

Inflammation is a critical pathogenic component in acute coronary syndromes. As a consequence the potential use of inflammatory markers as predictors of clinical outcome in acute coronary syndromes has been investigated. This review outlines the pathology underlying acute coronary syndromes and reviews the published data on inflammatory markers in acute coronary syndromes.     

Admission and fasting blood glucose are important prognostic markers in acute coronary syndromes

This paper reviews current evidence on the role of admission and fasting glycaemia as prognostic markers in patients with acute coronary syndromes. Though both parameters are correlated, they give different prognostic information and are related to both in-hospital complications, including death, and long-term outcomes. As hyperglycemia at the acute stage of myocardial infarction is an independent predictor of untoward cardiovascular events, blood glucose measurements should become routine in all patients presenting with acute coronary syndromes.     

延迟PCI与直接PCI治疗急性心肌梗死的比较

目的　探讨经皮延迟冠脉介入 (PCI)与直接PCI在治疗急性心肌梗死 (AMI)疗效的差异。方法　 14 5例连续行PCI的AMI患者分为直接PCI组 (75例 )和延迟PCI组 (70例 ) ,分析两组患者一般临床特征及心血管事件的发生率。结果　住院期间两组患者各项心脏事件均无显著差异。平均随访 (12 1± 4 5 )个月时 ,直接PCI组患者在不稳定性心绞痛 (9 3%vs 32 9% ,P <0 0 1)、非致死性心衰 (4 0 %vs14 3% ,P <0 0 5 )、死亡 (0vs 7 1% ,P <0 0 5 )及复合终点事件 (12 %vs 4 0 % ,P <0 0 1)方面较延迟PCI组明显降低。但两组间在非致死性再次心肌梗死、缺血性靶血管重建及总的心脏性死亡率无显著差异。近期内LVEF值延迟PCI组较直接PCI组显著降低 (0 5 8± 0 14vs 0 6 3± 0 10 ,P <0 0 5 )。结论　与直接PCI相比 ,延迟PCI治疗AMI近期内同样安全有效 ,1年死亡率无显著降低 ,但不稳定性心绞痛、非致死性心衰、死亡及复合终点事件发生率增加。     

Identifying generic predictors of outcome in patients presenting to primary care with nonspinal musculoskeletal pain

Objective

To identify which generic prognostic factors, such as pain intensity, levels of disability, and psychological factors, are most strongly associated with outcome from musculoskeletal pain, regardless of the location of pain. We tested the hypothesis that pain location does not add predictive value to these generic prognostic models, and that such prognostic factors are equally important across different pain locations.

Methods

Data from a prospective observational cohort of primary care patients with acute (n = 413) and chronic (n = 414) nonspinal musculoskeletal pain were used to develop predictive models. The analysis was carried out in 3 steps: derivation of predictive models including generic factors only, investigation of the added predictive value of pain location, and investigation of effect modification by pain location.

Results

Generic factors predicted outcome over different time periods (3 months and 12 months) and for both acute and chronic musculoskeletal pain (area under the receiver operating characteristic curve 0.73–0.75). The most consistent predictors of poor outcome were having had the same complaint in the previous year (odds ratio range 2.03–3.46), a lower level of education, lower scores on the Short Form 36 vitality subscale, using pain medication at baseline, and being bothered by the complaint more often in the past 3 months. Pain location variables only slightly improved the predictive ability of the models over generic factors and were inconsistent across the models.

Conclusion

Generic factors appear to play an important role in the prognosis of acute and chronic nonspinal musculoskeletal pain, regardless of the location of pain.     

Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease

BACKGROUND & AIMS: Prediction of relapse of inflammatory bowel disease has important implications for therapeutic strategies. We assessed whether measurement of intestinal permeability and inflammation could predict relapse of inflammatory bowel disease (IBD). METHODS: Forty-three patients with Crohn's disease (CD) and 37 with ulcerative colitis (UC) in clinical remission provided a stool sample to be assayed for calprotectin (a neutrophil-specific marker), and patients with CD additionally underwent a small intestinal permeability test. Relapse was defined using clinical disease activity indices. RESULTS: Twenty-five (58%) patients with CD and 19 (51%) with UC had a relapse over the 12-month period. Median calprotectin levels in the relapse groups (122 mg/L for CD, 123 mg/L for UC; normal <10 mg/L) differed significantly (P<0.0001) from those of the nonrelapse groups (41.5 mg/L for CD, 29.0 mg/L for UC). At 50 mg/L, the sensitivity and specificity of calprotectin for predicting relapse in all patients with IBD were 90% and 83%, respectively. Permeability in the CD patients who relapsed (median, 0.075; normal <0.04) differed significantly (P = 0. 004) from that in the nonrelapse group (median, 0.038). At the level of 0.05, the sensitivity and specificity of permeability in predicting relapse were 84% and 61%, respectively. CONCLUSIONS: Fecal calprotectin predicts clinical relapse of disease activity in patients with CD and UC, whereas small intestinal permeability is a useful predictor of relapse in patients with small intestinal CD.