Blood biomarkers role in acute ischemic stroke patients: higher is worse or better?

Background

Thrombolytic therapy (TT) for acute ischemic stroke (AIS) can provoke bleeding’s complication depending on the ischemic lesion (IL) dimension. Inflammation involved in the setting of acute ischaemic stroke, is associated with infarct size. We aimed to study the independent correlation and association between clinical panel of routinely identified biomarkers, including inflammatory parameters, and cerebral IL dimension and site.

Results

We evaluated eleven biomarkers in 105 unrelated patients during their hospitalization after acute stroke event. Our data indicate a significant association of: a) confluent IL size with 4th quartile of Erythrocyte Sedimentation Rate (ESR) (OR = 5.250; 95% CI, 1.002 to 27.514) and an independent correlation with sex; b) confluent IL size with 3rd quartile of fibrinogen (OR = 5.5; 95% CI, 1.027 to 29.451); c) confluent IL size with 3rd quartile of platelets (OR= 0.059; 95% CI, 0.003 to 1.175) and independent correlation with sex; d) smaller IL size (OR = 5.25; 95% CI, 1.351 to 20.396) with 3rd quartile of albumin levels and nodular and parenchimal IL size with 2nd (OR = 0.227; 95% CI, 0.053 to 0.981), 3rd (OR = 0.164; 95% CI, 0.038 to 0.711) and 4th (OR = 0.205; 95% CI, 0.048 to 0.870) quartiles albumin levels; e) smaller IL size with 3rd quartile triglycerides (TG) levels (OR = 9; 95% CI, 2.487 to 32.567) and an independent correlation with anterior location. Smaller IL size, anterior AIS turned out to be independently correlated with high serum albumin levels. Finally, high INR and PTT values were associated with worse NIHSS clinical outcomes in contrast to that observed with higher albumin level.

Conclusions

We provide evidence of routine biomarkers levels correlation with acute IL size, independently of age and sex. In addition, we highlight the importance of differentiation of biomarkers normal interval levels for further improvement not only of the clinical decision making but also in post-acute clinical outcome management.

     

Role of resistin as a marker of inflammation in systemic lupus erythematosus

Introduction

Resistin is a cystein-rich secretory adipokine. It is proposed to have proinflammatory properties in humans. The aim of this study was to determine associations between serum levels of resistin and markers of inflammation and bone mineral density (BMD) in female patients with systemic lupus erythematosus (SLE).

Methods

One hundred sixty-three female patients with SLE (20 to 82 years old) were examined in a cross-sectional study. Venous blood samples were analyzed for resistin, erythrocyte sedimentation rate (ESR), C-reactive protein, creatinine, fasting lipids, complements, tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, sIL-6R (soluble IL-6 receptor), ICTP (C-terminal telopeptide of type I collagen), and PINP (N-terminal propeptide of type I procollagen). Simple and multiple regression analyses as well as logistic regression analyses were performed. Resistin in serum was compared with 42 healthy female controls with respect to age.

Results

Serum resistin levels in controls were similar to those of patients with SLE. Markers of inflammation and current dose of glucocorticosteroids correlated positively to resistin in serum. Markers of renal function, number of prevalent vertebral fractures, and BMD were also significantly associated with resistin. In a multiple regression model, ESR, creatinine, C3, current glucocorticosteroid dose, high-density lipoprotein, and BMD radius remained significantly associated with resistin. In logistic regression analyses with resistin as the independent variable, a significant association was found with ESR (normal or elevated) but not with S-creatinine or z score for hip and radius total.

Conclusion

Although resistin measurements did not differ between patients and controls, resistin was clearly associated with general inflammation, renal disease, treatment with glucocorticosteroids, and bone loss. We hypothesize that resistin has proinflammatory and disease-promoting properties in SLE. Further studies are needed to elucidate the mechanism behind these associations.     

Association between resistin + 299A/A genotype and nonalcoholic fatty liver disease in Chinese patients with type 2 diabetes mellitus

Objective

To investigate the relationship between the resistin intronic + 299G/A polymorphism and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM).

Methods

We selected 738 T2DM patients, including 395 with NAFLD and 343 without fatty liver disease, as well as 279 healthy control individuals, and analyzed their resistin + 299G/A polymorphism genotype by polymerase chain reaction–restriction fragment length polymorphism.

Results

Plasma resistin levels in T2DM patients with NAFLD were at the highest (P < 0.05). The frequency of AA genotype at the + 299 site of the resistin gene in patients with concurrent T2DM combined with NAFLD was significantly different from that in the control (P < 0.05). The AA genotype was found to be associated with a 1.80-fold increased risk for T2DM combined with NAFLD, 2.05-fold increased risk for obesity and 2.37-fold increased risk for obesity of abdominal type compared to the GG (P < 0.05, respectively). The multivariate non-conditional logistic regression model analysis further shows that the AA genotype is a risk factor for the development of NAFLD in T2DM patients (OR, 2.32; 95% CI, 1.05–4.68; P < 0.05).

Conclusion

The resistin + 299AA genotype may be associated with increases in the risk of the NAFLD development in T2DM patients.     

Increased glycated albumin and decreased esRAGE levels in serum are related to negative coronary artery remodeling in patients with type 2 diabetes: an Intravascular ultrasound study

Background

Negative coronary artery remodeling is frequent in patients with diabetes, but its mechanism remains unclear. We here evaluated the association of serum levels of glycated albumin (GA) and endogenous secretory receptor for advanced glycation end products (esRAGE) with coronary artery remodeling in type 2 diabetic patients.

Methods

Serum levels of GA and esRAGE were measured and intravascular ultrasound was performed in 136 consecutive diabetic patients with 143 coronary intermediate lesions. The remodeling index (RI) was calculated as the ratio between external elastic membrane (EEM) area at the lesion site and EEM area at the reference segment. Negative remodeling (NR) was defined as an RI?<?0.95 and intermediate or positive remodeling as an RI?≥?0.95.

Results

Mean plaque burden at the lesion site was 70.96?±?9.98%, and RI was 0.96?±?0.18. Negative coronary arterial remodeling existed in 81 (56.6%) lesions. RI correlated closely with serum esRAGE level (r?=?0.236, P?=?0.005) and was inversely related to serum GA level (r?=???0.240, P?=?0.004) and plasma low-density lipoprotein cholesterol (LDL-C) (r?=???0.206, P?=?0.014) and total cholesterol levels (r?=???0.183, P?=?0.028). Generalized estimating equations logistic regression analysis identified esRAGE (OR 0.037; 95% CI 0.012–0.564, P?=?0.021), GA (OR 1.093; 95% CI 1.013–1.179, P?=?0.018) and LDL-C (OR 1.479; 95% CI 1.072–2.835, P?=?0.023) as independent predictors for negative remodeling.

Conclusions

In diabetic patients, negative coronary artery remodeling is associated with increased GA and decreased esRAGE levels in serum.

     

Association of the CAG repeat polymorphisms in androgen receptor gene with polycystic ovary syndrome: A systemic review and meta-analysis

Background

Many studies have reported the associations of polymorphic CAG repeats in androgen receptor (AR) gene with PCOS risk, but with inconsistent results. So, the aim of present meta-analysis was to clarify such inconsistence, so as to provide more conclusive results.

Methods

PubMed was searched for the eligible reports published until February 2012 without language limitation. The studies reporting the relationship between CAG repeat length and PCOS were selected for the meta-analysis according to the inclusion criteria. Two reviewers independently extracted the data and evaluated the study quality.

Principal findings

As for the relationship between CAG repeat length and PCOS risk, the pooled results showed that the biallelic mean was not significantly different between PCOS and controls (SMD − 0.03, 95% CI − 0.16–0.10, P = 0.603), and that the ORs of PCOS were not demonstrated for the individuals with the biallelic mean less than median (OR 0.96, 95% CI 0.68–1.35, P = 0.794), with the short CAG allele (OR 0.94, 95% CI 0.80–1.10, P = 0.424), or with the X-weighted biallelic mean (OR 0.81, 95% CI 0.46–1.41, P = 0.447). Further, as for the relationship between CAG repeat length and T levels in PCOS patients, the biallelic mean was not significantly different between PCOS patients with high T and those with low T (SMD 0.79, 95% CI − 0.12–1.70, P = 0.088), while the summary correlation r indicated that the CAG biallelic mean appeared to be positively associated with T levels in PCOS (r 0.20, 95% CI 0.11–0.30, p = 0.000).

Conclusions

This meta-analysis demonstrates no evident association between the CAG length variations in AR gene and PCOS risk, while the CAG length appears to be positively associated with T levels in PCOS patients.     

Pediatric germ cell tumors and parental infertility and infertility treatment: a Children's Oncology Group report

Background

Few risk factors have been established for childhood germ cell tumors (GCT). Parental infertility and infertility treatment may be associated with GCT development but these risk factors have not been fully investigated.

Methods

A case–control study of childhood GCT was conducted through the Children's Oncology Group (COG). Cases, under the age of 15 years at diagnosis, were recruited through COG institutions from January 1993 to December 2002. Controls were obtained through random digit dialing. Information about infertility and infertility treatment along with demographic factors was collection through maternal interviews. Subgroups created by gender, age at diagnosis, and tumor location were examined separately. Statistical analysis was performed using multivariate logistic regression models.

Results

Overall, no association between GCT and infertility or its treatment was found. In subgroup analysis, females whose mothers had two or more fetal losses were found to be at increased risk for non-gonadal tumors (Odds ratio (OR) = 3.32, 95% Confidence interval (CI) = 1.12–9.88). Younger maternal age was associated with a lower risk of gonadal GCT in females (OR = 0.52, 95% CI = 0.28–0.96). There was an increased risk of all GCT and gonadal GCT in males born to older mothers (OR = 2.88, 95% CI = 1.13–7.37 and OR = 3.70, 95% CI = 1.12–12.24).

Conclusion

While no association between parental infertility or its treatment and childhood GCT was found overall, possible associations with maternal age and history of recurrent fetal loss were found in subgroups defined by gender.     

Low vitamin D levels are associated with cognitive impairment in patients with Hashimoto thyroiditis

Background

Cognitive impairment is commonly observed in patients with Hashimoto thyroiditis (HT). Low levels of vitamin D have been correlated with cognitive impairment in non-HT population. We examined the association of vitamin D levels with cognitive impairment in patients with HT.

Methods

We recruited 194 patients with HT and 200 healthy volunteers. Levels of serum 25-hydroxyvitamin D (25(OH)D) were measured using a competitive protein-binding assay. Cognitive funtion was assessed using Montreal Cognitive Assessment score (MoCA). Subjects with a MoCA scores <?26 are considered as having mild cognitive impairment (MCI). Multivariate analysis was performed using logistic regression models.

Results

Fifty-five HT patients (28.4%) were diagnosed as having MCI. Patients with MCI had significantly lower 25(OH)D levels when compared with patients without MCI (33.9?±?6.2 vs. 44.3?±?9.6?nmol/L, P?<?0.001). Significant differences in 25(OH)D quartiles of HT patients were observed between the patients with MCI and the patients without MCI (P?<?0.001). In multivariate analyses, serum 25(OH)D levels (≤ 34.0 and?≥?47.1?nmol/L) were significantly associated with cognitive impairment in patients with HT (OR 6.279, 95% CI 2.673–14.834, P?<?0.001; OR 0.061, 95% CI 0.008–0.491, P?=?0.009, respectively).

Conclusion

Our results demonstrate an important association between serum vitamin D levels and cognitive impairment in patients with HT.

     

Statins research unfinished saga: desirability versus feasibility

Aims

Resistin is an adipocyte-derived factor implicated in obesity-associated type 2 diabetes (T2DM). This study examines the association between human serum resistin, T2DM and coronary heart disease.

Methods

One hundred and fourteen Saudi Arabian patients (male: female ratio 46:68; age 51.4 (mean ± SD)11.7 years; median and range: 45.59 (11.7) years and BMI: 27.1 (mean ± SD) 8.1 Kgm² median and range: 30.3 (6.3) were studied. Serum resistin and C-reactive protein (CRP), a marker of inflammation CRP levels, were measured in all subjects. (35 patients had type 2 diabetes mellitus (T2DM); 22 patients had coronary heart disease (CHD).

Results

Serum resistin levels were 1.2-fold higher in type 2 diabetes and 1.3-fold higher in CHD than in controls (p = 0.01). In addition, CRP was significantly increased in both T2DM and CHD patients (p = 0.007 and p = 0.002 respectively). The use of regression analysis also determined that serum resistin correlated with CRP levels (p = 0.04, R² 0.045).

Conclusion

The findings from this study further implicate resistin as a circulating protein associated with T2DM and CHD. In addition this study also demonstrates an association between resistin and CRP, a marker of inflammation in type 2 diabetic patients.     

Association of resistin gene polymorphisms with insulin resistance in Egyptian obese patients

Background

Obesity associated insulin resistance is a major risk factor for type 2 diabetes mellitus. Resistin is recently reported to provide a link between obesity, insulin resistance and type 2 diabetes mellitus. We aimed to investigate the possible associations of resistin gene (RETN) polymorphisms with obesity, and to detect whether these polymorphisms are associated with glucose intolerance and type 2 diabetes mellitus in obese patients.

Methods

One hundred and forty-five Egyptian obese patients with or without glucose intolerance and 155 unrelated healthy controls were enrolled in this study. Polymorphisms of RETN + 299G>A and RETN –420 C>G gene were detected by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). Serum resistin was measured by ELISA.

Results

RETN + 299 AA and RETN − 420 GG genotypes were significantly associated with obesity in Egyptian population. Moreover, the mutant alleles or genotypes of both examined polymorphisms were associated with impaired glucose tolerance and diabetes mellitus compared to normal glucose tolerant obese patients. Furthermore, our results revealed elevated waist/hip ratio, BMI, blood pressure, fasting blood glucose level, HOMA-IR, triglycerides, total cholesterol, resistin level, and decreased HDL cholesterol level in homozygote mutant genotypes carriers of both RETN polymorphisms among obese patients.

Conclusion

Resistin gene polymorphisms may play an important role in pathogenesis and susceptibility to obesity, impaired glucose tolerance, and type 2 diabetes mellitus in Egyptian population.     

Association of iron overload based quantitative T2* MRI technique and carotid intima-media thickness in patients with beta-thalassemia: A cross-sectional study

Background

Heart failure (HF) is a major cause of hospitalization and death in the aging population around the world. Home care utilization is associated with improved survival for the patients with HF, and varies by ethno-culture. The purpose of this study was to investigate the difference in hospital readmission rate and mortality between Asian and other Canadian HF patients.

Methods

HF patients were identified using hospital discharge abstracts from March 31, 2000 to April 1, 2006 in Calgary Health Region. Readmission and one-year mortality for HF were determined by linking hospital discharge and vital statistics data. Stratified by home care services use, readmission and mortality rates were compared between the Asians and other Canadians while controlling for age, sex, comorbidities, and household income.

Results

Of 26,171 HF patients discharged from hospital, 56.6% of Asians and 58.0% of other Canadians used home care services [adjusted odds ratio (OR) for Asian: 0.84, 95% confidence interval (CI): 0.74-0.89]. The hospital readmission rate was similar between Asians and other Canadians regardless of home care services use. Mortality was similar between those who used home care services (adjusted OR for Asian: 0.96, 95% CI: 0.81-1.13). For patients who did not use home care services, Asians had significantly lower mortality than other Canadians (adjusted OR for Asian: 0.76, 95% CI: 0.60-0.86).

Conclusion

Mortality was similar between Asian and other Canadian patients when home care services were utilized. However, among those without home care, Asian patients had a significantly lower mortality than other Canadian patients.     

Primary respiratory disease in patients with systemic lupus erythematosus: data from the Spanish rheumatology society lupus registry (RELESSER) cohort

Background

The purpose of this study was to assess the prevalence, associated factors, and impact on mortality of primary respiratory disease in a large systemic lupus erythematosus (SLE) retrospective cohort.

Methods

All adult patients in the RELESSER-TRANS (Registry of Systemic Lupus Erythematosus Patients of the Spanish Society of Rheumatology [SER], cross-sectional phase) registry were retrospectively investigated for the presence of primary pleuropulmonary manifestations.

Results

In total 3215 patients were included. At least one pleuropulmonary manifestation was present in 31% of patients. The most common manifestation was pleural disease (21%), followed by lupus pneumonitis (3.6%), pulmonary thromboembolism (2.9%), primary pulmonary hypertension (2.4%), diffuse interstitial lung disease (2%), alveolar hemorrhage (0.8%), and shrinking lung syndrome (0.8%).In the multivariable analysis, the variables associated with the development of pleuropulmonary manifestation were older age at disease onset (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.02–1.04), higher SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) scores (OR 1.03, 95% CI 1.00–1.07), the presence of Raynaud’s phenomenon (OR 1.41, 95% CI 1.09–1.84), secondary antiphospholipid syndrome (OR 2.20, 95% CI 1.63–2.97), and the previous or concomitant occurrence of severe lupus nephritis, (OR 1.48, 95% CI 1.12–1.95) neuropsychiatric manifestations (OR 1.49, 95% CI 1.11–2.02), non-ischemic cardiac disease (OR 2.91, 95% CI 1.90–4.15), vasculitis (OR 1.81, 95% CI 1.25–2.62), hematological manifestations (OR 1.31, 95% CI 1.00–1.71), and gastrointestinal manifestations, excluding hepatitis (OR 2.05, 95% CI 1.14–3.66). Anti-RNP positivity had a clear tendency to significance (OR 1.32, 95% CI 1.00–1.75; P = 0.054).The development of pleuropulmonary manifestations independently contributes to a diminished survival (hazard ratio of 3.13). However, not all complications will influence the prognosis in the same way. Whereas the occurrence of pleural disease or pulmonary thromboembolism has a minimal impact on the survival of these patients, the remaining manifestations have a major impact on mortality.

Conclusion

Except for pleural disease, the remaining respiratory manifestations are very uncommon in SLE (<4%). Pleuropulmonary manifestations independently contributed to a decreased survival in these patients.

     

Relationships between the Osteocalcin Gene Polymorphisms,Serum Osteocalcin Levels,and Hepatitis B Virus-Related Hepatocellular Carcinoma in a Chinese Population

Background

Available evidence has demonstrated that osteocalcin may play a role in pathogenesis of cancer, and mutation of the osteocalcin gene may be involved in the cancer development. The aim of this study is to determine whether osteocalcin gene polymorphisms are associated with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) among Chinese population.

Methods

A total of 515 subjects were divided into four groups: 129 patients with chronic hepatitis B (CHB), 62 patients with HBV-related liver cirrhosis (LC), 154 patients with HBV-related HCC, and 170 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect osteocalcin gene rs1800247 and rs1543297 polymorphisms.

Results

Compared with healthy controls, the rs1800247 HH and Hh genotypes were associated with a significantly increased susceptibility to HCC (HH versus hh: OR = 6.828, 95% CI 2.620–17.795, P <0.001; Hh versus hh: OR = 6.306, 95% CI 3.480–11.423, P <0.001, respectively). Similarly, the subjects bearing the H allele of rs1800247 had more than a 2.4-fold increased risk for development of HCC (OR = 2.484, 95% CI 1.747–3.532, P <0.001) compared with those bearing the h allele. In addition, we found significant decreased serum osteocalcin levels in HBV-related HCC patients (11.73±8.18 ng/mL) compared with healthy controls (15.3±6.06 ng/mL). Furthermore, the serum osteocalcin levels were significantly lower in HCC patients than healthy controls among the individuals with heterozygous Hh genotype (P = 0.003) and CT genotype (P <0.001). In contrast, there were no significant differences in the genotype and allele of rs1543297 polymorphisms between the groups of patients and healthy controls.

Conclusions

These findings for the first time suggest that genetic variant in osteocalcin gene rs1800247 polymorphisms may be a risk factor for HBV-related HCC. We also find an inverse association of serum osteocalcin levels with HCC.     

Three single nucleotide variants of the HDAC gene are associated with type 2 diabetes mellitus in a Chinese population: A community-based case–control study

Objectives

There are no data regarding the possible role of the single nucleotide polymorphism (SNP) of class I histone deacetylases (HDACs) in type 2 diabetes mellitus (DM). We designed this study to examine whether polymorphisms of HDACs can be implicated in that disease.

Methods

A community-based, case–control study was conducted, with a total of 568 subjects (284 patients and 284 controls) enrolled. Four polymorphisms of HDAC1 (rs1741981) and HDAC3 (rs11741808, rs2547547, rs2530223) were examined by the use of TaqMan technology.

Results

We found a significant association with risk of type 2 DM for three SNPs of HDAC3, including rs11741808 [odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.35–0.81], rs2547547 [OR = 1.72, 95% CI: 1.13–2.64], and rs2530223 [OR = 1.39; 95% CI: 1.01–1.91]. Subgroup analysis showed that BMI ≥ 23 kg/m², high triglyceride and high blood pressure, together with the rs11741808AG genotype, were associated with a significantly decreased risk for type 2 DM, with ORs of 0.50 (95% CI: 0.27–0.91), 0.38 (95% CI: 0.20–0.71) and 0.43 (95% CI: 0.24–0.76) compared with the AA genotype, respectively. In a population with normal total cholesterol, the AG genotype yielded a significantly decreased risk of type 2 DM risk, with an OR of 0.42 (95% CI: 0.25–0.70) when compared with the persons of the AA genotype. For rs2547547, in a population with normal total cholesterol and triglyceride, the AG genotype was associated with a significantly increased risk of type 2 DM, with ORs of 1.92 (95% CI: 1.17–3.15) and 2.24 (95% CI: 1.28–3.94) when compared with the population carrying the AA genotype.

Conclusions

The results suggest that variants of HDAC3 contribute to an increased prevalence of type 2 DM in the Chinese Han population.     

Genetic polymorphisms of IFNG and IFNGR1 in association with the risk of pulmonary tuberculosis

Objective

Genetic host factors play an important role in controlling individual's susceptibility to the pathogen. This study aims to explore the single and joint effect of genetic polymorphisms of interferon-gamma (IFNG) and its receptor (IFNGR1) in association with the pulmonary tuberculosis in a Chinese Han population.

Methods

This population-based case control study consisted of 1434 pulmonary tuberculosis patients and 1412 healthy controls. Six tag SNPs in IFNG/IFNGR1 were genotyped using TaqMan allelic discrimination technology. The logistic regression model was carried out to analyze the associations between the genotypes and haplotypes and the risk of tuberculosis by calculating the odds ratio (OR) and 95% confidence interval (CI).

Results

After the Bonferroni correction for multiple comparisons, three SNPs (rs2234711, rs1327475 and rs7749390) in IFNGR1 gene were observed to be significantly associated with the altered risks of tuberculosis. For the SNP rs2234711, individuals carrying C allele (vs. T) showed a decreased risk, with the adjusted OR(95% CI) of 0.82(0.76–0.91). The additive model revealed that each additional allele contributed about 14% decreased risk (OR: 0.86, 95% CI: 0.77–0.95). Moreover, we observed a strong linkage disequilibrium between rs2234711 and rs3799488. Compared with the common rs2234711C–rs3799488C haplotype, the haplotype rs2234711T–rs3799488C contributed to a significant increase in the risk of tuberculosis (adjusted OR: 1.24, 95% CI: 1.09–1.41).

Conclusions

Our results suggest that genetic polymorphisms in IFNGR1 gene are involved in the risk of tuberculosis in the Chinese population. Future studies should include a comprehensive sequencing analysis to identify the specific causative sequence variants underlying the observed associations.     

Prognostic Value of TNF-Related Apoptosis Inducing Ligand (TRAIL) in Acute Coronary Syndrome Patients

Background

Apoptosis plays an important role in the development of heart failure. The aim of the prospectively designed study was to assess whether the concentration of apoptotic markers apoptosis-stimulating fragment (Fas, CD95/APO-1) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can predict prognosis in patients with acute coronary syndromes.

Methods

The concentrations of soluble Fas and TRAIL were determined in 295 patients with acute coronary syndromes. The status of all patients was evaluated at 6 months. The primary goal was a composite end-point of death and hospitalization for heart failure. The secondary end-points were re-MI, death alone and stroke alone.

Results

During the median follow-up of 6 months, 26 patients experienced the composite end-point. Using multivariate logistic regression, the concentration of TRAIL was the strongest significant and independent predictor of composite end-point (OR 0.11 (95% CI 0.03–0.45), p = 0.002). Low concentration was associated with poor prognosis of patients. Other significant predictors of composite end-point were serum creatinine (OR 7.7 (95% CI 1.1–54.5, p = 0.041) and complete revascularization (OR 0.19 (95% CI 0.05–0.78, p = 0.02). Independent significant predictors of death in the multivariate analysis were the concentration of TRAIL (OR 0.053 (95% CI 0.004–0.744), p = 0.029), older age (OR 1.20 (95% CI 1.02–1.41, p = 0.026) and serum creatinine (OR 15.1 (95% CI 1.56–145.2), p = 0.0193). Re-MI or stroke could not be predicted by any combination of obtained parameters.

Conclusions

Low concentrations of soluble TRAIL represent a strong predictor of a poor prognosis in patients with acute coronary syndrome. The predictive value of TRAIL concentration is independent of age, ejection fraction, index peak troponin level, concentration of BNP or serum creatinine.     

Relative hyperglycemia is associated with complications following an acute myocardial infarction: a post-hoc analysis of HI-5 data

Background

Hyperglycemia is associated with increased morbidity and mortality in patients with an acute myocardial infarction (AMI). We evaluated whether complications after AMI are associated with absolute or relative glycemia.

Methods

A total of 192 patients with AMI were randomized to intensive or conventional insulin therapy. Absolute glycemia was defined as mean blood glucose level (BGL) during the first 24 h following randomization. Relative glycemia was defined by the stress hyperglycaemia ratio (SHR), calculated as mean BGL divided by average glucose concentration over the prior 3 months estimated from glycosylated haemoglobin. The primary endpoint was a “complicated AMI”, defined as an AMI complicated by death, congestive cardiac failure, arrhythmia, cardiac arrest, reinfarction, cardiogenic shock, inotrope use or emergency revascularization.

Results

There was not a significant association between mean BGL and complicated AMI (odds ratio (OR) 1.05 per mmol/L glucose increment, 95% confidence intervals (CI) 0.93–1.19). In contrast, SHR was positively associated with a complicated myocardial infarction (OR 1.22 per 0.1 SHR increment, 95% CI 1.06–1.42), and individual complications of death (OR 1.55, 95% CI 1.14–2.11), congestive cardiac failure (OR 1.27, 95% CI 1.05–1.54), arrhythmia (OR 1.31, 95% CI 1.12–1.54) and cardiogenic shock (OR 1.42, 95% CI 1.03–1.97). The relationship between SHR and a complicated AMI was independent of diabetic status, intensive insulin therapy, sex and hypoglycemia.

Conclusions

Relative, but not absolute, glycemia during insulin treatment is independently associated with complications after an AMI. Future studies should investigate whether basing therapeutic glycaemic targets on relative glycemia improves patient outcomes.

     

Synergistic effect of anti and pro-inflammatory cytokine genes and their promoter polymorphism with ST-elevation of myocardial infarction

Background

The single-gene approach in association studies of polygenic diseases such as acute myocardial infarction (AMI) is likely to provide limited value. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) plasma levels may be genetically influenced.

Aim

We evaluate the impact of single nucleotide polymorphism of the promoter region of these genes, as well as reciprocal interaction of these genes with ST-elevation of myocardial infarction (STEMI).

Methods

In a case–control study 500 STEMI patients and 500 age- and sex-matched controls were studied. Three single-nucleotide polymorphism genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis and assessed their association with STEMI. The synergistic effects of IL-6, TNF-α and IL-10 gene polymorphisms were evaluated by using logistic regression analysis.

Results

We found that IL-6 and TNF-α concentrations of studied population were significantly different (p < 0.0001) in each genotype of IL-6 − 174G>C and TNF-α − 308G>A gene polymorphisms respectively. A significant association was found in multivariate analysis for the IL-6 − 174G>C [odds ratio (OR): 0.390; 95% confidence interval (CI): 0.176–0.865, p = 0.020] and TNF-α − 308G>A [OR: 0.372; 95% CI: 0.171–808, p = 0.012] gene polymorphisms with STEMI. In contrast, IL-10 − 592C>A gene polymorphism was no longer significant in the multivariate model (OR: 0.678; 95% CI: 0.288 to 1.594, p = 0.373) whereas significant in univariate analysis (OR: 0.697; 95% CI: 0.523–0.929, p = 0.014).

Conclusions

Our findings suggest that IL-6, TNF-α and IL-10 gene polymorphisms all contribute in the association with STEMI whereas the association persisted only for IL-6 and TNF-α but not for IL-10 gene polymorphism with this disease in the multivariate analysis.     

Vasoplegia after implantation of a continuous flow left ventricular assist device: incidence,outcomes and predictors

Background

Vasoplegia after routine cardiac surgery is associated with severe postoperative complications and increased mortality. It is also prevalent in patients undergoing implantation of pulsatile flow left ventricular assist devices (LVAD). However, less is known regarding vasoplegia after implantation of newer generations of continuous flow LVADs (cfLVAD). We aim to report the incidence, impact on outcome and predictors of vasoplegia in these patients.

Methods

Adult patients scheduled for primary cfLVAD implantation were enrolled into a derivation cohort (n?=?118, 2006–2013) and a temporal validation cohort (n?=?73, 2014–2016). Vasoplegia was defined taking into consideration low mean arterial pressure and/or low systemic vascular resistance, preserved cardiac index and high vasopressor support. Vasoplegia was considered after bypass and the first 48?h of ICU stay lasting at least three consecutive hours. This concept of vasoplegia was compared to older definitions reported in the literature in terms of the incidence of postoperative vasoplegia and its association with adverse outcomes. Logistic regression was used to identify independent predictors. Their ability to discriminate patients with vasoplegia was quantified by the area under the receiver operating characteristic curve (AUC).

Results

The incidence of vasoplegia was 33.1% using the unified definition of vasoplegia. Vasoplegia was associated with increased ICU length-of-stay (10.5 [6.9–20.8] vs 6.1 [4.6–10.4] p?=?0.002), increased ICU-mortality (OR 5.8, 95% CI 1.9–18.2) and one-year-mortality (OR 3.9, 95% CI 1.5–10.2), and a higher incidence of renal failure (OR 4.3, 95% CI 1.8–10.4). Multivariable analysis identified previous cardiothoracic surgery, preoperative dopamine administration, preoperative bilirubin levels and preoperative creatinine clearance as independent preoperative predictors of vasoplegia. The resultant prediction model exhibited a good discriminative ability (AUC 0.80, 95% CI 0.71–0.89, p?<? 0.01). Temporal validation resulted in an AUC of 0.74 (95% CI 0.61–0.87, p?<? 0.01).

Conclusions

In the era of the new generation of cfLVADs, vasoplegia remains a prevalent (33%) and critical condition with worse short-term outcomes and survival. We identified previous cardiothoracic surgery, preoperative treatment with dopamine, preoperative bilirubin levels and preoperative creatinine clearance as independent predictors.

     

Elevated Serum and Cerebrospinal Fluid Free Fatty Acid Levels Are Associated with Unfavorable Functional Outcome in Subjects with Acute Ischemic Stroke

The aim of this study was to evaluate the prognostic value of serum and cerebrospinal fluid (CSF) free fatty acid (FFA) levels in a cohort of patients with an acute ischemic stroke (AIS). In a prospective study, FFA levels were measured using an enzyme cycling method on admission in serum and CSF of 252 consecutive patients with AIS. The prognostic value of FFA to predict the functional outcome and mortality within 90-day was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. Serum and CSF levels of FFA increased with increasing severity of stroke as defined by the NIHSS score (all P?<?0.001). Patients with an unfavorable outcomes and non-survivors had significantly increased FFA serum and CSF levels on admission (all P?<?0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that serum FFA ≥0.71 mmol/L (third quarters) was an independent predictor of functional outcome (odds ratios (OR)?=?4.86; 95 % confidence interval (CI) 2.26–10.48) and mortality (OR?=?7.72; 95 % CI 3.01–21.48). The area under the receiver operating characteristic curve of serum FFA was 0.79 (95 % CI, 0.72–0.86) for functional outcome and 0.86 (95 % CI, 0.78–0.94) for mortality. Similarly, CSF FFA level also was an indicator for predicting of functional outcome and mortality. FFA levels in serum and CSF may serve as independent biomarkers in addition of the traditional methods for assessing the functional outcome and mortality of AIS.     

A comparison of the prognostic value of BNP versus NT-proBNP after hospitalisation for heart failure

Aims

Concentrations of circulating B?type natriuretic peptides provide important prognostic information in heart failure (HF) patients. We directly compared the prognostic performance of brain natriuretic peptide (BNP) versus N?terminal-proBNP (NT-proBNP) measurements in a large population of HF patients at hospital discharge after an admission for decompensated HF.

Methods and results

BNP and NT-proBNP were measured in 563 stable HF patients before discharge. All patients were followed for a fixed period of 18 months. The primary endpoint was time to first major event (HF hospitalisation or death).Patients were in NYHA class II (47%) or III/IV (53%) at discharge and the mean age of the patients was 71?±?11 years, 217 (39%) females, mean left ventricular ejection fraction was 0.32?±?0.14 and 234 (42%) had an ischaemic aetiology of HF. During the study, 236 patients (42%) reached the primary endpoint. Multivariate odds ratios of the primary endpoint for doubling of baseline levels of BNP and NT-proBNP were 1.46 (95% CI 1.19–1.80, p?<?0.001) and 1.45 (95% CI 1.18–1.78, p?<?0.001), respectively. The multivariable adjusted areas under the receiver-operating characteristic curve for prediction of the primary endpoint for doubling of BNP and NT-proBNP were 0.69 and 0.68, respectively. Direct comparison of the prognostic value of BNP and NT-proBNP did not reveal significant differences.

Conclusions

BNP and NT-proBNP at discharge for hospitalisation for HF are powerful, and equally strong and independent predictors of all-cause death and HF rehospitalisation.