The prognostic value of serum tau in patients with intracerebral hemorrhage

ObjectivesThis study aimed to investigate the relationship between serum tau concentrations and 3-month clinical outcomes in patients with intracerebral hemorrhage.Design and methodsSerum tau concentrations of 176 patients were quantified by enzyme-linked immunosorbent assay. The end points were mortality and poor outcome (modified Rankin Scale score > 2) after 3 months.Results110 patients (62.5%) had a poor outcome at 3 months. The 3-month mortality rate was 36.4% (64/176). A forward stepwise logistic regression selected serum tau concentration as an independent predictor for 3-month mortality (P = 0.002) and poor outcomes (P = 0.009) of patients. A receiver operating characteristic curve analysis showed that serum tau concentration predicted 3-month mortality (P = 0.001) and poor outcomes (P = 0.001) statistically significantly. The area under curve of tau was similar to that of the National Institutes of Health Stroke Scale score for 3-month mortality (P = 0.715) and poor outcomes (P = 0.315). In a combined logistic-regression model, tau statistically significantly improved the area under curve of the National Institutes of Health Stroke Scale score for the prediction of 3-month poor outcome (P = 0.039), but not for the prediction of 3-month mortality (P = 0.106).ConclusionsSerum tau concentration represents a novel biomarker for predicting mortality and poor outcomes at 3 months in patients with intracerebral hemorrhage.     

The myeloperoxidase -463G/A polymorphism and coronary artery disease risk: A meta-analysis of 1938 cases and 1990 controls

ObjectivesGenetic polymorphism of human myeloperoxidase (MPO) -463G/A has been implicated to alter the risk of coronary artery disease (CAD), but the results are controversial. To improve the reliability of the conflicting results, we conducted a meta-analysis of studies relating the MPO -463G/A polymorphism with the risk of CAD.Design and methodsTwo investigators independently searched the MEDLINE, EMBASE and Cochrane Library up to June, 2012. Summary odds ratios (OR) and 95% confidence interval (CI) for the MPO -463G/A polymorphism and CAD risk were calculated, and potential sources of heterogeneity and publication bias were explored. Statistical analysis was performed with the software program of Stata 9.0.Results5 case–control studies were finally identified for analyses, involving 1938 cases with CAD and 1990 controls. We found that the MPO -463G/A polymorphism has no significant association with overall CAD risk (G/G vs A/A: OR = 0.595, 95%CI = 0.298–1.188, P = 0.141; G/G vs G/A + A/A: OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G/G + G/A vs A/A: OR = 0.611, 95%CI = 0.334–1.119, P = 0.111; OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G vs A: OR = 0.843, 95%CI = 0.675–1.053, P = 0.133). The heterogeneity test showed that there were significant differences between individual studies in additive, recessive and allelic genetic models (P = 0.008, P = 0.021, P = 0.019, respectively); further analyses revealed that age and sex possibly account for the heterogeneity.ConclusionsOur meta-analysis demonstrated the evidence that there was no significant association between the MPO -463G/A polymorphism and the risk of CAD; larger and well-designed multicenter studies are needed to confirm our results.     

Myeloperoxidase is not useful for the early assessment of patients with chest pain

BackgroundMyeloperoxidase (MPO) has been listed as a potentially useful risk marker in acute coronary syndrome. However, its clinical utility in patients with acute chest pain is not yet defined.Design and methodsMPO (Architect, Abbott Diagnostics) was measured in 120 healthy controls and 303 chest pain patients who had been admitted to the coronary care units of three Swedish hospitals.ResultsChest pain patents had significantly higher median MPO levels compared to healthy controls (120.6 vs. 78. 9 pmol/L; p < 0.001). However, MPO was not useful for the diagnosis of myocardial infarction (c-statistics 0.61 [95% CI 0.54–0.67]), and Cox regression analysis revealed no independent association between MPO and mortality (adjusted hazard ratio 1.3 [95% CI 0.8–2.0]) or the composite endpoint (adjusted hazard ratio 1.1 [95% CI 0.8–1.5]) after a median follow-up of 4.9 years.ConclusionsMPO provided no clinically relevant information in the present population of chest pain patients.     

High-level expression of early growth response-1 and association of polymorphism with total IgE and atopy in allergic rhinitis adults

BackgroundEarly growth response-1 (Egr-1) is expressed in human airways and its polymorphisms have been associated with total IgE and atopy in asthmatic patients. We investigated the effects of Chinese-tagging single nucleotide polymorphism (SNP) of Egr-1 and its mRNA expression on allergic rhinitis (AR) traits.MethodsAmong 214 Chinese AR adults and 259 controls, tag SNP ?4071 A → G was genotyped and mRNA expression in peripheral blood was quantified by real-time PCR.ResultsEgr-1 mRNA expression was significantly higher in patients than controls (median of 0.23 vs 0.15 fold GAPDH expression; p < 0.001). Its expression was not associated with ? 4071 polymorphism. However, significant correlations were found between ? 4071 A → G with increased plasma total IgE (p = 0.028) and atopy (p = 0.030) in patients. Logistic regression confirmed the association (p = 0.034) with age and gender adjusted. Patients homozygous for the A allele had a 2.3-fold and 1.9-fold risks, respectively of having increased plasma total IgE and atopy than those G allele carriers.ConclusionsWe showed high levels of Egr-1 mRNA expression and demonstrated a significant association of polymorphism with increased plasma total IgE and atopy in AR patients. It may be useful to explore the pharmacogenetics of Egr-1 inhibitors.     

Matrix metalloproteinase-1 promoter genotypes and haplotypes are associated with carotid plaque presence

ObjectivesMatrix metalloproteinase (MMP)-1 degrades fibrillar collagens suggesting important role in vascular remodeling. Data about MMP-1 promoter polymorphisms and carotid atherosclerosis (CA) are scarce. The aim of this study was to evaluate association of MMP-1 genotypes/haplotypes with carotid plaque (CP) presence in Serbian population.Design and methodsStudy enrolled a total of 702 participants: 274 controls and 428 consecutive patients with CA who underwent carotid endarterectomy. MMP-1 polymorphisms ? 1607 1G/2G, ? 519 A/G and ? 340 T/C were genotyped by PCR and RFLP methods.ResultsIndividuals carrying MMP-1 ? 1607 2G allele had significantly increased allele dose-dependent risk for CP presence (1G1G vs. 1G2G vs. 2G2G; OR = 1; OR = 1.87 95% CI 1.29–2.07; OR = 3.49 95% CI 1.67–7.30, p = 0.0009, respectively). Compared to the referent haplotype 2G_? 1607-T_? 340-A_? 519, the haplotypes 1G_? 1607-T_? 340-A_? 519, 1G_? 1607-T_? 340-G_? 519 and 2G_? 1607-C_? 340-A_? 519 had statistically significant protective effect on CP presence (OR = 0.41, 95% CI 0.29–0.81, p = 0.01; OR = 0.56, 95% CI 0.44–0.89, p = 0.01; OR = 0.43, 95% CI 0.27–0.86, p = 0.02, respectively).ConclusionsMMP-1 ? 1607 G/2G polymorphism solely and specific haplotypes of three analyzed promoter polymorphisms are significantly and independently associated with occurrence of CP. Replication studies in other populations are needed.     

Plasma high sensitivity C-reactive protein and its relationship with cytokine levels in children with newly diagnosed type 1 diabetes and ketoacidosis

BackgroundHigh-sensitivity C-reactive protein (hs-CRP) and pro-inflammatory cytokines have been suggested as sensitive markers of endothelial dysfunction. Our aim was to monitor plasma hs-CRP levels at different time-points and in different degrees of ketoacidosis severity, its association with cytokine levels and its role as a marker of severe ketoacidosis complications.Patients and methodsWe studied in 38 newly diagnosed children with type 1 diabetes and ketoacidosis, aged 7.7 ± 3.1 years, hs-CRP, white blood cell count (WBC), and plasma levels of cytokines IL-1β (interleukin-1β), IL-2, IL-6, IL-8, IL-10, TNF-α (tumor necrosis factor-α) prior to and during DKA management.ResultsOn admission, the levels of WBC, PMN, IL-6 and IL-10 were elevated, but were all reduced within 120 h after ketoacidosis management. In the group with moderate/severe ketoacidosis, but not in mild ketoacidosis, hs-CRP levels were significantly reduced at 24 h (p = 0.021), WBC and IL-6 at 120 h (p = 0.003), while IL-10 was prematurely reduced at 6–8 h (p = 0.008). Moreover hs-CRP was significantly associated with WBC (p = 0.023) and IL-6 (p = 0.028) on admission, with IL-6 (p = 0.002) and IL-8 (p = 0.014) at 24 h and with IL-10 (p = 0.027) at 120 h. The above were not observed in the group with mild ketoacidosis.ConclusionsIn the children with moderate/severe diabetic ketoacidosis of our study, increased levels of hs-CRP and IL-6 were observed, together with leukocytosis and neutrophilia, without the presence of infection. As hs-CRP was found to be strongly associated with the inflammatory IL-6, the prolonged elevation of hs-CRP levels in children with severe ketoacidosis could serve as a marker for the development of its severe complications.     

Association between myeloperoxidase polymorphisms and its plasma levels with severity of coronary artery disease

ObjectivesMyeloperoxidase (MPO) polymorphism ?463 has been related to higher cardiovascular risk. This study was conducted to test whether the MPO promoter polymorphism ?463A/G and MPO plasma levels are associated with coronary artery disease (CAD) severity.Design and methodsPatients submitted to elective coronariography were enrolled, CAD severity was assessed and blood samples collected to identify the MPO polymorphism and its plasma levels.ResultsGenotypes were determined in 118 patients. Among these patients, 12 (10%) were homozygous for AA, 69 (58%) for GG and 37 (32%) were heterozygous. Mean MPO plasma levels were 8.6 ± 4.7 ng/mL for AA, 8.6 ± 7.0 ng/mL for AG and 9.4 ± 5.6 ng/mL for GG genotypes. The CAD severity was not associated with MPO genotypes (p = 0.43), however, patients with higher CAD score presented higher MPO levels (p = 0.02).ConclusionWe found no association between MPO polymorphism and CAD severity, although a relation was observed for MPO plasma levels and extension of CAD.     

Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus

ObjectivesTo find whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among type 2 diabetes mellitus (T2DM) patients from Western Iran.Design and methodsThe MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric T2DM patients by PCR-RFLP.ResultsThe possession of both MTHFR 677T and 1298C alleles increase the risk of microalbuminuria to 4.3-fold (p = 0.007) in T2DM patients. The presence of either MTHFR 677T, 1298C allele is sufficient to increase the risk of macroalbuminuria in T2DM patients by 4.1 and 5.5 times (p = 0.027, and p = 0.006, respectively). The concomitant presence of both 677T and 1298C alleles act in synergy to increase the risk of macroalbuminuria by 20.4-fold (p < 0.001) and progression of DN from microalbuminuria to macroalbuminuria (OR = 4.73, p = 0.01).ConclusionBoth MTHFR 677T and 1298C alleles increased the susceptibility to the onset and progression of DN in Iranians with T2DM.     

Oxidative stress and myeloperoxidase activity during bacterial meningitis: Effects of febrile episodes and the BBB permeability

ObjectiveTo investigate participation of extracellular myeloperoxidase (MPO) in oxidative stress during different courses of the bacterial meningitis (BM).Materials and methodsWe sequentially assessed WBC count, blood-brain barrier (BBB) permeability, serum and cerebrospinal fluid (CSF) lipid peroxidation (LPO), MPO and antioxidative activity (AOA) in proven pediatric BM.ResultsBM patients exhibited increased systemic and local LPO and MPO, and reduced AOA, which was exaggerated in the febrile episodes. Serum MPO and LPO products were related to the BBB permeability at the baseline. CSF hydroperoxide level was influenced by the BBB permeability, CSF albumin concentration, and serum hydroperoxide (r = 0.502; p < 0.001, and r = 0.611; p < 0.001, and r = 0.358; p < 0.001, respectively). CSF hydroperoxide and MPO correlated in complicated cases during the study.ConclusionsThese results suggest that CSF LPO and MPO were closely related in BM, had different courses if febrile episodes had occurred, but were partly influenced by the BBB permeability.     

Impact of intensified postresuscitation treatment on outcome of comatose survivors of out-of-hospital cardiac arrest according to initial rhythm

AimWe investigated the impact of intensified postresuscitation treatment in comatose survivors of out-of-hospital cardiac arrest (OHCA) of presumed cardiac etiology according to the initial rhythm at the emergency medical team arrival.MethodsInterventions and survival with Cerebral Performance Category (CPC) 1–2 within each group were retrospectively compared between the periods of conservative (1995–2003) and intensified (2004–2012) postresuscitation treatment.ResultsIn shockable group, therapeutic hypothermia (TH) increased from 1 to 93%, immediate invasive coronary strategy from 28 to 78%, intraaortic balloon pump from 4 to 21%, vasopressors/inotropes from 47 to 81% and antimicrobial agents from 65 to 86% during the intensified period as compared to conservative period (p < 0.001). This was associated with increased survival with CPC 1–2 from 27 to 47% (p < 0.001). After adjusting for age, sex and prehospital confounders, TH (OR = 2.12, 95% CI 1.25–3.61), percutaneous coronary intervention (OR 1.77, 95% CI 1.15–2.73) and antimicrobial agents (OR = 12.21, 95% CI 5.13–29.08) remained associated with survival with CPC 1–2. In non-shockable patients, TH also significantly increased from 1 to 74%, immediate invasive coronary strategy from 8 to 51%, intraaortic balloon pump from 2 to 9% and vasopressors/inotropes from 56 to 84% during intensified period without concomitant increase in survival with CPC 1–2 (7% vs. 9%; p = 0.27). After adjustment, only antimicrobial agents (OR = 8.43, 95% CI: 1.05–67.72) remained associated with survival with CPC 1–2.ConclusionIntensified postresuscitation treatment was associated with doubled survival in comatose survivors of OHCA with shockable rhythm. Such association could not be demonstrated in patients with non-shockable rhythm.     

The prognostic value of serum pregnancy-associated plasma protein A,S100 and high sensitivity C-reactive protein in acute ischemic stroke patients without heparin administration

ObjectivesThe concerns regarding the pre-analytical bias caused by medicine treatments have been raised in the diagnosis and prognosis of ischemic stroke recently. The aim of this study was to examine the prognostic value of serum pregnancy-associated plasma protein A (PAPP-A), S100 and high sensitivity C-reactive protein (hs-CRP) in heparin-naïve patients of acute ischemic stroke.Design and methodsSerum levels of PAPP-A, S100 and hs-CRP were determined in 205 heparin-naïve patients of acute ischemic stroke and 50 healthy controls. Clinical information and radiological information were collected. Unfavorable outcomes (stroke recurrence, myocardial infarction or death) were also recorded after six months. The associations between serum biomarker levels and stroke severity/outcome were assessed.ResultsSerum PAPP-A, S100 and hs-CRP levels increased in patients compared with controls (P < 0.05). S100 and hs-CRP levels were significantly higher in patients with larger cerebral infarction sizes (P < 0.05) and more severe neurological impairment (P < 0.05). Serum PAPP-A level showed a progressive increase with the increase of stroke severity (P < 0.05). Serum hs-CRP and National Institutes of Health Stroke Scale (NIHSS) scores were identified as independent predictors for unfavorable outcomes with odds ratios of 2.884 (1.154 to 7.210, P = 0.023) and 2.887 (1.146 to 7.273, P = 0.024), respectively.ConclusionSerum PAPP-A, S100 and hs-CRP were associated with stroke severity or outcome after ischemic stroke and may offer complementary information, essential for clinical decision making. Serum PAPP-A showed a potential value for the evaluation of stroke clinically.     

Identification of NPPA variants associated with atrial fibrillation in a Chinese GeneID population

BackgroundA frameshift mutation in the NPPA gene was identified in 1 family with atrial fibrillation (AF), however, further studies are needed to establish unequivocally the genetic association between NPPA and AF.MethodsA case control association study and mutational analysis of NPPA were performed with 384 sporadic AF patients and 844 controls from a Chinese GeneID population. Genotyping was performed using High-Resolution Melt analysis. Mutational analysis was performed using direct DNA sequencing analysis.ResultsSignificant allelic association was detected between single nucleotide polymorphism (SNP) rs5063 and lone AF (p = 0.015, OR = 1.63; adjusted p = 0.003). Genotypic association was significant assuming an additive or dominant model (adjusted p = 0.005 and 0.007, respectively). Six new variants were identified in NPPA, including 2 in the 5′-UTR, 2 in the 3′-UTR, and 2 missense substitutions. Variants c.413T > C, c.*48G > A and c.*133G > T were not present in 844 controls, and the others were identified in controls.ConclusionsVariants in NPPA confer risk of lone AF in a Chinese population. Thus, in addition to being a disease-causing gene with mutations identified in familial AF cases, NPPA is a susceptibility gene for lone AF.     

Time of sampling is crucial for measurement of cell-free plasma DNA following acute aseptic inflammation induced by exercise

ObjectivesTo determine the time-course changes of cell-free plasma DNA (cfDNA) following heavy exercise.MethodscfDNA concentration, C-reactive protein levels (hs-CRP), uric acid concentration (UA), creatine kinase activity (CK) were measured before and post-exercise (immediately post, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 24 h).ResultscfDNA increased (15-fold) 30-min post-exercise and normalized thereafter. hs-CRP increased (56%, p < 0.001) 1 h post-exercise, remained elevated throughout recovery (52–142%, p < 0.0001), and peaked (200% rise, p < 0.0001) at 24 h post-exercise. UA and CK increased (p < 0.05), immediately post-exercise, remained elevated throughout recovery (p < 0.0001), and peaked (p < 0.0001) at 24 h of post-exercise recovery.ConclusionscfDNA sampling timing is crucial and a potential source of error following aseptic inflammation.     

Prognostic implication of out-of-hospital cardiac arrest in patients with cardiogenic shock and acute myocardial infarction

ObjectivesTo compare outcome in patients with acute myocardial infarction (MI) and cardiogenic shock (CS) presenting with and without out-of-hospital cardiac arrest (OHCA).BackgroundDespite general improvement in outcome after acute MI, CS remains a leading cause of death in acute MI patients with a high 30-day mortality rate. OHCA on top of cardiogenic shock may further increase mortality in these patients resulting in premature withdrawal of supportive therapy, but this is not known.Methods and resultsIn a retrospective study from 2008 to 2013, 248 consecutive patients admitted alive to a tertiary centre with the diagnosis of CS and acute MI were enrolled, 118 (48%) presented with OHCA and 130 (52%) without (non-OHCA patients). Mean lactate level at admission was significantly higher in OHCA patients compared with non-OCHA patients (9 mmol/l (SD 6) vs. 6 mmol/l (SD 4) p < 0.0001). Co-morbidities were more prevalent in the non-OHCA group. By univariate analysis age (Hazard ratio (HR) = 1.02 [CI 1.00–1.03], p = 0.01) and lactate at admission (HR = 1.06 [CI 1.03–1.09], p < 0.001), but not OHCA (HR = 1.1 [CI 0.8–1.4], p = NS) was associated with mortality. In multivariate analysis, only age (HR = 1.02 [CI 1.01–1.04], p = 0.003) and lactate level at admission (HR = 1.06 [1.03–1.09], p < 0.001) were independent predictors of mortality. One-week mortality was 63% in the OHCA group and 56% in the non-OHCA group, p = NS.ConclusionOHCA is not an independent predictor of mortality in patients with acute MI complicated by cardiogenic shock. This should encourage active intensive treatment of CS patients regardless of OHCA.     

Methionine sulfoxide reductase A rs10903323 G/A polymorphism is associated with increased risk of coronary artery disease in a Chinese population

ObjectiveCoronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms in methionine sulfoxide reductase A (MSRA: rs10903323 G/A) and vascular endothelial growth factor A (VEGFA: rs699947 C/A, rs2010963 G/C, and rs3025039 C/T) contribute to CAD susceptibility.Designs and methodsWe examined the association between the four polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and 480 controls. Genotyping was performed using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF-MS).ResultsWhen the MSRA rs10903323 GG homozygous genotype was used as the reference group, the GA and GA/AA genotypes were associated with a significantly increased risk of CAD (GA vs GG: adjusted OR = 1.36, 95% CI = 1.02–1.82, p = 0.038; GA/AA vs GG: adjusted OR = 1.33, 95% CI = 1.01–1.76, p = 0.042). The AA homozygous genotype was not associated with a risk of CAD. In the recessive model, when the MSRA rs10903323 GG/GA genotypes were used as the reference group, the AA homozygous genotype was not associated with a risk of CAD. Logistic regression analyses revealed that the VEGFA rs699947 C/A, VEGFA rs2010963 G/C, and VEGFA rs3025039 C/T polymorphisms were not associated with a risk of CAD.ConclusionsThese findings suggest that the functional MSRA rs10903323 G/A polymorphism is associated with CAD development. However, our results allow only a preliminary conclusion, which must be validated with a larger study of a more diverse ethnic population.     

A meta-analysis of the bradykinin B2 receptor gene − 58C/T polymorphism with hypertension

Background and objectiveNumerous studies have attempted to associate ? 58C/T polymorphism of bradykinin B2 receptor gene (BDKRB2) with hypertension, whereas results were often irreproducible. We performed a meta-analysis aiming to provide a comprehensive evaluation of this polymorphism and hypertension.MethodsCase-control reports published in English were searched totaling four studies with six populations (823 cases and 916 controls). Random-effects model was applied irrespective of between-study heterogeneity, and study quality was assessed in duplicate.ResultsCompared with ? 58C allele carriers, those with ? 58T allele had a lower yet nonsignificant risk for hypertension (OR = 0.86; 95% CI: 0.68–1.09; P = 0.21). Lack of significance persisted after combining those with genotypes ? 58TC and ? 58TT together (OR = 0.87; 95% CI: 0.67–1.09; P = 0.21) or with ? 58TC and ? 58CC together (OR = 0.75; 95% CI: 0.48–1.18; P = 0.22) in association with hypertension. Sensitivity analyses by race indicated that comparison of ? 58T versus ? 58C generated a protective effect for hypertension in Asians (OR = 0.77; 95% CI: 0.58–1.02; P = 0.07) and African-Americans (OR = 0.65; 95% CI: 0.43–0.98; P = 0.04), but a risk effect in Caucasians (OR = 1.22; 95% CI: 0.92–1.61; P = 0.17). No publication bias was observed.ConclusionsOur results suggested that ? 58T allele exhibited a protective effect on hypertension in Asians and African-Americans, yet a risk effect in Caucasians.     

Common genetic polymorphisms in pre-microRNAs were associated with increased risk of dilated cardiomyopathy

BackgroundCommon single nucleotide polymorphisms (SNPs) in pre-microRNAs may change their property through altering microRNAs (miRNAs) expression and/or maturation, resulting diverse functional consequences. We conducted a pilot study to test whether SNPs in pre-microRNAs were associated with dilated cardiomyopathy (DCM).MethodsGenotypes of 3 SNPs in pre-miRNAs (has-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, hsa-mir-146a rs2910164 C/G) in 221 DCM patients and 321 control subjects were determined with the use of PCR-restriction fragment length polymorphism (RFLP) assay.ResultsSignificantly increased DCM risks were found to be associated with variant allele of has-mir-196a2 rs11614913 C/T (T allele) and hsa-mir-499 rs3746444 A/G (G allele) (P < 0.0001, OR = 1.730, 95% CI = 1.345–2.227, and P < 0.0001, OR = 1.794, 95% CI = 1.350–2.385, respectively). We found that increased DCM risk was statistically significantly associated with these 2 SNPs in a dominant model (P = 0.0001 and P < 0.0001 for rs11614913 and rs3746444, respectively). No association between DCM risk and hsa-mir-146a rs2910164 C/G was observed (P = 0.451, OR = 1.102, 95% CI = 0.856–1.418).ConclusionsBoth the has-mir-196a2 rs11614913 C/T and hsa-mir-499 rs3746444 A/G, but not hsa-mir-146a rs2910164 C/G, are associated with a significantly increased risk of DCM, indicating that common genetic polymorphisms in pre-microRNAs are associated with DCM.     

Sinus bradycardia during hypothermia in comatose survivors of out-of-hospital cardiac arrest – A new early marker of favorable outcome?

BackgroundBradycardia is a common finding in patients undergoing therapeutic hypothermia (TH) following out-of-hospital cardiac arrest (OHCA), presumably as a normal physiological response to low body temperature. We hypothesized that a normal physiological response with sinus bradycardia (SB) indicates less neurological damage and therefore would be associated with lower mortality.MethodsWe studied 234 consecutive comatose survivors of OHCA with presumed cardiac etiology and shockable primary rhythm, who underwent a full 24-h TH-protocol (33 °C) at a tertiary heart center (years: 2004–2010). Primary endpoint was 180-day mortality; secondary endpoint was favorable neurological outcome (180-day cerebral performance category: 1–2).ResultsSB, defined as sinus rhythm <50 beats per minute during TH, was present in 115 (49%) patients. Baseline characteristics including sex, witnessed arrest, bystander cardiopulmonary resuscitation and time to return of spontaneous circulation were not different between SB- and no-SB patients. However, SB-patients were younger, 57 ± 14 vs. 63 ± 14 years, p < 0.001 and less frequently had known heart failure (7% vs. 20%, p < 0.01).Patients experiencing SB during the hypothermia phase of TH had a 17% 180-day mortality rate compared to 38% in no-SB patients (p < 0.001), corresponding to a 180-day hazard ratio (HR_adjusted = 0.45 (0.23–0.88, p = 0.02)) in the multivariable analysis. Similarly, SB during hypothermia was directly associated with lower odds of unfavorable neurological outcome (OR_unadjusted = 0.42 (0.23–0.75, p < 0.01).ConclusionSinus bradycardia during therapeutic hypothermia is independently associated with a lower 180-day mortality rate and may thus be a novel, early marker of favorable outcome in comatose survivors of OHCA.