DNA methylation alternation in Stanford- A acute aortic dissection.

BACKGROUND:Acute aortic dissection (AAD) is a life-threatening cardiovascular disease. Recent studies have shown that DNA methylation may be associated with the pathological mechanism of AAD, but the panorama of DNA methylation needs to be explored.METHODS:DNA methylation patterns were screened using Infinium Human Methylation 450 K BeadChip in the aortic tissues from 4 patients with Stanford-A AAD and 4 controls. Gene enrichment was analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO). DNA methylation levels of candidate genes were determined by pyrosequencing in the replication cohort including 16 patients with AAD and 7 controls. Protein expression level of candidate gene was assessed by Western blot.RESULTS:A total of 589 differentially methylated positions including 315 hypomethylated and 274 hypermethylated positions were found in AAD group. KEGG analysis demonstrated that differentially methylated position-associated genes were enriched in MAPK signaling pathway, TNF signaling pathway and apoptosis pathway, et al. GO analysis demonstrated that differentially methylated position-associated genes were enriched in protein binding, angiogenesis and heart development et al. The differential DNA methylation in five key genes, including Fas, ANGPT2, DUSP6, FARP1 and CARD6, was authenticated in the independent replication cohort. The protein expression level of the Fas was increased by 1.78 times, indicating the possible role of DNA methylation in regulation of gene expression.CONCLUSION:DNA methylation was markedly changed in the aortic tissues of Stanford-A AAD and associated with gene dysregulation, involved in AAD progression.

Genetic variants in Chinese patients with sporadic Stanford type A aortic dissection.

BACKGROUND:Genetic disorders are strongly associated with aortic disease. However, the identities of genetic mutations in sporadic Stanford type A aortic dissection (STAAD) are not clear. The present study analysed the possible genetic mutations of the known pathogenic genes of aortic disease and the clinical characteristics in patients with sporadic STAAD.METHODS:We analysed genetic mutations in 26 genes that underlie aortic aneurysms and dissections in 100 sporadic STAAD patients and 568 healthy controls after whole-genome sequencing (WGS). Clinical features and in-hospital death were determined in all STAAD patients.RESULTS:In total, 60 suspicious pathogenic mutations (56 novel and 4 previously reported) in 19 genes were identified in 50% (50/100) of patients, and 14 patients had more than 1 mutation. The ascending aortic diameter was extended in patients with mutations (49.1±12.3 vs. 43.7±11.2 mm, P=0.023), and the DeBakey type I phenotype was more common in patients with mutations in genes that coded extracellular matrix (ECM) components than in patients with mutations in other genes (96.6% vs. 66.7%, P=0.007). Patients with fibrillin-1 (FBN1) mutations were younger than patients without FBN1 mutations (44.7±11.0 vs. 53.5±12.1, P=0.030). Subgroup analyses revealed an increased risk of in-hospital mortality in mutation carriers (44.4% vs. 10.5%, P=0.029) but only in patients who received conservative treatment.CONCLUSIONS:Half of Chinese patients with a sporadic form of STAAD may carry mutations in known pathogenic genes of aortic disease, and these patients may exhibit distinct clinical features and poor clinical outcomes with the use of conservative treatment.

Angiopoietin 2 as a Novel Potential Biomarker for Acute Aortic Dissection.

Biomarker-assisted diagnosis of acute aortic dissection (AAD) is important for initiation of treatment and improved survival. However, identification of biomarkers for AAD in blood is a challenging task. The present study aims to find the potential AAD biomarkers using a transcriptomic strategy. Arrays based genome-wide gene expression profiling were performed using ascending aortic tissues which were collected from AAD patients and healthy donors. The differentially expressed genes were validated using quantitative reverse transcriptase PCR (qRT-PCR) and western blot. The plasma levels of a potential biomarker, angiopoietin 2 (ANGPT2) were determined in case-control cohort (77 AAD patients and 82 healthy controls) by enzyme linked immunosorbent assay. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic power of ANGPT2 for AAD. Transcriptome data demonstrated that a total of 18 genes were significantly up-regulated and 28 genes were significantly down-regulated among AAD tissues (foldchange>3.0, p < 0.01). By bioinformatic analysis, we identified ANGPT2 as a candidate biomarker for blood-based detection of AAD. The qRT-PCR and protein expression demonstrated that ANGPT2 increased 2.4- and 4.2 folds, respectively in aortic tissue of AAD patients. Immunohistochemical staining demonstrated that ANGPT2 was markedly increased in intima of the aortic wall in AAD. Furthermore, ANGPT2 was significantly elevated in AAD patients as compared with controls (median 1625 vs. 383 pg/ml, p < 1E-6). ROC curve analysis showed that ANGPT2 was highly predictive of a diagnosis of type A AAD (area under curve 0.93, p < 1E-6). Sensitivity and specificity were 81 and 90%, respectively at the cutoff value of 833 pg/ml. In conclusion, ANGPT2 could be a promising biomarker for diagnosis of AAD; however, more studies are still needed to verify its specificity in diagnosing of AAD.

Integrin α9 is involved in the pathopoiesis of acute aortic dissection via mediating phenotype switch of vascular smooth muscle cell.

Acute aortic dissection (AAD) is a devastating disease with high mortality; however, the pathogenic mechanisms of AAD remain poorly understood. Our present study aimed to identify genes associated with AAD and explore the molecular function of candidate genes in the pathogenesis of AAD. We used a whole-genome transcriptional microarray to identify putative AAD genes using ascending aortic tissues from four patients with AAD and four healthy organ donors. The differentially expressed genes were further validated in eight patients with AAD and eight healthy organ donors. Functional assessments were conducted to analyze the effects of the identified AAD genes on the phenotype of aortic vascular smooth muscle cells (VSMCs). The whole-genome transcriptional microarray analysis found 129 dysregulated genes in the ascending aortic tissues of AAD (fold change≥2), which were mainly associated with the focal adhesion pathway and actin cytoskeleton regulation pathway. Among these genes, integrin α9 (ITGA9) was identified to be involved in both pathways and downregulated by 50% in AAD patients. The association of ITGA9 with AAD was confirmed by Western blotting analysis (P = 0.003). Functional studies showed that knocking down ITGA9 in VSMCs resulted in a decrease in contractile markers (SM22α and α-SMA) and an increase in synthetic markers (OPN and SMemb), suggesting that the VSMCs switched from a contractile to a synthetic phenotype. After overexpression of ITGA9 by a recombinant adenovirus vector in VSMCs, SM22α and α-SMA were upregulated, while SMemb was downregulated, indicating a phenotypic switch from the synthetic to contractile phenotype of VSMCs. In conclusion, our study identified ITGA9 as a novel AAD gene. This gene is downregulated in patients with AAD and is involved in the regulation of the phenotypic switch of VSMCs from a contractile to a synthetic phenotype.

Influence of Age on Clinical Presentation, Therapeutic Options, and Outcome in Chinese Patients with Acute Aortic Dissection.

It has been shown in previous studies that Chinese patients with acute aortic dissection (AD) were approximately 10 years younger than patients from western countries. However, there is a lack of studies concerning the age-related differences in clinical characteristics and outcomes in Chinese patients with acute AD. A total of 1,061 patients with AD (570 type A and 491 type B AD) were enrolled between 2006 and 2008. The clinical characteristics were compared between the patients in our study and those in the International Registry of Acute Aortic Dissection (IRAD). Compared with patients in the IRAD, those in our study were relatively younger, comprised more males, and had a higher proportion of Marfan syndrome but received fewer surgical interventions. When stratified by 10-year age, younger patients were more likely to have type A AD, familial AD, and Marfan syndrome, whereas older patients tended to comprise more females and type B AD. As age increased, the proportion of surgical intervention gradually decreased regardless of the type of AD. During a median follow-up of 2.2 years, 147 patients died, of whom 94 (63.9%) had type A AD and 53 (36.1%) had type B AD. Long-term mortality increased with increasing age, especially in patients above 70 years old. Furthermore, the recurrence rate of AD was higher in both the young and the older patients. In conclusion, compared with western patients with AD, Chinese patients have distinct characteristics and more attention should be paid to the young and older patients because of their high long-term mortality and recurrence rate.

Onset seasons and clinical outcomes in patients with Stanford type A acute aortic dissection: an observational retrospective study.

OBJECTIVES:To evaluate the association of onset season with clinical outcome in type A acute aortic dissection (AAD).DESIGN:A single-centre, observational retrospective study.SETTING:The study was conducted in Fuwai Hospital, the National Centre for Cardiovascular Disease, Beijing, China.PARTICIPANTS:From 2008 to 2010, a set of consecutive patients with type A AAD, confirmed by CT scanning, were enrolled and divided into four groups according to onset season: winter (December, January and February), spring (March, April and May), summer (June, July and August) and autumn (September, October and November). The primary end points were in-hospital death and all-cause mortality during follow-up.RESULTS:Of the 492 cases in this study, 129 occurred in winter (26.2%), 147 in spring (29.9%), 92 in summer (18.7%), and 124 in autumn (25.2%). After a median follow-up of 20.4 months (IQR 9.7-38.9), the in-hospital mortality in cases occurring in autumn was higher than in the other three seasons (23.4% vs 8.4%, p<0.01). Long-term mortality was comparable among the four seasonal groups (p=0.63). After adjustment for age, gender and other risk factors, onset in autumn was still an independent factor associated with increased risk of in-hospital mortality (HR 2.05; 95% CI 1.15 to 3.64, p=0.02) in addition to surgical treatment. Further analysis showed that the seasonal effect on in-hospital mortality (autumn vs other seasons: 57.4% vs 27.3%, p<0.01) was only significant in patients who did not receive surgical treatment. No seasonal effect on long-term clinical outcomes was found in this cohort.CONCLUSIONS:Onset in autumn may be a factor that increases the risk of in-hospital death from type A AAD, especially in patients who receive conservative treatment. Immediate surgery improves the short-term and long-term outcomes regardless of onset season.

Reply to 'Body mass index and the risk of all-cause mortality among patients with nonvalvular atrial fibrillation: a multicenter prospective observational study in China; methodological issues'.

Body mass index and the risk of all-cause mortality among patients with nonvalvular atrial fibrillation: a multicenter prospective observational study in China.

BACKGROUND/OBJECTIVES:High body mass index (BMI) is associated with increased incident atrial fibrillation (AF) and mortality rate. In patients presenting with nonvalvular AF (NVAF), the prognostic relevance of BMI remains unclear.SUBJECTS/METHODS:In this prospective observational study, a total of 1759 patients with NVAF (69.9±12.9 years old, 47.9% male) were divided into three clinical settings according to estimated stroke risks (CHADS2 score ⩽1 (low), =2 (moderate) and ⩾3 (high)). The primary outcome was all-cause mortality, and the secondary outcomes included thromboembolism and major bleeding. Cox-proportional hazard models were used to estimate the association between BMI levels and clinical outcomes.RESULTS:During a mean follow-up of 1 year representing 1974 patient-years at risk, 256 patients died, 142 suffered from thromboembolism and 17 developed major bleeding. Multivariate adjusted Cox analysis indicated that a BMI of 24.0-27.9 kg/m2 was independently associated with improved survival among all patients (hazard ratio (HR) 0.689, 95% confidence interval (CI) 0.512-0.928; P=0.018) and patients at high stroke risk (HR 0.622, 95% CI 0.410-0.943; P=0.024), but not among those at low or moderate stroke risks. No associations were observed between BMI levels and the incidence of thromboembolic events in various clinical settings.CONCLUSIONS:A paradoxical BMI-all-cause mortality risk association was observed in Chinese patients with NVAF, and this association was pronounced among patients at high stroke risk rather than in those at low stroke risk.

The effect of admission serum potassium levels on in-hospital and long-term mortality in type A acute aortic dissection.

BACKGROUND:Mild fluctuations in serum potassium (K+) levels are related to the prognosis of cardiovascular disease. This study aimed to determine the effect of admission serum potassium levels on in-hospital and long-term mortality in patients with Stanford type A acute aortic dissection (AAD).MATERIALS AND METHODS:A total of 588 consecutive patients with type A AAD were enrolled, and they were grouped according to admission serum potassium level: <3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, and ≥5.0mmol/L. Clinical outcomes were in-hospital death and long-term all-cause mortality.RESULTS:The in-hospital and long-term all-cause mortality rates were 10.7% and 16.3%, respectively. A U-shaped relationship was observed between admission serum potassium levels and both in-hospital death and long-term mortality. Univariate Cox regression identified potassium levels outside the interval of <3.5 to 4.5mmol/L to be a risk factor for both in-hospital and long-term death. After adjusting for age, gender, surgery and other risk factors, potassium levels outside the interval of <3.5 to 4.5mmol/L still had a significant association with long-term death [hazard ratio (HR)=1.72, 95% confidence interval (95% CI): 1.07-2.74, P=0.024]. Surgical intervention was the main protective factor associated with both in-hospital (HR=0.01, 95% CI 0.01-0.06, P<0.001) and long-term survival (HR=0.06, 95% CI 0.03-0.12, P<0.001).CONCLUSIONS:Among patients with Stanford type A AAD, admission serum potassium levels other than 3.5 to 4.5mmol/L might be associated with an increased risk of in-hospital death and long-term mortality.

Admission D-dimer testing for differentiating acute aortic dissection from other causes of acute chest pain.

INTRODUCTION:The present study aims to evaluate the utility of D-dimer testing for differentiating the causes of acute chest pain, including acute aortic dissection (AAD), pulmonary embolism (PE), acute myocardial infarction (AMI), unstable angina (UA), and other uncertain diagnoses of chest pain.MATERIAL AND METHODS:Consecutive patients admitted for acute chest pain within 24 h from symptom onset were enrolled prospectively, and plasma D-dimer levels were measured on admission. Diagnoses of AAD, PE, AMI, and UA were confirmed by standard methods.RESULTS:A total of 790 patients were enrolled, including 202 AAD, 43 PE, 315 AMI, 136 UA, and 94 cases of other uncertain diagnoses. D-dimer levels were significantly higher in patients with AAD and PE than in those with AMI, UA, and other uncertain diagnoses (p < 0.001), but they were comparable between patients with AAD and PE (p = 0.065). Moreover, patients with type A AAD had higher D-dimer levels than those with type B AAD (p = 0.022). Receiver operating characteristic (ROC) curve analysis showed that a D-dimer level < 0.5 µg/ml was a good predictor for ruling out AAD, with a sensitivity of 94.0% and a specificity of 56.8%. At a cut-off level of 0.5 µg/ml, the negative and positive likelihood ratios were 0.10 and 2.18, respectively, with a positive predictive value of 42.6% and a negative predictive value of 96.6%.CONCLUSIONS:The D-dimer level within 24 h after symptom onset might be helpful for differentiating AAD from other causes of chest pain.

DNA methylation alternation in Stanford- A acute aortic dissection.

BACKGROUND:Acute aortic dissection (AAD) is a life-threatening cardiovascular disease. Recent studies have shown that DNA methylation may be associated with the pathological mechanism of AAD, but the panorama of DNA methylation needs to be explored.METHODS:DNA methylation patterns were screened using Infinium Human Methylation 450 K BeadChip in the aortic tissues from 4 patients with Stanford-A AAD and 4 controls. Gene enrichment was analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO). DNA methylation levels of candidate genes were determined by pyrosequencing in the replication cohort including 16 patients with AAD and 7 controls. Protein expression level of candidate gene was assessed by Western blot.RESULTS:A total of 589 differentially methylated positions including 315 hypomethylated and 274 hypermethylated positions were found in AAD group. KEGG analysis demonstrated that differentially methylated position-associated genes were enriched in MAPK signaling pathway, TNF signaling pathway and apoptosis pathway, et al. GO analysis demonstrated that differentially methylated position-associated genes were enriched in protein binding, angiogenesis and heart development et al. The differential DNA methylation in five key genes, including Fas, ANGPT2, DUSP6, FARP1 and CARD6, was authenticated in the independent replication cohort. The protein expression level of the Fas was increased by 1.78 times, indicating the possible role of DNA methylation in regulation of gene expression.CONCLUSION:DNA methylation was markedly changed in the aortic tissues of Stanford-A AAD and associated with gene dysregulation, involved in AAD progression.

Genetic variants in Chinese patients with sporadic Stanford type A aortic dissection.

BACKGROUND:Genetic disorders are strongly associated with aortic disease. However, the identities of genetic mutations in sporadic Stanford type A aortic dissection (STAAD) are not clear. The present study analysed the possible genetic mutations of the known pathogenic genes of aortic disease and the clinical characteristics in patients with sporadic STAAD.METHODS:We analysed genetic mutations in 26 genes that underlie aortic aneurysms and dissections in 100 sporadic STAAD patients and 568 healthy controls after whole-genome sequencing (WGS). Clinical features and in-hospital death were determined in all STAAD patients.RESULTS:In total, 60 suspicious pathogenic mutations (56 novel and 4 previously reported) in 19 genes were identified in 50% (50/100) of patients, and 14 patients had more than 1 mutation. The ascending aortic diameter was extended in patients with mutations (49.1±12.3 vs. 43.7±11.2 mm, P=0.023), and the DeBakey type I phenotype was more common in patients with mutations in genes that coded extracellular matrix (ECM) components than in patients with mutations in other genes (96.6% vs. 66.7%, P=0.007). Patients with fibrillin-1 (FBN1) mutations were younger than patients without FBN1 mutations (44.7±11.0 vs. 53.5±12.1, P=0.030). Subgroup analyses revealed an increased risk of in-hospital mortality in mutation carriers (44.4% vs. 10.5%, P=0.029) but only in patients who received conservative treatment.CONCLUSIONS:Half of Chinese patients with a sporadic form of STAAD may carry mutations in known pathogenic genes of aortic disease, and these patients may exhibit distinct clinical features and poor clinical outcomes with the use of conservative treatment.

Angiopoietin 2 as a Novel Potential Biomarker for Acute Aortic Dissection.

Biomarker-assisted diagnosis of acute aortic dissection (AAD) is important for initiation of treatment and improved survival. However, identification of biomarkers for AAD in blood is a challenging task. The present study aims to find the potential AAD biomarkers using a transcriptomic strategy. Arrays based genome-wide gene expression profiling were performed using ascending aortic tissues which were collected from AAD patients and healthy donors. The differentially expressed genes were validated using quantitative reverse transcriptase PCR (qRT-PCR) and western blot. The plasma levels of a potential biomarker, angiopoietin 2 (ANGPT2) were determined in case-control cohort (77 AAD patients and 82 healthy controls) by enzyme linked immunosorbent assay. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic power of ANGPT2 for AAD. Transcriptome data demonstrated that a total of 18 genes were significantly up-regulated and 28 genes were significantly down-regulated among AAD tissues (foldchange>3.0, p < 0.01). By bioinformatic analysis, we identified ANGPT2 as a candidate biomarker for blood-based detection of AAD. The qRT-PCR and protein expression demonstrated that ANGPT2 increased 2.4- and 4.2 folds, respectively in aortic tissue of AAD patients. Immunohistochemical staining demonstrated that ANGPT2 was markedly increased in intima of the aortic wall in AAD. Furthermore, ANGPT2 was significantly elevated in AAD patients as compared with controls (median 1625 vs. 383 pg/ml, p < 1E-6). ROC curve analysis showed that ANGPT2 was highly predictive of a diagnosis of type A AAD (area under curve 0.93, p < 1E-6). Sensitivity and specificity were 81 and 90%, respectively at the cutoff value of 833 pg/ml. In conclusion, ANGPT2 could be a promising biomarker for diagnosis of AAD; however, more studies are still needed to verify its specificity in diagnosing of AAD.

Integrin α9 is involved in the pathopoiesis of acute aortic dissection via mediating phenotype switch of vascular smooth muscle cell.

Acute aortic dissection (AAD) is a devastating disease with high mortality; however, the pathogenic mechanisms of AAD remain poorly understood. Our present study aimed to identify genes associated with AAD and explore the molecular function of candidate genes in the pathogenesis of AAD. We used a whole-genome transcriptional microarray to identify putative AAD genes using ascending aortic tissues from four patients with AAD and four healthy organ donors. The differentially expressed genes were further validated in eight patients with AAD and eight healthy organ donors. Functional assessments were conducted to analyze the effects of the identified AAD genes on the phenotype of aortic vascular smooth muscle cells (VSMCs). The whole-genome transcriptional microarray analysis found 129 dysregulated genes in the ascending aortic tissues of AAD (fold change≥2), which were mainly associated with the focal adhesion pathway and actin cytoskeleton regulation pathway. Among these genes, integrin α9 (ITGA9) was identified to be involved in both pathways and downregulated by 50% in AAD patients. The association of ITGA9 with AAD was confirmed by Western blotting analysis (P = 0.003). Functional studies showed that knocking down ITGA9 in VSMCs resulted in a decrease in contractile markers (SM22α and α-SMA) and an increase in synthetic markers (OPN and SMemb), suggesting that the VSMCs switched from a contractile to a synthetic phenotype. After overexpression of ITGA9 by a recombinant adenovirus vector in VSMCs, SM22α and α-SMA were upregulated, while SMemb was downregulated, indicating a phenotypic switch from the synthetic to contractile phenotype of VSMCs. In conclusion, our study identified ITGA9 as a novel AAD gene. This gene is downregulated in patients with AAD and is involved in the regulation of the phenotypic switch of VSMCs from a contractile to a synthetic phenotype.

Influence of Age on Clinical Presentation, Therapeutic Options, and Outcome in Chinese Patients with Acute Aortic Dissection.

It has been shown in previous studies that Chinese patients with acute aortic dissection (AD) were approximately 10 years younger than patients from western countries. However, there is a lack of studies concerning the age-related differences in clinical characteristics and outcomes in Chinese patients with acute AD. A total of 1,061 patients with AD (570 type A and 491 type B AD) were enrolled between 2006 and 2008. The clinical characteristics were compared between the patients in our study and those in the International Registry of Acute Aortic Dissection (IRAD). Compared with patients in the IRAD, those in our study were relatively younger, comprised more males, and had a higher proportion of Marfan syndrome but received fewer surgical interventions. When stratified by 10-year age, younger patients were more likely to have type A AD, familial AD, and Marfan syndrome, whereas older patients tended to comprise more females and type B AD. As age increased, the proportion of surgical intervention gradually decreased regardless of the type of AD. During a median follow-up of 2.2 years, 147 patients died, of whom 94 (63.9%) had type A AD and 53 (36.1%) had type B AD. Long-term mortality increased with increasing age, especially in patients above 70 years old. Furthermore, the recurrence rate of AD was higher in both the young and the older patients. In conclusion, compared with western patients with AD, Chinese patients have distinct characteristics and more attention should be paid to the young and older patients because of their high long-term mortality and recurrence rate.

Onset seasons and clinical outcomes in patients with Stanford type A acute aortic dissection: an observational retrospective study.

OBJECTIVES:To evaluate the association of onset season with clinical outcome in type A acute aortic dissection (AAD).DESIGN:A single-centre, observational retrospective study.SETTING:The study was conducted in Fuwai Hospital, the National Centre for Cardiovascular Disease, Beijing, China.PARTICIPANTS:From 2008 to 2010, a set of consecutive patients with type A AAD, confirmed by CT scanning, were enrolled and divided into four groups according to onset season: winter (December, January and February), spring (March, April and May), summer (June, July and August) and autumn (September, October and November). The primary end points were in-hospital death and all-cause mortality during follow-up.RESULTS:Of the 492 cases in this study, 129 occurred in winter (26.2%), 147 in spring (29.9%), 92 in summer (18.7%), and 124 in autumn (25.2%). After a median follow-up of 20.4 months (IQR 9.7-38.9), the in-hospital mortality in cases occurring in autumn was higher than in the other three seasons (23.4% vs 8.4%, p<0.01). Long-term mortality was comparable among the four seasonal groups (p=0.63). After adjustment for age, gender and other risk factors, onset in autumn was still an independent factor associated with increased risk of in-hospital mortality (HR 2.05; 95% CI 1.15 to 3.64, p=0.02) in addition to surgical treatment. Further analysis showed that the seasonal effect on in-hospital mortality (autumn vs other seasons: 57.4% vs 27.3%, p<0.01) was only significant in patients who did not receive surgical treatment. No seasonal effect on long-term clinical outcomes was found in this cohort.CONCLUSIONS:Onset in autumn may be a factor that increases the risk of in-hospital death from type A AAD, especially in patients who receive conservative treatment. Immediate surgery improves the short-term and long-term outcomes regardless of onset season.

Reply to 'Body mass index and the risk of all-cause mortality among patients with nonvalvular atrial fibrillation: a multicenter prospective observational study in China; methodological issues'.

Body mass index and the risk of all-cause mortality among patients with nonvalvular atrial fibrillation: a multicenter prospective observational study in China.

BACKGROUND/OBJECTIVES:High body mass index (BMI) is associated with increased incident atrial fibrillation (AF) and mortality rate. In patients presenting with nonvalvular AF (NVAF), the prognostic relevance of BMI remains unclear.SUBJECTS/METHODS:In this prospective observational study, a total of 1759 patients with NVAF (69.9±12.9 years old, 47.9% male) were divided into three clinical settings according to estimated stroke risks (CHADS2 score ⩽1 (low), =2 (moderate) and ⩾3 (high)). The primary outcome was all-cause mortality, and the secondary outcomes included thromboembolism and major bleeding. Cox-proportional hazard models were used to estimate the association between BMI levels and clinical outcomes.RESULTS:During a mean follow-up of 1 year representing 1974 patient-years at risk, 256 patients died, 142 suffered from thromboembolism and 17 developed major bleeding. Multivariate adjusted Cox analysis indicated that a BMI of 24.0-27.9 kg/m2 was independently associated with improved survival among all patients (hazard ratio (HR) 0.689, 95% confidence interval (CI) 0.512-0.928; P=0.018) and patients at high stroke risk (HR 0.622, 95% CI 0.410-0.943; P=0.024), but not among those at low or moderate stroke risks. No associations were observed between BMI levels and the incidence of thromboembolic events in various clinical settings.CONCLUSIONS:A paradoxical BMI-all-cause mortality risk association was observed in Chinese patients with NVAF, and this association was pronounced among patients at high stroke risk rather than in those at low stroke risk.

The effect of admission serum potassium levels on in-hospital and long-term mortality in type A acute aortic dissection.

BACKGROUND:Mild fluctuations in serum potassium (K+) levels are related to the prognosis of cardiovascular disease. This study aimed to determine the effect of admission serum potassium levels on in-hospital and long-term mortality in patients with Stanford type A acute aortic dissection (AAD).MATERIALS AND METHODS:A total of 588 consecutive patients with type A AAD were enrolled, and they were grouped according to admission serum potassium level: <3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, and ≥5.0mmol/L. Clinical outcomes were in-hospital death and long-term all-cause mortality.RESULTS:The in-hospital and long-term all-cause mortality rates were 10.7% and 16.3%, respectively. A U-shaped relationship was observed between admission serum potassium levels and both in-hospital death and long-term mortality. Univariate Cox regression identified potassium levels outside the interval of <3.5 to 4.5mmol/L to be a risk factor for both in-hospital and long-term death. After adjusting for age, gender, surgery and other risk factors, potassium levels outside the interval of <3.5 to 4.5mmol/L still had a significant association with long-term death [hazard ratio (HR)=1.72, 95% confidence interval (95% CI): 1.07-2.74, P=0.024]. Surgical intervention was the main protective factor associated with both in-hospital (HR=0.01, 95% CI 0.01-0.06, P<0.001) and long-term survival (HR=0.06, 95% CI 0.03-0.12, P<0.001).CONCLUSIONS:Among patients with Stanford type A AAD, admission serum potassium levels other than 3.5 to 4.5mmol/L might be associated with an increased risk of in-hospital death and long-term mortality.

Admission D-dimer testing for differentiating acute aortic dissection from other causes of acute chest pain.

INTRODUCTION:The present study aims to evaluate the utility of D-dimer testing for differentiating the causes of acute chest pain, including acute aortic dissection (AAD), pulmonary embolism (PE), acute myocardial infarction (AMI), unstable angina (UA), and other uncertain diagnoses of chest pain.MATERIAL AND METHODS:Consecutive patients admitted for acute chest pain within 24 h from symptom onset were enrolled prospectively, and plasma D-dimer levels were measured on admission. Diagnoses of AAD, PE, AMI, and UA were confirmed by standard methods.RESULTS:A total of 790 patients were enrolled, including 202 AAD, 43 PE, 315 AMI, 136 UA, and 94 cases of other uncertain diagnoses. D-dimer levels were significantly higher in patients with AAD and PE than in those with AMI, UA, and other uncertain diagnoses (p < 0.001), but they were comparable between patients with AAD and PE (p = 0.065). Moreover, patients with type A AAD had higher D-dimer levels than those with type B AAD (p = 0.022). Receiver operating characteristic (ROC) curve analysis showed that a D-dimer level < 0.5 µg/ml was a good predictor for ruling out AAD, with a sensitivity of 94.0% and a specificity of 56.8%. At a cut-off level of 0.5 µg/ml, the negative and positive likelihood ratios were 0.10 and 2.18, respectively, with a positive predictive value of 42.6% and a negative predictive value of 96.6%.CONCLUSIONS:The D-dimer level within 24 h after symptom onset might be helpful for differentiating AAD from other causes of chest pain.