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Rationale: The progressive disruption of extracellular matrix (ECM) proteins, particularly early elastin fragmentation followed by abnormalities in collagen fibril organization, are key pathological processes that contribute to dissecting abdominal aortic aneurysm (AAA) pathogenesis. Lysyl hydroxylase 1 (LH1) is essential for type I/III collagen intermolecular crosslinking and stabilization. However, its function in dissecting AAA has not been explored. Here, we investigated whether LH1 is significantly implicated in dissecting AAA progression and therapeutic intervention. Methods and Results: Sixteen-week-old male LH1-deficient and wild-type (WT) mice on the C57Bl/6NCrl background were infused with angiotensin II (Ang II, 1000 ng/kg per minute) via subcutaneously implanted osmotic pumps for 4 weeks. Ang II increased LH1 levels in the abdominal aortas of WT mice, whereas mice lacking LH1 developed dissecting AAA. To evaluate the related mechanism, we performed whole-transcriptomic analysis, which demonstrated that LH1 deficiency aggravated gene transcription alterations; in particular, the expression of thrombospondin-1 was markedly upregulated in the aortas of LH1-deficient mice. Furthermore, targeting thrombospondin-1 with TAX2 strongly inhibited the proinflammatory process, matrix metalloproteinase (MMP) activity and vascular smooth muscle cells (VSMCs) apoptosis, ultimately decreasing the incidence of dissecting AAA. Restoration of LH1 protein expression in LH1-deficient mice by intraperitoneal injection of an adeno-associated virus normalized thrombospondin-1 levels, subsequently alleviating dissecting AAA formation and preserving aortic structure and function. Consistently, in human AAA specimens, decreased LH1 expression was associated with increased thrombospondin-1 levels. Conclusions: LH1 deficiency contributes to dissecting AAA pathogenesis, at least in part, by upregulating thrombospondin-1 expression, which subsequently enables proinflammatory processes, MMP activation and VSMCs apoptosis. Our study provides evidence that LH1 is a potential critical therapeutic target for AAA.

Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs., Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Here the authors report altered gut microbiota including low abundance of Hungatella hathewayi in patients with UIAs, and show that supplementation with Hungatella hathewayi or the metabolite taurine prevents UIAs in mice.

Intracerebral hemorrhage (ICH) is a catastrophic stroke with high mortality, and the mechanism underlying ICH is largely unknown. Previous studies have shown that high serum uric acid (SUA) levels are an independent risk factor for hypertension, cardiovascular disease (CVD), and ischemic stroke. However, our metabolomics data showed that SUA levels were lower in recurrent intracerebral hemorrhage (R-ICH) patients than in ICH patients, indicating that lower SUA might contribute to ICH. In this study, we confirmed the association between low SUA levels and the risk for recurrence of ICH and for cardiac-cerebral vascular mortality in hypertensive patients. To determine the mechanism by which low SUA effects ICH pathogenesis, we developed the first low SUA mouse model and conducted transcriptome profiling of the cerebrovasculature of ICH mice. When combining these assessments with pathological morphology, we found that low SUA levels led to ICH in mice with angiotensin II (Ang II)-induced hypertension and aggravated the pathological progression of ICH. In vitro, our results showed that p-Erk1/2-MMP axis were involved in the low UA-induce degradation of elastin, and that physiological concentrations of UA and p-Erk1/2-specific inhibitor exerted a protective role. This is the first report describing to the disruption of the smooth muscle cell (SMC)-elastin contractile units in ICH. Most importantly, we revealed that the upregulation of the p-Erk1/2-MMP axis, which promotes the degradation of elastin, plays a vital role in mediating low SUA levels to exacerbate cerebrovascular rupture during the ICH process.

Background: We used a targeted metabolomics approach to identify fatty acid (FA) metabolites that distinguished patients with coronary artery ectasia (CAE) from healthy Controls and patients with coronary artery disease (CAD).Materials and methods: Two hundred fifty-two human subjects were enrolled in our study, such as patients with CAE, patients with CAD, and Controls. All the subjects were diagnosed by coronary angiography. Plasma metabolomic profiles of FAs were determined by an ultra-high-performance liquid chromatography coupled to triple quadrupole mass spectrometric (UPLC-QqQ-MS/MS).Results: Ninety-nine plasma metabolites were profiled in the discovery sets (n = 72), such as 35 metabolites of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), 10 FAs, and 54 phospholipids. Among these metabolites, 36 metabolites of AA, EPA, and DHA showed the largest difference between CAE and Controls or CAD. 12-hydroxyeicosatetraenoic acid (12-HETE), 17(S)-hydroxydocosahexaenoic acid (17-HDoHE), EPA, AA, and 5-HETE were defined as a biomarker panel in peripheral blood to distinguish CAE from CAD and Controls in a discovery set (n = 72) and a validation set (n = 180). This biomarker panel had a better diagnostic performance than metabolite alone in differentiating CAE from Controls and CAD. The areas under the ROC curve of the biomarker panel were 0.991 and 0.836 for CAE versus Controls and 1.00 and 0.904 for CAE versus CAD in the discovery and validation sets, respectively.Conclusions: Our findings revealed that the metabolic profiles of FAs in the plasma from patients with CAE can be distinguished from those of Controls and CAD. Differences in FAs metabolites may help to interpret pathological mechanisms of CAE.

We present a novel stacked autoencoder framework for feature extraction to improve classification of hyperspectral image, leveraging graph regularization to address the shortcomings of classical autoencoder that mainly focuses on learning spectral features. In the proposed method, we firstly construct a graph to represent the spectral-spatial similarity between pixels in a hyperspectral image by measuring their spatial and spectral distances. And then the graph regularized autoencoder is learned to transform the original spectral signatures of pixels into a new feature space used for the downstream pixel classification or other tasks. Our feature extraction method can preserve the intrinsic spectral-spatial distribution in a hyperspectral image and obtain more discriminative and robust features. The experiments on pixel classification show the competitive performance compared with classical autoencoder based and manifold learning based feature extraction approaches.

Objectives Lacunar stroke had an unfavorable prognosis in the long term with a high risk of recurrent stroke, aspirin has been widely used to prevent ischemic stroke, but data on the effect of antiplatelet therapy on lacunar infarction are limited. We investigated the long-term effect of aspirin treatment on stroke recurrence risk in patients with lacunar stroke in a multicenter prospective cohort. Methods Between November 2000 and November 2001, 2000 consecutive stroke patients (age 35-74 years) were recruited from seven clinical centers. For the present study, a total of 544 patients with lacunar infarction were finally included in the analysis. The patients were divided into two groups (aspirin group, n = 342 and non-aspirin group, n = 202).The effect of aspirin on stroke recurrence was evaluated by using Kaplan-Meier analysis and Cox regression models. Results During a median 4.1-year follow-up for 544 patients with lacunar stroke, 99 recurrent strokes, 125 major vascular events (stroke, myocardial infarction, and vascular death), 31 vascular deaths, and 59 all-cause deaths were identified. Kaplan-Meier analysis showed that aspirin non-users had a higher risk of future recurrent stroke and of vascular events than did aspirin users (log-rank test, P = 0.049, 0.047, respectively). Aspirin significantly reduced the stroke recurrence in patients with lacunar stroke analyzed with multivariate stepwise analysis using model of Cox proportional hazards with backward elimination (HR = 0.67, 95% CI 0.45-0.99). Conclusion We concluded that aspirin significantly reduced stroke recurrence in patients with lacunar stroke.

Background: Fast resting heart rate (RHR) is easily neglected in clinical practice of hypertension treatment.Aims: We aimed to investigate the prevalence of fast RHR and associated factors in hyper...

BACKGROUND AND PURPOSE This study aimed to test the hypothesis that long noncoding RNA (lncRNA) AL110200 exerts a proinflammatory effect on atherosclerosis and that the variant rs901681 contributes to ischaemic stroke incidence and recurrence. METHODS The expression of AL110200 was analyzed in THP-1 cells treated with oxidized low-density lipoprotein and in human peripheral blood in a coronary heart disease and control population to determine the role of AL110200 in atherosclerosis. The effect of AL110200 on cell adhesion and invasion was tested. The plasma level of leukotriene B4 and rs901681 genotype distribution were assessed in 220 participants. In 1004 ischaemic stroke patients and 1434 controls, the association between rs901681 and stroke incidence was analyzed by logistic regression, and the association of rs901681 and stroke prognosis was analyzed using Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS Increased expression of AL110200 was observed in THP-1 cells under oxidized low-density lipoprotein treatment. Knockdown of AL110200 reduced the adhesive and invasive ability of THP-1 cells. AL110200 expression in peripheral blood was significantly higher in the coronary heart disease group than in the controls. The GG genotype of rs901681 is associated with reduced plasma leukotriene B4. In the ischaemic stroke population, rs901681 was not associated with ischaemic stroke incidence (p = 0.686). Patients carrying rs901681 GG had a lower risk for stroke recurrence at age ≥60 years (p = 0.001), cardiovascular stroke death (p = 0.022) and all-cause mortality (p = 0.034) in the all-age group. CONCLUSIONS AL110200 might exert a proinflammatory effect on atherosclerosis, and the variant rs901681 might be a strong predictor of stroke prognosis in ischaemic stroke patients.

Background: Circular RNAs (circRNAs) have shown promise as biomarkers because of their stability in peripheral blood, and they participate in various pathological processes of ischemic stroke; however, their expression profiles and the potential functions for intracerebral hemorrhage (ICH) stroke remain unclear. Methods: RNA sequencing was used to investigate the expression profiles of circRNA in a discovery sample of 129 subjects (44 patients with ICH, 42 hypertension (HTN) controls, and 43 patients with cerebral infarction (CI)), and an independent validation sample of 54 subjects (20 patients with ICH, 18 HTN controls, and 16 patients with CI). Quantitative real-time polymerase chain reaction was used to validate the circRNA expression levels. Logistic regression models were conducted to assess circRNAs as potential biomarkers for ICH. Bioinformatics analysis was performed to identify potential functions of circRNAs.Results: We found that 15 circRNAs including 5 upregulated circRNAs and 10 downregulated circRNAs were consistently altered only after ICH (fold change >1.5 and FDR < 0.05). We validated that hsa_circ_0001240 and hsa_circ_0001947 were upregulated and that hsa_circ_0001386 was downregulated in ICH compared with HTN and CI. The combination of 3 circRNAs showed an area under the curve of 0.92 with a sensitivity of 86% and a specificity of 88% for diagnosing ICH. Together with ICH risk factors, the circRNAs showed an area under the curve of 0.97 in diagnosing ICH. Functional analysis revealed circRNA target miRNA and mRNA are mainly involved in fatty acid biogenesis, lysine degradation, integrin cell surface interactions and the immune system.Conclusion: This is the first report to study the expression profile of circRNAs in peripheral blood after ICH, and a set of 3 circRNAs could serve as potential biomarkers for predicting and diagnosing ICH.

Plasma metabolic profiles were compared between patients with hypertension with and without left ventricular hypertrophy and significantly decreased oleic acid (OA) levels were observed in the peripheral blood of patients with hypertension with left ventricular hypertrophy. We sought to determine the effect and underlying mechanisms of OA on cardiac remodeling. In vitro studies with isolated neonatal mouse cardiomyocytes and cardiac fibroblasts revealed that OA significantly attenuated Ang II (angiotensin II)-induced cardiomyocyte growth and cardiac fibroblast collagen expression. In vivo, cardiac function, hypertrophic growth of cardiomyocytes, and fibrosis were analyzed after an Ang II (1000 ng/kg/minute) pump was implanted for 14 days. We found that OA could significantly prevent Ang II-induced cardiac remodeling in mice. RNA sequencing served as a gene expression roadmap highlighting gene expression changes in the hearts of Ang II-induced mice and OA-treated mice. The results revealed that FGF23 (fibroblast growth factor 23) expression was significantly upregulated in mouse hearts in response to Ang II infusion, which was significantly suppressed in the hearts of OA-treated mice. Furthermore, overexpression of FGF23 in the heart by injection of an AAV-9 vector aggravated Ang II-induced cardiac remodeling and impaired the protective effect of OA on cardiac remodeling. Further study found that OA could suppress Ang II-induced FGF23 expression by inhibiting the translocation of Nurr1 (nuclear receptor–related 1 protein) from the cytoplasm to the nucleus. Our findings suggest a novel role of OA in preventing Ang II-induced cardiac remodeling via suppression of FGF23 expression.

The study aimed to investigate the relationship between mtDNA copy number and the risk of all-cause mortality in stroke. One thousand four hundred eighty-four stroke patients were documented including 273 deaths (127 thrombosis, 52 lacunar, 94 hemorrhage). Patients in the third quartile had the lowest mortality rates in overall stroke and the three subtypes. The lowest quartile of mtDNA copy number (Q1 85.85) indicated an increased risk of all-cause mortality in stroke patients (adjusted HR, 1.52; 95% CI, 1.08-2.14; p = 0.017). In the subtype analysis, the risk of all-cause mortality appeared only in lacunar infarct, and the patients in the Q1 ( 87.76) and Q4 ( 150.61) mtDNA copy number groups showed significantly higher risks of HRs (Q1, adjusted HR, 3.87, 95% CI, 1.52-9.83; Q4, adjusted HR, 3.08, 95% CI, 1.16-8.18). Stroke patients with lacunar infarct in mtDNA copy number 87.76 or 150.61 were at a high risk of poor outcomes in all-cause mortality.

Deep learning has been widely used for hyperspectral pixel classification due to its ability of generating deep feature representation. However, how to construct an efficient and powerful network suitable for hyperspectral data is still under exploration. In this paper, a novel neural network model is designed for taking full advantage of the spectral-spatial structure of hyperspectral data. Firstly, we extract pixel-based intrinsic features from rich yet redundant spectral bands by a subnetwork with supervised pre-training scheme. Secondly, in order to utilize the local spatial correlation among pixels, we share the previous subnetwork as a spectral feature extractor for each pixel in a patch of image, after which the spectral features of all pixels in a patch are combined and feeded into the subsequent classification subnetwork. Finally, the whole network is further fine-tuned to improve its classification performance. Specially, the spectral-spatial factorization scheme is applied in our model architecture, making the network size and the number of parameters great less than the existing spectral-spatial deep networks for hyperspectral image classification. Experiments on the hyperspectral data sets show that, compared with some state-of-art deep learning methods, our method achieves better classification results while having smaller network size and less parameters., Comment: 12 pages, 10 figures

Hypertensive intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease with no effective treatment. Lysyl hydroxylase 3 (LH3) is essential for collagen IV intermolecular crosslinking and stabilization. Deficiency in LH3 affects the assembly and secretion of collagen IV and basement membrane (BM) integrity of vessels. Here, we investigated whether LH3 has significant implications for disease progression and therapeutic intervention. Spontaneous hypertensive ICH of mice was induced by angiotensin II and L-NAME treatment. The adeno-associated virus was delivered into brain by stereotactic injection to knockdown or overexpress LH3. We found LH3 levels were reduced in human patients with ICH and gradually decreased in mice before ICH. LH3 knockdown increased the incidence of hypertensive ICH in mice. The incidence, number, and size of ICHs in mice were markedly reduced by LH3 overexpression. RNA-seq revealed that LH3 overexpression significantly reversed the profound alterations in gene transcriptional profiles of cerebral vessels. LH3 overexpression was sufficient to enhance BM integrity, inhibit matrix metalloproteinase activity, attenuate microglial activation and leukocyte infiltration, and reduce VSMC apoptosis before ICH. These results indicate that LH3 overexpression attenuates susceptibility to hypertensive ICH. We emphasize that LH3 modulation may serve as a viable approach for future investigations of ICH prevention.

Coronary atherosclerosis is one of the major factors causing cardiovascular diseases. However, identifying the tipping point (predisease state of disease) and detecting early-warning signals of human coronary atherosclerosis for individual patients are still great challenges. The landscape dynamic network biomarkers (l-DNB) methodology is based on the theory of dynamic network biomarkers (DNBs), and can use only one-sample omics data to identify the tipping point of complex diseases, such as coronary atherosclerosis. Based on the l-DNB methodology, by using the metabolomics data of plasma of patients with coronary atherosclerosis at different stages, we accurately detected the early-warning signals of each patient. Moreover, we also discovered a group of dynamic network biomarkers (DNBs) which play key roles in driving the progression of the disease. Our study provides a new insight into the individualized early diagnosis of coronary atherosclerosis and may contribute to the development of personalized medicine.

Aims To explore whether the combination of atorvastatins and resveratrol is superior to each individual drug alone regarding re-endothelialization after drug-eluting stents (DESs) implantation. Materials and methods Ninety-four rabbits were randomized into control, atorvastatin, resveratrol, and combined medication groups. Abdominal aorta injury was induced via ballooning, followed by DES implantation. Neointimal formation and re-endothelialization after stent implantation were assessed via optical coherence tomography and scanning electron microscopy. The effects of resveratrol and atorvastatin on bone marrow-derived mesenchymal derived stem cells (BMSCs) were assessed. Key findings Compared with the findings in the resveratrol and atorvastatin groups, the neointimal area and mean neointimal thickness were greater in the combined medication group, which also exhibited improved re-endothelialization. Compared with the effects of monotherapy, combined treatment further protected BMSCs against rapamycin-induced apoptosis and improved cell migration. Combined medication significantly upregulated Akt, p-Akt, eNOS, p-eNOS, and CXCR4 expression in BMSCs compared with the effects of monotherapy, and these effects were abolished by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Significance The combination of atorvastatin and resveratrol has the potential of accelerating re-endothelialization after stent implantation, reducing the risk of thrombosis and improving the safety of DESs.

High-dimensional spectral feature and limited training samples have caused a range of difficulties for hyperspectral image (HSI) classification. Feature extraction is effective to tackle this problem. Specifically, tensor factorization is superior to some prominent methods such as principle component analysis (PCA) and non-negative matrix factorization (NMF) because it takes spatial information into consideration. Recently, deep learning has gotten more and more attention for efficiently extracting hierarchical features for various tasks. In this paper, we propose a novel feature extraction method, deep tensor factorization (DTF), to extract hierarchical and meaningful features from observed HSI. This method takes advantage of tensor in representing HSI and the merits of convolutional neural network (CNN) in hierarchical feature extraction. Specifically, a convolution operation is firstly applied in the spectral dimension of HSI to suppress the effect of noise. Then, the convolved HSI is fed into tensor factorization to learn a low rank representation of data. After that, the above two process are repeated to learn a hierarchical representation of HSI. Experimental results on two real hyperspectral data sets show the superiority of the proposed method.

Hyperspectral unmixing aims at decomposing a hyperspectral image (HSI) into a number of constituted materials and associated proportions. Recently, nonnegative tensor factorization (NTF) based methods have been proved effective and natural for hyperspectral unmixing owing to their virtue of representing an HSI without any information loss. However, these methods take an HSI as a whole, partly ignoring the local information in distinct local regions. In addition, HSIs are high likely to be disturbed by various noise, making the global information unnecessarily reliable. To alleviate these drawbacks, we propose a superpixel-based matrix-vector nonnegative tensor factorization (S-MV-NTF) method for hyperspectral unmixing, where both the global information and local information are taken into consideration. In this method, the HSI is firstly partitioned into numerous superpixels, homogeneous regions with adaptive sizes and compact boundaries, representing the local spatial structure information. Then, such local information is integrated to the tensor factorization to make the pixels lying in the same superpixel share similar abundances. Experimental results on synthetic data and real-world data show that the proposed method dominates the state-of-the-art methods.

Coronary heart disease (CHD) is associated with complex metabolic disorders, but its molecular aetiology remains unclear. Using a novel nontargeted metabolomics approach, we explored the global metabolic perturbation profile for CHD. Blood samples from 150 patients with severe obstructive CHD and 150 angiographically normal controls were collected. Metabolic fingerprinting was performed by ultra-high performance liquid chromatography coupled to quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS) technique. After adjusting for CHD traditional risk factors and metabolic batch, a comprehensive list of 105 metabolites was found to be significantly altered in CHD patients. Among the metabolites identified, six metabolites were discovered to have the strongest correlation with CHD after adjusting for multiple testing: palmitic acid (β = 0.205; p

This paper presents a fluid-thermal coupled analysis method to compute the temperature distribution in a 31.5 MVA/110 kV oil natural air natural (ONAN) three-phase three-limb transformer. The power losses of windings and core are measured by load-loss test and no-load test respectively. The convective heat transfer process, radiation and oil flow inside the transformer are investigated by finite volume method (FVM). In order to validate the feasibility and accuracy of the presented method, the temperature measuring system based on fiber Brag grating (FBG) sensor is constructed for the temperature rise test of the 31.5 MVA/110 kV ONAN transformer. The simulation results deduced from the proposed method agree well with experimental data. This model can be applied to optimizing design and load scheduling.

This paper takes a typical 220 kV three-phase three-limb oil-immersed transformer as an example, this paper building transient field-circuit coupled model and 3D coupled magneto -fluid-thermal model. Considering a nonlinear B–H curve, the magneto model uses the field-circuit coupled finite element method (FEM) to calculate the magnetic flux distribution of the core and the current distribution of the windings when the transformer is at a rated current and under direct current (DC) bias. Taking the electric power losses of the core and windings as a heat source, the temperature inside the transformer and the velocity of the transformer oil are analyzed by the finite volume method (FVM) in a fluid-thermal field. In order to improve the accuracy of the calculation results, the influence of temperature on the electrical resistivity of the windings and the physical parameter of the transformer oil are taken into account in the paper. Meanwhile, the convective heat transfer coefficient of the FVM model boundary is determined by its temperature. By iterative computations, the model is updated according to the thermal field calculation result until the maximum difference in hot spot temperature between the two adjacent steps is less than 0.01 K. The result calculated by the coupling method agrees well with the empirical equation result according to IEC 60076-7.

Intracranial aneurysms (IAs) are acquired lesions in the brain and can pose potential risk of rupture leading to subarachnoid hemorrhage. Endoglin plays a pivotal role in the vascular development and disease. Variations of endoglin gene have been shown to be risk factors for IAs in different racial population. In the present study, we investigated the correlation between polymorphism in the endoglin gene with IAs in Chinese Han population. The association of endoglin D366H variant (rs1800956) with sporadic IAs was tested in 313 patients with intracranial aneurysms, and 450 controls. The difference in allelic frequency between patients and control group was evaluated with the chi-square test. The frequency of the GG+CG genotype of rs1800956 was significantly higher in patients with IAs than in controls [22.0% vs 15.3%, P = .018; crude OR(odds ratio), 1.56; 95% CI(confidence interval), 1.08-2.26]. Multivariate analysis showed that rs1800956G conferred a risk to IAs [adjusted OR, 1.56 [95% CI, 1.08-2.26]; P=.019], independent of conventional factors, including age, sex, blood pressure, smoking, and alcohol consumption. The variant rs1800956 of endoglin might raise the risk of sporadic IAs among individuals of Chinese Han ethnicity.

To explore the association between the dopamine β-hydroxylase (DBH) gene C-1021T polymorphism and the occurrence of orthostatic hypotension (OH) in Chinese patients, the DBH C-1021T polymorphism was genotyped in 317 patients with OH and 664 age- and sex-matched controls with orthostatic normotension. All subjects underwent an upright posture study for the measurement of orthostatic blood pressure. OH was defined as a drop in blood pressure of 20/10 mm Hg or more within 3 min of assuming the upright posture. The allele frequency of the DBH C-1021T polymorphism in the orthostatic hypotensive group was similar to the orthostatic normotensive group (17.4 versus 14.9%, P>0.05). No statistical significant association was found between the distribution of the C-1021T genotypes and the risk of OH in both the orthostatic hypotensive and orthostatic normotensive groups even after adjustment for demographic parameters. Among the three different genotypes, blood pressure levels did not significantly differ in the general population in this study. The changes in orthostatic systolic or diastolic blood pressures among the different genotype groups were not detected (all P>0.05). The C-1021T polymorphism of the DBH was not associated with orthostatic hypotensive risk in a Chinese population.

Object Variants of Kallikreins have been shown to be risk factors for intracranial aneurysm (IA) in a Finnish population. In the present study, the authors investigated the correlation between polymorphisms in the Kallikrein gene cluster and IAs in the Chinese population. Methods The association of Kallikrein variants (rs1722561 and rs1701946) with sporadic IAs was tested in 308 cases and 443 controls. The differences in allelic frequencies between patients and the control group were evaluated with the chi-square test. Results The C allele of rs1722561 showed a significant reduction in the risk of sporadic IA (OR 0.71, 95% CI 0.53–0.95; p = 0.023). However, no association of the variant rs1701946 with sporadic IA was found (OR 0.78, 95% CI 0.57–1.06; p = 0.115). Conclusions The variant rs1722561 of Kallikreins might reduce the risk of sporadic IAs among individuals of Chinese Han ethnicity. This study confirms the association between Kallikreins and IAs.

The genetic susceptibility to orthostatic blood pressure dysregulation remains poorly understood. The association between polymorphisms of beta‐adrenergic receptor (β‐AR) genes and orthostatic blood pressure dysregulation in hypertensive patients was investigated. Two polymorphisms of β(1)‐AR (Arg389/Gly) and β(2)‐AR (Arg16/Gly) were genotyped in untreated hypertensive patients and normotensive patients. In patients with untreated hypertension, the frequency of β(1)‐AR Gly389 homozygote was significantly higher in patients with orthostatic hypotension (OH) (P

Supplemental Digital Content is available in the text, Growth differentiation factor 15 (GDF-15) is a relatively new biomarker that predicts adverse stroke outcomes. However, the association of GDF-15 with first-ever stroke in hypertensive patients has not yet been evaluated. The objective of this study was to evaluate the clinical implications of plasma GDF-15 on the development of first-ever stroke in patients with hypertension. In total, 254 patients with hypertension without a history of stroke were included from March 2010 to August 2010 and followed up until June 2013. The baseline circulating GDF-15 was determined by enzyme-linked immunosorbent assays. During a follow-up of 3.0 ± 0.6 years, 22 (8.7%) first-ever strokes were identified, including 12 ischemic strokes and 10 intracerebral hemorrhages (ICH). According to tertiles of GDF-15, survival free of first-ever stroke was lower in the highest tertile of GDF-15 (log-rank P = 0.001). By backward stepwise Cox-regression analysis, adjusted for age, gender, diabetes mellitus, hyperlipidemia, hypertension stage, body mass index, cigarette smoking, anti-hypertensive drugs, and uric acid, every 100 pg/mL-increase in plasma of GDF-15 predicted an 11% greater risk of first-ever stroke (hazard ratios [HR]: 1.11, 95% confidence interval [CI]: 1.03–1.20, P = 0.010) and an 18% increase in ischemic stroke risk (HR: 1.18, 95% CI: 1.07–1.30, P = 0.001). Receiver operating characteristic analysis indicated that GDF-15 had reasonable accuracy to predict first-ever stroke (area under curve = 0.73, 95% CI: 0.62–0.83, P

We conducted a case-control study investigating the association between the single-nucleotide polymorphism rs2910164 in microRNA (miR)-146a and the risk and prognosis of stroke. We recruited a total of 1139 ischemic stroke patients and 1585 sex- and age-matched control subjects. After a median follow-up period of 4.5 years, 1071 of these ischemic stroke patients were then recruited for a prospective study. Our study revealed that rs2910164 was not associated with ischemic stroke incidence (odds ratio = 1.00; 95% confidence interval (CI) = 0.80–1.24; p = 0.985) by multivariate logistic regression. Meta-analysis of our case-control study and three others on Asian populations also suggested that there was no relationship between rs2910164 and ischemic stroke incidence. The significance of differences in long-term outcomes was examined by the log-rank test of the respective comparison groups. The prospective study showed that rs2910164 led to a 1.56-fold increased risk of stroke recurrence (hazard ratio (HR) = 1.56; 95% CI = 1.10–2.20; p = 0.013) and a 2.13-fold increased risk of death caused by cardiovascular disease or stroke (Csdeath) (HR = 2.13; 95% CI = 1.31–3.46; p = 0.002). The independent association of rs2910164 with stroke prognosis was evaluated using Cox regression models. Therefore, rs2910164 appears to be a strong predictor of stroke prognosis but not of stroke incidence in Asian populations.

Background: The association of metabolic syndrome (MS) with left ventricular (LV) hypertrophy is controversial. The objective of our study was to investigate the infl uence of MS on LV mass and geometry in community-based hypertensive patients among Han Chinese.Materials and Methods: This study included 1733 metabolic syndrome patients according to the International Diabetes Federation (IDF) defi nition and 2373 non-MS hypertension patients. LV hypertrophy was diagnosed by the criteria of LV mass ?49.2 g/m2.7 for men and 46.7 g/m2.7 for women. LV geometric patterns (normal, concentric remodeling, concentric or eccentric hypertrophy) were calculated according to LV hypertrophy and relative wall thickness. Logistic regression analysis was used to determine odds ratio (OR) and 95% confidence interval (CI) of MS for LV hypertrophy and LV geometry abnormality. Results: The LV mass and LV mass index were higher in the MS group than in the non-MS group. In multiple adjusted models. LV mass index, LV mass, interventricular septum, and post wall were raised with the increased number of MS disorders. MS was associated with increased LV hypertrophy risk (unadjusted OR 1.38; 95% CI 1.21-1.57); age, sex, and blood pressure (BP; adjusted OR 1.39; 95% CI 1.22-1.59). MS was also associated with increased risk of eccentric hypertrophy in male and female patients. MS was only associated with increased risk of concentric hypertrophy in female patients; and MS was not associated with concentric remodeling. Conclusion: LV mass and LV mass index were associated with the increased number of MS disorders in the Chinese community-based hypertensive population.MS was not only associated with increased LV hypertrophy risk, but also associated with concentric and eccentric LV geometry abnormality, especially in females. Key words: Hypertension, left ventricular (LV) geometry abnormality, LV hypertrophy, metabolic syndrome (MS)

OBJECTIVE The calmodulin-binding transcription activator 2 (CAMTA2) promotes transcription of genes involved in cardiac hypertrophy through its interaction with Nkx2.5 and is an indispensable transcription coactivator for cardiac hypertrophy. We hypothesized that variants in the coding region of CAMTA2 would affect its function and confer a risk of cardiac hypertrophy. METHODS The effects of the variant rs238234 on the activity of the atrial natriuretic factor promoter and on the cardiomyocytes hypertrophy were assessed in the H9C2 cell line and primary neonatal rat cardiomyocytes, respectively. Furthermore, the association of this variant with left ventricular hypertrophy (LVH) was tested in hypertensive patients with and without hypertrophy (N = 325 and 697), and this analysis was replicated in an independent population of 987 hypertensive patients without hypertrophy and 463 hypertensive patients with hypertrophy. RESULTS We found that the G allele of rs238234 activated the atrial natriuretic factor promoter more strongly than the C allele. The cell size of cardiomyocytes was larger in the presence of the Ad-CAMTA2 G allele, and the G allele was associated with significantly increased susceptibility to LVH in hypertensive [odds ratio (OR), 1.29; P = 0.009]. In the discovery cohort, after adjusting for age and sex, the GG genotype was significantly associated with increased LVH risk (OR, 1.75; P = 0.015). There was little attenuation of the ORs (1.62; P

Aims Clinical and animal studies suggest that beta1-adrenergic and M2 muscarinic receptor autoantibodies (beta1-AAbs and M2-AAbs) play important roles in the pathophysiological process of chronic heart failure (CHF). Removal of these autoantibodies improved haemodynamic parameters and left ventricular ejection fraction patients with CHF. The goal of this project is to evaluate whether beta1-AAbs and M2-AAbs predict prognosis and sudden cardiac death (SCD) in CHF. Methods and results A total of 2062 patients with CHF and 824 control subjects were recruited. Beta1-AAbs and M2-AAbs were detected by the enzyme-linked immunosorbent assay (ELISA) method, and the correlation between these autoantibodies and the prognosis of CHF was analysed. During a median follow-up period of 36 months (0.40 ± 65 months), 379 (21.56%) cases died—164 had dilated cardiomyopathy (DCM) and 215 had ischaemic cardiomyopathy (ICM). Of these, SCD occurred in 69 cases (40.37%) of DCM and in 84 cases (39.07%) of ICM. Positivity for beta1-AAbs in DCM and ICM was significantly higher than for the controls (8.1% and 8.25% v.s 2.2%, both P < 0.01). However, positive M2-AAbs did not show any statistical difference between the three groups. Cox regression analysis revealed that positive beta1-AAbs were associated with higher mortality in CHF and that it predicted SCD for DCM [hazard ratio (HR) 4.51, 95% confidence interval (CI) 2.405–8.471] and ICM (HR 3.749, 95% CI 2.389–5.884) patients, but not non-SCD (NSCD) patients. Conclusions The rates of positive beta1-AAbs were higher in CHF patients than in the controls. Positive beta1-AAbs might serve as an independent predictor for SCD in patients with CHF.

The IC53 gene was reported to be upregulated in the colon adenocarcinoma cell line SW480. Here, we show that the expression level of IC53 is positively correlated with the grade and depth of invasion in adenocarcinoma of the colon. Injection of IC53 stably transfected HCT-116 cells into athymic nude mice promoted tumor growth. Furthermore, overexpression of IC53 increased cell invasive growth, which could be dramatically prevented by knocking down IC53 with siRNA. The effects of IC53 on cell-invasive growth were mediated by upregulation of integrins, activation of phosphatidylinositol 3-kinase and phosphorylation of Akt. A single-nucleotide polymorphism rs2737 in the IC53 gene created a potential microRNA379 target site, and microRNA379 expression inhibited IC53 translation. Among 222 patients with colorectal cancer, the C/C rs2737 genotype was associated with late onset of colorectal cancer (median age 63.0 versus 55.3 years, P = 0.003). The frequency of the C/C rs2737 genotype was much lower in patients who developed colorectal cancer below the age of 45 years than in individuals over age 45 years (10.8% versus 26.6%, P = 0.039). These data indicated that IC53 is a positive mediator for colon cancer progression, and IC53-rs2737 may serve as protection from the onset of colorectal cancer.

Objective: Previous case-control studies have suggested that the variations of the oxidized-lipoprotein receptor 1 (OLR1) gene (G501C, 3′-UTR-C188T) are associated with coronary artery disease (CAD). However, other studies have not confirmed this relationship. The objective of this study was to assess the relationship between OLR1 variations and CAD. Methods: We conducted a meta-analysis. Databases, including PubMed, EMbase, Chinese Biological Medical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI), were searched to obtain genetic association studies. Data were extracted by two authors, and pooled odds ratios (OR) with 95% CI were calculated. Results: The meta-analysis included 8 studies with 4,963 cases and 14,864 controls for 3′-UTR-C188T and 9 studies with 5,660 cases and 15,405 controls for G501C. The pooled OR for 3′-UTR-188T was 1.29 (95% CI 1.05–1.58, p = 0.02) compared to the C allele in the dominant model, and it was 1.38 (95% CI 1.09–1.74, p = 0.007) in the recessive model. The pooled OR for 501C was 0.79 (95% CI 0.57–1.10, p = 0.16) compared to the G allele in the dominant model, and it was 0.86 (95% CI 0.71–1.04, p = 0.12) in the recessive model. No publication bias was found in the present meta-analysis. Conclusion: The synthesis of available evidence supports that OLR1 3′-UTR-188T increases the susceptibility to CAD. However, G501C is not associated with CAD.

Angiopoietin-2 has been reported to regulate the inflammation process, which is associated with recurrence of stroke. The purpose of this study was to test the hypothesis that plasma levels of angiopoietin-2 and variants of angiopoietin-2 will confer risk of stroke recurrence. The association of plasma angiopoietin-2 (determined by using ELISA) and the variants in angiopoietin-2 promoter with stroke recurrence was tested in 1735 patients with stroke of three subtypes, lacunar infarct (n = 475), atherothrombotic (n = 794) and hemorrhage (n = 466), for a period of following-up 4.5 years (mean), the association was evaluated by using Kaplan–Meier analysis and the Cox regression models. We found that angiopoietin-2 levels were associated with risk of stroke recurrence in lacunar infarct patients. Taking the lowest quartile as reference, the adjusted hazard ratio (HR) and 95% confidence intervals (CI) for stroke recurrence was 1.48 (0.74–2.95) for the second quartile, 2.56 (1.35–4.86) for the third and 2.15 (1.11–4.17) for the fourth. Allele T of rs3739391 in angiopoietin-2 promoter was associated with elevated angiopoietin-2 levels and increased risk of stroke recurrence in patients with lacunar infarct with HR 1.67 (1.06–2.63) relative to the allele C, but neither in those with atherothrombotic nor in those with hemorrhagic stroke. Our results indicate that both angiopoietin-2 and allele T of rs3739391 might be the risk marker for stroke recurrence in the patients with lacunar infarction. These findings may help to improve future prevention or therapy strategies for stroke. Even some conventional risk factors have been identified responsible for stroke recurrence, but these factors could not fully explain all the recurrent stroke events. Our study opens a new page for the first time that angiopoietin/tie2 pathway has a potential role in lacunar stroke recurrence. Since several strategies are available for blocking or neutralizing plasma angiopoietin-2, especially eicosapentaenoic acid rich in sea food. Our finding obviously has its clinical implication if it was proved by large, prospective clinical studies.

Ca 2+ cycling plays a critical role in heart failure and lethal arrhythmias. As susceptibility to sudden cardiac death is considered to be a heritable trait in general population, we have therefore investigated whether potentially functional variants of genes encoding RyR2 (ryanodine receptor 2) and the L-type Ca 2+ channel are related to the risk of ventricular arrhythmias and sudden cardiac death in CHF (chronic heart failure) in a case-control study. We found that the A allele of rs3766871 in RYR2 was associated with an increased risk of ventricular arrhythmias in patients with CHF {odds ratio, 1.66 [95% CI (confidence interval), 1.21–2.26]; P =0.002}. During a median follow-up period of 32 months in 1058 (85.0%) patients, 296 (28.0%) patients died from heart failure, of whom 141 (47.6%) had sudden cardiac death. After adjustment for age, gender and suspected risk factors, patients carrying the A allele of rs3766871 had an increased risk of cardiac death {HR (hazard ratio), 1.53 [95% CI, 1.11–2.12]; P =0.010} and sudden cardiac death [HR, 1.92 (95% CI, 1.25–2.94); P =0.003]. Patients carrying the A allele of rs790896 in RYR2 had a reduced risk of sudden cardiac death [HR, 0.65 (95% CI, 0.45–0.92); P =0.015]. In conclusion, the A allele of rs3766871 in RYR2 not only associates with ventricular arrhythmias, but also serves as an independent predictor of sudden cardiac death, and the A allele of rs790896 in RYR2 is a protective factor against sudden cardiac death in patients with CHF.

Background: C-reactive protein (CRP) has been shown to contribute to the risk of cardiovascular disease. Several single nucleotide polymorphisms (SNPs) at the CRP locus have been found to be associated with CRP concentrations. We hypothesized that genetic variants associated with high CRP may confer a greater risk of stroke and recurrence. The hypothesis was tested in a case-control study and during follow-up of the case population. Methods: Two genetic variants associated with serum CRP in the CRP gene were genotyped in a Chinese case-control study comprised of 1572 stroke patients and 1485 controls. The case population was followed for a median of 4.5 years (range, 0.1–6.0 years). Results: During a median 4.5-year follow-up for 1526 stroke patients, 299 recurrent strokes were identified. No association was found between the SNPs or haplotypes of the CRP gene and stroke and its recurrence. Conclusions: Although these variants and corresponding haplotypes in the CRP gene are associated with serum CRP concentrations, our study does not support that variants and corresponding haplotypes studied here have a major influence on risk of stroke and stroke recurrence. Therefore, we speculate that CRP is not a causal factor for stroke. Clin Chem Lab Med 2010;48:551–4.

BACKGROUND The effect of isoflavone on endothelial function in postmenopausal women is controversial. OBJECTIVE The objective of this study was to evaluate the effect of oral isoflavone supplementation on endothelial function, as measured by flow-mediated dilation (FMD), in postmenopausal women. DESIGN A meta-analysis of randomized placebo-controlled trials was conducted to evaluate the effect of oral isoflavone supplementation on endothelial function in postmenopausal women. Trials were searched in PubMed, Embase, the Cochrane Library database, and reviews and reference lists of relevant articles. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. RESULTS A total of 9 trials were reviewed in the present meta-analysis. Overall, the results of the 9 trials showed that isoflavone significantly increased FMD (WMD: 1.75%; 95% CI: 0.83%, 2.67%; P = 0.0002). Meta-regression analysis indicated that the age-adjusted baseline FMD was inversely related to effect size. Subgroup analysis showed that oral supplementation of isoflavone had no influence on FMD if the age-adjusted baseline FMD was > or = 5.2% (4 trials; WMD: 0.24%; 95% CI: -0.94%, 1.42%; P = 0.69). This improvement seemed to be significant when the age-adjusted baseline FMD levels were

Objective Previous case–control studies suggested the single nucleotide polymorphisms of lymphotoxin-α (LTA) gene and galectin-2 (LGASL2) gene are associated with coronary artery disease and myocardial infarction. However, other studies did not confirm this relationship. The objective was to assess the relationship of LTA gene, LGALS2 gene and coronary artery disease, using a meta-analysis. Methods Databases, including PubMed, EMbase, CBM and CNKI, were searched to get the genetic association studies. Data were extracted by two authors and pooled odds ratio (OR) and 95% confidence interval (CI) were calculated. Result The meta-analysis included 20640 ( LTA -A252G) and 10552 ( LGALS2 -C3279T) cases, 15388 (A252G) and 10545 (C3279T) controls. The pooled OR of 252G was 1.02 (95%CI: 0.97–1.07) compared to wild type allele in dominant model, and was 1.00 (95%CI: 0.94–1.07) in recessive model. The pooled OR of 3279T was 0.95 (95%CI: 0.89–1.01) compared to wild type allele in dominant model, and was 0.89 (95%CI: 0.78–1.00) in recessive model. None of the polymorphisms was found to associate with coronary artery disease. Conclusion In present study, the LTA gene and LGALS2 -C3279T are not associated with coronary artery disease.

Angiopoietin-2 is an important mediator of angiogenesis, and we hypothesized that genetic variants of ANGPT2 (the gene encoding angiopoietin-2) would result in abnormal angiogenesis and contribute to stroke susceptibility. To test our hypothesis, we investigated the association of variants in the promoter of ANGPT2 with stroke in a multi-centre case-control study. We found that the C allele of rs3739390 conferred a 1.42-fold risk of lacunar infarction {adjusted OR (odds ratio), 1.42 [95% CI (confidence interval), 1.08–1.87]; P =0.012} and a 2.10-fold higher transcriptional activity than did the corresponding G allele rs3739390G. The haplotype G-G-T conferred a 1.54-fold risk of atherothrombotic stroke and a 1.64-fold risk for haemorrhagic stroke, whereas the haplotype G-C-C conferred approx. a 2.0-fold risk of each subtype of stroke. In conclusion, our results indicate that haplotypes in the promoter of ANGPT2 confer a high risk of stroke in a Chinese population. Abbreviations: ACS, acute coronary syndrome; BMI, body mass index; BP, blood pressure; CI, confidence interval; DM, diabetes mellitus; HDL-C, high-density lipoprotein cholesterol; HUVEC, human umbilical vein endothelial cell; HW, Hardy–Weinberg; LD, linkage disequilibrium; MMP, matrix metalloproteinase; OR, odds ratio; SHRSP, spontaneously hypertensive stroke-prone rats; SNP, single nucleotide polymorphism; TAG, triacylglycerol; TC, total cholesterol; VEGF, vascular endothelial growth factor

Background: Previous trials suggest that oral L-arginine administration affects endothelial function. However, most of these studies were small, the conclusions were inconsistent, and the precise effects are therefore debatable. Objective: The objective was to assess the effect of oral L-arginine supplementation on endothelial function, as measured with the use of fasting flow-mediated dilation (FMD). Design: We conducted a meta-analysis of randomized, placebocontrolled L-arginine supplementation trials that evaluated endothelial function. Trials were identified in PubMed, Cochrane Library, Embase, reviews, and reference lists of relevant papers. The weighted mean difference (WMD) was calculated for net changes in FMD by using random-effect models. Previously defined subgroup analyses and meta-regression analyses were performed to explore the influence of study characteristics. Results: Thirteen trials were included and evaluated. Because there was only one long-term study, we focused on short-term effects of L-arginine (12 studies, 492 participants). In an overall pooled estimate, L-arginine significantly increased FMD (WMD: 1.98%; 95% CI: 0.47, 3.48; P ¼ 0.01). Meta-regression analysis indicated that the baseline FMD was inversely related to effect size (regression coefficient ¼ 20.55; 95% CI: 21.00, 20.1; P ¼ 0.016). A subgroup analysis suggested that L-arginine supplementation significantly increased FMD when the baseline FMD levels were ,7% (WMD: 2.56%; 95% CI: 0.87, 4.25; P ¼ 0.003), but had no effect on FMD when baseline FMD was .7% (WMD: 20.27%; 95% CI: 21.52, 0.97; P ¼ 0.67). Conclusion: Short-term oral L-arginine is effective at improving the fasting vascular endothelial function when the baseline FMD is low. Am J Clin Nutr 2009;89:77‐84.

Background Even carrying an identical gene mutation, inter- and intra-family variations have been noticed worldwide in the presence and the severity of left ventricular hypertrophy and sudden death in patients with hypertrophic cardiomyopathy (HCM). Modifier genes may contribute to the diversity. Angiotensin-converting enzyme 2 (ACE2) gene has been established to be associated with parameters of left ventricular hypertrophy in community based male subjects. The objective of the present study was to investigate the association of ACE2 gene polymorphisms with the phenotype of HCM. Methods A total of 261 consecutive HCM patients and 609 healthy controls were enrolled into this study. The polymorphism of rs2106809 and rs6632677 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Logistic regression model and multivariate analysis were used to determine the odds ratio (OR) and 95% confidence intervals (CI) of variations of ACE2 for HCM. Results The T allele of rs2106809 and C allele of rs6632677 conferred increasing risk for HCM (OR 1.34, 95% CI 1.01 - 1.77, P = 0.04; OR 1.11, 95% CI 1.03 - 1.21, P = 0.002, respectively), and the 2 single nucleotide polymorphisms (SNPs) were in strong linkage disequilibrium (LD), the TC haplotype was independently associated with a higher OR for HCM (OR = 1.59, 95% CI 1.21 - 1.87) after adjusted for conventional risk factors. And the risk alleles were associated with thicker interventricular septal thickness of HCM ((20.0 +/- 6.3) mm vs (17.9 +/- 5.5) mm, P = 0.03 and (21.3 +/- 5.9) mm vs (17.9 +/- 5.8) mm, P = 0.04, respectively). No association was found between the two polymorphisms with female patients with HCM. Conclusion Minor alleles of ACE2 gene might be the genetic modifier for the magnitude of left ventricular hypertrophy in male patients with HCM.

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.

The purpose of this study was to evaluate whether CC-AAbs levels could predict prognosis in CHF patients. A total of 2096 patients with CHF (841 DCM patients and 1255 ICM patients) and 834 control subjects were recruited. CC-AAbs were detected and the relationship between CC-AAbs and patient prognosis was analyzed. During a median follow-up time of 52 months, there were 578 deaths. Of these, sudden cardiac death (SCD) occurred in 102 cases of DCM and 121 cases of ICM. The presence of CC-AAbs in patients was significantly higher than that of controls (bothP<0.001). Multivariate analysis revealed that positive CC-AAbs could predict SCD (HR 3.191, 95% CI 1.598–6.369 for DCM; HR 2.805, 95% CI 1.488–5.288 for ICM) and all-cause mortality (HR 1.733, 95% CI 1.042–2.883 for DCM; HR 2.219, 95% CI 1.461–3.371 for ICM) in CHF patients. A significant association between CC-AAbs and non-SCD (NSCD) was found in ICM patients (HR = 1.887, 95% CI 1.081–3.293). Our results demonstrated that the presence of CC-AAbs was higher in CHF patients versus controls and corresponds to a higher incidence of all-cause death and SCD. Positive CC-AAbs may serve as an independent predictor for SCD and all-cause death in these patients.

Type III collagen plays an important role in activating platelets, forming thrombus, and maintaining the mechanical properties of arteries. This study aimed to test the hypothesis that genetic variants of COL3A1 (gene encoding type III collagen) contribute to recurrence and prognosis of stroke. We investigated the associations of three variants (rs2138533, rs11887092, and rs1800255) in the COL3A1 gene with stroke recurrence and prognosis in 1,544 patients with three subtypes of stroke: lacunar infarction (n = 442), atherothrombotic infarction (n = 670), and hemorrhage (n = 432). These associations were evaluated by Kaplan–Meier analysis and Cox regression models. Patients were followed up for 4.5 years. The A allele of rs1800255 in the COL3A1 gene coding region was significantly associated with a reduced risk of stroke recurrence in patients with lacunar infarction (adjusted hazard ratio [HR] 0.58, 95 % confidence interval [CI] 0.36–0.93, P = 0.024), but there was an increased risk of all-cause mortality of atherothrombotic patients (adjusted HR 1.43, 95 % CI 1.01–2.00, P = 0.044). The TT genotype of rs2138533 showed a significantly increased risk of death caused by cardiovascular disease or stroke in lacunar infarct patients (adjusted HR 2.98, 95 % CI 1.27–6.98, P = 0.012), but there was a reduced risk of all-cause mortality for patients with intracerebral hemorrhage (adjusted HR 0.34, 95 % CI 0.12–0.93, P = 0.036). The G allele of rs11887092 increased the risk of stroke recurrence in patients with atherothrombotic stroke (adjusted HR 1.59, 95 % CI 1.04–2.44, P = 0.035). In conclusion, variants of COL3A1 might play a vital role in determining the risk of recurrence and prognosis after stroke.

Background and Purpose— Perilipin is encoded by the gene PLIN and mediates lipid metabolism. Its upregulation has been linked to the formation of foam cells, rupture of atherosclerotic plaques, and perhaps acute coronary syndrome. We hypothesized that genetic variations in PLIN might contribute to the susceptibility to stroke. The hypothesis was tested in 2 case–control studies. Methods— Six PLIN tag single nucleotide polymorphisms (rs7176403, rs8179078, rs6496589, rs8179043, rs894160, rs1052700) were genotyped in 1571 patients with stroke (690 cerebral thrombosis, 429 lacunar infarction, 452 intracerebral hemorrhage) and 1638 control subjects. A SHEsis software platform was used to analyze pairwise linkage disequilibrium and haplotype association in the case–control study. The study was replicated in another independent case–control study including 120 patients with stroke and 240 control subjects. Results— No association of the PLIN variants with stroke ( P >0.05) or with stroke subtypes ( P >0.05) was found in the first study. The findings were confirmed in the second population ( P >0.05). Conclusions— The data represent an important negative finding that the common variants of PLIN do not have a major effect on susceptibility to stroke in a Chinese population.

Aims To investigate the relationship between electrocardiogram (ECG) parameters [J wave, fragmented QRS (fQRS), QTc, the peak-to-end interval of T wave (Tp–Te)], and sudden cardiac death (SCD) in chronic heart failure (CHF). Methods and results The ECGs of 1570 CHF patients, 572 cases with dilated cardiomyopathy (DCM) and 998 cases with ischaemic cardiomyopathy (ICM) were analysed with the endpoint being an SCD or non-SCD (NSCD). During a median follow-up period of 36 months (0.40–65 months), 438 (27.89%) patients died, of which 158 (35.84%) were SCD. Overall, the occurrence of J wave, fQRS, and long Tp–Te were greater in SCD patients than that of NSCD patients (all P < 0.01). For DCM cases, more SCD patients had J waves observed in the inferior leads than that in the NSCD group (26.78 vs. 13.07%, P

Background and Purpose— ANRIL encodes a long antisense noncoding RNA in the INK4 locus. Although ANRIL has been proven to be associated with coronary heart disease, its roles in stroke are inconsistent, and sparse data are available regarding hemorrhagic stroke. Methods— A Chinese case-control study was conducted, comprising 1657 cases (724 atherothrombosis, 466 lacunar infarction, and 462 hemorrhagic strokes) and 1664 controls. Stroke patients were prospectively followed-up for a median of 4.5 (range, 0.1–6.0) years. Expression of ANRIL transcripts was examined in 42 human atherosclerotic plaques. Results— After adjustment for vascular risk factors and correction for multiple comparisons, subjects carrying the GG genotype of rs10757278 had 1.47-fold (95% CI, 1.11–1.89; P =0.05) and 1.60-fold (95% CI, 1.16–2.15; P =0.04) increased risk for atherothrombotic and hemorrhagic strokes, respectively. During the follow-up, 317 recurrent strokes and 301 deaths from all causes were documented. Subjects carrying rs10757278GG had higher risk for stroke recurrence (relative risk [RR],1.56; 95% CI,1.15–2.12; P =0.005) and cardiovascular mortality (RR, 2.0; 95% CI, 1.26–3.18; P =0.003), respectively. Rs10757274 was also associated with stroke risk and recurrence. Family history of stroke further increased the stroke risk by 2.37-fold (95% CI, 1.38–4.06; P =0.01) and recurrent stroke risk by 2.45-fold (95% CI, 1.56–3.86; P ANRIL transcripts. Conclusions— Our findings indicated that the ANRIL may serve as a novel genetic marker for the risk of atherothrombotic and hemorrhagic stroke and their recurrence.

Objectives Our purpose was to investigate whether with-no-K[Lys] kinase ( WNK ) 1 and WNK4 genetic polymorphisms are associated with both hypertension and diuretics response. Design and methods Two WNK1 and one WNK4 polymorphisms were detected in two independent populations (n = 1592 and 602) for association with hypertension, and in two clinical trials of hydrochlorothiazide treatment (n = 542 and 274) for association with diuretics response. Results Two polymorphisms were found to be associated with hypertension risk with odds ratio of 1.55 for WNK1 rs1468326 ( P WNK4 rs9916754 ( P WKN1 rs1468326, and 1.82 for WNK4 rs9916754 in the second population. However, two clinical trials found no relationship between these WNK polymorphisms and systolic/diastolic blood pressure responses to 4 or 8 weeks treatment of hydrochlorothiazide. Conclusion Our findings suggest that hypertension associated polymorphisms in WNK1 and WNK4 may not be predictors for antihypertensive response to diuretics.

BACKGROUND: Organic anion transporter (OAT) 1 and OAT3, encoded by a tightly linked gene pair, play a key role in renal secretion of diuretics. However, no study has yet examined the influence of OAT1 and OAT3 polymorphisms on high blood pressure (BP) and the response to thiazide diuretics. We hypothesized that intergenic polymorphisms between OAT1 and OAT3 might be associated with adult hypertension and the antihypertensive effects of hydrochlorothiazide (HCTZ). METHODS: The association of an intergenic polymorphism (rs10792367) with hypertension risk was investigated in two independent case-control studies (n = 1,592 and 602), and then a combined analysis was performed for improving power (1,106 cases and 1,088 controls) with adjustment for geographic location. Two clinical trials (n = 542 and 274) were conducted in untreated hypertensive patients for the association of rs10792367 with antihypertensive responses to 4 and 8 weeks of HCTZ treatment. RESULTS: No significant association was found between rs10792367 and hypertension after adjustment for conventional risk factors in either the two populations, respectively, or the combined two population. After adjustment for pretreatment BP and other confounders, HCTZ-induced reduction in systolic BP was 4.8 mm Hg (P = 0.006, first trial) and 6.1 mm Hg (P = 0.003, in second trial) lower, respectively, in C allele carriers than in GG carriers in the two clinical trials. CONCLUSIONS: Intergenic polymorphism rs10792367 between OAT1 and OAT3 is not associated with hypertension, but appears to be involved in between-individual variations in antihypertensive responses to HCTZ.

GDF15 (growth-differentiation factor 15) is a novel antihypertrophic factor which is induced in the heart in response to pressure overload and plays an important regulatory role in the process of hypertrophy. In the present study, we have investigated the relationship between GDF15 gene variants and left ventricular hypertrophy in human essential hypertension. A community-based hypertensive population sample of 1527 individuals (506 men and 1021 women) was genotyped for three GDF15 genetic variants, including one tag variant −3148C>G (rs4808793) and two exonic variants +157A>T (rs1059369) and +2438C>G (rs1058587). The effects of those variants on gene expression were studied by use of luciferase reporter assays and the determination of plasma GDF15 levels. Only the tag variant −3148G was significantly associated with a lower risk of left ventricular hypertrophy [odds ratio=0.75 (95% confidence interval, 0.63–0.89); P=0.0009]. Multiple regression analyses confirmed that −3148G predicted the decrease in left ventricular end-diastolic diameter (β=−0.10, P=0.0001), end-systolic diameter (β=−0.09, P=0.0007), mass (β=−0.11, P