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Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features. Furthermore, we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data. Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings. Consequently, two subtypes characterized by different clinical outcomes were identified in HCM. Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course, while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression. Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities. Furthermore, the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction. By employing echocardiography and genetic screening for the 46 genes, HCM can be classified into two subtypes with distinct clinical outcomes.
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Objective: To compare the long-term prognosis of fulminant myocarditis (FM) and non-fulminant myocarditis (NFM) patients who survived and discharged from hospital, and to explore the factors associated with the long-term prognosis and impaired cardiac function. Methods: This study was a retrospective study. Consecutive patients with acute myocarditis hospitalized in Tongji Hospital from January 2017 to December 2020 were enrolled and divided into FM group and NFM group according to the type of myocarditis. Then, patients in the FM group were further divided into normal cardiac function group and impaired cardiac function group according the left ventricular ejection fraction (LVEF). All patients with acute myocarditis were treated with antiviral, immunomodulatory, immunosuppressive medications and symptomatic and supportive treatment, while FM patients were treated with comprehensive treatment plan. Clinical data at admission of enrolled patients were collected through the electronic medical record system. Patients were clinically followed-up at 1, 3, 6 and 12 months, then once a year after discharge by clinical visit. The primary endpoints included major cardiovascular events, impaired cardiac function was defined by LVEF<55%. Kaplan-Meier survival curve was used to analyze the occurrence of LVEF<55% and left ventricular enlargement during the follow-up of patients in FM group and NFM group, and Log-rank test was used for comparison between groups. Cox regression model was used to analyze the risk factors of impaired cardiac function in patients with FM during follow-up. Results: A total of 125 patients with acute myocarditis were enrolled (66 in FM group and 59 in NFM group). Compared with NFM group, the proportion of FM patients with the lowest LVEF<55% during hospitalization was higher (P<0.01), and the recovery time of normal LVEF during hospitalization was longer (P<0.01). The proportion of LVEF<55% at discharge was similar between the two groups (P=0.071). During the follow-up of 12 (6, 24) months, 1 patient (1.5%) died due to cardiac reasons in FM group after discharge, 16 patients (24.2%) had sustained LVEF<55% after discharge, and 8 patients (12.1%) had left ventricular enlargement. In NFM group, 3 patients (5.1%) had sustained LVEF<55%, and 1 patient (1.7%) had left ventricular enlargement. Kaplan-Meier survival curve analysis showed that the incidence of sustained LVEF<55% in FM group was higher than that in NFM group (P=0.003), and the incidence of left ventricular enlargement was also higher than that in NFM group (P=0.024). Subgroup analysis of patients in the FM group showed that, compared with the normal cardiac function group, the time from onset to admission was shorter (P=0.011), the proportion of LVEF<55% at discharge was higher (P=0.039), the proportion of coronary angiography was higher (P=0.014), and the LVEF recovery time during hospitalization was longer (P=0.036) in FM patients with impaired cardiac function. Multivariate Cox regression analysis showed that longer LVEF recovery time during hospitalization was an independent risk factor for cardiac function impairment after discharge of FM patients (HR=1.199, 95%CI 1.023-1.406, P=0.025). Conclusions: The incidence of reduced LVEF is significantly higher in FM patients than that in NFM patients. Longer LVEF recovery time during hospitalization is an independent risk factor for cardiac function impairment in FM patients after discharge.
Subject(s)
Humans , Aftercare , Myocarditis , Patient Discharge , Prognosis , Retrospective Studies , Stroke Volume , Ventricular Function, LeftABSTRACT
Cardiovascular diseases account for approximately 80% of deaths among individuals with diabetes mellitus, with diabetic cardiomyopathy as the major diabetic cardiovascular complication. Hyperglycemia is a symptom that abnormally activates multiple downstream pathways and contributes to cardiac hypertrophy, fibrosis, apoptosis, and other pathophysiological changes. Although glycemic control has long been at the center of diabetes therapy, multicenter randomized clinical studies have revealed that intensive glycemic control fails to reduce heart failure-associated hospitalization and mortality in patients with diabetes. This finding indicates that hyperglycemic stress persists in the cardiovascular system of patients with diabetes even if blood glucose level is tightly controlled to the normal level. This process is now referred to as hyperglycemic memory (HGM) phenomenon. We briefly reviewed herein the current advances that have been achieved in research on the underlying mechanisms of HGM in diabetic cardiomyopathy.
Subject(s)
Humans , Cardiovascular Diseases , Diabetes Complications , Diabetes Mellitus , Diabetic Cardiomyopathies/etiology , Hyperglycemia/metabolism , Multicenter Studies as TopicABSTRACT
The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.
Subject(s)
Humans , Carnitine , Choline/metabolism , Chronic Disease , Heart Failure/genetics , Methylamines , Oxygenases , Prospective StudiesABSTRACT
Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10
Subject(s)
Humans , Aortic Dissection/genetics , Case-Control Studies , Cluster Analysis , Cohort Studies , Collagen Type III/genetics , Computational Biology , Genetic Predisposition to DiseaseABSTRACT
The COVID-19 pandemic has caused numerous deaths around the world. A growing body of evidence points to the important role of overwhelming inflammatory responses in the pathogenesis of COVID-19 and the effectiveness of anti-inflammation therapy against COVID-19 is emerging. In addition to affecting the lungs, COVID-19 can be a severe systemic inflammatory disease that is related to endothelial dysfunction. We are calling for closer attention to endothelial dysfunction in COVID-19 not only for fully revealing the pathogenic mechanism of COVID-19 but also for properly adjusting the strategy of clinical intervention.
Subject(s)
Humans , COVID-19 , Endothelium , Inflammation , Pandemics , SARS-CoV-2ABSTRACT
The morbidity and mortality of cardiovascular diseases are increasing annually, which is one of the primary causes of human death. Recent studies have shown that epoxyeicosatrienoic acids (EETs), endogenous metabolites of arachidonic acid (AA) via CYP450 epoxygenase, possess a spectrum of protective properties in cardiovascular system. EETs not only alleviate cardiac remodeling and injury in different pathological models, but also improve subsequent hemodynamic disturbances and cardiac dysfunction. Meanwhile, various studies have demonstrated that EETs, as endothelial-derived hyperpolarizing factors, regulate vascular tone by activating various ion channels on endothelium and smooth muscle, which in turn can lower blood pressure, improve coronary blood flow and regulate pulmonary artery pressure. In addition, EETs are protective in endothelium, including inhibiting inflammation and adhesion of endothelial cells, attenuating platelet aggregation, promoting fibrinolysis and revascularization. EETs can also prevent aortic remodeling, including attenuating atherosclerosis, adventitial remodeling, and aortic calcification. Therefore, it is clinically important to study the physiological and pathophysiological effects of EETs in the cardiovascular system to further elucidate the mechanisms, as well as provide new strategy for the prevention and treatment of cardiovascular diseases. This review summarizes the endogenous cardioprotective effects and mechanisms of EETs in order to provide a new insight for research in this field.
Subject(s)
Humans , 8,11,14-Eicosatrienoic Acid/pharmacology , Cardiovascular System , Cytochrome P-450 Enzyme System , Eicosanoids , Endothelial CellsABSTRACT
We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
Subject(s)
Humans , COVID-19 , Medicine, Chinese Traditional , Research , SARS-CoV-2 , Treatment OutcomeABSTRACT
PurposeTo examine the risk factors for Intensive Care Unit (ICU) admission, mechanical ventilation and mortality in hospitalized patients with COVID-19. MethodsThis was a retrospective cohort study including 432 patients with laboratory-confirmed COVID-19 who were admitted to three medical centers in Hubei province from January 1st to April 10th 2020. Primary outcomes included ICU admission, mechanical ventilation and death occurring while hospitalized or within 30 days. ResultsOf the 432 confirmed patients, 9.5% were admitted to the ICU, 27.3% required mechanical ventilation, and 33.1% died. Total leukocyte count was higher in survivors compared with those who died (8.9 vs 4.8 x 109/l), but lymphocyte counts were lower (0.6 vs 1.0 x 109/l). D-dimer was significantly higher in patients who died compared to survivors (6.0ug/l vs 1.0ug/l, p<0.0001. This was also seen when comparing mechanically versus non-mechanically-ventilated patients. Other significant differences were seen in AST, ALT, LDH, total bilirubin and creating kinase. The following were associated with increased odds of death: age > 65 years (adjusted hazard ratio (HR 2.09, 95% CI 1.02-4.05), severe disease at baseline (5.02, 2.05-12.29), current smoker (1.67, 1.37-2.02), temperature >39{degrees} C at baseline (2.68, 1.88-4.23), more than one comorbidity (2.12, 1.62-3.09), bilateral patchy shadowing on chest CT or X-ray (3.74, 1.78-9.62) and organ failure (6.47, 1.97-26.23). The following interventions were associated with higher CFR: glucocorticoids (1.60, 1.04-2.30), ICU admission (4.92, 1.37-17.64) and mechanical ventilation (2.35, 1.14-4.82). ConclusionDemographics, including age over 65 years, current smoker, diabetes, hypertension, and cerebrovascular disease, were associated with increased risk of mortality. Mortality was also associated with glucocorticoid use, mechanical ventilation and ICU admission. Take-Home MessageCOVID-19 patients with risk factors were more likely to be admitted into ICU and more likely to require mechanical ventilation.
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ImportanceCoronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high mortality. The most urgent thing is to find effective treatments. ObjectiveTo determine whether hydroxychloroquine application may be associated with a decreased risk of death in critically ill COVID-19 patients and what is potential mechanism. Design, Setting and PatientsThis retrospective study included all 568 critically ill COVID-19 patients who were confirmed by pathogen laboratory tests despite antiviral treatment and had severe acute respiratory distress syndrome, PAO2/FIO2 <300 with need of mechanical ventilation in Tongji Hospital, Wuhan, between February 1 of 2020 to April 8 of 2020. All 568 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them additionally received oral hydroxychloroquine (HCQ) treatment (200 mg twice a day for 7-10 days). Primary endpoint is mortality of patients, and inflammatory cytokines levels were compared between hydroxychloroquine and non-hydroxychloroquine (NHCQ) treatments. MAIN OUTCOMES AND MEASURESIn-hospital death and hospital stay time (day) were obtained, level of inflammatory cytokine (IL-6) was measured and compared between HCQ and NHCQ treatments. RESULTSThe median age of 568 critically ill patients is 68 (57, 76) years old with 37.0% being female. Mortalities are 18.8% (9/48) in HCQ group and 45.8% (238/520) in NHCQ group (p<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4 - 14) days for the HCQ and NHCQ groups, respectively (p<0.05). The level of inflammatory cytokine IL-6 was significantly lowered from 22.2 (8.3-118.9) pg/mL at the beginning of the treatment to 5.2 (3.0-23.4) pg/ml (p<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. CONCLUSIONS AND RELEVANCEHydroxychloroquine treatment is significantly associated with a decreased mortality in critically ill patients with COVID-19 through attenuation of inflammatory cytokine storm. Therefore, hydroxychloroquine should be prescribed for treatment of critically ill COVID-19 patients to save lives. Key PointsO_ST_ABSQuestionC_ST_ABSCould hydroxychloroquine administration be beneficial in the treatment of critically ill patients with COVID-19? FindingsIn this retrospective study, a total of 568 critically ill patients with COVID-19 all received basic therapy and additionally 48 of them received hydroxychloroquine for 7-10 days (200 mg twice per day). Hydroxychloroquine treatment is significantly associated with a decreased mortality in critically ill COVID-19 patients and attenuated inflammatory cytokine IL-6 level. MeaningOur data suggest that hydroxychloroquine could be used to treat critically ill patients with COVID-19 which may save a lot of lives.
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The features of myocardial strains from speckle-tracking echocardiography (STE) have not been well defined in fulminant myocarditis (FM) patients. In this study, changes in the left ventricular ejection fraction (LVEF) and global and layer-specific myocardial strains over time were monitored. We aimed to determine the echocardiographic patterns of FM and ascertain their significance in FM treatment. Twenty patients who were clinically diagnosed with FM and received mechanical life support were prospectively enrolled. Conventional echocardiographic measurements were obtained, and serial strain echocardiography was performed from admission to hospital discharge until LVEF recovery (> 50%). Global/regional peak systolic longitudinal strains (GLS/RLS) and layer-specific longitudinal strains were quantified, and their changes with time were monitored in 14 FM patients. All patients had severely impaired cardiac function. Steep improvement in LVEF and GLS were observed within 6 days. Layer-specific strain analysis showed that reduction at admission or recovery at discharge in the endocardium and epicardium strains were equal. In conclusion, FM patients who received mechanical circulatory supports exhibited steep improvement in ventricular function within 6 days. The patchy and diffused distribution pattern of reduced RLS and equally and severely impaired strain in the endocardium and epicardium are valuable features in the diagnosis of FM.
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Objective: To evaluate the cardiovascular damage of patients with COVID-19, and determine the correlation of serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTnI) with the severity of COVID-19, and the impact of concomitant cardiovascular disease on severity of COVID-19 was also evaluated. Methods: A cross-sectional study was designed on 150 consecutive patients with COVID-19 in the fever clinic of Tongji Hospital in Wuhan from January 19 to February 13 in 2020, including 126 mild cases and 24 cases in critical care. Both univariate and multivariate logistic regression were used to analyze the correlation of past medical history including hypertension, diabetes and coronary heart disease (CHD), as well as the levels of serum NT-proBNP and cTnI to the disease severity of COVID-19 patients. Results: Age, hypersensitive C-reactive protein(hs-CRP) and serum creatinine levels of the patients were higher in critical care cases than in mild cases(all P<0.05). Prevalence of male, elevated NT-proBNP and cTnI, hypertension and coronary heart disease were significantly higher in critical cases care patients than in the mild cases(all P<0.05). Univariate logistic regression analysis showed that age, male, elevated NT-proBNP, elevated cTnI, elevated hs-CRP, elevated serum creatinine, hypertension, and CHD were significantly correlated with critical disease status(all P<0.05). Multivariate logistic regression analysis showed that elevated cTnI(OR=26.909,95%CI 4.086-177.226,P=0.001) and CHD (OR=16.609,95%CI 2.288-120.577,P=0.005) were the independent risk factors of critical disease status. Conclusions: COVID-19 can significantly affect the heart function and lead to myocardial injury. The past medical history of CHD and increased level of cTnI are 2 independent determinants of clinical disease status in patients with COVID-19.
Subject(s)
Female , Humans , Male , Betacoronavirus , Biomarkers/blood , COVID-19 , Cardiovascular Diseases/virology , China , Coronavirus Infections/pathology , Cross-Sectional Studies , Myocardium/pathology , Natriuretic Peptide, Brain/blood , Pandemics , Peptide Fragments , Pneumonia, Viral/pathology , Prognosis , SARS-CoV-2 , Troponin I/bloodABSTRACT
In the 2017 AHA Hypertension Guidelines, BP≥130/80 mm Hg was used as the new diagnostic criterion for hypertension, and risk stratification was emphasized according to the 10-year CVD risk. Lifestyle intervention, without pharmacological treatment, was recommended for low-risk patients whose BP≥130/80 mmHg. However, high risk patients should receive antihypertensive pharmacological treatment as soon as their BP≥130/80 mmHg. In the 2018 European Guidelines for the management of hypertension, the definition and classification of office hypertension still followed the standard of the 2013's edition, but more aggressive therapeutic strategies were recommended.Hypertension can be divided into primary hypertension and secondary hypertension. To screen and diagnose secondary hypertension, it is necessary not only to construct a systematic and standardized method to avoid missed diagnosis and misdiagnosis but also to avoid screening blindly.
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Global longitudinal strain (GLS) at rest on two-dimensional speckle tracking echocardiography (2D STE) was demonstrated to help detect coronary artery disease (CAD).However,the optimal cut-off point of GLS and its diagnostic power for detecting critical CAD in non-diabetes mellitus (DM) patients are unknown.In the present study,211 patients with suspected CAD were prospectively included,with DM patients excluded.All patients underwent echocardiography and subsequently coronary angiography within 3 days.Left ventricular (LV) GLSs were quantified by 2D STE.Territorial peak systolic longitudinal strains (TLSs) were calculated based on the perfusion territories of the 3-epicardial coronary arteries in a 17-segment LV model.Critical CAD was defined as an area stenosis ≥70% in ≥1 epicardial coronary artery (≥50% in left main coronary artery).Totally 145 patients were diagnosed as having critical CAD by coronary angiography.Significant differences were observed in all strain parameters between patients with and without critical CAD.The area under the receiver operating charcteristic (ROC) curve (AUC) for GLS in the detection of left main (LM) or threevessel CAD was 0.875 at a cut-off value of-19.05% with sensitivity of 78.1% and specificity of 72.7%,which increased to 0.926 after exclusion of apical segments (cut-off value-18.66%;sensitivity 84.4% and specificity 81.8%).The values of TLSs were significantly lower in regions supplied by stenotic arteries than in those by non-stenotic arteries.The AUC for the TLSs to identify critical stenosis of left circumflex (LCX) artery,left anterior descending (LAD) artery and right coronary artery (RCA),in order of diagnostic accuracy,was 0.818 for LCX,0.764 for LAD and 0.723 for RCA,respectively.In conclusion,in non-DM patients with suspected CAD,GLS assessed by 2D STE is an excellent predictor for LM or three-vessel CAD with high diagnostic accuracy,and a higher cut-off point than reported before should be used.Excluding apical segments in the calculation of GLS can further improve the predictive accuracy of GLS.It is unsatisfactory for TLSs to be used to identify stenotic coronary arteries.
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Antithrombin and protein C are two crucial members in the anticoagulant system and play important roles in hemostasis. Mutations in SERPINC1 and PROC lead to deficiency or dysfunction of the two proteins, which could result in venous thromboembolism (VTE). Here, we report a Chinese 22-year-old young man who developed recurrent and serious VTE in cerebral veins, visceral veins, and deep veins of the lower extremity. Laboratory tests and direct sequencing of PROC and SERPINC1 were conducted for the patient and his family members. Coagulation tests revealed that the patient presented type I antithrombin deficiency combined with decreased protein C activity resulting from a small insertion mutation c.848_849insGATGT in SERPINC1 and a short deletion variant c.572_574delAGA in PROC. This combination of the two mutations was absent in 400 healthy subjects each from southern and northern China. Then, we summarized all the mutations of the SERPINC1 and PROC gene reported in the Chinese Han population. This study demonstrates that the combination of antithrombin deficiency and decreased protein C activity can result in severe VTE and that the coexistence of different genetic factors may increase the risk of VTE.
Subject(s)
Female , Humans , Male , Middle Aged , Young Adult , Antithrombin III , Genetics , Antithrombin III Deficiency , Genetics , China , Mutation , Pedigree , Protein C , Genetics , Metabolism , Venous Thromboembolism , GeneticsABSTRACT
Kidney diseases are important causes of mortality world widely. Renal microvascular dysfunction plays a pivotal role in the development of kidney diseases. Pharmacological and biochemical tools have been used to conduct detailed studies on the metabolization of arachidonic acid by cytochrome P450 (CYP450) in renal microvasculature. CYP450 epoxygenase metabolites epoxyeicosatrienoic acids (EETs) are mainly produced in renal microvessels. EETs exhibit renoprotective effects through vasodilation, anti-hypertension, anti-apoptosis and anti-inflammation, and were reported as therapeutic targets of renal diseases. However, the ability of the kidney in generating EETs is reduced in renal diseases. Recently, the studies from transgenic animal overexpressing CYP450 epoxygenases and application of soluble epoxide hydrolase inhibitors revealed that increasing of EETs exhibits renoprotective effects in vivo. The present review focuses on the protective mechanisms of EETs in kidney physiology and diseases.
Subject(s)
Animals , Humans , Animals, Genetically Modified , Arachidonic Acid , Metabolism , Cytochrome P-450 Enzyme System , Physiology , Disease Models, Animal , Inflammation , Kidney , Physiology , Kidney Diseases , VasodilationABSTRACT
Global longitudinal strain (GLS) at rest on two-dimensional speckle tracking echocardiography (2D STE) was demonstrated to help detect coronary artery disease (CAD).However,the optimal cut-off point of GLS and its diagnostic power for detecting critical CAD in non-diabetes mellitus (DM) patients are unknown.In the present study,211 patients with suspected CAD were prospectively included,with DM patients excluded.All patients underwent echocardiography and subsequently coronary angiography within 3 days.Left ventricular (LV) GLSs were quantified by 2D STE.Territorial peak systolic longitudinal strains (TLSs) were calculated based on the perfusion territories of the 3-epicardial coronary arteries in a 17-segment LV model.Critical CAD was defined as an area stenosis ≥70% in ≥1 epicardial coronary artery (≥50% in left main coronary artery).Totally 145 patients were diagnosed as having critical CAD by coronary angiography.Significant differences were observed in all strain parameters between patients with and without critical CAD.The area under the receiver operating charcteristic (ROC) curve (AUC) for GLS in the detection of left main (LM) or threevessel CAD was 0.875 at a cut-off value of-19.05% with sensitivity of 78.1% and specificity of 72.7%,which increased to 0.926 after exclusion of apical segments (cut-off value-18.66%;sensitivity 84.4% and specificity 81.8%).The values of TLSs were significantly lower in regions supplied by stenotic arteries than in those by non-stenotic arteries.The AUC for the TLSs to identify critical stenosis of left circumflex (LCX) artery,left anterior descending (LAD) artery and right coronary artery (RCA),in order of diagnostic accuracy,was 0.818 for LCX,0.764 for LAD and 0.723 for RCA,respectively.In conclusion,in non-DM patients with suspected CAD,GLS assessed by 2D STE is an excellent predictor for LM or three-vessel CAD with high diagnostic accuracy,and a higher cut-off point than reported before should be used.Excluding apical segments in the calculation of GLS can further improve the predictive accuracy of GLS.It is unsatisfactory for TLSs to be used to identify stenotic coronary arteries.
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<p><b>OBJECTIVE</b>To establish the high-resolution melting curve (HRM) approach for genotyping CYP2C9*3 (1075A/C, rs1057910) and VKORC1 (-1639A/G, rs9923231) and explore its value on estimation of the Warfarin initial dose in comparison with various traditional genotyping methods.</p><p><b>METHODS</b>CYP2C9*3 (1075A/C, rs1057910) and VKORC1 (-1639A/G, rs9923231) genotyping was detected in 100 patients receiving Warfarin therapy by the newly developed HRM method and traditional genotyping methods including PCR-restriction fragment length polymorphism (PCR-RFLP), TaqMan probe and DNA sequencing.</p><p><b>RESULTS</b>The results of the genotypes obtained from above mentioned methods to detect CYP2C9*3 (1075A/C, rs1057910) and VKORC1 (-1639A/G, rs9923231) were similar and consistent. The HRM method is simpler, more economical, and faster compared to the traditional methods. The frequencies of the VKORC1-1639 AA, AG, GG genotypes from these 100 clinical samples were 73 (73%), 23 (23%), 4 (4%), respectively; Frequencies of the CYP2C9 1075 AA, AC, CC genotypes were 94(94%), 6 cases (6%), 0, respectively.</p><p><b>CONCLUSIONS</b>HRM approach can effectively detect CYP2C9*3 (1075A/C, rs1057910) and VKORC1 (-1639A/G, rs9923231) polymorphisms and this method is simpler, more economical, and faster compared to the traditional methods for detecting CYP2C9*3 (1075A/C, rs1057910) and VKORC1 (-1639A/G, rs9923231) polymorphisms.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Aryl Hydrocarbon Hydroxylases , Genetics , Cytochrome P-450 CYP2C9 , Dose-Response Relationship, Drug , Freezing , Genotype , Genotyping Techniques , Mixed Function Oxygenases , Genetics , Polymorphism, Restriction Fragment Length , Vitamin K Epoxide Reductases , Warfarin , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To investigate the association between rs751141 gene polymorphisms in EPHX2 gene and essential hypertension in Kazak and Han in Xinjiang.</p><p><b>METHODS</b>A total of 267 essential hypertensive patients in Kazaks, 368 essential hypertensive patients in Hans, 284 normotensive controls in Kazaks and 348 normotensive controls in Hans were enrolled in this study. TaqMan assay was used to detect the rs751141 G/A gene polymorphisms of EPHX2 gene.</p><p><b>RESULTS</b>The rs751141 G/A genotype frequencies for GA + AA genotypes was 40.2 percent in essential hypertensive subjects and 52.0 percent in control subjects in Hans, respectively. The genotype frequencies were significant difference between the two groups in Hans in Xinjiang (P < 0.01). The rs751141G/A gene polymorphism had no significant difference between essential hypertensive patients and normotensive controls in Kazaks in Xinjiang (P > 0.05).</p><p><b>CONCLUSION</b>The essential hypertension in Kazaks in Xinjiang is not associated with rs751141G/A gene polymorphism of EPHX2 gene, but the essential hypertension in Hans in Xinjiang is associated with rs751141G/A allele gene polymorphism of EPHX2 gene. A type of rs751141 allele gene polymorphism may be the independent protective factor of essential hypertension in Hans in Xinjiang.</p>
Subject(s)
Adult , Humans , Middle Aged , Alleles , Asian People , Genetics , China , Epidemiology , Epoxide Hydrolases , Genetics , Gene Frequency , Genotype , Hypertension , Epidemiology , Genetics , Polymorphism, Single NucleotideABSTRACT
<p><b>OBJECTIVE</b>To analyze the characteristics of a new clinical syndrome, including throat infection, neck spinal disease, chest pain and cardiac response.</p><p><b>METHODS</b>A total of 165 patients with above mentioned symptoms admitted to Tongji hospital from 2003 to 2005 were included in this study and underwent further medical history inquiry, physical examination and laboratory tests. Eighty-five healthy subjects served as controls. Serum myocardial auto-antibodies against beta(1)-adrenoceptor, alpha-myosin heavy chain, M(2)-muscarinic receptor and adenine-nucleotide translocator were detected, inflammatory cytokines, high sensitivity C-reaction protein, serum antibodies against Coxsackie virus-B, cytomegalovirus, Mycoplasma pneumoniae and Chlamydia pneumoniae were determined and lymphocyte subclasses were assayed by flow cytometry.</p><p><b>RESULTS</b>All patients had a complex of four symptoms or tetralogy: (1) persistent throat or upper respiratory tract infection; (2) neck pain; (3) chest pain; (4) chest depression or dyspnea, some of them with anxiety. Anti-myocardial auto-antibodies (AMCA) were present in all patients vs. 8% in controls. TNF-alpha, IL-1 and IL-6 were significantly higher in patients than controls (P < 0.01). CD3(+) and CD4(-)CD8(+) lymphocytes were significantly higher and CD56(+) lymphocytes lower in patients than those in controls (P < 0.01). The ratios of serum pathogen antibodies positive against Coxsackie virus-B, cytomegalovirus, Mycoplasma pneumoniae and Chlamydia pneumoniae were all significantly higher in patients than in controls.</p><p><b>CONCLUSIONS</b>These data led to identification of a persistent respiratory infection-related clinical syndrome, including persistent throat infection, neck spinal lesion, rib cartilage inflammation, symptoms of cardiac depression and dyspnea with or without anxiety.</p>