柳青
中国医学科学院阜外医院 移植病房
BACKGROUND AND OBJECTIVES:Effective management of immunosuppressants is extemely important to improve prognosis of heart transplant recipients. We aim to investigate the effects of cytochrome P450 (CYP) 3A5 (rs776746) single nucleotide polymorphisms (SNPs) on serum tacrolimus concentrations/doses (C/Ds, ng/mL per mg/kg) and long-term prognosis in Chinese heart transplant recipients.METHODS:We detected the CYP3A5 SNPs of 203 consecutive Chinese heart transplant recipients between August 2005 and July 2012, and 55 of them who received tacrolimus-based immunosuppressive therapy were enrolled in this study. The tacrolimus C/Ds at 1, 3, 6, 12, 24 and 36 months after transplantation were routinely calculated. X-ray-guided endomyocardial biopsies (EMBs) were performed at 1, 3 and 6 months after heart transplantion to evaluate acute rejection degrees. All participants were then followed up annually until May 2018. The designed primary endpoint was all-cause mortality.RESULTS:In 55 heart transplant recipients (43 males and 12 females), CYP3A5 non-expressors (CYP3A5*3/*3, n = 40) had significantly higher tacrolimus C/Ds than expressors (CYP3A5*1/*3, n = 15) at all time points (P < 0.001). Chi-squared test showed no significant differences in EMB-proven acute rejections between the two groups within 6 months after heart transplantion. The median follow-up period was 94.7 months, and eight patients died. Kaplan-Meier analysis showed CYP3A5 expressors tend to have higher mortality than non-expressors (20% vs 12.5%, log-rank: P = 0.314).CONCLUSIONS:CYP3A5 SNPs affect tacrolimus pharmacokinetics in Chinese heart transplant recipients, and non-expressors have higher tacrolimus C/Ds. In addition, expressors tend to have a worse long-term prognosis than non-expressors.
European journal of drug metabolism and pharmacokinetics 2019
OBJECTIVES:Despite the high prevalence of cardiovascular disease (CVD) among patients with Takayasu arteritis (TA), few studies have identified its clinical correlates. The aim of this study was to analyse the prevalence of CVD and its association with traditional CV risk factors and disease-related variables in patients with TA.METHODS:A total of 262 consecutive patients with a diagnosis of TA between January 2009 and July 2013 were included in this study. The primary outcome was CVD, defined as the presence of a previous history of myocardial infarction, angina, coronary disease, coronary bypass surgery, coronary angioplasty, and stroke. Multivariate logistic regression analysis was used to determine the relationship of conventional CV risk factors and TA-related variables to the presence of CVD.RESULTS:CVD was present in 64 (24.4%) of patients with TA. Of the total cohort, 16 (6.1%) had a history of myocardial infarction, 31 (11.8%) had angina and 24 (9.2%) had stroke. Multivariate logistic regression analysis revealed that anaemia (OR, 2.449; 95% CI: 1.167-5.141, p=0.018), low body mass index (OR, 0.821; 95% CI: 0.723-0.932, p=0.002), advancing age (OR, 1.050; 95% CI: 1.013-1.088, p=0.007), hyperlipidaemia (OR, 3.792; 95% CI: 1.647-8.727, p=0.002), and family history of CVD (OR, 2.915; 95% CI: 1.188-7.153, p=0.019) were significantly associated with the presence of CVD.CONCLUSIONS:Our study suggests that in addition to traditional CV risk factors, anaemia and low body mass index are independently associated with increased CVD in patients with TA.
Clinical and experimental rheumatology 2016
AIM:Takayasu arteritis (TA) is associated with increased cardiovascular morbidity and mortality, and the degree of arterial stiffness is an independent predictor of cardiovascular mortality in a variety of diseases. In addition, the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of ventricular dysfunction, have been found to be higher in patients with TA than in healthy controls. In this study, we aimed to investigate the relationship between the plasma NT-proBNP levels and arterial stiffness in patients with TA.METHODS:Seventy-two patients with TA were recruited in this study. The participants were analyzed with respect to the NT-proBNP levels, cardiovascular risk factors, TA-related variables and arterial stiffness assessed according to the brachial-ankle pulse wave velocity (baPWV). The patients were divided into two groups based on the mean baPWV, and the association between the NT-proBNP and baPWV values was tested using uni- and multivariate analyses.RESULTS:Twenty-four patients (33.3%) were classified into the high-baPWV group. The body mass index (p=0.035), systolic blood pressure (p＜0.001), diastolic blood pressure (p=0.001), mean blood pressure (p＜0.001), plasma NT-proBNP levels (p=0.036) and total cholesterol levels (p=0.030) were significantly higher in the high-baPWV group than in the low-baPWV group. A stepwise multiple linear regression analysis revealed the mean blood pressure (p＜0.001), age (p=0.002), and NT-proBNP level (p=0.002) to be independent determinants of the ba-PWV after adjusting for other confounding factors.CONCLUSIONS:The plasma NT-proBNP levels are independently associated with the degree of arterial stiffness measured according to the baPWV in patients with TA.
Journal of atherosclerosis and thrombosis 2015
OBJECTIVE:To investigate the probable pathogenesis, clinical features, diagnosis, and therapy of patients with pulmonary hypertension (PH) in Takayasu arteritis (TA).METHODS:A total of 48 patients with TA who had PH, 20 patients with TA who had pulmonary arterial involvement (PA) without PH, and 30 patients with idiopathic pulmonary arterial hypertension (IPAH) were enrolled in the study from 2009 to 2013.RESULTS:Among the 48 patients with TA who had PH, 36 (75.0%) had PA, and left heart disease (LHD) was present in 12 (25.0%). Serum levels of big endothelin 1 (ET-1) were independently correlated with pulmonary arterial systolic pressure (r = 0.33, p = 0.04). Compared to patients with IPAH, patients with PH because of PA who underwent right heart catheterization had lower average cardiac indexes (2.0 ± 0.5 vs 3.0 ± 1.2 l/min/m(2), p = 0.05), and they all developed favorable responses to acute vasodilator testing (100%) in comparison to 10 of the patients with IPAH (33.3%). During a mean followup of 36.0 ± 13.2 months (12.0-65.0 mos), of the patients with PH associated with PA, 3 died of heart failure. Six patients who underwent pulmonary artery revascularization were found to have good prognoses after followup for a mean duration of 6.2 ± 1.9 months. Additionally, 12 patients with PH with LHD were followed for 38.4 ± 15.6 months (12.0-60.0 mos), and 1 patient died of heart failure during the followup period.CONCLUSION:Patients with TA are at increased risk for PH. Early screening of patients with TA with unexplained symptoms related to PH should be applied. PH-specific therapies or revascularization may be effective treatments in the early stages of patients with PA, PH, and severe pulmonary artery stenosis.
The Journal of rheumatology 2015
BACKGROUND:Red blood cell distribution width (RDW) has been shown to be related to both anemia and inflammation in various diseases. However, the role of RDW in patients with Takayasu arteritis (TA) is unknown. Therefore, we investigated the association of RDW with anemia, inflammation, and disease activity in TA.METHODS:RDW was determined in 156 patients with TA and in 156 control subjects. Anemia status and disease activity were defined according to the World Health Organization and National Institutes of Health criteria, respectively.RESULTS:RDW was significantly increased in patients with anemia (14.6±2.2) compared with those without anemia (13.6±1.3, p<0.001) and control subjects (12.7±0.6, p<0.001). Regardless of the presence of anemia, RDW showed correlation with high-sensitivity C-reactive protein (hs-CRP) (both p<0.05). RDW was higher in active TA than inactive TA in patients without anemia (14.1±1.5 vs. 13.3±1.1, p=0.001). Moreover, multiple regression analysis showed that hs-CRP and mean corpuscular volume were independently associated with RDW.CONCLUSIONS:RDW is influenced by both anemia and inflammation, and RDW may be a useful marker to assess disease activity in patients without anemia.
Clinica chimica acta; international journal of clinical chemistry 2015
BACKGROUND:The relationship between aortic stiffness and coronary artery disease has been proven. Logistic Clinical SYNTAX score (LogCSS), which combined the anatomical evaluation of coronary artery disease and three clinical factors (age, left ventricular ejection fraction, and creatinine clearance), showed improved predictive value for cardiovascular events in patients after percutaneous coronary intervention (PCI). The combination of pulse wave velocity (PWV) and clinical factors may show equivalent predictive value.METHODS:Three hundred and seventy-six patients who were diagnosed with non-ST-segment elevation coronary syndrome (ACS) and showed at least one ≥50% angiographic stenosis in a major coronary artery were enrolled. The Clinical PWV score was calculated by assigning points to different levels of age, creatinine clearance, left ventricular ejection fraction, and carotid-femoral PWV (cfPWV). The points for cfPWV were determined based on the cutoff values of quintiles (model 1) or the relationship between cfPWV and SYNTAX scores (model 2). The predictive values of LogCSS and Clinical PWV score for 3-year major adverse cardiac events (MACE), which were defined as all-cause death, nonfatal myocardial infarction, and nonfatal target vessel revascularization, were analyzed in 298 patients undergoing PCI.RESULTS:The Clinical PWV score based on model 2 demonstrated a similar predictive ability for 3-year MACE compared with LogCSS (AUC 0.72 vs. 0.75; p=0.11). The AUC of LogCSS was significantly higher than the AUC of Clinical PWV score based on model 1 (AUC=0.70, p=0.03). Compared with cfPWV in isolation (AUC=0.61), Clinical PWV score from model 2 showed significantly better predictive power (p=0.03).CONCLUSION:Combination of PWV with age, creatinine clearance, and left ventricular ejection fraction appears to be a promising tool to predict MACE after PCI in patients with ACS.
Journal of cardiology 2015
OBJECTIVE:To assess the value of cardiopulmonary exercise test in the evaluation of cardiac function in patients with chronic left heart failure caused by dilated cardiomyopathy.METHODS:Fifty-three inpatients aged 18 year and over with chronic left heart failure caused by dilated cardiomyopathy at Fuwai Hospital from October 2010 to October 2011 were selected and divided into 2 groups according to the New York Heart Association (NYHA) heart function classification. One group had 20 cases for class II and another 33 cases for class III-IV. All of them received cardiopulmonary exercise tests. Synchronous measurement and record of gas exchange indices were taken during every breath, and so were heart rate, blood pressure, electrocardiogram and blood oxygen saturation. At the same time, other routine tests were also performed. After exercise test, anaerobic threshold and peak oxygen consumption indices were calculated and statistically analyzed. They also received subsequent follow-ups of 1 day, 1 week, 1 month, 6 months and 1 year, including activities, clinical manifestations and cardiac adverse events.RESULTS:At baseline, the differences in gender, age, body mass index, concurrent diseases, left ventricular end-diastolic diameter, left ventricular ejection fraction and serum creatinine had no statistical significance (P > 0.05). Compared with cardiac function class II group, the class III-IV group had higher left atrial diameter, level of amino terminal pro-B-type natriuretic peptide (NT-proBNP), incidence of atrial fibrillation ((51.4 ± 7.5) vs (43.6 ± 7.7) mm, (2 607 ± 1 782) vs (1 312 ± 901) µg/L, 42.4% (14/33) vs 5.0% (1/20)) and lower glomerular filtration rate, peak oxygen consumption, levels of anaerobic threshold ((72 ± 20) vs (97 ± 23) ml/min, (13.7 ± 2.6) vs (20.5 ± 3.6) ml·min(-1)·kg(-1), (10.7 ± 1.5) vs (13.3 ± 2.1) ml·min(-1)·kg(-1)) (all P < 0.01). And NT-proBNP and cardiac function classification showed a positive correlation (OR = 1.002, P = 0.003) while peak oxygen consumption, anaerobic threshold and cardiac function classification were negatively correlated (OR = 0.736, 0.608; P = 0.011, 0.001).CONCLUSIONS:Cardiopulmonary exercise test objectively reflects the cardiopulmonary reserve of heart failure patients with dilated cardiomyopathy. And the parameters of anaerobic threshold and peak oxygen consumption may reflect the patient's motor ability quantitatively and accurately.
Zhonghua yi xue za zhi 2014
PURPOSE:Although dual-chamber (DC) cardioverter defibrillators (ICDs) offer theoretical advantage over single-chamber (SC) ICDs, clinical studies showed conflicting results. The aim of this systematic review and meta-analysis was to compare DC and SC ICDs.METHODS:A systematic search of publications in PubMed, Embase, and the Cochrane Library without language restriction was performed. Randomized or nonrandomized controlled studies that compared DC and SC ICDs were included.RESULTS:Six randomized studies including 2,388 patients and 14 nonrandomized studies including 113,931 patients were identified. No difference in mortality was observed between DC and SC ICDs recipients in randomized studies. In nonrandomized studies, higher mortality was shown in DC group. There was no difference in the rate of inappropriate therapy between the DC and SC group after pooling the results from randomized studies as well as nonrandomized studies. More complications were observed with DC ICDs recipients.CONCLUSIONS:DC ICDs showed no conclusive superiority over SC ICDs. Without indications for antibradycardia therapy, SC ICDs seem to be the preferred selection.
Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing 2014
OBJECTIVE:Increased levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cardiovascular morbidity and mortality. Inflammation may also affect levels of NT-proBNP. We investigated the relationship of NT-proBNP with inflammation, disease activity, disease severity, and progression of Takayasu arteritis (TA).METHODS:Plasma levels of NT-proBNP were determined in 68 patients with TA and in 90 control subjects. Disease activity and disease severity in patients with TA were defined according to the National Institutes of Health and Ishikawa's criteria, respectively.RESULTS:NT-proBNP levels were higher in patients with active disease (915.0 ± 328.0 pmol/l) and patients in remission (618.2 ± 243.4 pmol/l) than in controls (427.2 ± 81.4 pmol/l) (p < 0.001). Patients with severe TA showed significantly higher NT-proBNP levels than those with mild-moderate TA (924.0 ± 332.4 pmol/l vs 653.8 ± 269.1 pmol/l; p = 0.001). In patients with longitudinal data, NT-proBNP levels at the active phase were significantly higher than those at the stable phase (944.1 ± 216.7 pmol/l vs 552.1 ± 178.2 pmol/l; p = 0.001). Inflammatory markers, including C-reactive protein, erythrocyte sedimentation rate, and white blood cell count, were independently associated with NT-proBNP levels after adjustment for other confounding factors (R(2) adjusted = 0.307, p = 0.001).CONCLUSION:NT-proBNP levels were significantly increased in patients with active TA exhibiting complications. NT-proBNP levels were independently associated with inflammation. These results indicate that NT-proBNP may be a useful marker to assess the status, severity, and progression of TA.
The Journal of rheumatology 2014
OBJECTIVE:To access the prevalence and risk factors for hypertension after heart transplantation (HT), and the impact of post-transplant hypertension on medium-term survival among HT patients.METHODS:Data from 265 consecutive patients underwent HT between June 2004 and May 2012 in Fuwai hospital and survived for at least 6 months were retrospectively analyzed. Hypertension was defined as systolic pressure ≥ 140 mm Hg (1 mm Hg = 0.133 kPa) and/or diastolic pressure ≥ 90 mm Hg or current treatment with antihypertensive drugs. Patients were divided into post-HT hypertension group and non-hypertension group. Logistic regression analysis was used to determine preoperative and postoperative risk factors for hypertension after HT. Kaplan-Meier method and log rank test were used for survival analysis.RESULTS:Hypertension was present in 17.4% (46/265) patients before HT and in 57.4% (152/265) patients post HT. The median follow-up time was 37 months (20 - 57 months). Logistic regression analysis showed that male gender (OR: 2.27, 95%CI: 1.16 - 4.42, P < 0.05), history of pre-HT hypertension (OR: 2.22, 95%CI: 1.05 - 4.71, P < 0.05), and cyclosporine A based immunosuppressive therapy (OR: 2.54, 95%CI: 1.51 - 4.29, P < 0.01) were independent risk factors for the development of post-HT hypertension. At the end of 1, 3, 5 years, the survival rate of heart transplant patients by Kaplan-Meier method estimation were 100%, 97.2%, 86.7% in post-HT hypertension group; 98.1%, 93.8%, 93.8% in non-hypertension group. Log rank test displayed that there was no significant difference between the two survival curves (P > 0.05).CONCLUSIONS:Hypertension is a frequent comorbidity after HT. Male gender, pre-HT hypertension together with cyclosporine A based immunosuppressive therapy are independent predictors for the development of post-HT hypertension. By adjusting the controllable risk factors and active control of blood pressure, the medium-term survival is similar between patients with or without postoperative hypertension in this cohort.
Zhonghua xin xue guan bing za zhi 2013
