Publications by authors named "Xiao-Han Fan"

30 Publications

  • Page 1 of 1

Association of time-varying changes in physical activity with cardiac death and all-cause mortality after ICD or CRT-D implantation.

J Geriatr Cardiol 2022 Mar;19(3):177-188

Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: To evaluate the association of longitudinal changes in physical activity (PA) with long-term outcomes after implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) implantation.

Methods: Patients with ICD/CRT-D implantation from SUMMIT registry were retrospectively analyzed. Accelerometer-derived PA changes over 12 months post implantation were obtained from the archived home monitoring data. The primary endpoints were cardiac death and all-cause mortality. The secondary endpoints were the first ventricular arrthymia (VA) and first appropriate ICD shock.

Results: In 705 patients, 446 (63.3%) patients showed improved PA over 12 months after implantation. During a mean 61.5-month follow-up duration, 99 cardiac deaths (14.0%) and 153 all-cause deaths (21.7%) occurred. Compared to reduced/unchanged PA, improved PA over 12 months could result in significantly reduced risks of cardiac death (improved PA ≤ 30 min: hazard ratio (HR) = 0.494, 95% CI: 0.288-0.848; > 30 min: HR = 0.390, 95% CI: 0.235-0.648) and all-cause mortality (improved PA ≤ 30 min: HR = 0.467, 95%CI: 0.299-0.728; > 30 min: HR = 0.451, 95% CI: 0.304-0.669). No differences in the VAs or ICD shocks were observed across different groups of PA changes. PA changes can predict the risks of cardiac death only in the low baseline PA group, but improved PA was associated with 56.7%, 57.4%, and 62.3% reduced risks of all-cause mortality in the low, moderate, and high baseline PA groups, respectively, than reduced/unchanged PA.

Conclusions: Improved PA could protect aganist cardiac death and all-cause mortality, probably reflecting better clinical efficacy after ICD/CRT-D implantation. Low-intensity exercise training might be encouraged among patients with different baseline PA levels.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2022.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9002081PMC
March 2022

Beneficial effects of endoscopic screening on gastric cancer and optimal screening interval: a population-based study.

Endoscopy 2021 Dec 28. Epub 2021 Dec 28.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China.

BACKGROUND : The effectiveness of endoscopic screening on gastric cancer has not been widely investigated in China and the screening interval of repeated screening has not been determined. METHODS : In a population-based prospective study, we included 375,800 individuals, 14,670 of whom underwent endoscopic screening (2012-2018). We assessed the associations between endoscopic screening and risk of incident gastric cancer and gastric cancer-specific mortality, and examined changes in overall survival and disease-specific survival following screening. The optimal screening interval for repeated endoscopy for early detection of gastric cancer was explored. RESULTS : Ever receiving endoscopic screening significantly decreased the risk of invasive gastric cancer (age- and sex-adjusted relative risk [RR] 0.69, 95 % confidence interval [CI] 0.52-0.92) and gastric cancer-specific mortality (RR 0.33, 95 %CI 0.20-0.56), particularly for noncardia gastric cancer. Repeated screening strengthened the beneficial effect on invasive gastric cancer-specific mortality of one-time screening. Among invasive gastric cancers, screening-detected individuals had significantly better overall survival (RR 0.18, 95 %CI 0.13-0.25) and disease-specific survival (RR 0.18, 95 %CI 0.13-0.25) than unscreened individuals, particularly for those receiving repeated endoscopy. For individuals with intestinal metaplasia or low grade intraepithelial neoplasia, repeated endoscopy at an interval of < 2 years, particularly within 1 year, significantly enhanced the detection of early gastric cancer, compared with repeated screening after 2 years (-trend = 0.02). CONCLUSION : Endoscopic screening prevented gastric cancer occurrence and death, and improved its prognosis in a population-based study. Repeated endoscopy enhanced the effectiveness. Screening interval should be based on gastric cancer severity.
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http://dx.doi.org/10.1055/a-1728-5673DOI Listing
December 2021

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

J Thorac Dis 2021 Jul;13(7):4008-4022

State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Genetic disorders are strongly associated with aortic disease. However, the identities of genetic mutations in sporadic Stanford type A aortic dissection (STAAD) are not clear. The present study analysed the possible genetic mutations of the known pathogenic genes of aortic disease and the clinical characteristics in patients with sporadic STAAD.

Methods: We analysed genetic mutations in 26 genes that underlie aortic aneurysms and dissections in 100 sporadic STAAD patients and 568 healthy controls after whole-genome sequencing (WGS). Clinical features and in-hospital death were determined in all STAAD patients.

Results: In total, 60 suspicious pathogenic mutations (56 novel and 4 previously reported) in 19 genes were identified in 50% (50/100) of patients, and 14 patients had more than 1 mutation. The ascending aortic diameter was extended in patients with mutations (49.1±12.3 43.7±11.2 mm, P=0.023), and the DeBakey type I phenotype was more common in patients with mutations in genes that coded extracellular matrix (ECM) components than in patients with mutations in other genes (96.6% 66.7%, P=0.007). Patients with fibrillin-1 () mutations were younger than patients without mutations (44.7±11.0 53.5±12.1, P=0.030). Subgroup analyses revealed an increased risk of in-hospital mortality in mutation carriers (44.4% 10.5%, P=0.029) but only in patients who received conservative treatment.

Conclusions: Half of Chinese patients with a sporadic form of STAAD may carry mutations in known pathogenic genes of aortic disease, and these patients may exhibit distinct clinical features and poor clinical outcomes with the use of conservative treatment.
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http://dx.doi.org/10.21037/jtd-20-2758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339749PMC
July 2021

Plasma big endothelin-1 is an effective predictor for ventricular arrythmias and end-stage events in primary prevention implantable cardioverter- defibrillator indication patients.

J Geriatr Cardiol 2020 Jul;17(7):427-433

Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: To investigate whether plasma big endothelin-1 (ET-1) predicts ventricular arrythmias (VAs) and end-stage events in primary prevention implantable cardioverter-defibrillator (ICD) indication patigents.

Methods: In total, 207 patients fulfilling the inclusion criteria from Fuwai Hospital between January 2013 and December 2015 were retrospectively analyzed. The cohort was divided into three groups according to baseline plasma big ET-1 tertiles: tertile 1 (< 0.38 pmol/L, = 68), tertile 2 (0.38-0.7 pmol/L, = 69), and tertile 3 (> 0.7 pmol/L, = 70). The primary endpoints were VAs. The secondary endpoints were end-stage events comprising all-cause mortality and heart transplantation.

Results: During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class ( = 0.165, = 0.018), serum creatinine concentration (Scr; = 0.147, = 0.034), high-sensitivity C-reactive protein (hs-CRP; = 0.217, = 0.002), Lg NT-pro BNP ( = 0.463, < 0.001), left ventricular end diastolic diameter (LVEDD; = 0.234, = 0.039) and negatively correlated with left ventricular ejection fraction (LVEF; = -0.181, = 0.032). Kaplan-Meier analysis showed that elevated big ET-1 was associated with increased risk of VAs and end-stage events ( < 0.05). In multivariate Cox regression models, big ET-1 was an independent risk factor for VAs (hazard ratio (HR) = 3.477, 95% confidence interval (CI): 1.352-8.940, = 0.010, tertile 2 tertile 1; HR = 4.112, 95% CI: 1.604-10.540, = 0.003, tertile 3 tertile 1) and end-stage events (HR = 2.804, 95% CI: 1.354-5.806, = 0.005, tertile 2 tertile 1; HR = 4.652, 95% CI: 2.288-9.459, < 0.001, tertile 3 tertile 1).

Conclusions: In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2020.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416061PMC
July 2020

Correlations between low thyroid function and incidence of atrial fibrillation in hypertrophic obstructive cardiomyopathy.

Chronic Dis Transl Med 2020 Mar 13;6(1):35-45. Epub 2020 Mar 13.

Department of Cardiovascular Medicine, Clinical EP Lab & Arrhythmia Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.

Background: Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic obstructive cardiomyopathy (HOCM). Data regarding the correlations of thyroid dysfunction and the incidence of AF in HOCM are quite limited. This study aimed to reveal the correlations between different thyroid status and the corresponding incidence of AF in a large HOCM cohort.

Methods: A total of 806 HOCM patients with complete information on thyroid function tests and comprehensive cardiac evaluations were recruited. The participants were divided into the AF group (n = 159) and non-AF group (n = 647) according to established medical history and results of Holter monitoring. The thyroid status of the study population and the corresponding incidence of AF were assessed and analyzed.

Results: Hypothyroidism accounted for the greatest proportion of thyroid dysfunction in HOCM patients. The incidence of AF significantly increased in individuals with both overt ( = 0.022) and subclinical ( = 0.007) hypothyroidism. Compared with participants in the non-AF group, those with positive AF episodes presented with lower free triiodothyronine (FT3) (2.86 ± 0.52 pg/mL vs. 3.01 ± 0.42 pg/mL,  = 0.001), higher free thyroxine (FT4) (1.24 ± 0.25 ng/dL vs. 1.15 ± 0.16 ng/dL,  < 0.001), and remarkably increased levels of thyrotropin (TSH) (12.6% vs. 5.3%,  = 0.001). Multivariable analyses demonstrated that the concentrations of FT3 (odds ratio [OR] = 0.470, 95% confidence interval [CI]: 0.272-0.813,  = 0.007) and FT4 (OR = 17.992, 95% CI: 5.750-56.296,  < 0.001), as well as TSH levels above normal ranges (OR = 2.276, 95% CI: 1.113-4.652,  = 0.024) were independently associated with the occurrence of AF in the large HOCM cohort.

Conclusions: This study indicated a strong link between low thyroid function and the presence of AF in HOCM. Hypothyroidism (both overt and subclinical states) seems to be valuable for assessing the incidence of AF in patients with HOCM.
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http://dx.doi.org/10.1016/j.cdtm.2020.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096325PMC
March 2020

Predictive value of Tpeak-Tend interval for ventricular arrhythmia and mortality in heart failure patients with an implantable cardioverter-defibrillator: A cohort study.

Medicine (Baltimore) 2019 Dec;98(49):e18080

The Cardiac Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Tpeak-Tend interval (TpTe), a measurement of transmural dispersion of repolarization (TDR), has been shown to predict ventricular tachyarrhythmia in cardiac resynchronization therapy with defibrillator (CRT-D) patients. However, the ability of TpTe to predict ventricular tachyarrhythmia and mortality for heart failure patients with a cardioverter-defibrillator (ICD) is not clear. The purpose of this study was to assess the predictive ability of TpTe in heart failure patients with ICD.

Methods And Results: We enrolled 318 heart failure patients treated after ICD. Patients were divided into 3 groups according to their post-implantation TpTe values and were evaluated every 6 months. The primary endpoint was appropriate ICD therapy. The secondary endpoint was all-cause mortality. During long-term follow-up, the TpTe > 110 ms group (n = 111) experienced more VT/VF episodes (45%) and all-cause mortality (25.2%) than the TpTe 90-110 ms group (n = 109) (26.4%, 14.5%) and TpTe < 90 ms group (n = 98) (11.3%, 11.3%) (overall P < .05, respectively). In Cox regression, longer post-implantation TpTe was associated with an increased number of VT/VF episodes [HR: 1.017; 95% CI: 1.008-1.026; P < .001], all-cause mortality [HR: 1.015; 95% CI: 1.004-1.027; P = .010] and the combined endpoint [HR: 1.018; 95%CI: 1.010-1.026; P < .001].

Conclusions: Post-implantation TpTe was an independent predictor of both ventricular arrhythmias and all-cause mortality in heart failure patients with an implanted ICD.
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http://dx.doi.org/10.1097/MD.0000000000018080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6919476PMC
December 2019

Predictors of non-response to cardiac resynchronization therapy implantation in patients with class I indications: the markedly dilated left ventricular end-diastolic dimension and the presence of fragmented QRS.

J Geriatr Cardiol 2019 Jul;16(7):514-521

State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, Fuwai Hospital; National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Cardiac resynchronization therapy (CRT) is a highly effective treatment in patients with a class I recommendation. However, a small proportion of the strictly selected patients still fail to respond. This study was designed to identify predictors of non-response in patients with class I indications for CRT and determine the non-response probability of the patients.

Methods: A total of 296 consecutive patients with a class I recommendation received CRT from January 2009 to January 2017 were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify predictors for non-response (defined as cardiac death, heart transplantation, or HF hospitalization during 1-year follow-up).

Results: Among 296 patients, 30 (10.1%) met non-response. Multivariate analysis demonstrated that non-response to CRT was associated with a fragmented QRS (odd ratio (OR) = 2.86, 95% CI: 1.14-7.12; = 0.025) and left ventricular end-diastolic dimension (LVEDD) ≥ 77 mm (OR = 3.02, 95% CI: 1.17-7.82; = 0.022). Patients with both of the predictors had a non-response probability of 46.2% (95% CI: 19.1%-73.3%).

Conclusion: In patients with left bundle branch block and wider QRS duration, the proportion of non-response to CRT is not low in real world. The presence of the dilated LVEDD or fragmented QRS is a strong predictor of non-response to CRT. The probability of non-response in the patients with the two predictors was 46.2%.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2019.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689517PMC
July 2019

Heart rate-adjusted PR as a prognostic marker of long-term ventricular arrhythmias and cardiac death in ICD/CRT-D recipients.

J Geriatr Cardiol 2019 Mar;16(3):259-264

State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: To evaluate the PR to RR interval ratio (PR/RR, heart rate-adjusted PR) as a prognostic marker for long-term ventricular arrhythmias and cardiac death in patients with implantable cardioverter defibrillator (ICDs) and cardiac resynchronization therapy with defibrillators (CRT-D).

Methods: We retrospectively analyzed data from 428 patients who had an ICD/CRT-D equipped with home monitoring. Baseline PR and RR interval data prior to ICD/CRT-D implantation were collected from standard 12-lead electrocardiograph, and the PR/RR was calculated. The primary endpoint was appropriate ICD/CRT-D treatment of ventricular arrhythmias (VAs), and the secondary endpoint was cardiac death.

Results: During a mean follow-up period of 38.8 ± 10.6 months, 197 patients (46%) experienced VAs, and 47 patients (11%) experienced cardiac death. The overall PR interval was 160 ± 40 ms, and the RR interval was 866 ± 124 ms. Based on the receiver operating characteristic curve, a cut-off value of 18.5% for the PR/RR was identified to predict VAs. A PR/RR ≥ 18.5% was associated with an increased risk of VAs [hazard ratio (HR) = 2.243, 95% confidence interval (CI) = 1.665-3.022, < 0.001) and cardiac death (HR = 2.358, 95%CI = 1.240-4.483, = 0.009) in an unadjusted analysis. After adjustment in a multivariate Cox model, the relationship remained significant among PR/RR ≥ 18.5%, VAs (HR = 2.230, 95%CI = 1.555-2.825, < 0.001) and cardiac death (HR = 2.105, 95%CI = 1.101-4.025, = 0.024.

Conclusions: A PR/RR ≥ 18.5% at baseline can serve as a predictor of future VAs and cardiac death in ICD/CRT-D recipients.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2019.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500573PMC
March 2019

Does 'super-responder' patients to cardiac resynchronization therapy still have indications for neuro-hormonal antagonists? Evidence from long-term follow-up in a single center.

J Geriatr Cardiol 2019 Mar;16(3):251-258

Cardiac Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Whether cardiac resynchronization therapy super-responders (CRT-SRs) still have indications for neuro-hormonal antagonists or not remains uninvestigated.

Methods: We reviewed clinical data from 376 patients who underwent CRT implantation in Fuwai Hospital from 2009 to 2015 and followed up to 2017. CRT-SRs were defined by an improvement of the New York Heart Association functional class and left ventricular ejection fraction to ≥ 50% in absolute values at 6-month follow-up. All CRT-SRs were assigned into two groups on the basis of whether persistently receiving neuro-hormonal antagonists (NHA) (defined as angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and β-blockers) after 6-month follow-up and then we compared long-term outcome.

Results: A total of 60 patients met criteria for super-response. One of thirteen (7.7%) CRT-SRs without NHA had all-cause death, which also occurred in 2 of 47 (4.3%) in CRT-SRs with NHA ( = 0.526). However, 3 of 13 (23.1%) CRT-SRs without NHA had heart failure (HF) hospitalization, 1 of 47 (2.1%) CRT-SRs with NHA had this endpoint ( = 0.040). Besides, subgroup analysis indicated that, for ischemic etiology group, CRT-SRs receiving NHA had considerably lower incidence of HF hospitalization than those without NHA (0 75%, = 0.014), which was not observed in non-ischemic etiology group (2.6% 0, = 1.000) during long-term follow-up.

Conclusions: Our study found that for ischemic etiology, compared with CRT-SRs with NHA, CRT-SRs without NHA were associated with a higher risk of HF hospitalization. However, for non-ischemic etiology, we found that CRT-SRs with NHA or without NHA at follow-up were associated with similar outcomes, which needed further investigation by prospective trials.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2019.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500568PMC
March 2019

Predictors of super-response to cardiac resynchronization therapy: the significance of heart failure medication, pre-implant left ventricular geometry and high percentage of biventricular pacing.

J Geriatr Cardiol 2017 Dec;14(12):737-742

The Cardiac Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Super-responders (SRs) are defined as patients who show crucial cardiac function improvement after cardiac resynchronization therapy (CRT). The purpose of this study is to identify and validate predictors of SRs after CRT.

Methods: This study enrolled 201 patients who underwent CRT during the period from 2010 to 2014. Clinical and echocardiographic evaluations were conducted before CRT and 6 months after. Patients with a decrease in New York Heart Association (NYHA) functional class ≥ 1, a decrease in left ventricular end-systolic volume (LVESV) ≥ 15%, and a final left ventricular ejection fraction (LVEF) ≥ 45% were classified as SRs.

Results: 29% of the 201 patients who underwent CRT were identified as SRs. At baseline, SRs had significantly smaller left atrial diameter (LAD), LVESV, left ventricular end-diastolic volume (LVEDV) and higher LVEF than the non-super-responders (non-SRs). The percentage of patients using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) was higher in SRs than non-SRs. Most SRs had Biventricular (BiV) pacing percentage greater than 98% six months after CRT. In the multivariate logistic regression analysis, the independent predictors of SRs were lower LVEDV [odd ratios (OR): 0.93; confidence intervals (CI): 0.90-0.97], use of ACEI/ARB (OR: 0.33; CI: 0.13-0.82) and BiV pacing percentage greater than 98% (OR: 0.29; CI: 0.16-0.87).

Conclusion: Patients with a better compliance of ACEI/ARB and a less ectatic ventricular geometry before CRT tends to have a greater probability of becoming SRs. Higher percentage of BiV pacing is essential for becoming SRs.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2017.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863051PMC
December 2017

Repetitive optimizing left ventricular pacing configurations with quadripolar leads improves response to cardiac resynchronization therapy: A single-center randomized clinical trial.

Medicine (Baltimore) 2017 Sep;96(37):e8066

The Cardiac Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: This study aimed to investigate whether repetitive optimizing left ventricular pacing configurations (LVPCs) with quadripolar leads (QUAD) can improve response to cardiac resynchronization therapy (CRT).

Methods: Fifty-two eligible patients were enrolled and 1:1 randomized to either the quadripolar LV leads (QUAD) group or the conventional bipolar leads (CONV) group. In the QUAD group, optimization of LVPC was performed for all patients before discharge and for nonresponders at 3 months follow-up. Clinical evaluations and transthoracic echocardiograms were performed before, 3, and 6 months after CRT implantation.

Results: At 3 months follow-up, 16 of 25 (64%) patients in the CONV group (1 patient was lost to follow-up) and 18 of 26 (69%) patients in the QUAD group were classified as responders. After optimizing the LVPCs in 3-month nonresponders in the QUAD group, 21 of 26 (80.8%) patients in the QUAD group were classified as responders at 6 months as compared with 17 of 25 (68%) patients in the CONV group. Left ventricular end-systolic volume (LVESV) reduction, left ventricular ejection fraction (LVEF) increase, and New York Heart Association (NYHA) functional class reduction at 6 months were significantly greater in the QUAD group than in the CONV group (LVESV: -26.9 ± 13.8 vs -17.2 ± 13.3%; P = .013; LVEF: +12.7 ± 8.0 vs +7.8 ± 6.3 percentage points; P = .017; NYHA: -1.27 ± 0.67 vs -0.72 ± 0.54 functional classes; P = .002).

Conclusions: Compared with conventional bipolar leads, CRT using quadripolar leads with repetitive optimized LVPCs resulted in an additional increase in LVEF and reduction in LVESV and NYHA functional class at 6-month follow-up.
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http://dx.doi.org/10.1097/MD.0000000000008066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604674PMC
September 2017

Clinical outcome of cardiac resynchronization therapy in dilated-phase hypertrophic cardiomyopathy.

J Geriatr Cardiol 2017 Apr;14(4):238-244

Cardiac Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Backgrounds: Clinical trials have demonstrated that cardiac resynchronization therapy (CRT) is effective in patients with "non-ischemic cardiomyopathy". However, patients with dilated-phase hypertrophic cardiomyopathy (DHCM) have been generally excluded from such trials. We aimed to compare the clinical outcome of CRT in patients with DHCM, idiopathic dilated cardiomyopathy (IDCM), or ischemic cardiomyopathy (ICM).

Methods: A total of 312 consecutive patients (DHCM: = 16; IDCM: = 231; ICM: = 65) undergoing CRT in Fuwai hospital were studied respectively. Response to CRT was defined as reduction in left ventricular end-systolic volume (LVESV) ≥ 15% at 6-month follow-up.

Results: Compared with DHCM, IDCM was associated with a lower total mortality (HR: 0.35, 95% CI: 0.13-0.90), cardiac mortality (HR: 0.29; 95% CI: 0.11-0.77), and total mortality or heart failure (HF) hospitalizations (HR: 0.34, 95% CI: 0.17-0.69), independent of known confounders. Compared with DHCM, the total mortality, cardiac mortality and total mortality or HF hospitalizations favored ICM but were not statistically significant (HR: 0.59, 95% CI: 0.22-1.61; HR: 0.59, 95% CI: 0.21-1.63; HR: 0.54, 95% CI: 0.26-1.15; respectively). Response rate to CRT was lower in the DHCM group than the other two groups although the differences didn't reach statistical significance.

Conclusions: Compared with IDCM, DHCM was associated with a worse outcome after CRT. The clinical outcome of DHCM patients receiving CRT was similar to or even worse than that of ICM patients. These indicate that DHCM behaves very differently after CRT.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2017.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483592PMC
April 2017

Admission white blood cell count predicts short-term clinical outcomes in patients with uncomplicated Stanford type B acute aortic dissection.

J Geriatr Cardiol 2017 Jan;14(1):49-56

State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objectives: Inflammation has been shown to be related with acute aortic dissection (AAD). The present study aimed to evaluate the association of white blood cell counts (WBCc) on admission with both in-hospital and long-term all-cause mortality in patients with uncomplicated Stanford type B AAD.

Methods: From 2008 to 2010, a total of 377 consecutive patients with uncomplicated type B AAD were enrolled and then followed up. Clinical data and WBCc on admission were collected. The primary end points were in-hospital death and long-term all-cause death.

Results: The in-hospital death rate was 4.2%, and the long-term all-cause mortality rate was 6.9% during a median follow-up of 18.9 months. WBCc on admission was identified as a risk factor for in-hospital death by univariate Cox regression analysis as both a continuous variable and a categorical variable using a cut off of 11.0 × 10 cell/L (all < 0.05). After adjusting for age, sex and other risk factors, elevated admission WBCc was still a significant predictor for in-hospital death as both a continuous variable [hazard ratio (HR): 1.052, 95% CI: 1.024-1.336, = 0.002] and a categorical variable using a cut off of 11.0 × 10 cell/L (HR: 2.056, 95% CI: 1.673-5.253, = 0.034). No relationship was observed between WBCc on admission and long-term all-cause death.

Conclusions: Our results indicate that elevated WBCc upon admission might be used as a predictor for increased risk of in-hospital death in uncomplicated type B AAD. There might be no predictive value of WBCc for the long-term survival of type B AAD.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2017.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329733PMC
January 2017

Short-Term Availability of Viable Left Ventricular Pacing Sites with Quartet™ Quadripolar Leads.

Med Sci Monit 2017 Feb 11;23:767-773. Epub 2017 Feb 11.

The Cardiac Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (mainland).

BACKGROUND Whether quadripolar leads can provide sufficient viable left ventricular pacing sites (LVPSs) for device optimization and multipoint pacing remains unclear. This study aimed to evaluate the acute and 3-month availability of viable LVPSs provided by a quadripolar LV pacing lead. MATERIAL AND METHODS A single-center cohort study evaluated consecutive patients who underwent a CRT implant with the QuartetTM LV lead under local guidelines. The availability of viable LVPSs was assessed at the pre-discharge and 3-month follow-up visit. Bipolar lead configurations, which served as the control group, were modeled by eliminating the 2 proximal electrodes on the Quartet™ LV lead. RESULTS A total of 24 patients were enrolled and finished 3-month follow-up. The mean follow-up period was 93±3 days. At pre-discharge, the Quartet™ LV lead provided more viable LVPSs compared with the bipolar equivalents (median 3 [IQR 2-4] vs. median 2 [IQR 1-2], P<0.001). The percentage of patients with at least 1, 2, 3, and 4 viable LVPSs were 100% (24/24), 91.7% (22/24), 58.3% (14/24), and 33.3% (8/24) for Quartet™ leads and 91.7% (22/24), 70.8% (17/24), 0% (0/24), and 0% (0/24) for bipolar lead configurations, respectively. The median and IQR values of viable LVPSs provided by the Quartet™ LV lead remained the same (3 [IQR 2-4]) between pre-discharge and 3-month follow-up (P=0.45). CONCLUSIONS Compared with the bipolar equivalent, QuartetTM LV lead provides more viable LVPSs and opportunities for CRT optimization and multipoint LV pacing. The number of LVPSs provided by Quartet™ leads remained unchanged between pre-discharge and 3-month follow-up.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5317280PMC
http://dx.doi.org/10.12659/msm.902743DOI Listing
February 2017

Acute and Chronic Changes and Predictive Value of Tpeak-Tend for Ventricular Arrhythmia Risk in Cardiac Resynchronization Therapy Patients.

Chin Med J (Engl) 2016 09;129(18):2204-11

Cardiac Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.

Background: Prolongation of the Tpeak-Tend (TpTe) interval as a measurement of transmural dispersion of repolarization (TDR) is an independent risk factor for chronic heart failure mortality. However, the cardiac resynchronization therapy's (CRT) effect on TDR is controversial. Therefore, this study aimed to evaluate CRTs acute and chronic effects on repolarization dispersion. Furthermore, we aimed to investigate the relationship between TpTe changes and ventricular arrhythmia.

Methods: The study group consisted of 101 patients treated with CRT-defibrillator (CRT-D). According to whether TpTe was shortened, patients were grouped at immediate and 1-year follow-up after CRT, respectively. The echocardiogram index and ventricular arrhythmia were observed and compared in these subgroups.

Results: For all patients, TpTe slightly increased immediately after CRT-D implantation, and then decreased at the 1-year follow-up (from 107 ± 23 to 110 ± 21 ms within 24 h, to 94 ± 24 ms at 1-year follow-up, F = 19.366,P< 0.001). No significant difference in the left ventricular reverse remodeling and ventricular tachycardia/ventricular fibrillation (VT/VF) episodes between the TpTe immediately shortened and TpTe immediately nonshortened groups. However, patients in the TpTe at 1-year shorten had a higher rate of the left ventricular (LV) reverse remodeling (65% vs. 44%, χ2 = 4.495, P = 0.038) and less VT/VF episodes (log-rank test, χ2 = 10.207, P = 0.001) compared with TpTe 1-year nonshortened group. TpTe immediately after CRT-D independently predicted VT/VF episodes at 1-year follow-up (hazard ratio [HR], 1.030; P = 0.001).

Conclusions: Patients with TpTe shortened at 1-year after CRT had a higher rate of LV reverse remodeling and less VT/VF episodes. The acute changes of TpTe after CRT have minimal value on mechanical reverse remodeling and ventricular arrhythmia.
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http://dx.doi.org/10.4103/0366-6999.189916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5022342PMC
September 2016

Differential expression of microRNAs in aortic tissue and plasma in patients with acute aortic dissection.

J Geriatr Cardiol 2015 Nov;12(6):655-61

State Key Laboratory of Cardiovascular Disease, Sino-German Laboratory for Molecular Medicine, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Background: Biomarker-assisted diagnosis of acute aortic dissection (AAD) is important for diagnosis and treatment. However, identification of biomarkers for AAD in blood is a challenging task. The aim of this study is to search for new potentially microRNA (miRNAs) biomarkers in AAD.

Methods: The miRNAs expression profiles in ascending aortic tissue and plasma were examined by microarray analysis in two sets or groups. The tissue group was composed of four patients with AAD and four controls of healthy male organ donors. The plasma group included 20 patients with AAD and 20 controls without cardiovascular disease. Bioinformatics was used to analyze the potential targets of the differentially expressed miRNAs.

Results: Our study revealed that in AAD patients, the aortic tissue had 30 differentially expressed miRNAs with 13 up-regulated and 17 down-regulated, and plasma had 93 differentially expressed miRNAs, of which 33 were up-regulated and 60 were down-regulated. Four miRNAs were found to be up-regulated in both aortic tissue and plasma in AAD patients. The predicted miRNA targets indicated the four dysregulated miRNAs mainly targeted genes that were associated with cell-cell adhesion, extracellular matrix metabolism, cytoskeleton organization, inflammation, and multiple signaling pathways related to cellular cycles.

Conclusions: Four miRNAs, which are up-regulated both in aortic tissue and in plasma in AAD patients, have been identified in this study. These miRNAs might be potential diagnostic biomarkers for AAD. Larger sample investigations are needed for further verification.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2015.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712372PMC
November 2015

Screening of pathogenic genes in Chinese patients with arrhythmogenic right ventricular cardiomyopathy.

Chin Med J (Engl) 2013 Nov;126(22):4238-41

Arrhythmia Center and Clinical EP Laboratory, State Key Laboratory of Cardiovascular Diseases, National Center for Cardiovascular Disease, Fuwai Hospital, Peking Union Medical College-Chinese Academy of Medical Sciences, Beijing 100037, China.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes.

Methods: A total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C.

Results: Fifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in non-desmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them (one of each gene) appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers.

Conclusions: Plakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Non-desmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.
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November 2013

Upregulation of TRPM7 channels by angiotensin II triggers phenotypic switching of vascular smooth muscle cells of ascending aorta.

Circ Res 2012 Oct 14;111(9):1137-46. Epub 2012 Aug 14.

Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan 2nd Rd, Guangzhou, China 510080.

Rationale: Angiotensin II (Ang II) has pleiotropic effects on vascular smooth muscle cells (VSMCs). It has been demonstrated to promote the proliferative phenotype of VSMCs in mouse ascending aorta, but the underlying mechanisms remain incompletely understood.

Objective: The present study was designed to explore whether the Ca(2+)-permeable transient receptor potential melastatin 7 (TRPM7) channel is involved in Ang II-induced phenotype switching of ascending aortic VSMCs and to dissect the molecular mechanisms by which TRPM7 modulates VSMC phenotype.

Methods And Results: As revealed by current recording, Ang II infusion increased TRPM7 whole-cell currents in ascending aortic VSMCs. The increase in TRPM7 currents was found to result from enhanced expression of TRPM7 protein rather than elevated single-channel activity (open probability and slope conductance) and/or reduced Mg(2+)-mediated channel block. Mechanistically, Ang II elevated TRPM7 expression via Ang II type 1 receptor-mediated ERK1/2 signaling. As indicated by the expression levels of VSMC differentiation marker genes, phenotypic switching of ascending aorta occurred during Ang II infusion. Meanwhile, ERK1/2-Elk-1 signaling pathway known to suppress VSMC differentiation was activated in Ang II-infused ascending aorta. Knockdown of TRPM7 with small interfering RNA established a causative role of TRPM7 in Ang II-induced phenotypic change and promotion of cell proliferation. Moreover, TRPM7 was shown to be required for Pyk2-ERK1/2-Elk-1 pathway activation by Ang II, which potentiated TRPM7 channel function and thus activated the Ca(2+)-sensitive kinase Pyk2. Finally, TRPM7 knockdown attenuated Ang II-induced displacement of myocardin from SM22 promoter, but the effects could be reversed by expression of constitutively active c-Src.

Conclusions: Our data establish that upregulation of TRPM7 channels by Ang II contributes to the development of the proliferative phenotype of ascending aortic VSMCs, and TRPM7 channel suppresses VSMC gene expression via Ca(2+) influx-mediated activation of Pyk2-ERK1/2-Elk-1 pathway.
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http://dx.doi.org/10.1161/CIRCRESAHA.112.273755DOI Listing
October 2012

The association of an adenine insertion variant in the 5'UTR of the endothelin-1 gene with hypertension and orthostatic hypotension.

Arch Med Sci 2012 May;8(2):219-26

Department of Cardiology, Cardiovascular Institute and FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Introduction: An adenine insertion polymorphism in the 5' untranslated region of the endothelin-1 gene is functional and increases the expression of endothelin mRNA and protein in the insertion homozygote. In the present study we hypothesized that this functional polymorphism might be associated with hypertension and/or orthostatic hypotension.

Material And Methods: The adenine insertion polymorphism was genotyped in 381 untreated hypertensive patients and 298 normotensive subjects, all of whom underwent an upright posture study for orthostatic blood pressure measurements. Orthostatic hypotension was defined as a drop in blood pressure of 20/10 mm Hg or more within 3 min of assuming the upright posture.

Results: The allele frequency of the adenine insertion was similar in hypertensive and normotensive subjects (15.2% vs. 15.3%, p > 0.05). After adjustment for age, sex and body mass index, blood pressure levels did not differ significantly among the genotypes in both hypertensives and normotensives. No associations were found between the distribution of the adenine insertion genotypes and the risk of orthostatic hypotension in both hypertensive patients and normotensive subjects even after adjustment for demographic parameters and supine systolic or diastolic blood pressure. Neither hypertensive nor normotensive subjects showed significant differences in orthostatic systolic or diastolic blood pressure changes among the genotype groups (all p > 0.05).

Conclusions: We concluded that the functional adenine insertion polymorphism in the endothelin-1 gene is not associated with either hypertension or orthostatic hypotension risk in Chinese.
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http://dx.doi.org/10.5114/aoms.2012.28548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361033PMC
May 2012

Genetic diagnosis of Liddle's syndrome by mutation analysis of SCNN1B and SCNN1G in a Chinese family.

Chin Med J (Engl) 2012 Apr;125(8):1401-4

Department of Cardiology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.

Background: Liddle's syndrome is a rare autosomal-dominant monogenic form of salt-sensitive hypertension. This study aimed to screen the gene mutation in β and γ subunits of the epithelial sodium channel (ENaC) of a Chinese family with Liddle's syndrome, an autosomal dominant form of hypertension.

Methods: DNA samples from the proband with early-onset, treatment-resistant hypertension and suppressed plasma renin activity were initially screened for mutations in the C-terminal exons of the ENaC β or γ subunit genes, using amplification by polymerase chain reaction and direct DNA sequencing. We also screened the C-terminus of SCNN1B and SCNN1G in family members, and screened for the mutation in 150 controls.

Results: Genetic analysis of the β ENaC gene revealed a missense mutation of CCC to TCC at codon 616 in the proband, her mother and her grandmother. One hundred and fifty randomly selected controls had not the mutation, indicating that this is not a common genetic polymorphism. There was no mutation of the γ ENaC gene in any of the individuals examined.

Conclusions: Through direct DNA sequencing analysis, we established the diagnosis of Liddle's syndrome for the proband and her families, and provided tailored therapies to this abnormality. These results provide further evidence that Pro616Ser is a critical amino acid that has a key role in the inhibition of sodium channel activity.
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April 2012

[Association of orthostatic hypertension and hypotension with target organ damage in middle and old-aged hypertensive patients].

Zhonghua Yi Xue Za Zhi 2011 Jan;91(4):220-4

Hypertension Division, Department of Cardiology, Cardiovascular Institute & Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China.

Objective: To investigate the association of orthostatic hypertension and hypotension with hypertensive target organ damage in middle and old-aged hypertensive patients.

Methods: This cross-section study was conducted in 4711 hypertensive patients aged 40-75 years old in 7 communities of Xinyang County, Henan Province by a multistage cluster sampling method. All patients received a standardized questionnaire, physical and biochemical examinations, echocardiography, ankle-brachial blood pressure index and orthostatic blood pressure measurement. Orthostatic hypertension was defined as an elevation of systolic blood pressure by 20 mm Hg or more while orthostatic hypotension as a drop of blood pressure by 20/10 mm Hg or more. When an upright posture was assumed. Others not belonging to these two conditions were classified into orthostatic normotension.

Results: The prevalence of orthostatic hypertension and hypotension was 16.3% and 23.8% in hypertensive patients. Peripheral artery disease was significantly more frequent in hypertensives with orthostatic hypertension (10.1%) or hypotension (10.7%) than those with orthostatic normotensives (7.4%) (both P<0.05). Patients with orthostatic hypotension had more common left ventricular hypertrophy (53.0% vs 43.2%, P<0.001) and a decreased estimated glomerular filtration rate (38.6% vs 34.4%, P<0.05) than did those with orthostatic normotension. After controlling for age, gender, body mass index and other confounders, orthostatic hypertension was positively associated with peripheral arterial disease (OR 1.39, 95%CI 1.05-1.84) while orthostatic hypotension was significantly associated with peripheral arterial disease (OR 1.45, 95%CI 1.13-1.86) and left ventricular hypertrophy (OR 1.46, 95%CI 1.11-1.84). But no independent association was found between orthostatic hypertension or hypotension and a decreased estimated glomerular filtration rate in hypertensive patients. The adjusted odds ratios (OR) for left ventricular hypertrophy, as predicted by the quintiles of orthostatic systolic blood pressure changes, showed a J-shaped relationship in hypertensive women, and so did peripheral artery disease in untreated hypertensive patients.

Conclusion: Hypertensive patients with orthostatic hypertension or hypotension may have an elevated risk of developing target organ damage.
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January 2011

Association of intergenic polymorphism of organic anion transporter 1 and 3 genes with hypertension and blood pressure response to hydrochlorothiazide.

Am J Hypertens 2011 Mar 16;24(3):340-6. Epub 2010 Dec 16.

Hypertension Division, Department of Cardiology, Cardiovascular Institute & Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

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.
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http://dx.doi.org/10.1038/ajh.2010.191DOI Listing
March 2011

Disorders of orthostatic blood pressure response are associated with cardiovascular disease and target organ damage in hypertensive patients.

Am J Hypertens 2010 Aug 22;23(8):829-37. Epub 2010 Apr 22.

Department of Cardiology, Cardiovascular Institute and FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: The prevalence and clinical significance of orthostatic hypertension (OHT) remain largely undetermined in hypertensive patients. This study investigated the association of OHT and orthostatic hypotension (OH) with cardiovascular disease (CVD) and target organ damage (TOD) in hypertensive patients.

Methods: A cross-sectional study was conducted in 4,711 hypertensives and 826 normotensives, aged 40-75 years. OHT was defined as an increase in systolic blood pressure (SBP) of > or =20 mm Hg, and OH was defined as either a reduction in SBP of at least 20 mm Hg or a reduction in diastolic BP (DBP) of at least 10 mm Hg during the first 3 min after standing.

Results: Hypertension was only independently associated with a risk of OHT. After controlling for age, sex, and other confounders, OH was associated with peripheral artery disease (PAD) (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.15-1.89, P < 0.01), left ventricular hypertrophy (LVH) (OR 1.48, 95% CI 1.12-1.93, P < 0.001), coronary artery disease (CAD) (OR 1.71, 95% CI 1.12-2.61, P < 0.01), and stroke (OR 1.72, 95% CI 1.19-2.34, P < 0.01), but OHT was only associated with PAD (OR 1.36, 95% CI 1.05-1.81, P < 0.05) and stroke (OR 1.76, 95% CI 1.27-2.26, P < 0.01). The adjusted OR for PAD, predicted by the quintiles of the orthostatic SBP changes, showed a J-shaped relationship in untreated hypertensive patients, as was also the case for LVH in hypertensive women.

Conclusions: OH is associated with CV risk; the associations of OHT with TOD and stroke in hypertensive patients still need to be confirmed in prospective studies.
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http://dx.doi.org/10.1038/ajh.2010.76DOI Listing
August 2010

[Prevalence and associated risk factors of hyperuricemia in rural hypertensive patients].

Zhonghua Yi Xue Za Zhi 2009 Oct;89(38):2667-70

Hypertension Division, Department of Cardiology, Cardiovascular Institute and Fu wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.

Objective: To investigate the prevalence of hyperuricemia and its associated risk factors in treated and untreated hypertensive patients in Chinese rural area.

Methods: This cross-section study was performed in 5235 hypertensive patients aged 40 - 75 years old at Xinyang, Henan by using a multistage cluster sampling method. All patients underwent an investigation composed of a standardized questionnaire, physical and biochemical examination. Hyperuricemia was defined as serum uric acid levels > or = 420 micromol/L in men or > or = 360 micromol/L in women.

Results: The overall prevalence of hyperuricemia was 14.1%, and it was higher in men than in women (21.5% vs 10.2%, P < 0.01). With an increase of body mass index (BMI), the prevalence of hyperuricemia and serum uric acid level increased significantly in both sexes [BMI < 25, > or = 30: 14.4%, 30.4%, (328 +/- 83) micromol/L, (383 +/- 86) micromol/L in males; and 7.2%, 17.0%, (251 +/- 70) micromol/L, (293 +/- 75) micromol/L in females, respectively, all P < 0.01]. So did that with increase of age only in female patients (40 - 49 years vs > or = 70 years: 5.8% - 18.0%, respectively, P < 0.01). Antihypertensive treatment, lipid disorder, smoking and alcohol consumption also significantly increased the incidence of hyperuricemia and the serum uric acid level (all P < 0.01). However, no significant differences were found among patients with I, II, and III blood pressure levels (all P > 0.05). After adjustment for age and other conventional risk factors by using multiple logistic regression analysis, hyperuricemia was significantly associated with BMI, alcohol consumption and diuretics in males as well as BMI, lipid disorder, age, smoking, and antihypertensive treatment in females.

Conclusions: Hyperuricemia is relatively less common in rural hypertensive patients. The associated risk factors of hyperuricemia and elevated serum uric acids include sex, age, BMI, antihypertensive medicines, lipid disorder, smoking and alcohol consumption. The effect of these factors is different between sexes.
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October 2009

Polymorphisms of angiotensin-converting enzyme (ACE) and ACE2 are not associated with orthostatic blood pressure dysregulation in hypertensive patients.

Acta Pharmacol Sin 2009 Sep 17;30(9):1237-44. Epub 2009 Aug 17.

Department of Cardiology and Hypertension Division, Ministry of Education, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.

Aim: The genetic background of orthostatic blood pressure dysregulation remains poorly understood. Since the renin-angiotensin system plays an important role in blood pressure regulation and response to position change, we hypothesized that angiotensin-converting enzyme (ACE) and ACE2 genetic polymorphisms might contribute, at least partially, to orthostatic blood pressure dysregulation in hypertensive patients.

Methods: Two tag single nucleotide polymorphisms (SNPs) of ACE2 and ACE I/D were genotyped in 3630 untreated hypertensive patients and 826 normotensive subjects. Orthostatic hypertension was defined as an increase in systolic blood pressure of 20 mmHg or more and orthostatic hypotension as a drop in blood pressure of 20/10 mmHg or more within three minutes of assumption of upright posture.

Results: Female and male patients had similar rates of orthostatic hypertension (16.5% vs 15.3%) and hypotension (22.5% vs 23.8%). No significant differences were detected in the minor allele frequency of ACE2 rs2106809, rs2285666, or ACE I/D in either female or male patients with orthostatic hypertension (15.1%, 22.7%, 19.6%, respectively), hypotension (13.8%, 25%, 16.5%), or normal orthostatic blood pressure response (14.4%, 21.9%, 15.8%) in additive, dominant or recessive models after adjustment for confounders (all P>0.05). The orthostatic changes in systolic and diastolic blood pressure were also comparable among patients carrying different genotypes. Similar results were observed in normotensive subjects.

Conclusion: These data provide no support for the involvement of ACE or ACE2 in the genetic predisposition to orthostatic hypotension or hypertension.
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http://dx.doi.org/10.1038/aps.2009.110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007186PMC
September 2009

[The role of ACE 2 in blood pressure regulation (no abstract)].

Zhonghua Xin Xue Guan Bing Za Zhi 2008 Jun;36(6):569-72

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June 2008

Ghrelin receptor gene polymorphisms are associated with female metabolic syndrome in Chinese population.

Chin Med J (Engl) 2008 Sep;121(17):1666-9

Hypertension Division, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China.

Background: The ghrelin plays an important role in the regulation of food intake and energy homeostasis. Therefore, the ghrelin receptor gene (GHSR) is an excellent candidate for studying metabolic syndrome. This study aimed to investigate whether polymorphisms in ghrelin receptor gene are associated with metabolic syndrome in Chinese population.

Methods: Subjects consisted of 698 patients aged 41 to 80 years, diagnosed as metabolic syndrome by International Diabetes Federation (IDF) 2005 criteria, and 762 age- and gender-matched controls. Three variants within the GHSR were selected and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Odds ratios were estimated using a case-control study design by controlling confounding factors.

Results: The A/A genotype (rs2922126) in the promoter was associated with metabolic syndrome (OR 1.41, 95% CI 1.03-1.94), increased waist circumference (OR 1.75, 95% CI 1.26-2.42), and increased fast blood glucose (OR 1.49, 95% CI 1.07-2.06) in women. The A/A genotype (rs509030) in the intron was associated with lower plasma high density lipoprotein in women (OR 1.37, 95% CI 1.02-1.84).

Conclusion: The polymorphisms within GHSR might be a genetic risk factor for metabolic syndrome in women.
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September 2008

[Advancement in pharmacogenomics of beta-blocker therapy].

Zhonghua Xin Xue Guan Bing Za Zhi 2006 Oct;34(10):947-50

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October 2006
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