Liang-jian Zou

Four genetic polymorphisms of paraoxonase gene and risk of coronary heart disease: A meta-analysis based on 88 case–control studies

OBJECTIVE The human paraoxonase (PON) is calcium dependent HDL associated ester hydrolase which has attracted considerable attention as a candidate gene for coronary heart disease based on its enzyme function as a key factor in lipoprotein catabolism pathways. Many studies have examined the association between polymorphisms in the PON gene and risk of coronary heart disease (CHD), but the results have been inconsistent. METHODS We conducted a meta-analysis of 88 studies on 4 PON polymorphisms [Q192R, L55M, and T(-107)C in the PON1 and the S311C in the PON2] published before August 2010, including a total of 24,702 CHD cases and 38,232 controls. We also systematically explored potential sources of heterogeneity. RESULT In a combined analysis, the summary per-allele odds ratio for CHD of the 192R was 1.11 (95% CI: 1.05-1.17). However, when the analyses were restricted to 10 larger studies (n>500 cases), the summary per-allele odds ratio was 0.96 (95% CI: 0.90-1.02). Our analyses detected a possibility of publication bias with an overestimate of the true association by smaller studies. A meta-analysis of studies on the 55M, (-107)T, and 311C variant showed no significant overall association with CHD, yielding a per-allele odds ratio of 0.94 (95% CI: 0.88-1.00), 1.02 (95% CI: 0.91-1.15) and 1.02 (95% CI: 0.90-1.16) respectively. CONCLUSIONS This meta-analysis suggested an overall weak association between the R192 polymorphism and CHD risk.

Genetic polymorphisms of glutathione S-transferase genes GSTM1, GSTT1 and risk of coronary heart disease

To clarify the role of glutathione S-transferases (GSTs; GSTM1 and GSTT1) status in susceptibility to coronary heart disease (CHD), a meta-analysis of published studies was performed. A total of 19 studies including 8020 cases and 11 501 controls were included in this meta-analysis. In a combined analysis, the relative risks for CHD of the GSTM1 null and GSTT1 null polymorphisms were 1.47 [95% confidence interval (CI): 1.08-2.01] and 1.26 (95% CI: 0.90-1.75), respectively. Three potential sources of heterogeneity including ethnicity, source of control and sample size of study were also assessed. However, no significant association was found in stratified analyses. By pooling data from eight studies (2909 cases and 3745 controls) that considered combinations of GSTT1 and GSTM1 genotypes, a statistically significant increased risk for CHD [odds ratio (OR = 2.38, 95% CI: 1.03-5.48)] was detected for individuals with combined deletion mutations in both genes compared with positive genotypes. Results from the meta-analysis of five studies on GSTs stratified according to smoking status showed an increased risk for individuals with null genotype (OR = 2.21, 95% CI: 1.24-3.92 for GSTM1 and OR = 3.29, 95% CI: 1.49-7.26 for GSTT1) versus non-null genotypes. This meta-analysis suggests that the GSTM1 null genotype may slightly increase the risk of CHD and that interaction between unfavourable GSTs genotypes may exist.

Clinical Application of Pharmacogenetic-Based Warfarin-Dosing Algorithm in Patients of Han Nationality after Rheumatic Valve Replacement: A Randomized and Controlled Trial

Background The polymorphisms of VKORC1 and CYP2C9 play increasingly important roles in the inter-individual variability in warfarin dose. This study aimed to evaluate the feasibility of clinical application of pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality with rheumatic heart disease after valve replacement in a randomized and controlled trial. Methods One hundred and one consecutive patients of Han nationality with rheumatic heart disease undergoing valve surgery were enrolled and randomly assigned to an experimental group (n=50, based on CYP2C9 and VKORC1 genotypes, pharmacogenetic-based “predicted warfarin dose” for 3 days and then was adjusted to INR until stable warfarin maintenance dose) or a control group (n=51, 2.5mg/d for 3 days and then was adjusted to INR until stable warfarin maintenance dose). All included patients were followed for 50 days after initiation of warfarin therapy. The primary end-point was the time to reach a stable warfarin maintenance dose. Results During the follow-up, 84.0% patients in the experimental group and 58.8% patients in the control group received warfarin maintenance dose. Compared with control group, patients in the experimental group had shorter mean time elapse from initiation of warfarin therapy until warfarin maintenance dose (27.5±1.8 d versus 34.7±1.8 d, p<0.001). Cox regression revealed that group (HR for experimental versus control group: 1.568, 95%CI 1.103-3.284) and age were two significant variables related to the time elapse from initiation of warfarin therapy until warfarin maintenance dose. The predicted warfarin maintenance dose was prominently correlated with the actual warfarin maintenance dose (r=0.684, p<0.001). Conclusion: Based on CYP2C9 and VKORC1 genotypes, the pharmacogenetic-based warfarin-dosing algorithm may shorten the time elapse from initiation of warfarin therapy until warfarin maintenance dose. It is feasible for the clinical application of the pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality with rheumatic heart disease after valve replacement.

Quantitative Assessment of the Influence of Paraoxonase 1 Activity and Coronary Heart Disease Risk

Human paraoxonase 1 (PON1) is a calcium-dependent high-density lipoprotein associated ester hydrolase that has attracted considerable attention as a candidate factor for coronary heart disease (CHD) based on its function as a key factor in lipoprotein catabolism pathways. This meta-analysis aimed to clarify the inconsistency of published studies and to establish a comprehensive picture of the relationship between PON1 activity and CHD susceptibility. A systematic search was performed from PubMed, Web of Science, EMBASE, and CNKI databases. Ratio of means (RoM) between case and control and 95% confidence intervals (CIs) were calculated using a random-effects model. The source of heterogeneity was explored by subgroup analysis and meta-regression. We identified 47 eligible studies including a total of 9853 CHD cases and 11,408 controls. The pooled analysis showed that CHD patients had a 19% lower PON1 activity than did the controls (RoM=0.81; 95% CI: 0.74-0.89, p<10(-5)). In the subgroup analyses by CHD end points, a similar effect size was observed with coronary stenosis and myocardial infarction subgroups, with corresponding RoM of 0.81 (95% CI: 0.73-0.89, p<10(-4)) and 0.83 (95% CI: 0.74-0.93, p=0.001), respectively. Decreased PON1 activity associated with CHD risk was observed in almost all subgroup analysis according to ethnicity, sample size, study design, mean age of cases, source, and type of control. Decreased PON1 activity may act as a risk factor for the development of CHD. Progressive decrease in serum PON1 activity may exist for an individual with severe disease. However, larger studies using a prospective approach are needed to confirm our results.

Does PGA external stenting reduce compliance mismatch in venous grafts

BackgroundAutogenous vein grafting is widely used in regular bypassing procedures. Due to its mismatch with the host artery in both mechanical property and geometry, the graft often over expands under high arterial blood pressure and forms a step-depth where eddy flow develops, thus causing restenosis, fibrous graft wall, etc. External stents, such as sheaths being used to cuff the graft, have been introduced to eliminate these mismatches and increase the patency. Although histological and immunochemical studies have shown some positive effects of the external stent, the mechanical mismatch under the protection of an external stent remains poorly analyzed.MethodsIn this study, the jugular veins taken from hypercholesterolemic rabbits were transplanted into the carotid arteries, and non-woven polyglycolic acid (PGA) fabric was used to fabricate the external stents to study the effect of the biodegradable external stent. Eight weeks after the operation, the grafts were harvested to perform mechanical tests and histological examinations. An arc tangent function was suggested to describe the relationship between pressure and cross-sectional area to analyse the compliance of the graft.ResultsThe results from the mechanical tests indicated that grafts either with or without external stents displayed large compliance in the low-pressure range and were almost inextensible in the high-pressure range. This was very different from the behavior of the arteries or veins in vivo. The data from histological tests showed that, with external stents, collagen fibers were more compact, whilst those in the graft without protection were looser and thicker. No elastic fiber was found in either kind of grafts. Furthermore, grafts without protection were over-expanded which resulted in much bigger cross-sectional areas.ConclusionThe PGA external extent contributes little to the reduction of the mechanical mismatch between the graft and its host artery while remodeling develops. For the geometric mismatch, it reduces the cross-section area, therefore matching with the host artery much better. Although there are some positive effects, conclusively the PGA is not an ideal material for external stent.

Surgical treatment of multivalvular endocarditis: Twenty-one–year single center experience

OBJECTIVE Little information is available about surgical outcomes in patients with multivalvular endocarditis. The aim of this article is to review the 21-year experience with surgical treatment of patients with multivalvular endocarditis at our institution and, in particular, to determine the incidence, pathologic status, diagnosis, surgical strategies, and outcomes of patients with this disease. METHODS From January 1986 to December 2006, a total of 48 patients (40 men, 8 women), with a mean age of 42 +/- 12 years, underwent surgery for multivalvular endocarditis. Endocarditis was active in 32 patients and healed in 16. Preoperative transthoracic echocardiographic evaluation was performed in all 48 patients with addition of transesophageal echocardiography in 22 (45.8%). Intraoperative findings showed that the endocarditis involved mostly the mitral and aortic valves (40/48 patients). Triple or quadruple valve involvement was found in 1 and 2 patients, respectively. Preoperative, perioperative, and postoperative data were retrospectively analyzed and risk factors for early and late survival were determined. RESULTS In only 24 (50.0%) patients was multivalvular endocarditis diagnosed by preoperative transthoracic echocardiography; 17 (77.3%) patients had multivalvular endocarditis confirmed by preoperative transesophageal echocardiography. The 30-day hospital mortality was 12.5% (n = 6). Preoperative renal failure, New York Heart Association class IV, and emergency surgery were identified as independent risk factors for hospital mortality. Overall long-term survival was 74% +/- 6% at 5 years and 62% +/- 3% at 10 years. Multivariate analysis revealed that renal failure and recurrent endocarditis were associated with increased late mortality. Ten-year freedom from recurrent endocarditis was 74% +/- 5% and 10-year freedom from reoperation was 73% +/- 6%. CONCLUSIONS In our institution, multivalvular endocarditis was diagnosed by transthoracic echocardiography in only half of the patients. Intraoperative transesophageal echocardiography provided a more effective means to identify this disease. Radical resection of all infected tissues for patients with multivalvular endocarditis and additional intraoperative interventions, depending on the intraoperative pathologic condition, produced satisfactory in-hospital and long-term results, similar to those in patients with a single infected heart valve.

Valve Repair With Autologous Pericardium for Organic Lesions in Rheumatic Tricuspid Valve Disease

BACKGROUND Surgical repair of pathologic tricuspid valve disease often fails because of severe anatomic distortion of the valve apparatus, particularly in patients with rheumatic heart disease. This usually leads to tricuspid valve replacement despite the associated prosthesis-related complications. This study examines our experience of tricuspid valve repair with autologous pericardium for organic rheumatic tricuspid valve disease. METHODS From 1996 to 2007, 31 patients underwent repairs for rheumatic tricuspid valve disease characterized by retracted leaflets and inadequate leaflet area. The patients, aged 14 to 56 years, had a mean New York Heart Association (NYHA) class of 2.9 +/- 0.6. All patients presented with severe tricuspid regurgitation and coexisting left-sided heart valve disease. Glutaraldehyde-treated autologous pericardial patch was used to augment tricuspid valve leaflets. Other techniques were applied as needed, including commissurotomy, leaflet mobilization, annuloplasty, and prosthetic ring implantation. Concomitant operations included left-sided valve replacement in all, and left atrial thrombus removal in 3 patients. Follow-up duration was 4 to 126 months. RESULTS No deaths or late reoperations occurred. All patients demonstrated clinical improvements on follow-up. Echocardiographic studies before hospital discharge showed less than mild tricuspid regurgitation in all patients. The most recent echocardiographic follow-up showed no tricuspid regurgitation in 10 patients (32.3%), trivial regurgitation in 12 (38.7%), mild regurgitation in 8 (25.8%), and moderate regurgitation in 1 (3.2%). CONCLUSIONS In selected patients, organic rheumatic tricuspid valve disease can be treated with pericardial patch to augment the retracted leaflets in combination with other techniques. Follow-up reveals excellent tricuspid valve function.

Aortic valve replacement in Chinese adults (1990-2009)：a single center retrospective study

Objective To investigate the etiological spectrum of aortic valve diseases and the early prognosis of Chinese adults undergoing aortic valve replacement during 1990-2009.Methods The clinical data of 927 patients,who received aortic valve replacement in Changhai Hospital during 1990-2009,were retrospectively analyzed.Results It was showed that the major causes of the aortic valve replacement included congenital disease and degenerative conditions,with the proportions of rheumatic and infectious etiologies gradually decreased while those of degenerative and congenital etiologies kept increasing.The latter ten years witnessed a significantly decreased duration of postoperative ventilation,time in the intensive care unit(ICU)and length of postoperative hospital stay compared with those of the first ten years(P0.05).The overall in-hospital mortality was 4.7%(44 of 927 patients)in our study,showing no gender difference.The in-hospital mortality in the latter 15 years was significantly lower than that of the first 5 years(P0.05).Conclusion The causes of aortic valve disease in China have changed over the past 20 years,and the in-hospital mortality of adults undergoing aortic valve replacement has decreased than before.

Reinforced aortic root reconstruction for acute type A aortic dissection involving the aortic root

OBJECTIVE There are debates regarding the optimal approach for AAAD involving the aortic root. We described a modified reinforced aortic root reconstruction approach for treating AAAD involving the aortic root. METHODS A total of 161 patients with AAAD involving the aortic root were treated by our modified reinforced aortic root reconstruction approach from January 1998 to December 2008. Key features of our modified approach were placement of an autologous pericardial patch in the false lumen, lining of the sinotubular junction lumen with a polyester vascular ring, and wrapping of the vessel with Teflon strips. Outcome measures included post-operative mortality, survival, complications, and level of aortic regurgitation. RESULTS A total of 161 patients were included in the study (mean age: 43.3 1 15.5 years). The mean duration of follow-up was 5.1 1 2.96 years (2-12 years). A total of 10 (6.2%) and 11 (6.8%) patients died during hospitalization and during follow-up, respectively. Thirty-one (19.3%) patients experienced postoperative complications. The 1-, 3-, 5-, and 10-year survival rates were 99.3%, 98%, 93.8%, and 75.5%, respectively. There were no instances of recurrent aortic dissection, aortic aneurysm, or pseudoaneurysm during the entire study period. The severity of aortic regurgitation dramatically decreased immediately after surgery (from 28.6% to 0% grade 3-4) and thereafter slightly increased (from 0% to 7.2% at 5 years and 9.1% at 10 years). CONCLUSION This modified reinforced aortic root reconstruction was feasible, safe and durable/effective, as indicated by its low mortality, low postoperative complications and high survival rate.