Charn Sriratanasathavorn

Apolipoprotein E gene polymorphism: effects on plasma lipids and risk of type 2 diabetes and coronary artery disease

BackgroundThe most common apolipoprotein E (apoE) gene polymorphism has been found to influence plasma lipid concentration and its correlation with coronary artery disease (CAD) has been extensively investigated in the last decade. It is, however, unclear whether apoE gene polymorphism is also associated with increased risk of type 2 diabetes mellitus (T2DM). The knowledge of this study may provide the primary prevention for T2DM and CAD development before its initiation and progression. Therefore, this study was carried out to determine the association between apoE gene polymorphism and T2DM with and without CAD and its role in lipid metabolism.MethodsThe case-control study was carried out on a total of 451 samples including 149 normal control subjects, 155 subjects with T2DM, and 147 subjects with T2DM complicated with CAD. The apoE gene polymorphism was tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Univariable and multivariable logistic regression analyses were used to identify the possible risks of T2DM and CAD.ResultsA significantly increased frequency of E3/E4 genotype was observed only in T2DM with CAD group (p = 0.0004), whereas the ε4 allele was significantly higher in both T2DM (p = 0.047) and T2DM with CAD (p = 0.009) as compared with controls. E3/E4 genotype was also the independent risk in developing CAD after adjusting with established risk factors with adjusted odds ratio (OR) 2.52 (95%CI 1.28-4.97, p = 0.008). The independent predictor of individuals carrying ε4 allele still remained significantly associated with both CAD (adjusted OR 2.32, 95%CI 1.17-4.61, p = 0.016) and T2DM (adjusted OR 2.04, 95%CI 1.07-3.86, p = 0.029). After simultaneously examining the joint association of E3/E4 genotype combined with either obesity or smoking the risk increased to approximately 5-fold in T2DM (adjusted OR 4.93, 95%CI 1.74-13.98, p = 0.003) and 10-fold in CAD (adjusted OR 10.48, 95%CI 3.56-30.79, p < 0.0001). The association between apoE genotypes on plasma lipid levels was compared between E3/E3 as a reference and E4-bearing genotypes. E4-bearing genotypes showed lower HDL-C and higher VLDL-C and TG, whereas other values of plasma lipid concentrations showed no significant difference.ConclusionsThese results indicate that ε4 allele has influence on lipid profiles and is associated with the development of both T2DM with and without CAD, and furthermore, it increased the risk among the subjects with obesity and/or smoking, the conditions associated with high oxidative stress.

A randomised study comparing the efficacy and safety of rosuvastatin with atorvastatin for achieving lipid goals in clinical practice in Asian patients at high risk of cardiovascular disease (DISCOVERY-Asia study).

ABSTRACT Background: Most studies investigating the benefits of statins have focused on North American and European populations. This study focuses on evaluating the lipid-lowering effects of rosuvastatin and atorvastatin in Asian patients. Objectives: The DIrect Statin COmparison of LDL‐C Values: an Evaluation of Rosuvastatin therapY (DISCOVERY)-Asia study is one of nine independently powered studies assessing the efficacy of starting doses of statins in achieving target lipid levels in different countries worldwide. DISCOVERY-Asia was a 12-week, randomised, open-label, parallel-group study conducted in China, Hong Kong, Korea, Malaysia, Taiwan, and Thailand. Results: A total of 1482 adults with primary hypercholesterolaemia and high cardiovascular risk (> 20%/10 years, type 2 diabetes, or a history of coronary heart disease) were randomised in a 2 : 1 ratio to receive rosuvastatin 10 mg once daily (o.d.) or atorvastatin 10 mg o.d. The percentage of patients achieving the 1998 European Joint Task Force low-density lipoprotein cholesterol (LDL‐C) goal of < 3.0 mmol/L at 12 weeks was significantly higher in the rosuvastatin group (n = 950) compared with the atorvastatin group (n = 471) (79.5 vs. 69.4%, respectively; p < 0.0001). Similar results were observed for 1998 European goals for total cholesterol (TC), and the 2003 European goals for LDL‐C and TC. LDL‐C and TC levels were reduced significantly more with rosuvastatin compared with atorvastatin. Both drugs were well-tolerated and the incidence and type of adverse events were similar in each group. Conclusions: This 12-week study showed that the starting dose of rosuvastatin 10 mg o.d. was significantly more effective than the starting dose of atorvastatin 10 mg o.d. at enabling patients with primary hypercholesterolaemia to achieve European goals for LDL‐C and TC in a largely Asian population in real-life clinical practice. The safety profile of rosuvastatin 10 mg is similar to that of atorvastatin 10 mg in the Asian population studied here, and is consistent with the known safety profile of rosuvastatin in the white population. Trial registration: ClinicalTrials.gov identifier: NCT00241488.

Prospective Randomized Study to Assess the Efficacy of Site and Rate of Atrial Pacing on Long-Term Progression of Atrial Fibrillation in Sick Sinus Syndrome

Background— Atrial-based pacing is associated with lower risk of atrial fibrillation (AF) in sick sinus syndrome compared with ventricular pacing; nevertheless, the impact of site and rate of atrial pacing on progression of AF remains unclear. We evaluated whether long-term atrial pacing at the right atrial (RA) appendage versus the low RA septum with (ON) or without (OFF) a continuous atrial overdrive pacing algorithm can prevent the development of persistent AF. Methods and Results— We randomized 385 patients with paroxysmal AF and sick sinus syndrome in whom a pacemaker was indicated to pacing at RA appendage ON (n=98), RA appendage OFF (n=99), RA septum ON (n=92), or RA septum OFF (n=96). The primary outcome was the occurrence of persistent AF (AF documented at least 7 days apart or need for cardioversion). Demographic data were homogeneous across both pacing site (RA appendage/RA septum) and atrial overdrive pacing (ON/OFF). After a mean follow-up of 3.1 years, persistent AF occurred in 99 patients (25.8%; annual rate of persistent AF, 8.3%). Alternative site pacing at the RA septum versus conventional RA appendage (hazard ratio=1.18; 95% confidence interval, 0.79–1.75; P=0.65) or continuous atrial overdrive pacing ON versus OFF (hazard ratio=1.17; 95% confidence interval, 0.79–1.74; P=0.69) did not prevent the development of persistent AF. Conclusions— In patients with paroxysmal AF and sick sinus syndrome requiring pacemaker implantation, an alternative atrial pacing site at the RA septum or continuous atrial overdrive pacing did not prevent the development of persistent AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00419640.

Prospective Randomized Study to Assess the Efficacy of Site and Rate of Atrial Pacing on Long-term Progression of Atrial Fibrillation in Sick Sinus Syndrome: Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) Study

Background— Atrial-based pacing is associated with lower risk of atrial fibrillation (AF) in sick sinus syndrome compared with ventricular pacing; nevertheless, the impact of site and rate of atrial pacing on progression of AF remains unclear. We evaluated whether long-term atrial pacing at the right atrial (RA) appendage versus the low RA septum with (ON) or without (OFF) a continuous atrial overdrive pacing algorithm can prevent the development of persistent AF. Methods and Results— We randomized 385 patients with paroxysmal AF and sick sinus syndrome in whom a pacemaker was indicated to pacing at RA appendage ON (n=98), RA appendage OFF (n=99), RA septum ON (n=92), or RA septum OFF (n=96). The primary outcome was the occurrence of persistent AF (AF documented at least 7 days apart or need for cardioversion). Demographic data were homogeneous across both pacing site (RA appendage/RA septum) and atrial overdrive pacing (ON/OFF). After a mean follow-up of 3.1 years, persistent AF occurred in 99 patients (25.8%; annual rate of persistent AF, 8.3%). Alternative site pacing at the RA septum versus conventional RA appendage (hazard ratio=1.18; 95% confidence interval, 0.79–1.75; P=0.65) or continuous atrial overdrive pacing ON versus OFF (hazard ratio=1.17; 95% confidence interval, 0.79–1.74; P=0.69) did not prevent the development of persistent AF. Conclusions— In patients with paroxysmal AF and sick sinus syndrome requiring pacemaker implantation, an alternative atrial pacing site at the RA septum or continuous atrial overdrive pacing did not prevent the development of persistent AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00419640.

Atrial fibrillation management in Asia: From the Asian expert forum on atrial fibrillation

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with increased morbidity and mortality. AF has a slightly lower incidence and prevalence in Asian populations than in Western populations, but the associated relative risk of stroke and mortality is similar. Patients with AF in Asia have similar disease profiles and CHADS2 score distributions compared to those in the West, with the exception of a slightly higher prevalence of valvular heart diseases in Asia. Acute ventricular rate control should be the initial consideration in patients with AF and rapid ventricular rate. Anti-arrhythmic drugs have only a modest long-term effect on maintenance of sinus rhythm, and clinical trials in both the West and the East show that chronic rhythm control is not superior to chronic rate control in terms of cardiovascular outcomes, most likely because the benefit of anti-arrhythmic drugs in these trials was often offset by proarrhythmic effects. ECG-driven trials for AF should be replaced by outcome-driven ones. ATHENA is the largest outcome trial to confirm the superiority of a new anti-arrhythmic drug in improving cardiovascular outcomes. The choice of anti-arrhythmic drugs for AF should be based on both safety and efficacy in improving cardiovascular outcomes. For long-term rate control, a lenient strategy with a ventricular rate of less than 110bpm may be adequate, but more strict rate control may be required if patients continue to complain of symptoms. Catheter ablation should be reserved for patients who remain symptomatic despite optimal medical therapy.

One-year outcome after radiofrequency catheter ablation of symptomatic ventricular arrhythmia from right ventricular outflow tract

Although ventricular premature complexes (VPCs) in patients without structural heart disease are benign, many patients experience disabling symptoms. Many patients need long-term medication, which is often ineffective and may have adverse effects. Radiofrequency catheter ablation (RFCA) may be an alternative treatment. RFCA was performed in 33 patients with severely symptomatic VPCs that were refractory to medication. Mean VPCs were 23,987 +/- 2,077 beats/24 hours. Twenty-four-hour ambulatory electrocardiographic monitoring, quality of life, and symptoms were assessed at a screening visit and 1 and 12 months after RFCA. RFCA was successfully performed in 32 patients (97%). This resulted in a significant improvement in symptoms, severity of ventricular arrhythmia, and quality of life at 1 and 12 months after the procedure. There were no major complications related to the procedure. Eight patients (24%) had residual arrhythmia. Five of them underwent repeated ablation with successful results. Thus, catheter ablation is a safe and effective treatment for symptomatic ventricular arrhythmia from the right ventricular outflow tract. It also improves the quality of life. Catheter ablation is a viable alternative to drugs in the presence of disabling symptoms.

Insights Into Management of Atrial Fibrillation in Asia Pacific Gained From Baseline Data from REgistry on Cardiac rhythm disORDers (RecordAF-Asia Pacific [AP]) Registry

The burden of atrial fibrillation (AF) and the lack of data on AF and its management in the Asia Pacific highlight the need for a comprehensive prospective study of AF management in this region. To address this need, the REgistry on Cardiac rhythm disORDers (RecordAF-Asia Pacific [AP]) has been initiated to assess the management of AF in 8 countries across the Asia Pacific. RecordAF-AP is a prospective, observational survey of the management of recently diagnosed AF with 1 year of follow-up. Eligible patients with AF, treated or not, were included in the registry; with data recorded prospectively during the follow-up visits at 6 and 12 months. A total of 2,721 patients with AF were recruited, of whom 2,629 were eligible for evaluation (intent-to-treat population). At study inclusion, rhythm- and rate-control strategies were applied to 37% (n = 959) and 62% (n = 1,610) of the patients, respectively. At baseline, the rhythm-control patients were mainly prescribed class III agents (49%), class Ic agents (39%), or β blockers (except for sotalol; 35%). The rate-control patients were mainly prescribed β blockers (except for sotalol; 57%) or cardiac glycosides (32%). Patients receiving rate-control strategies were more likely to have a history of heart failure or valvular heart disease and persistent AF. In contrast, those receiving rhythm-control strategies were more likely to have recently diagnosed or paroxysmal AF. In conclusion, RecordAF-AP will provide much needed insight into the real-life management of patients with AF in the Asia Pacific region.

A Prospective Randomized Study to Assess the Efficacy of Rate and Site of Atrial Pacing on Long-Term Development of Atrial Fibrillation

The Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) study is a single‐blinded, parallel randomized designed multicenter study in pacemaker indicated patients with paroxysmal atrial fibrillation (AF). The objective is to evaluate whether the site of atrial pacing–‐conventional right atrial appendage versus low atrial septal—with or without atrial overdrive pacing will influence the development of persistent AF. The study will provide a definitive answer to whether a different atrial pacing site or the use of AF suppression pacing or both can give incremental antiarrhythmic benefit when one is implanting a device for a patient with a history of paroxysmal AF.

Lipid-lowering therapy using statins in patients with cardiovascular risk in clinical practice in Thailand.

Background Since the release in Thailand in 2001 of the Third Guidelines by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults or the Adult Treatment Panel (ATP III), there have been no nationwide studies on the proportion of dyslipidaemic patients who have achieved the low-density lipoprotein cholesterol (LDL-C) goals. The authors therefore aimed to estimate the percentage achievement of LDL-C goals based on the modified NCEP ATP III guidelines in intermediate- to high-risk patients. Methods The authors conducted a hospital-based, cross-sectional, epidemiological survey. Patients (1240) were selected consecutively from 50 hospitals across Thailand. Patients were included if they had been treated with statins for at least 3 months. Results Two-thirds were female, and the mean age was 61.7±9.5 years. The median duration of statin treatment was 21 months. Half (633/ 1240) of the patients achieved the LDL-C goal levels as defined by the NCEP guidelines (51.1%, 95% CI 48.3% to 53.8%). The very-high-risk group had the lowest percentage achievement (11.6%; 95% CI 1.6% to 21.6%), compared with 54.2% (95% CI 50.9% to 57.4%) for the high-risk group and 47.0% (95% CI 41.1% to 52.8%) for the moderate-risk group. More males achieved the LDL-C goals than females (55.6% vs 48.9%; p=0.029). Conclusions Overall, 51.1% of the patients with cardiovascular risk, on statins treatment, achieved the NCEP ATP III LDL-C goal levels.

Determining the Site of Accessory Pathways in Orthodromic Reciprocating Tachycardia by Using the Response to Right Ventricular Pacing.

Postpacing interval (PPI) after right ventricular (RV) pacing entrainment minus tachycardia cycle length (TCL) with a correction for atrioventricular (AV) node delay (corrected PPI‐TCL) was useful to differentiate atrioventricular node reentrant tachycardia (AVNRT) from orthodromic reciprocating tachycardia (ORT). However, the value of corrected PPI‐TCL in determining the site of the accessory pathway (AP) in ORT has not been investigated. The purpose of this study was to assess whether the corrected PPI‐TCL is useful in differentiating ORT using a left‐sided AP from a right‐sided AP.