High-Normal Thyroid Function and Recurrence of Atrial Fibrillation after Catheter Ablation: A Prospective Observational Study.

BACKGROUND: Thyroid function is increasingly recognized as an important modifiable factor for atrial fibrillation (AF); however, it is unclear if the changes in thyroid hormones, even within the normal range, are associated with AF recurrence after catheter ablation. METHODS: Consecutive paroxysmal AF patients who underwent catheter ablation were enrolled. Patients with abnormal thyroid hormones or previous thyroid illnesses were excluded. Patients were followed for 12 months or until they presented with the first episode of atrial tachyarrhythmia after a blanking period. RESULTS: The study included 448 patients with a mean age of 61 (14) years, and 46% were women. After a 1-year follow-up, 104 (23.2%) patients experienced atrial tachyarrhythmia recurrences after an ablation procedure. Recurrence was significantly different among quartile groups of thyroid function, with highest FT4 and FT3 levels associated with the greatest risk of recurrence (p < 0.001 and p = 0.024, respectively). FT4 and FT3 levels were independent predictors of atrial tachyarrhythmia recurrence (hazard ratio 1.07 per 1 pmol/L increase in FT4, 95% confidence interval [CI] 1.01-1.15, p = 0.036 and 1.31 per 1 pmol/L increase in FT3, 95% CI 1.01-1.71, p = 0.032). CONCLUSIONS: High-normal FT3 and FT4 levels are associated with AF recurrence after catheter ablation in this Chinese population. Attention to thyroid hormones could be valuable to assist in the management of AF.

U-Shaped Relationship Between Left Atrium Size on Echocardiography and 1-Year Recurrence of Atrial Fibrillation After Radiofrequency Catheter Ablation　- Prognostic Value Study.

BACKGROUND: The larger the left atrium anteroposterior dimension (LAD) and left atrium volume (LAV), the stronger the association with recurrent atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA). Patients with a smaller left atrium (LA) size, however, also have increased AF recurrence.Methods and Results:In 521 patients, routine 48-h Holter electrocardiogram and echocardiography were obtained at each outpatient visit every 3 months for 12 months. On multivariate analysis, AF type, LAD, and LAV calculated using the ellipsoid model/body surface area (LAVe/BSA) were independent predictors of AF recurrence. Patients were divided into 7 groups at 0.4-cm increments of LAD: ≤3 cm, LAD≤3 cm, 3.05.0 cm. Compared with the 3.4-3.8-cm group, the adjusted HR were 3.88 (95% CI: 2.02-7.46, P<0.001), 1.03 (95% CI: 0.50-2.12, P=0.939), 0.96 (95% CI: 0.52-1.77, P=0.901), 1.36 (95% CI: 0.72-2.57, P=0.347), 3.04 (95% CI: 1.67-5.53, P<0.001), and 4.07 (95% CI: 1.93-8.60, P<0.001), respectively. Similarly, we divided LAVe/BSA into 8 groups and also observed a U-shaped curve for AF recurrence. CONCLUSIONS: Both larger and smaller LAD and LAVe/BSA were associated with a higher risk of AF recurrence 1 year after RFCA. The association of LA size and AF recurrence after RFCA is represented by a U-shaped curve.

Efficacy and tolerability of adding coenzyme A 400 U/d capsule to stable statin therapy for the treatment of patients with mixed dyslipidemia: an 8-week, multicenter, double-blind, randomized, placebo-controlled study.

BACKGROUND: Patients with mixed hyperlipidemia usually are in need of combination therapy to achieve low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) target values for reduction of cardiovascular risk. This study investigated the efficacy and safety of adding a new hypolipidemic agent, coenzyme A (CoA) to stable statin therapy in patients with mixed hyperlipidemia. METHODS: In this multi-center, 8-week, double-blind study, adults who had received ≥8 weeks of stable statin therapy and had hypertriglyceridemia (TG level at 2.3-6.5 mmol/L) were randomized to receive CoA 400 U/d or placebo plus stable dosage of statin. Efficacy was assessed by the changes in the levels and patterns of lipoproteins. Tolerability was assessed by the incidence and severity of adverse events (AEs). RESULTS: A total of 304 patients with mixed hyperlipidemia were randomized to receive CoA 400 U/d plus statin or placebo plus statin (n = 152, each group). After treatment for 8 weeks, the mean percent change in TG was significantly greater with CoA plus statin compared with placebo plus statin (-25.9% vs -4.9%, respectively; p = 0.0003). CoA plus statin was associated with significant reductions in TC (-9.1% vs -3.1%; p = 0.0033), LDL-C (-9.9% vs 0.1%; p = 0.003), and non- high-density lipoprotein cholesterol (-13.5% vs -5.7%; p = 0.0039). There was no significant difference in the frequency of AEs between groups. No serious AEs were considered treatment related. CONCLUSIONS: In these adult patients with persistent hypertriglyceridemia, CoA plus statin therapy improved TG and other lipoprotein parameters to a greater extent than statin alone and has no obviously adverse effect. TRIAL REGISTRATION: Current Controlled Trials ClinicalTrials.gov ID NCT01928342.

Investigation of proper home blood pressure with atrial fibrillation recurrence in patients undergoing radiofrequency catheter ablation.

BACKGROUND: Hypertension is an important target for interventions to improve ablation outcome in atrial fibrillation (AF) patients. No studies to date have determined the blood pressure level at which AF is less likely to recur in patients without hypertension. METHODS: A total of 503 AF patients undergoing radiofrequency catheter ablation (RFCA) (mean age, 59.6±9.6 years; 319 males [63.4%]) were identified for the study cohort and analysis. Patients received a pocket diary to record their home blood pressure (HBP) before RFCA and routine 48-hour Holter-ECGs to evaluate AF recurrence after RFCA. RESULTS: A total of 383 (76.1%) patients were free of AF recurrence one year after RFCA. Blood pressure (BP), including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP), had different effects on AF recurrence one year after RFCA. A χ2 test showed that when SBP was <110 mmHg, it was associated with a lower AF recurrence in patients with hypertension (P=0.029). AF recurrence decreased (P=0.002) when SBP increased from <110 mmHg to >130 mmHg in patients without hypertension. Regression analysis indicated a significant linear correlation between BP and LAD in all patients. CONCLUSIONS: SBP should be strictly maintained at 110 mmHg after RFCA to minimize AF recurrence in patients with hypertension. Low SBP might be a risk factor for AF recurrence among patients without hypertension.

Reduced testosterone levels in males with lone atrial fibrillation.

BACKGROUND: Sex hormones play an important role in the development of cardiovascular disease. Testosterone and estradiol have been reported to be down-regulated in subjects with coronary artery disease and heart failure, but has not been studied in atrial fibrillation (AF). HYPOTHESIS: Levels of sex hormones may be associated with susceptibility to lone AF in men. METHODS: Fifty-eight male subjects who had electrocardiographic evidence of paroxysmal or chronic AF and a structurally normal heart on echocardiography were enrolled. Subjects were excluded if they had been taking angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), or statins within 3 mo or had a history of coronary artery disease, rheumatic heart disease, cardiomyopathy, significant valvular disease, hyperthyroidism, or hypertension. Fifty-eight controls were recruited from a healthy outpatient population. Serum total testosterone and estradiol levels were determined using a commercially available radioimmunoassay. RESULTS: Mean levels of testosterone were significantly lower in subjects with lone AF when compared with controls (476 ng/dl versus 514 ng/dl, p = 0.005). No significant differences were found in the estradiol levels between the 2 groups (31.9 pg/ml versus 32.4 pg/ml, p = 0.789). CONCLUSION: Reduced testosterone levels may be associated with susceptibility to lone AF in men.

Association of interleukin-1 gene cluster polymorphisms with ischemic stroke in a Chinese population.

BACKGROUND AND AIMS: Chronic inflammatory process plays an important role in atherothrombosis. Interleukin-1 (IL-1) is one of the key modulators of the inflammatory response and its activity is critically regulated by its receptor antagonist (IL-1Ra). A variable number tandem repeat polymorphism in intron 2 of IL-1Ra gene and a C to T single base polymorphism in the promoter of IL-1beta gene (C(-511)-->T) have been reported to affect the levels of IL-1 as well as its antagonist, IL-1Ra. It is also reported in several studies that these polymorphisms are associated with the susceptibility to cardio-cerebral vascular disease. However, data are limited in China. In this article, we studied the relationships between these polymorphisms and the risk of ischemic stroke in China. MATERIALS AND METHODS: One hundred and twelve patients committed ischemic stroke were compared with 95 demographically matched healthy volunteers. RESULTS: The frequencies of the IL-1Ra 1/1 genotype and IL-1Ra allele 1 (Ra*1 allele) in stroke patients were significantly higher than those in healthy volunteers [93.7% vs. 82.1%, P =0.014; 0.964 vs. 0.905, P =0.007]. No significant differences were found in the IL-1beta -511 genotype and the allele distribution between the two groups. CONCLUSIONS: Our results implicated that IL-1 gene polymorphism might be associated with the susceptibility to ischemic stroke.

Low serum testosterone level was associated with extensive coronary artery calcification in elderly male patients with stable coronary artery disease.

BACKGROUND: Coronary artery calcification (CAC) is a pandemic condition in elderly patients with coronary artery disease (CAD) and associated with a worse prognosis. Although available data have shown an association between testosterone levels in men and CAD, the association between testosterone and CAC in elderly male patients with CAD remains unknown. METHODS: A total of 211 consecutive male patients (age ≥ 65 years) who underwent first multidetector computed tomography and following angiography were enrolled from our institution between March 2009 and September 2014. CAD was angiographically documented as significant stenoses (reduction ≥ 50% of the lumen diameter) on any major coronary vessel. The standard Agatston calcium score was calculated. The relationship of serum testosterone level with the CAC score measured by multidetector computed tomography in elderly male patients with stable CAD was evaluated. For data analyses, the CAC score was divided into four categories: ≤ 10, 11-99, 100-399, and ≥ 400, corresponding to minimal, moderate, increased, and extensive calcification. RESULTS: Patients with higher CAC scores had significantly lower testosterone levels than patients with lower CAC scores (P = 0.048). In logistic regression analysis, testosterone level remained an independent predictor of extensive CAC (odds ratio 0.997, 95% confidence interval 0.994-0.999, P = 0.043). CONCLUSION: Our findings indicate an inverse association between testosterone level and the susceptibility to extensive CAC in elderly men with stable CAD.

Efficacy of statin monotherapy or in combination with coenzyme a capsule in patients with metabolic syndrome and mixed dyslipidemia.

BACKGROUND: Patients with metabolic syndrome are at increased risk for cardiovascular disease. Combination lipid-lowering therapy is often needed in patients with metabolic syndrome and mixed dyslipidemia. The aim of this study was to compare the effect of statin combined with a new hypolipidemic agent, coenzyme A (CoA) with moderate-dose statin monotherapy in subjects with metabolic syndrome and mixed dyslipidemia by evaluating data from a subgroup of patients with metabolic syndrome and mixed dyslipidemia from a previously conducted randomized study. METHODS: In the present post hoc analysis, 212 patients were included, receiving statin monotherapy (n = 94) or statin combined with CoA 400 U/day (n = 118) for 8 weeks. The lipoprotein profile was determined at baseline and week 8 visits. Attainment of low-density lipoprotein-cholesterol (LDL-C) < 100 mg/dL, non-high-density lipoprotein-cholesterol (HDL-C) < 130 mg/dL, and the combined goal of these two parameters was also evaluated. RESULTS: The mean percent change was more prominent with CoA plus statin compared with placebo plus statin in triglyceride (TG) (-32.5% vs. -8.7%, respectively; P = 0.0002), total cholesterol (-9.6% vs. -3.6%, P = 0.013), LDL-C (-7.5% vs. 2.1%, P = 0.033), and non-HDL-C (-14.3% vs. -6.4%, P = 0.011). Treatment with CoA plus statin resulted in larger percentages of participants attaining lipid goals for LDL-C (70.3% vs. 56.4%, P = 0.044), non-HDL-C (60.2% vs. 45.7%, P = 0.039), and the combined goal of LDL-C and non-HDL-C (57.6% vs. 42.6%, P = 0.038) than statin monotherapy. CONCLUSION: These results demonstrate that CoA plus statin therapy was more effective in improving lipoprotein parameters than statin alone in patients with metabolic syndrome and mixed hyperlipidemia.

In situ precipitation: a novel approach for preparation of iron-oxide magnetoliposomes.

BACKGROUND: Conventional methods of preparing magnetoliposomes are complicated and inefficient. A novel approach for magnetoliposomes preparation was investigated in the study reported here. METHODS: FeCl3/FeCl2 solutions were hydrated with lipid films to obtain liposome-encapsulated iron ions by ultrasonic dispersion. Non-encapsulated iron ions were removed by dialysis. NH3·H2O was added to the system to adjust the pH to a critical value. Four different systems were prepared. Each was incubated at a different temperature for a different length of time to facilitate the permeation of NH3·H2O into the inner phase of the liposomes and the in situ formation of magnetic iron-oxide cores in the liposomes. Single-factor analysis and orthogonal-design experiments were applied to determinate the effects of alkalization pH, temperature, duration, and initial Fe concentration on encapsulation efficiency and drug loading. RESULTS: The magnetoliposomes prepared by in situ precipitation had an average particle size of 168±14 nm, zeta potential of -26.2±1.9 mV and polydispersity index of 0.23±0.06. The iron-oxide cores were confirmed as Fe3O4 by X-ray diffraction and demonstrated a superparamagnetic response. Encapsulation efficiency ranged from 3% to 22%, while drug loading ranged from 0.2 to 1.58 mol Fe/mol lipid. The optimal conditions for in situ precipitation were found to be an alkalization pH of 12, temperature of 60°C, time of 60 minutes, and initial Fe concentration of 100 mM Fe(3+) + 50 mM Fe(2+). CONCLUSION: In situ precipitation could be a simple and efficient approach for the preparation of iron-oxide magnetoliposomes.

Long-term isosorbide mononitrate treatment impairs endothelial function in patients with coronary artery disease.

BACKGROUND: Sustained use of nitrates is associated with adverse effects on vascular function by increasing oxidative stress. It remains unclear whether oxidative stress impairs endothelial function in patients with coronary artery disease (CAD) during long-term oral use of nitrates. The purpose of this study was to evaluate the effects of long-term isosorbide mononitrate (ISMN) treatment on oxidative stress and endothelial function in patients with CAD. MATERIALS AND METHODS: In this prospective, double-blinded, placebo-controlled, randomized, single-center study, 60 patients were assigned to treatment with ISMN 20 mg retarded release orally twice per day (ISMN group, n=30) or placebo (control group, n=30) for 1 year. The primary endpoint was the change in brachial artery endothelium-dependent dilation [flow-mediated dilation (FMD)] from baseline to follow-up. Furthermore, serum superoxide dismutase, malondialdehyde, and hypersensitive C-reactive protein levels were also measured at baseline and follow-up. RESULTS: The FMD decreased significantly (from 5.97±2.88 to 5.33±2.56%) in the ISMN group, whereas it increased from 6.27±3.23 to 6.96±2.84% in the control group after treatment for 1 year. There was a significant difference in the changes in FMD when the two groups were compared (-0.64±1.83 vs. 0.69±1.77%, P=0.006). There were no significant changes in serum superoxide dismutase, malondialdehyde, and hypersensitive C-reactive protein levels in the two groups. CONCLUSION: Long-term ISMN treatment may impair endothelial function in patients with CAD.

The effects of coenzyme A on serum lipids in patients with hyperlipidemia: results of a multicenter clinical trial.

OBJECTIVES: The aim of the study was to evaluate the lipid-lowering effects and clinical safety of a natural hypolipidemic compound, coenzyme A (CoA) capsule, in Chinese patients with moderate dyslipidemia. METHODS: A total of 244 subjects (170 males and 74 females; aged 18-75 y) having moderate dyslipidemia (triglyceride [TG], 2.3-6.5 mmol · L(-1)) were randomly divided into 3 groups, to which placebo (group A, n = 81), CoA 200 U/d (group B, n = 79), and CoA 400 U/d (group C, n = 84) were administered, respectively. Blood lipoproteins, liver and renal functions, blood glucose, and complete blood count were measured at the baseline and after 4 or 8 weeks of treatment. RESULTS: After treatment for 4 weeks, TG was reduced by 5.1, 15.7, and 14.4% in groups A, B, and C, respectively. After treatment for 8 weeks, TG decreased .9, 21.7, and 36.1%, respectively. Compared with group A, the primary efficacy outcome TG in groups B and C significantly decreased (P < .01), and the difference between groups B and C was also significant (P < .01). Plasma total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were not significantly different. Furthermore, there was no difference in blood glucose, hepatic and renal function test parameters, incidence of myopathy, or gastrointestinal tract symptoms among the 3 groups. CONCLUSION: CoA can effectively reduce plasma TG levels in subjects with moderate dyslipidemia and has no obvious adverse effect.