Torsades de Pointes associated with QT prolongation after catheter ablation of paroxysmal atrial fibrillation.

A 79-year-old woman who underwent catheter ablation for paroxysmal atrial fibrillation presented with Torsades de Pointes (TdP). Aggravation of prolonged QT interval which is most likely due to neural modulation by catheter ablation, played major role in the initiation of TdP. The patient was successfully treated with isoproterenol during acute stage and discharged after stabilization without implantation of permanent pacemaker or implantable cardioverter defibrillator.

Efficacy and safety of aspirin, clopidogrel, and warfarin after coronary artery stenting in Korean patients with atrial fibrillation.

There are limited data on the optimal antithrombotic therapy for patients with atrial fibrillation (AF) who undergoing coronary stenting. We reviewed 203 patients (62.6 % men, mean age 68.3 ± 10.1 years) between 2003 and 2012, and recorded clinical and demographic characteristics of the patients. Clinical follow-up included major adverse cardiac and cerebrovascular events (MACCE) (cardiac death, myocardial infarction, target lesion revascularization, and stroke), stent thrombosis, and bleeding. The most commonly associated comorbidities were hypertension (70.4 %), diabetes mellitus (35.5 %), and congestive heart failure (26.6 %). Sixty-three percent of patients had stroke risk higher than CHADS2 score 2. At discharge, dual-antiplatelet therapy (aspirin, clopidogrel) was used in 166 patients (81.8 %; Group I), whereas 37 patients (18.2 %) were discharged with triple therapy (aspirin, clopidogrel, warfarin; Group II). The mean follow-up period was 42.0 ± 29.0 months. The mean international normalized ratio (INR) in group II was 1.83 ± 0.41. The total MACCE was 16.3 %, with stroke in 3.4 %. Compared with the group II, the incidence of MACCE (2.7 % vs 19.3 %, P = 0.012) and cardiac death (0 % vs 11.4 %, P = 0.028) were higher in the group I. Major and any bleeding, however, did not differ between the two groups. In multivariate analysis, no warfarin therapy (odds ratio 7.8, 95 % confidence interval 1.02-59.35; P = 0.048) was an independent predictor of MACCE. By Kaplan-Meier survival analysis, warfarin therapy was associated with a lower risk of MACCE (P = 0.024). In patients with AF undergoing coronary artery stenting, MACCE were reduced by warfarin therapy without increased bleeding, which might be related to tighter control with a lower INR value.

Hybrid endovascular repair for aortic arch pathology: intermediate outcomes and complications: a retrospective analysis.

OBJECTIVES: To evaluate the outcomes of hybrid endovascular repair for aortic arch pathology. METHODS: This study was a retrospective analysis involving patients who underwent hybrid endovascular repair for aortic arch pathologies. RESULTS: Twenty-one patients (16 men; mean age, 64.7 ± 16.2 years) with aortic arch pathologies were treated by hybrid endovascular repair. The indications for treatment included increased aneurysm size in 16 cases (71.4%), rupture or impending aneurysmal rupture in 5 cases (23.8%), and rapid growth of aortic dissection (≥ 10 mm/y) in 1 case (4.8%). Supra-aortic vessel transposition and stent-graft implantation were achieved in all cases. Two types of stent-graft was used, as follows: the Seal thoracic stent-graft in 14 patients (66.7%); and the Valiant stent grafts in 7 patients (33.3%). Perioperative complications affected 5 patients (23.8%), as follows: bleeding (n = 4, 19.0%); stroke (n = 3, 14.3%); renal failure (n = 2, 9.5%); vascular injury (n = 1, 4.8%), and respiratory failure (n = 1, 4.8%). Two patients died within 30 days (9.5%). Technical success was achieved in 15 patients (71.5%). Early endoleaks were noted in 4 patients (19.0%). One patient died during follow-up (mean, 21.3 ± 11.6 months) due to a de novo intramural hematoma. Persistent early endoleaks were noted in 4 patients (19.0%); 2 of the 4 patients were successfully managed with implantation of additional stent-grafts. No late onset endoleaks were noted. The death-free survival and reintervention-free survival rates during follow-up were 85.7% and 90.5%, respectively. CONCLUSION: Hybrid treatment with supra-aortic vessel transposition and endovascular repair may be an option in frail patients in who open procedures is too risky.

The impact of diabetes duration on left ventricular diastolic function and cardiovascular disease.

OBJECTIVES: The question of whether diabetes mellitus (DM) duration correlates with the severity of dysfunction has not been well studied. We hypothesised that the longer the duration of DM the worse the severity of left ventricular (LV) diastolic dysfunction and increased risk of cardiovascular disease (CVD). METHODS: We reviewed 547 diabetic patients between January 2005 and April 2010. Finally, 92 consecutive patients who presented with type 2 DM and who underwent echocardiographic assessment were enrolled according to the selection criteria. In all patients, ischaemic heart disease and heart failure were excluded. RESULTS: Diastolic parameters were significantly worsened with increasing duration of DM (p<0.05). In the ≥7 years DM duration group (n=50), the E/Ea ratio increased significantly and the Ea/Aa ratio decreased significantly, compared with those in the <7 years DM duration group (n=42). CVD developed in 28 patients (30.4%) during the follow-up period. However, the duration of DM showed less statistical correlation with the incidence of CVD (p=0.188) and other LV diastolic function indices did not differ significantly between groups with or without CVD. CONCLUSIONS: Alteration of diastolic function induced by DM worsens with increasing duration of DM. DM duration on echocardiographic evaluation time did not differ significantly between the CVD incident and the non-CVD incident groups. The rate of CVD development was not significantly different if the duration of DM was more than 7 years. Therefore, active medical care including echocardiography should be undertaken to prevent CVD from the point of diagnosis of type 2 DM.

Comparison of the effect of preinterventional arterial remodeling on intimal hyperplasia after implantation of a sirolimus- or paclitaxel-eluting stent.

BACKGROUND: We compared the effect of arterial remodeling on intimal hyperplasia (IH) after the implantation of a sirolimus-eluting stent (SES) and a paclitaxel-eluting stent (PES). METHODS: The study population consisted of patients with positive or intermediate remodeling and negative remodeling. RESULTS: Sixty-nine patients had positive or intermediate remodeling and 107 patients had negative remodeling. At follow-up, late loss was significantly larger (0.58 +/- 0.65 vs. 0.38 +/- 0.55 mm; p = 0.026) in the patients with positive or intermediate remodeling. The IH volume (22.6 +/- 26.2 vs. 12.4 +/- 17.4 mm(3); p = 0.002) and the percent IH (12.9 +/- 14.8 vs. 7.0 +/- 9.6%; p = 0.002) were significantly higher in the patients with positive or intermediate remodeling. Compared to negative remodeling, the IH volume was higher in the PES patients with positive or intermediate remodeling, but this difference was not noted in the SES patients. Multiple-regression analysis revealed that arterial remodeling was a significant independent variable for predicting IH volume in the PES patients (p = 0.018). A positive correlation was found between the remodeling index and the IH volume in the PES patients (r = 0.234, p = 0.028), but not in the SES patients. CONCLUSIONS: This prospective observational intravascular ultrasound study showed that drug-eluting stents may have a different effect on reducing IH accumulation in lesions with preinterventional positive remodeling characteristics which may be related to the different properties of the drug and delivery platform.

Efficacy of Xience/promus versus Cypher in rEducing Late Loss after stENTing (EXCELLENT) trial: study design and rationale of a Korean multicenter prospective randomized trial.

BACKGROUND: The everolimus-eluting stent (EES) is a newly developed drug-eluting stent using the MULTILINK VISION stent platform combined with the drug everolimus contained in a polymer coating. Recently reported randomized trials have shown the noninferiority and subsequent superiority of the EES compared with the paclitaxel-eluting stent regarding in-stent late loss (LL) at 180 days. However, there have been no studies comparing head to head the EES with the sirolimus-eluting stent (SES), which has shown the least amount of LL among the previously released drug-eluting stent (DES). In addition, adjunctive antiplatelet therapy is a critical factor in optimizing long-term DES safety. Despite the recommendation of the American Heart Association/American College of Cardiology to maintain 12 months of dual antiplatelet therapy, there have been no prospective randomized trials comparing the efficacy and safety of different durations. STUDY DESIGN: In the Efficacy of Xience/promus versus Cypher in rEducing Late Loss after stENTing (EXCELLENT) trial, approximately 1,400 patients are being prospectively and randomly assigned in a 2 x 2 factorial design according to the type of stent (EES vs SES) and the duration of dual antiplatelet therapy (6 vs 12 months). The primary end point is in-segment LL at 9 months for comparison of type of stent, and the coprimary end point is target vessel failure at 12 months for comparison of dual antiplatelet therapy duration. SUMMARY: The EXCELLENT trial is the largest study yet performed to directly compare the efficacy and safety of the EES versus the SES. In addition, this study will also address the issue of a 6- versus 12-month duration of dual antiplatelet therapy for post-percutaneous coronary intervention management.

Pseudo-no-reflow phenomenon in carotid artery stenting using FilterWire EX: successful recovery by aspiration thrombectomy.

Distal protection devices such as FilterWire EX have been widely used in carotid artery stenting, however, the large amount of atherothrombotic debris entrapped in the filter could reduce or stop antegrade flow. We present a case of pseudo-no-reflow phenomenon after postdilatation of the stent in a patient with asymptomatic carotid artery stenosis. After several passes using an Export Aspiration catheter, normal flow in the internal carotid artery was restored. Aspiration thrombectomy can successfully recover pseudo-no-reflow phenomenon.

Prevention of Kinked Stent Graft Limb Due to Severe Angulated Proximal Neck during Endovascular Repair for Abdominal Aortic Aneurysm.

Although the technology of endovascular aortic repair (EVAR) for abdominal aortic aneurysm (AAA) is evolving that make it appealing for challenging anatomy, proximal aortic neck morphology, especially severe angulation, is still one of the most determinants for a successful procedure. We describe a patient of AAA with severely angulated proximal neck, in whom kinked stent graft limb occurred against severe angulation of proximal neck. Then, we suggested how to prevent this complication in the second patient. Our case demonstrated the stent graft limb could be kinked by severe aortic neck angulation, making it challenging. However, the kinked stent graft limb could be prevented by deploying stent graft limbs below the most severely angulated aortic neck intentionally.

Early Response after Catheter Ablation of the Epicardial Substrate in a Patient with Brugada Syndrome Can Be Predicted by High Precordial Leads.

A 52-year-old male with Brugada syndrome presented with repeated and appropriate shock from an implantable cardioverter defibrillator (ICD). Catheter ablation for substrate elimination targeting low-voltage, complex, and fractionated electrocardiograms and late potentials in the epicardial right ventricular outflow tract was successfully performed. Brugada phenotype in the right precordial leads from the third intercostal space disappeared in the early stage after catheter ablation and that from the standard fourth intercostal space disappeared later. He remained free from ventricular fibrillation over the next fourteen months. We suggest that this novel ablation strategy is effective in Brugada syndrome patients with ICD, and early response after catheter ablation can be predicted by high precordial leads.

The effects of simvastatin, losartan, and combined therapy on soluble CD40 ligand in hypercholesterolemic, hypertensive patients.

The proinflammatory mediator CD40 ligand plays an important role in atherogenesis. Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared the effects of these therapies either alone or in combination on plasma soluble CD40 ligand (sCD40L). This was a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20mg and placebo, simvastatin 20mg and losartan 100mg, or losartan 100mg and placebo daily during each 2 month treatment period. Simvastatin alone did not significantly reduce sCD40L levels relative to baseline measurements when the entire cohort was analyzed. However, simvastatin significantly reduced sCD40L levels from 5.10+/-0.34 to 3.07+/-0.43ng/ml (P=0.002) in a subgroup of 18 patients with high baseline sCD40L levels >2.95ng/ml. Combined therapy or losartan alone significantly decreased plasma sCD40L levels relative to baseline measurements by 14+/-7% (P=0.001) and 13+/-10% (P=0.001), respectively. These decreases were significantly greater than those observed with simvastatin alone (P=0.023 by ANOVA). Significant inverse correlations between baseline sCD40L levels and percent changes in sCD40L levels were observed (r=-0.456, P=0.001 after simvastatin alone; r=-0.476, P<0.001 after combined therapy; r=-0.451, P=0.002 after losartan alone). Losartan alone or combined therapy significantly reduced plasma sCD40L levels more than simvastatin alone in our subjects. Simvastatin, losartan and combined therapy significantly reduced sCD40L to the greatest extent in patients with high baseline sCD40L levels.

Results of a phase III, 8-week, multicenter, prospective, randomized, double-blind, parallel-group clinical trial to assess the effects of amlodipine camsylate versus amlodipine besylate in Korean adults with mild to moderate hypertension.

BACKGROUND: Amlodipine besylate has been used in Korea for the treatment of hypertension for >17 years, with well-established efficacy and tolerability. Amlodipine camsylate is a newer formulation developed for generic use. It has been assessed in terms of physical stability and pharmacokinetic and pharmacodynamic properties and been found to be effective in lowering blood pressure in preclinical and Phase I and II trials. However, to date, no studies have compared the clinical effectiveness of amlodipine camsylate and amlodipine besylate in treating hypertension. OBJECTIVE: This study was designed to determine the effectiveness and tolerability of amlodipine camsylate compared with amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS: This Phase III, 8-week, prospective, randomized, double-blind, parallel-group study was conducted in 13 cardiology centers across the Republic of Korea. Male and female Korean patients aged 18 to 75 years having uncomplicated, mild to moderate, essential hypertension (sitting diastolic blood pressure [SiDBP] 90-<110 mm Hg) and receiving no antihypertensives in the 2 weeks before randomization were eligible. Patients were randomly assigned to receive oral treatment with amlodipine camsylate or amlodipine besylate. For the first 4 weeks, patients received amlodipine 5 mg QD (morning). After 4 weeks, if either blood pressure was > or =140/ > or =90 mm Hg or SiDBP had not decreased by > or =10 mm Hg from baseline, the dose of amlodipine was increased to 10 mg QD for 4 weeks. Trough blood pressure and heart rate were measured in duplicate with the patient in the sitting position at each clinic visit (baseline [week 0] and weeks 4 and 8 of treatment); mean values were calculated and recorded. At weeks 4 and 8, tolerability was assessed using history taking and laboratory analysis, and compliance was assessed using pill counts. The primary end point was change from baseline in SiDBP at week 8. Secondary end points were change from baseline in sitting systolic blood pressure (SiSBP) at week 8 in the total population and in the subgroup of patients who had previously received antihypertensive treatment versus those who had not. RESULTS: A total of 189 patients were enrolled (mean age, 53 years; 105 women, 84 men; mean body weight, 65.8 kg). One patient in the amlodipine camsylate group dropped out of the study at week 0 of treatment (this patient did not use any study medication) and was excluded from the modified intent-to-treat (ITT) analysis. Thus, 188 patients were treated and included in the ITT analysis (94 patients per treatment group; ITT analysis); 161 patients were included in the perprotocol (PP) analysis (n = 80 for amlodipine camsylate, n = 81 for amlodipine besylate) (14 patients in the amlodipine camsylate group and 13 patients in the amlodipine besylate group were excluded from the PP analysis due to consistent withdrawal or protocol violation). Mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (amlodipine camsylate, from 146.7 [12.3]/96.6 [5.4] to 127.9 [14.8]/83.4 [7.7] mm Hg [both, P < 0.001]; amlodipine besylate, from 146.8 [12.8]/96.7 [5.1] to 128.0 [10.1]/83.8 [7.5] mm Hg [both, P < 0.001]). The differences in SiSBP/SiDBP between the 2 groups at week 8 were not significant. The SiDBP response rates in the subgroups that had and had not been previously treated with antihypertensives were statistically similar (56/69 [81.2%] and 83/92 [90.2%], respectively). The prevalences of clinical adverse events (AEs) were not significantly different between the 2 treatment groups (amlodipine camsylate, 27.3 %; amlodipine besylate, 28.7%). The most common AEs were dizziness and dyspnea (both in 3/94 [3.2%] and 1/94 [1.1%] patients who received amlodipine camsylate and amlodipine besylate, respectively). CONCLUSION: The effectiveness and tolerability of amlodipine camsylate were not significantly different from those of amlodipine besylate in these Korean adults with mild to moderate hypertension.

Thrombosuction utilizing an export aspiration catheter during primary percutaneous coronary intervention in acute myocardial infarction.

PURPOSE: Effective myocardial reperfusion after primary PCI for an AMI in lesions with a thrombus is limited by distal embolization and the slow/no reflow phenomenon. We evaluated the efficacy of a thrombus reduction technique using an export aspiration catheter for thrombosuction during primary PCI. MATERIALS AND METHODS: We analyzed 62 patients with AMIs who underwent primary PCI and had a thrombi burden during thrombosuction using an EAC (EAC group; n=31) or without thrombosuction (control group; n=31). RESULTS: Thrombosuction with an EAC was performed safely in all the patients in EAC group without any complications. After the PCI, restoration to a TIMI flow grade 3 was significantly more frequent in the EAC group (26/31 vs. 20/31, p < 0.05). However, the TIMI perfusion grade did not differ between the two groups. Further, the corrected TIMI frame counts were lower in the EAC group (23.9 +/- 15.1 vs. 34.8 +/- 22.5, p < 0.05). Although there was no statistical significance, a greater incidence of distal embolization was observed in the control group (16.1%, 5/31) as compared to the EAC group (0/31) (p= 0.056). However, the incidence of major adverse cardiac events at 1 and 6 months did not differ between the two groups. CONCLUSION: For AMIs, thrombosuction with an EAC before or during PCI is a safe and potentially effective method for restoration of the coronary flow.

Additive beneficial effects of fenofibrate combined with candesartan in the treatment of hypertriglyceridemic hypertensive patients.

OBJECTIVE: Mechanisms underlying fibric acid and angiotensin II type 1 receptor blocker therapies differ. Signaling from peroxisome proliferator-activated receptor alpha may cross-talk with the angiotensin II system. We investigated vascular and metabolic responses to these therapies either alone or in combination in hypertriglyceridemic hypertensive patients. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, placebo-controlled, cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Forty-four patients were given 200 mg fenofibrate and placebo, 200 mg fenofibrate and 16 mg candesartan, or 16 mg candesartan and placebo daily during each treatment period. RESULTS: Fenofibrate, combined therapy, or candesartan therapy significantly reduced blood pressure. However, combined therapy significantly reduced blood pressure more than fenofibrate or candesartan alone (P < 0.001 by ANOVA). When compared with candesartan, fenofibrate or combined therapy significantly improved the lipoprotein profile. All three treatment arms significantly improved flow-mediated dilator response to hyperemia. Combined therapy significantly decreased plasma malondialdehyde, high-sensitivity C-reactive protein, and soluble CD40L levels relative to baseline measurements. Importantly, these parameters were changed to a greater extent with combined therapy when compared with monotherapy (P < 0.001, P = 0.002, P = 0.050, and P = 0.032 by ANOVA, respectively). Fenofibrate, combined therapy, and candesartan significantly increased plasma adiponectin levels and insulin sensitivity relative to baseline measurements. However, the magnitude of these increases were not significantly different among the three therapies (P = 0.246 and P = 0.153 by ANOVA, respectively). CONCLUSIONS: Fenofibrate combined with candesartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy in hypertriglyceridemic hypertensive patients.

Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia.

OBJECTIVES: We compared vascular and metabolic responses (and adverse responses) to statin and fibrate therapies alone or in combination in patients with combined hyperlipidemia. BACKGROUND: The mechanisms of action for statins and fibrates are distinct. METHODS: Fifty-six patients were given atorvastatin 10 mg and placebo, atorvastatin 10 mg and fenofibrate 200 mg, or fenofibrate 200 mg and placebo daily during each two-month treatment period of a randomized, double-blind, placebo-controlled crossover trial with two washout periods of two months' each. RESULTS: Lipoproteins were changed to a greater extent with combined therapy when compared with atorvastatin or fenofibrate alone. Flow-mediated dilator response to hyperemia and plasma high-sensitivity C-reactive protein and fibrinogen levels were changed to a greater extent with combined therapy when compared with atorvastatin or fenofibrate alone (p < 0.001, p = 0.182, and p = 0.015 by analysis of variance [ANOVA], respectively). The effects of combined therapy or fenofibrate alone on plasma adiponectin levels and insulin sensitivity (determined by the Quantitative Insulin-Sensitivity Check Index [QUICKI]) were significantly greater than those of atorvastatin alone (p = 0.022 for adiponectin and p = 0.049 for QUICKI by ANOVA). No patients were withdrawn from the study as the result of serious adverse effects. CONCLUSIONS: Combination therapy is safe and has beneficial additive effects on endothelial function in patients with combined hyperlipidemia.

The favorable clinical and angiographic outcomes of a high-dose dexamethasone-eluting stent: randomized controlled prospective study.

BACKGROUND: Previous studies with dexamethasone-eluting stents could not elucidate the role of dexamethasone in the prevention of neointimal hyperplasia because they did not compare their results with a control group. We prospectively evaluated the clinical and angiographic outcomes of dexamethasone-eluting stents, comparing them with unloaded stents of an identical design. METHODS: A total of 92 patients (98 lesions) were randomly assigned to the dexamethasone group (67 patients, 71 lesions) or control group (25 patients, 27 lesions). The inclusion criteria for a stent implantation were a de novo lesion with a diameter of 2.60 to 4.0 mm. BiodivYsio Drug Delivery phosphorylcholine-coated stents (Biocompatibles Ltd, Galway, Ireland) were immersed in a 20-mg/mL dexamethasone solution, yielding a total dexamethasone dose of 0.5 microg/mm2 per stent. RESULTS: The total major adverse cardiac events rate at 12 months was significantly lower in the dexamethasone group, as compared with the control group (10.4% [7/67] vs 28.0% [7/25], P = .037). The binary restenosis rate at 6 months was 11.9% (7/59) in the dexamethasone group and 42.9% (9/21) in the control group (P = .002). The use of dexamethasone-eluting stents was the only independent predictor for the major adverse cardiac event at 12 months (relative risk 0.20, 95% CI 0.06-0.68, P = .009) and binary restenosis at 6 months (relative risk 0.17, 95% CI 0.05-0.60, P = .006) by multivariate analysis. CONCLUSIONS: Dexamethasone-eluting stents exhibited an improvement in the clinical and angiographic outcomes, as compared with the control stents. These results suggest that dexamethasone may play an important role in the inhibition of the polymer-induced inflammation in the era of drug-eluting stents.

Anti-inflammatory and metabolic effects of candesartan in hypertensive patients.

BACKGROUND: Angiotensin II type 1 (AT1) receptor blocker therapy prevented or retarded the progression of coronary heart disease. The mechanisms of this benefit may relate to the ability of AT1 receptor blockers to reduce inflammation and insulin resistance. METHODS: We administered placebo or candesartan 16 mg daily during 2 months to 45 patients with mild to moderate hypertension. This study was randomized, double-blind, placebo-controlled, crossover in design. RESULTS: Candesartan therapy significantly lowered both systolic and diastolic blood pressure. Compared with placebo, candesartan therapy significantly lowered plasma hsCRP levels relative to baseline measurements from 1.10 to 0.70 mg/l (P=0.024) and soluble CD40 ligand levels by 30+/-11% (P<0.001). There were significant inverse correlations between body mass index and baseline plasma adiponectin levels (r=-0.480, P=0.009). There were significant correlations between baseline adiponectin levels and baseline insulin (r=-0.317, P=0.034) or baseline Quantitative Insulin-Sensitivity Check Index (QUICKI), a surrogate index of insulin sensitivity (r=0.371, P=0.012). Compared with placebo, candesartan therapy significantly lowered fasting insulin levels (P=0.011) and increased plasma levels of adiponectin by 15+/-4% (P=0.012) and increased QUICKI by 8+/-2% (P=0.007). There were significant correlations between percent changes in adiponectin levels and percent changes in insulin (r=-0.340, P=0.022) or QUICKI (r=0.325, P=0.029). CONCLUSIONS: Candesartan therapy significantly reduced inflammation and increased adiponectin levels and improved insulin sensitivity in hypertensive patients.

Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia.

OBJECTIVE: Improvement in endothelial function is predicted to improve insulin sensitivity, and this may be one mechanism by which fenofibrate decreases the incidence of coronary heart disease. We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity. RESEARCH DESIGN AND METHODS: We administered placebo or fenofibrate 200 mg daily for 8 weeks to 46 patients with primary hypertriglyceridemia (24 had metabolic syndrome). This study was randomized, double blind, placebo controlled, and crossover in design. RESULTS: Compared with placebo, fenofibrate decreased total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides and increased HDL cholesterol and apolipoprotein A-I (all P < 0.001) while tending to decrease LDL cholesterol (P = 0.069). Fenofibrate significantly improved percent flow-mediated dilator response to hyperemia by 48 +/- 5% (P < 0.001) and lowered plasma levels of high-sensitivity C-reactive protein (hsCRP) relative to baseline measurements from 0.80 to 0.70 mg/l (P = 0.001) and fibrinogen levels by 16 +/- 3% (P < 0.001). Compared with placebo, fenofibrate therapy significantly increased plasma levels of adiponectin by 14 +/- 5% (P = 0.008) and increased insulin sensitivity (assessed by quantitative insulin sensitivity check index [QUICKI]) by 6 +/- 2% (P = 0.048). There were significant correlations between percent changes in adiponectin levels and percent changes in flow-mediated dilation (r = 0.401, P = 0.006), hsCRP (r = -0.443, P = 0.002), or QUICKI (r = 0.292, P = 0.049). Multivariate regression analysis showed that only changes in adiponectin levels persisted as an independent predictor of changes in flow-mediated dilation (r = 0.504, P = 0.013). Overall, we observed similar results in 24 patients with metabolic syndrome. CONCLUSIONS: Fenofibrate therapy significantly improved percent flow-mediated dilator response to hyperemia, reduced inflammation marker levels, increased adiponectin levels, and improved insulin sensitivity in hypertriglyceridemic or metabolic syndrome patients.

Vascular and metabolic effects of candesartan: insights from therapeutic interventions.

BACKGROUND: Effects of angiotensin II type 1 receptor blockers (ARBs) to improve endothelial dysfunction may be due to mechanisms in addition to the reduction of high blood pressure per se. Endothelial dysfunction is characterized by vascular inflammation that contributes to clinically significant atherosclerosis and by an increased tendency for thrombus formation. Hypertensive patients have impaired endothelial functions that have positive predictive power with respect to future cardiovascular events. OBJECTIVES: The present review will focus on multiple mechanisms underlying vascular and metabolic effects of ARBs that may synergize to prevent or regress atherosclerosis, onset of diabetes, and coronary heart disease. CONCLUSIONS: Angiotensin II accelerates the development of atherosclerosis by activating angiotensin II type 1 receptors that then promote superoxide anion generation and oxidative stress, leading to activation of nuclear transcription factor and endothelial dysfunction. Activation of angiotensin II type 1 receptors also stimulates increased expression of plasminogen activator inhibitor type 1 and tissue factor. Endothelial dysfunction associated with the metabolic syndrome and other insulin-resistant states is characterized by impaired insulin-stimulated production of nitric oxide from the endothelium and decreased blood flow to skeletal muscle. Increasing insulin sensitivity therefore improves endothelial function, and this may be an additional mechanism whereby ARBs decrease the incidence of coronary heart disease and the onset of diabetes. Adiponectin serves to link obesity with insulin resistance. In addition, adiponectin has anti-atherogenic properties.

Vascular and metabolic effects of omega-3 fatty acids combined with fenofibrate in patients with hypertriglyceridemia.

BACKGROUND: Effects of omega-3 fatty acids (n-3 FA) combined with fenofibrate are not yet investigated, compared with fenofibrate. METHODS: This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Fifty patients with hypertriglyceridemia in each group were given placebo, n-3 FA 2g+fenofibrate 160mg (combination), or fenofibrate 160mg, respectively daily for 2months. RESULTS: Placebo, combination, and fenofibrate significantly decreased triglycerides by 7%, 41% and 30%, respectively and triglycerides/HDL cholesterol ratio by 11%, 45% and 32%, respectively relative to baseline measurements (all P<0.05 by paired t-test). When compared with placebo and fenofibrate, these with combination were significant (P<0.001 by ANOVA). When compared with placebo, both combination and fenofibrate significantly decreased apolipoprotein B and non-HDL cholesterol and improved flow-mediated dilation and reduced CRP and fibrinogen (all P<0.05 by ANOVA), however, there were no significant differences between combination and fenofibrate. When compared with placebo, both combination and fenofibrate significantly reduced insulin and glucose (both P<0.05 by ANOVA), and improved insulin sensitivity (P=0.005 by ANOVA). However, there were no significant differences between combination and fenofibrate. CONCLUSIONS: When compared with fenofibrate, combination significantly decreased triglycerides and triglycerides/HDL cholesterol ratio. Otherwise, combination and fenofibrate significantly reduced apolipoprotein B and non-HDL cholesterol and improved flow-mediated dilation and reduced CRP and fibrinogen to a similar extent. Also, combination and fenofibrate significantly improved insulin sensitivity to a similar extent by reducing insulin and glucose in patients with hypertriglyceridemia.

Rosuvastatin dose-dependently improves flow-mediated dilation, but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients.

BACKGROUND: Genetic analysis from patients participated in the randomized trials reported that the increased risk of type 2 diabetes noted with statins is at least partially explained by HMG-coenzyme A reductase inhibition. We investigated vascular and metabolic phenotypes of different dosages of rosuvastatin in hypercholesterolemic patients. METHODS: A randomized, single-blind, placebo-controlled, parallel study was conducted in 48 patients on placebo, and in 47, 48, and 47 patients given daily rosuvastatin 5, 10, and 20mg, respectively during a 2month treatment period. RESULTS: Rosuvastatin 5, 10, and 20mg improved flow-mediated dilation (34, 40, and 46%) after 2months therapy when compared with baseline (P<0.001 by paired t-test) and when compared with placebo (P<0.001 by ANOVA). Rosuvastatin 5,10, and 20mg dose-dependently and significantly increased insulin (mean % changes; 19, 29, and 31%, respectively) and glycated hemoglobin levels (mean % changes; 2, 2, and 3%, respectively), and decreased adiponectin levels (mean % changes; 3, 9, and 14%, respectively) and insulin sensitivity (mean % changes; 2, 3, and 4%, respectively) after 2months therapy when compared with baseline (all P<0.05 by paired t-test). These effects with rosuvastatin 5, 10, and 20mg were significant when compared with placebo (P=0.006 for insulin, P=0.012 for glycated hemoglobin, P=0.007 for adiponectin, and P=0.002 for insulin sensitivity by ANOVA). CONCLUSIONS: Despite beneficial reductions in LDL cholesterol and improvement of flow-mediated dilation, rosuvastatin dose-dependently and significantly resulted in decreasing insulin sensitivity and increasing ambient glycemia by reducing adiponectin levels and increasing insulin levels in hypercholesterolemic patients.