Improved intra-atrial conduction delay after successful ablation for atrial fibrillation by scar homogenization in right atrium.

Atrial fibrosis in the right atrium (RA) presenting as a low-voltage zone might be the mechanism of atrial fibrillation (AF) and intra-atrial conduction delay. The impact of scar homogenization in RA on intra-atrial conduction delay is unknown. We describe a patient with paroxysmal AF and significant intra-atrial conduction delay with repetitive atrial flutter, triggered from the lateral free wall in the RA between the significant low-voltage zone and slow conduction area after pulmonary vein isolation. Linear ablation along the trabeculated lateral free wall in the RA to homogenize the scar was successfully performed, and the intra-atrial conduction delay improved ultimately.

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.

Ventricular fibrillation and sudden cardiac arrest in apical hypertrophic cardiomyopathy: Two case reports.

BACKGROUND: Apical hypertrophic cardiomyopathy (HCM) is considered to have a benign prognosis in terms of cardiovascular mortality. This serial case report aimed to raise awareness of ventricular fibrillation (VF) and sudden cardiac death (SCD) in apical HCM. CASE SUMMARY: Here we describe two rare cases of apical HCM that presented with documented VF and sudden cardiac collapse. These patients were previously not recommended for primary prevention using implantable cardioverter-defibrillator (ICD) therapy based on current guidelines. However, both received ICD therapy for the secondary prevention of SCD. CONCLUSION: These cases illustrate serious complications including VF and aborted sudden cardiac arrest in apical HCM patients who are initially not candidates for primary prevention using ICD implantation based on current guidelines.

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.

Angiotensin-Converting Enzyme Inhibitors Provide Better Long-Term Survival Benefits to Patients With AMI Than Angiotensin II Receptor Blockers After Survival Hospital Discharge.

AIM: Renin-angiotensin-aldosterone system inhibitors (RASIs) are widely used in high-risk cardiovascular (CV) diseases, including acute myocardial infarction (AMI). However, it is not yet clear which class of RASIs provides specific benefits to patients with AMI. The present study aimed to evaluate whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) had any different effects on long-term CV and all-cause mortality in patients with AMI who received either agent from admission and were discharged alive from the hospital. METHODS: We analyzed data of patients with AMI from the Korea Acute Myocardial Infarction Registry-National Institutes of Health registry. Cardiovascular and all-cause mortality at 12 months after AMI were assessed. RESULTS: Among 12 481 patients with AMI who were discharged alive, RASI treatment was as follows: ACEIs (n = 5910), ARBs (n = 4009), and no RASI (n = 2562). After adjustment for multiple factors, compared with no RASI therapy, ACEI therapy was associated with lower hazard ratios (HRs) for 1-year CV and total mortality rates, whereas ARB therapy was not. In a direct comparison, compared with ARB treatment, ACEI treatment was associated with lower HRs (95% confidence interval) for CV and total mortality: 0.562 (0.420-0.753) and 0.567 (0.451-0.713), respectively. The superiority of ACEI to ARB was also observed across several subgroups. The mortality differences between the 2 treatment groups were reproduced in a propensity-score matched analysis (n = 2855 each). CONCLUSIONS: Our study of a recent AMI registry data revealed that ACEI therapy in patients with AMI was associated with better long-term survival benefits than ARB therapy.

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.

Newly developed post-operative atrial fibrillation is associated with an increased risk of late recurrence of atrial fibrillation in patients who underwent open heart surgery: Long-term follow up.

BACKGROUND: Herein is sought to determine whether the occurrence of post-operative atrial fibrillation (POAF) increases the risk of late recurrence of atrial fibrillation (AF) in patients undergoing open heart surgery (OHS). METHODS: This study included 938 patients (56.7 ± 13.1 years old, 550 males) with no history of AF who underwent OHS. All patients were monitored continuously for development of POAF after surgery until the time of hospital discharge and received clinical follow up with serial evaluation of rhythm status. RESULTS: Among the total population, POAF occurred in 207 (22.1%) patients and late AF in 88 (9.4%) patients during the mean follow up period of 78.1 ± 39.1 months. Development of late AF oc¬curred more frequently in patients with POAF than in those without [29.0% (60/207) vs. 3.8% (28/731), p < 0.01]. Higher septal E/e' ratio (HR 1.04, 95% CI 1.00-1.08, p = 0.04) was an independent predic¬tor of late occurrence of AF and an episode of POAF (HR 27.12, 95% CI 8.46-86.96, p < 0.01) was the most powerful predictor. CONCLUSIONS: POAF is significantly associated with an increased risk of late AF recurrence during long-term follow up. Careful concern regarding late recurrence of AF with serial evaluation of rhythm status is required in patients with POAF.

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.

Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients.

BACKGROUND: Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic, hypertensive patients. METHODS AND RESULTS: This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20 mg and placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo daily during each 2-month treatment period. Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone. Compared with losartan alone, simvastatin alone or combined therapy significantly changed lipoproteins. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone (both P<0.001 and P=0.030 for monocyte chemoattractant protein-1 by ANOVA). Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity (determined by QUICKI) relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (P<0.001 for adiponectin, P=0.029 for QUICKI by ANOVA). CONCLUSIONS: Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic, hypertensive patients.

Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients.

OBJECTIVES: We investigated the vascular effects of candesartan in hypertensive patients. BACKGROUND: The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The plausible mechanisms are that angiotensin II promotes superoxide anion generation, endothelial dysfunction, inflammation, and impaired fibrinolysis. The effects of candesartan on these conditions have not been clearly observed. METHODS: We administered placebo or candesartan 16 mg daily during two months to 45 patients with mild-to-moderate hypertension. This was a randomized, double-blind, placebo-controlled, crossover study in design. RESULTS: Candesartan did not significantly change lipoprotein levels. However, compared with placebo, candesartan significantly reduced plasma levels of malondialdehyde from 1.50 +/- 0.07 to 1.29 +/- 0.09 microM (p = 0.009); improved the percent flow-mediated dilator response to hyperemia from 5.17 +/- 0.24 to 6.22 +/- 0.26% (p < 0.001); and, furthermore, reduced plasma levels of monocyte chemoattractant protein (MCP-1) from 213 +/- 8 to 190 +/- 7 pg/ml (p = 0.003), tumor necrosis factor-alpha from 2.93 to 2.22 pg/ml (p = 0.026), and plasminogen activator inhibitor type 1 from 74 +/- 4 to 53 +/- 4 ng/ml (p < 0.001) but not C-reactive protein (CRP), matrix metalloproteinase protein, and fibrinogen. There were no significant correlations between these changes and reduction of systolic blood pressure (BP) (-0.247 < or = r < or = 0.195) and between these changes and reduction of diastolic BP (-0.262 < or = r < or = 0.197). There were no significant correlations between markers of inflammation and flow-mediated dilation percent or reduction of oxidant stress (-0.119 < or = r < or = 0.127). Furthermore, we observed no significant correlations between CRP and MCP-1 levels (r = -0.162). CONCLUSIONS: Inhibition of the angiotensin II type 1 (AT1) receptor in hypertensive patients reverses endothelial dysfunction, measured as an improvement in flow-mediated dilation and fibrinolysis and reduction of oxidant stress and inflammatory cytokines, suggesting that AT1 receptor blocker therapy has antiatherogenic effects.

Effects of continuous combined hormone replacement therapy on inflammation in hypertensive and/or overweight postmenopausal women.

OBJECTIVE: We observed that estrogen did not show cardioprotective benefits in type 2 diabetic postmenopausal women. We hypothesized that hypertensive and/or overweight women may be less likely to realize cardiovascular benefits from estrogen. METHODS AND RESULTS: We administered micronized progesterone (MP) 100 mg or medroxyprogesterone acetate (MPA) 2.5 mg with conjugated equine estrogen (CEE) 0.625 mg daily during 2 months to 35 hypertensive and/or overweight postmenopausal women with a randomized, double-blind, crossover design. With significant changes of lipoproteins, CEE+MP or MPA significantly improved flow-mediated dilation and reduced plasma E-selectin, intercellular adhesion molecule type-1, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha levels (P<0.001, P<0.001, P=0.021, P<0.001, and P<0.001 by ANOVA, respectively), but not C-reactive protein and fibrinogen levels. Of note, there were no significant differences between each therapy regarding these effects. However, the magnitude of improvement of flow-mediated dilation in these women was less than in healthy postmenopausal women and more than in diabetic postmenopausal women reported by our previous studies. The effects of CEE+MP or MPA on inflammatory markers were comparable to healthy postmenopausal women, but not comparable to diabetic postmenopausal women. CONCLUSIONS: Estrogen combined with synthetic progestin significantly improved flow-mediated brachial artery dilator response and reduced inflammation markers in hypertensive and/or overweight women, comparable to estrogen combined with natural progesterone.

Comparative effects of diet and statin on NO bioactivity and matrix metalloproteinases in hypercholesterolemic patients with coronary artery disease.

OBJECTIVE: We investigated the effects of statin compared with the American Heart Association (AHA) Step I Diet on lipoproteins, vasomotor function, tumor necrosis factor (TNF)-alpha, and serological markers of plaque stability. Furthermore, we investigated the mechanism of regulation suggested by experimental studies. METHODS AND RESULTS: For 14 weeks, we administered AHA diet+placebo and AHA diet+simvastatin (20 mg daily) to 31 and 32 randomly selected patients with coronary artery disease, respectively. Compared with diet alone, simvastatin significantly improved the percent flow-mediated dilator response to hyperemia from 3.37+/-2.28% to 5.89+/-2.35% (P<0.001) and lowered plasma levels of C-reactive protein from 0.48 to 0.10 mg/dL (P<0.001), TNF-alpha from 3.38 to 2.79 pg/mL (P<0.001), total matrix metalloproteinase (MMP)-9 from 36 to 28 ng/mL (P=0.006), and tissue inhibitor of matrix metalloproteinase-1 from 80+/-30 to 74+/-23 ng/mL (P=0.041), and simvastatin lowered to a greater extent MMP-9 activity (from 71 to 52 ng/mL, P=0.006) and MMP-9 activity/tissue inhibitor of matrix metalloproteinase-1 ratios (P=0.018), although this difference did not reach statistical significance. There were significant correlations between the degree of changes in TNF-alpha and the degree of changes in MMP-9 activity (r=0.424, P=0.016). However, no significant correlations between lipoprotein levels or flow-mediated dilation percentages and levels of plaque stability markers were determined (-0.208< or =r< or =0.243). CONCLUSIONS: Simvastatin reduced serological markers of inflammation and plaque stability, independent of lipoprotein changes.

Significant differential effects of hormone therapy or tibolone on markers of cardiovascular disease in postmenopausal women: a randomized, double-blind, placebo-controlled, crossover study.

OBJECTIVE: The objective was to compare the effects of tibolone and hormone therapy (HT) on lipid profile, vasodilation, and factors associated with inflammation and hemostasis. METHODS AND RESULTS: Fifty-three women received micronized progesterone (MP, 100 mg) with conjugated equine estrogen (CEE, 0.625 mg) or tibolone (2.5 mg) daily for 2 months, with a 2-month washout period. Compared with HT, tibolone significantly reduced total cholesterol (P<0.001), triglyceride (P<0.001), and HDL cholesterol (P<0.001) levels as well as triglyceride/HDL cholesterol ratios (P<0.001) but not LDL cholesterol levels. Tibolone significantly improved flow-mediated brachial artery dilator response to hyperemia from baseline values (P<0.001) by a magnitude similar to that found with HT (P=0.628). Compared with tibolone, which showed no changes, HT significantly increased high-sensitivity C-reactive protein (hsCRP, P=0.030) and reduced antithrombin III (P<0.001). HT and tibolone significantly increased prothrombin fragment 1+2 (F1+2) from baseline values (P<0.001 and P=0.004, respectively). The effects of HT and tibolone on hsCRP, antithrombin III, and F1+2 were significantly different. HT and tibolone significantly reduced plasma levels of plasminogen activator inhibitor type 1 antigen from baseline levels (P=0.006 and P=0.005, respectively) to a similar degree (P=0.988). CONCLUSIONS: Tibolone significantly improved flow-mediated brachial artery dilator response by a magnitude similar to that found with CEE+MP; however, tibolone did not significantly change hsCRP and antithrombin III, and tibolone increased F1+2 less than did CEE+MP.

The role of insulin resistance and metabolic risk factors on culprit coronary plaque.

BACKGROUND: Detailed relationships between insulin resistance (IR) and vulnerable plaque are not clear, therefore, we sought the role of IR and metabolic risk factors on culprit coronary plaque. METHODS: Plaque components at a region of interest (ROI, 10mm) were analyzed by virtual histology intravascular ultrasound. IR was defined as quantitative insulin sensitivity check index (QUICKI) ≤ 0.33. Seven metabolic risk factors (5 risk factors for metabolic syndrome defined by ATP III, history of smoking, and hsCRP) for IR were determined. RESULTS: The data for 150 (males 104) patients were analyzed. Patients with IR (n = 69) had greater necrotic core (NC) at the ROI (21.2 ± 15.8mm(3) vs 15.7 ± 11.9 mm(3), p = 0.02) than in patients without IR (n = 81). The NC at the ROI was correlated with QUICKI (r = -0.16, p = 0.05), HbA1c (r = 0.24, p < 0.01), body mass index (r = 0.17, p = 0.04), presence of diabetes mellitus (r = 0.29, p < 0.001), hsCRP (r = 0.17, p = 0.04) and the numbers of risk factors for IR (r = 0.41, p < 0.001). The multivariate analysis revealed that the numbers of risk factors for IR was an independent factor for the NC at the ROI (beta coefficient = 0.44, p = 0.003), but QUICKI was not (beta coefficient = -0.01, p = 0.94). CONCLUSIONS: Instead of a single measurement of IR index or each metabolic risk factor, clustering of risk factors for IR plays an important role on plaque vulnerability. CONDENSED ABSTRACT: We investigated the role of insulin resistance (IR) on culprit coronary plaque. Patients with IR had a greater amount of necrotic core in culprit coronary lesions than in patients without IR. Rather than a single measurement of IR index or each metabolic risk factor, clustering of metabolic risk factors for IR plays an important role in plaque vulnerability in patients with coronary artery disease. Our study demonstrates the role of IR on culprit coronary plaque and highlights the importance of the clustering of metabolic risk factors for IR in vulnerable plaque pathogenesis.

Angiotensin II type 1 receptor blockers reduce tissue factor activity and plasminogen activator inhibitor type-1 antigen in hypertensive patients: a randomized, double-blind, placebo-controlled study.

Angiotensin II stimulates the expression of tissue factor (TF) and plasminogen activator inhibitor type-1 (PAI-1), and AT1 receptor blockade (ARB) reduces PAI-1 and TF activities in experimental studies. We investigated the effects of ARBs on TF activity, tissue plasminogen activator (tPA), PAI-1 antigen levels, plasma renin activity (PRA) and aldosterone levels in hypertensive patients. Placebo, losartan 100mg, irbesartan 300 mg, and candesartan 16 mg daily were administered to 122 patients for 2 months. Compared with placebo, ARBs significantly reduced TF activity (P <0.001 by ANOVA), and candesartan was the most potent. Compared with placebo or losartan, irbesartan and candesartan significantly lowered plasma levels of PAI-1 antigen (P <0.001 by ANOVA) with no differences between the two. Compared with placebo, all ARBs lowered plasma levels of aldosterone (P=0.012 by ANOVA) and increased PRA (P=0.005 by ANOVA). There were significant correlations between the degree of change in TF activity and PAI-1 antigen levels (r=0.458, P <0.0001) and between the change in TF activity and PRA (r=-0.296, P=0.006), but not with the magnitude of reduction in blood pressure following ARB therapy. ARBs significantly reduced TF activity, PAI-1 antigen levels, and aldosterone levels in hypertensive patients. The clinical significance of the varying potency of some ARBs needs to be further investigated.

Vascular effects of step I diet in hypercholesterolemic patients with coronary artery disease.

We administered a step I diet to 50 hypercholesterolemic patients with coronary artery disease during 12 weeks. Compared with baseline, the step I diet significantly changed lipoprotein levels, significantly improved the percent flow-mediated dilation response to hyperemia by 32 +/- 7% (p <0.001), increased plasma levels of nitrate by 45 +/- 12% (p = 0.013), and lowered plasma levels of malondialdehyde by 7 +/- 4% (p = 0.011). However, the step I diet did not significantly change serologic markers of inflammation, plaque stability, and thrombosis. Step I diet therapy improved endothelium-dependent vasodilation with an increase in plasma nitrogen oxide and a decrease in oxidant stress in hypercholesterolemic patients with coronary artery disease.

Comparative effects of statin and fibrate on nitric oxide bioactivity and matrix metalloproteinase in hyperlipidemia.

OBJECTIVE: Because the lipoprotein effects of statin and fibric acid derivatives therapies differ, we studied the effects of these therapies in patients with hyperlipidemia on lipoproteins, vasomotor function, and plaque stability. METHODS: We administered simvastatin, 20 mg daily, to 27 patients with hypercholesterolemia and coronary artery disease, or fenofibrate, 200 mg daily, to 27 patients with pure hypertriglyceridemia during 8 weeks. RESULTS: As expected, simvastatin significantly lowered total cholesterol and low-density lipoprotein cholesterol (LDL-C) more, and fenofibrate decreased triglyceride and increased high-density lipoprotein cholesterol (HDL-C) more than either therapy. Simvastatin and fenofibrate significantly improved the percent flow-mediated dilator response to hyperemia by 183+/-41% and by 30+/-7%, respectively (each P<0.001); however, simvastatin significantly improved more (P<0.001). Simvastatin and fenofibrate significantly lowered plasma levels of tumor necrosis factor alpha (TNF-alpha) by 13+/-4% and by 10+/-4%, respectively (P=0.009 and P=0.006, respectively) with a similar degree (P=0.614). Simvastatin significantly reduced plasma levels of total MMP-9 and TIMP-1 more (P=0.005 and P=0.036, respectively), compared with fenofibrate showing no reduction. There were significant correlations between the degree of changes in TNF-alpha and the degree of changes in MMP-9 activity (r=0.376, P=0.053). CONCLUSIONS: Simvastatin and fenofibrate demonstrated antiatherosclerotic effects via different mechanisms.