Are obesity indices derived by dual-energy x-ray absorptiometry capable of identifying postmenopausal females with high risk for coronary heart disease?

OBJECTIVE: The aim of the study was to evaluate the predictive ability of obesity indices derived by dual-energy x-ray absorptiometry (DXA) regarding coronary heart disease (CHD). METHODS: DXA total body scans were performed on 71 consecutive postmenopausal women who were referred for myocardial perfusion imaging (MPI). Twenty-four women with CHD diagnosed by MPI were considered as cases, whereas the remaining 47 women with normal MPI results were considered as controls. Biochemical markers, body mass index (BMI) and waist circumference (WC) were also recorded for all women and correlated to DXA adiposity indices. Receiver operating characteristic curve analysis was performed to evaluate the ability of DXA and anthropometrically obtained obesity indices on predicting CHD. RESULTS: Participants with CHD were found to have increased fat mass in the trunk (P < 0.01), in the android area (P < 0.01), and in the total body (P < 0.05) in agreement with the anthropometric indices WC (P < 0.01) and BMI (P < 0.05). Strong correlation was observed between BMI and fat mass in total body (R = 0.835), trunk (R = 0.731), and android (R = 0.796) and between WC and fat mass in android (R = 0.713). DXA-derived central fat indices were found to have higher potential for identification of individuals at high risk for CHD than BMI and WC but differences were not statistically significant. CONCLUSIONS: DXA central fat indices were found to have the power to identify individuals with CHD; however, the superiority of DXA indices over the commonly used anthropometric indices (BMI, WC) in identifying women with CHD did not reach statistical significance.

Hypertrophic and antihypertrophic microRNA levels in peripheral blood mononuclear cells and their relationship to left ventricular hypertrophy in patients with essential hypertension.

MicroRNAs regulate several aspects of physiological and pathologic cardiac hypertrophy, and they represent promising therapeutic targets in cardiovascular disease. We assessed the expression levels of the microRNAs miR-1, miR-133a, miR-26b, miR-208b, miR-499, and miR-21, in 102 patients with essential hypertension and 30 healthy individuals. All patients underwent two-dimensional echocardiography. MicroRNA expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly lower miR-133a (5.06 ± 0.50 vs. 13.20 ± 2.15, P < .001) and miR-26b (6.76 ± 0.53 vs. 9.36 ± 1.40, P = .037) and higher miR-1 (25.99 ± 3.07 vs. 12.28 ± 2.06, P = .019), miR-208b (22.29 ± 2.96 vs. 8.73 ± 1.59, P = .016), miR-499 (10.06 ± 1.05 vs. 5.70 ± 0.91, P = .033), and miR-21 (2.75 ± 0.15 vs. 1.82 ± 0.20, P = .002) expression levels compared with healthy controls. In hypertensive patients, we observed significant negative correlations of miR-1 (r = -0.374, P < .001) and miR-133a (r = -0.431, P < .001) and significant positive correlations of miR-26b (r = 0.302, P = .002), miR-208b (r = 0.426, P < .001), miR-499 (r = 0.433, P < .001) and miR-21 (r = 0.498, P < .001) expression levels with left ventricular mass index. Our data reveal that miR-1, miR-133a, miR-26b, miR-208b, miR-499, and miR-21 show distinct expression profiles in hypertensive patients relative to healthy individuals and they are associated with clinical indices of left ventricular hypertrophy in hypertensive patients. Thus, they may be related to heart hypertrophy in hypertensive patients and are possibly candidate therapeutic targets in hypertensive heart disease.

Circulating mesenchymal stem cells in patients with hypertrophic cardiomyopathy.

BACKGROUND: This study examines the mobilization of mesenchymal stem cells (MSCs) in patients with hypertrophic cardiomyopathy (HCM) compared to healthy individuals. The pathogenesis of myocardial hypertrophy in HCM is not fully understood. MSCs are involved in the process of neovascularization, fibrosis, and ventricular wall remodeling. METHODS AND RESULTS: We included 40 patients with HCM and 23 healthy individuals. Using flow cytometry, we measured MSCs in peripheral blood, as a population of CD45-/CD34-/CD90+ cells and also as a population of CD45-/CD34-/CD105+ cells. The resulting MSC counts were expressed as percentages of the total cells. Patients with HCM were found to have a greater percentage of circulating CD45-/CD34-CD34-/CD90+ cells compared to controls (0.0041±0.005% vs. 0.0007±0.001%, respectively, P<.001). No significant difference in circulating CD45-/CD34-/CD105+ cells in the peripheral blood was found between HCM patients and controls (0.016±0.018% vs. 0.012±0.014%, respectively, P=.4). Notably, circulating CD45-/CD34-/CD90+ cells were positively correlated with left ventricular mass index (r=0.54, P<.001). CONCLUSIONS: Patients with HCM reveal an increased mobilization of MSCs compared to healthy individuals. Although further research is needed to reveal the clinical significance of our findings, our data open a new dimension in the pathophysiology of the disease and may indicate new future therapeutic possibilities.

Increased mobilization of mesenchymal stem cells in patients with essential hypertension: the effect of left ventricular hypertrophy.

Stem cells have great clinical significance in many cardiovascular diseases. However, there are limited data regarding the involvement of mesenchymal stem cells (MSCs) in the pathophysiology of arterial hypertension. The aim of this study was to investigate the circulation of MSCs in patients with essential hypertension. The authors included 24 patients with untreated essential hypertension and 19 healthy individuals. Using flow cytometry, MSCs in peripheral blood, as a population of CD45-/CD34-/CD90+ cells and also as a population of CD45-/CD34-/CD105+ cells, were measured. The resulting counts were translated into the percentage of MSCs in the total cells. Hypertensive patients were shown to have increased circulating CD45-/CD34-/CD90+ compared with controls (0.0069%±0.012% compared with 0.00085%±0.0015%, respectively; P=.039). No significant difference in circulating CD45-/CD34-/CD105+ cells was found between hypertensive patients' and normotensive patients' peripheral blood (0.018%±0.013% compared with 0.015%±0.014%, respectively; P=.53). Notably, CD45-/CD34-/CD90+ circulating cells were positively correlated with left ventricular mass index (LVMI) (r=0.516, P<.001). Patients with essential hypertension have increased circulating MSCs compared with normotensive patients, and the number of MSCs is correlated with LVMI. These findings contribute to the understanding of the pathophysiology of hypertension and might suggest a future therapeutic target.

MicroRNA-9 and microRNA-126 expression levels in patients with essential hypertension: potential markers of target-organ damage.

MicroRNAs (miRs), as essential gene expression regulators, modulate cardiovascular development and disease and thus they are emerging as potential biomarkers and therapeutic targets in cardiovascular disease, including hypertension. We assessed the expression levels of the microRNAs miR-9 and miR-126 in 60 patients with untreated essential hypertension and 29 healthy individuals. All patients underwent two-dimensional echocardiography and 24-hour ambulatory blood pressure monitoring. MicroRNA expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly lower miR-9 (9.69 ± 1.56 vs 41.08 ± 6.06; P < .001) and miR-126 (3.88 ± 0.47 vs 8.96 ± 1.69; P < .001) expression levels compared with healthy controls. In hypertensive patients, miR-9 expression levels showed a significant positive correlation (r = 0.437; P < .001) with left ventricular mass index. Furthermore, both miR-9 (r = 0.312; P = .015) and miR-126 (r = 0.441; P < .001) expression levels in hypertensive patients showed significant positive correlations with the 24-hour mean pulse pressure. Our data reveal that miR-9 and miR-126 are closely related to essential hypertension in humans, as they show a distinct expression profile in hypertensive patients relative to healthy individuals, and they are associated with clinical prognostic indices of hypertensive target-organ damage in hypertensive patients. Thus, they may possibly represent potential biomarkers and candidate therapeutic targets in essential hypertension.

Circulating endothelial progenitor cells in hypertensive patients with increased arterial stiffness.

The potential association between arterial stiffening and circulating endothelial progenitor cells (EPCs) in patients with essential hypertension was investigated. Pulse wave velocity (PWV) was used to evaluate arterial stiffness in 24 patients with essential hypertension and 19 healthy controls. Blood samples were taken and immunostained with antibodies against the cell surface markers CD34, CD45, and CD133. Using flow cytometry, EPCs as a population of CD45-/CD34+/CD133+ cells were measured. Hypertensive patients were not found to have higher levels of circulating CD45-/CD34+/CD133+ compared with the control group (0.0026%±0.0031% vs 0.0023%±0.0023%, respectively; P=.7). Correlation analysis revealed a strong association between the number of CD45-/CD34+/CD133+ cells and PWV (r=0.58, P<.001), indicating that hypertensive patients with increased PWV have a greater percentage of CD45-/CD34+/CD133+ cells. Data showed a correlation between the number of circulating CD45-/CD34+/CD133+ cells and arterial stiffness, suggesting that those cells might have a role in arterial remodeling.

Association of sodium and potassium intake with ventricular arrhythmic burden in patients with essential hypertension.

BACKGROUND: Hypertensive populations suffer from an increased susceptibility to ventricular arrhythmias and sudden cardiac death. A high-salt diet appears to be a major factor involved in cardiovascular complications in hypertension. We examined the relationship between dietary salt and potassium, as indicated by urinary sodium (UNa), urinary potassium (UK), and urinary sodium/potassium ratio (UNa/K), and the arrhythmic burden in patients with essential hypertension. METHODS: We included 255 consecutive adult patients with well-controlled hypertension who were being followed in the hypertension outpatient clinic of a university tertiary hospital and complained of episodes of atypical chest pain and/or palpitations. All underwent 24-hour ambulatory electrocardiograph monitoring and their UNa, UK, and UNa/K ratio from 24-hour urinary excretion specimens were evaluated. RESULTS: No significant correlation was found between premature supraventricular contractions and the parameters that were examined. However, the percentage of premature ventricular contractions (PVC%) showed a weak positive association with UNa (r = 0.2; P = .001) and a moderate negative association with UK (r = -0.396; P < .001). The partial correlation coefficient of PVC% with the UNa/UK ratio remained significant even after controlling for left ventricular mass index (r = 0.437; P < .001). CONCLUSIONS: A higher UNa/UK excretion ratio is significantly associated with PVCs, indicating an increased susceptibility to ventricular arrhythmias even among hypertensives with well-controlled blood pressure. Our findings reinforce recommendations for dietary interventions in those populations.

TLR2 and TLR4 gene expression in peripheral monocytes in nondiabetic hypertensive patients: the effect of intensive blood pressure-lowering.

The activation of innate immune receptors, such as Toll-like receptors (TLRs), participates in the pathogenesis of cardiovascular diseases. The authors evaluated TLR2 and TLR4 gene expression in the peripheral monocytes of nondiabetic hypertensive patients compared with normotensive individuals and investigated the effect of intensive systolic blood pressure (SBP)-lowering. Included were 43 nondiabetic hypertensive patients with essential hypertension who were randomly assigned to an intensive treatment arm, with an SBP target of <130 mm Hg, or a standard arm, with an SBP target of <140 mm Hg. TLR2 and TLR4 messenger RNA (mRNA) levels in monocytes were estimated before and 12 weeks after therapy initiation. Sixteen healthy individuals were included for comparison. Hypertensives revealed significantly higher TLR4 mRNA levels compared with normotensives (985 ± 885 vs 554 ± 234, P=.005). In contrast, no statistically significant difference was found in TLR2. Compared with standard treatment, intensive treatment significantly downregulated TLR2 and TLR4 mRNAs, expressed as fold induction (0.66 ± 0.49 vs 1.38 ± 1.65 and 0.62 ± 0.3 vs 1.9 ± 1.2, respectively; P<.001 for both). In conclusion, TLR4 mRNA levels in peripheral monocytes are significantly elevated in nondiabetic hypertensive patients. Intensive control of SBP results in attenuation of TLR2 and TLR4 gene expression in those patients. Our findings suggest that a strict SBP target in nondiabetic hypertensive patients may offer additional benefits.

Early cardiac gene transcript levels in peripheral blood mononuclear cells in patients with untreated essential hypertension.

OBJECTIVES: To assess the expression of early cardiac genes, implicated in the hypertrophic growth response of the adult heart, in peripheral blood mononuclear cells in patients with essential hypertension and its relationship to ambulatory blood pressure monitoring (ABPM) parameters and to echocardiographic left ventricular mass. METHODS: Twenty-four-hour ABPM, echocardiography and blood sampling were performed in 62 untreated participants with essential hypertension. Blood samples from 38 healthy individuals were included for comparison. Peripheral blood mononuclear cells (PBMCs) were isolated and gene transcript levels were determined by quantitative real-time reverse transcription PCR. RESULTS: Myocardin (3.92±0.68 versus 2.09±0.67, P<0.001), GATA4 (3.48±0.68 versus 0.32±0.08, P<0.001) and Nkx2.5 (208.91±35.01 versus 129.75±49.70, P<0.001) were upregulated in hypertensive patients compared with controls. In hypertensive patients, transcript levels of myocardin (r=0.698, P<0.001) and GATA4 (r=0.374, P=0.003) showed significant positive correlations with 24-h systolic blood pressure (BP) as well as with mean BP, (r=0.626, P<0.001) and (r=0.340, P=0.007), respectively. A significant positive correlation between myocardin and 24-h pulse pressure (r=0.467, P<0.001) was also observed. Myocardin (r=-0.606, P<0.001) and GATA4 (r=-0.453, P<0.001) transcript levels also showed significant negative correlations with the mean 24-h dipping status. Additionally, myocardin (r=0.341, P=0.007), GATA4 (r=0.337, P=0.007) and Nkx2.5 (r=0.325, P=0.010) transcript levels showed significant positive correlations with left ventricular mass index. CONCLUSION: Myocardin and GATA4 transcript levels correlate significantly with 24-h ABPM parameters, rendering them potential candidate biomarkers in hypertension. Early cardiac gene transcript levels in PBMCs of hypertensive patients are associated with left ventricular mass and may reflect activation of the hypertrophic response gene network in these patients.

Differential effect of telmisartan and amlodipine on monocyte chemoattractant protein-1 and peroxisome proliferator-activated receptor-gamma gene expression in peripheral monocytes in patients with essential hypertension.

Monocyte chemoattractant protein-1 (MCP-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ) play a significant role in monocyte activation, vascular inflammation, and atherogenesis. Angiotensin receptor blockers and calcium channel blockers are antihypertensive drugs with established efficacy and a favorable safety profile. We investigated the effect of telmisartan--an angiotensin receptor blocker with PPAR-γ agonist activity--and amlodipine on the activation state of peripheral blood monocytes with respect to MCP-1 and PPAR-γ gene expression in hypertensives. We recruited 31 previously untreated patients with essential hypertension who were randomly assigned to receive treatment with telmisartan (n = 16) or amlodipine (n = 15). Blood samples were taken before and 3 months after therapy initiation. Mononuclear cells were isolated and mRNAs of MCP-1 and PPAR-γ were estimated by real-time quantitative reverse transcription-polymerase chain reaction each time. The 2 treatments decreased all blood pressure components significantly (p <0.001). In contrast, in the amlodipine group, MCP-1 gene expression was significantly downregulated after treatment with telmisartan (from 21.4 ± 20.5 to 8.1 ± 6.5, p = 0.009), whereas the amlodipine group did not show any significant change (12.5 ± 8.5 vs 17.6 ± 16.4, p = NS). In addition, PPAR-γ mRNA levels showed a significant increase in telmisartan-treated patients (from 20 ± 18.5 to 42.6 ± 36, p = 0.006) and no significant alterations in the amlodipine group (from 29.6 ± 42.5 to 24.2 ± 27.7, p = NS). In conclusion, treatment with telmisartan results in a significant attenuation of MCP-1 gene expression and an increase of PPAR-γ gene expression in peripheral monocytes in patients with essential hypertension. Our findings may provide new insights into the cardiovascular protection of telmisartan in hypertensives.

Ivabradine improves coronary flow reserve in patients with stable coronary artery disease.

OBJECTIVES: Although treatment with ivabradine reduces the incidence of hospital admissions for myocardial infarction and coronary revascularisation, there are no data concerning its effect on coronary circulation. The purpose of this study was to assess the effects of ivabradine on coronary flow velocity and flow reserve (CFR) in patients with stable coronary artery disease (CAD). METHODS: During diagnostic coronary angiography (baseline), twenty-one patients with stable CAD underwent coronary flow velocity measurements (APV cm/s) in a non-culprit vessel, using a Doppler guidewire, at rest (r) and after adenosine administration to achieve maximal hyperaemia (h). During programmed coronary intervention in the culprit vessel, the same measurements were repeated one week after treatment with ivabradine (5 mg twice daily), both at the intrinsic heart rate and at a paced heart rate identical to that before treatment. CFR was defined as h-APV/r-APV. RESULTS: Heart rate was significantly lower after treatment with ivabradine (78±14 bpm vs 65±9 bpm, p<0.001). Also, a reduction of r-APV (17.0±5.5 vs 19.7±7.6, p=0.003) and augmentation of h-APV (57.9±17.8 vs 53.5±21.4, p=0.009) leading to CFR improvement (3.51±0.81 vs 2.78±0.61, p<0.001) were observed. During pacing, although r-APV reverted to values similar to those before treatment (20.0±6.5 vs 19.7±7.6, p=NS), a sustained improvement in h-APV was observed (59.5±19.7 vs 53.5±21.4, p=0.007) and CFR remained higher than before treatment (3.04±0.66 vs 2.78±0.61, p<0.001). CONCLUSIONS: Ivabradine treatment significantly improves hyperaemic coronary flow velocity and CFR in patients with stable CAD. These effects remain even after heart rate correction indicating improved microvascular function.

NT-proBNP response to dobutamine stress echocardiography predicts left ventricular contractile reserve in dilated cardiomyopathy.

BACKGROUND: Brain natriuretic peptide (BNP) and left ventricular (LV) inotropic reserve are major prognostic indexes in heart failure (HF). AIMS: To investigate the relationship between N-terminal-proBNP (NT-proBNP) changes in response to dobutamine stress echocardiography (DSE) and the LV inotropic reserve, in HF patients with dilated cardiomyopathy (DC). METHODS: We studied 41 patients with DC, LVEF 31.6+/-7.7%, NYHA class II-III and 15 controls. Plasma NT-proBNP levels were measured before and 60 min after three 5-min stages of dobutamine (5 to 15 microg/kg/min). RESULTS: Based on NT-proBNP changes in response to dobutamine, patients were categorized into two groups: In Group A circulating NT-proBNP levels fell (-16.6+/-7.8%), and in Group B they increased (8.4+/-9.1%). Group A had a marked improvement in WMSI compared to Group B (32.1+/-9.7% vs. 18.8+/-15.9%, p<0.001). Multivariate analysis showed that NT-proBNP changes were an independent predictor of LV inotropic reserve (b= -0.55, p<0.001). A reduction of 21.3% in plasma NT-proBNP levels in response to dobutamine predicted an improvement in WMSI of >25% with a sensitivity of 100% and a specificity of 92.3%. CONCLUSIONS: NT-proBNP changes in response to dobutamine reflect improvement in LV contractility and constitute an independent predictor of LV inotropic reserve in patients with DC.

Endothelial cell function during atrial fibrillation and after restoration of sinus rhythm.

Beat-to-beat variation in blood flow dynamics during atrial fibrillation (AF) has been associated with evidence of endothelial dysfunction. The aim of the present work is to confirm endothelial dysfunction in patients with AF and test the hypothesis that endothelial dysfunction is reversible upon restoration of normal sinus rhythm. Endothelium-dependent (flow-mediated dilation [FMD]) and endothelium-independent (nitroglycerin-mediated dilation [NMD]) vasodilator function of the brachial artery were measured using high-resolution ultrasound in 46 patients with persistent AF who were scheduled for internal electrical cardioversion and in 25 control subjects. In patients who remained in sinus rhythm after cardioversion, these measurements were repeated after 24 hours (n = 32) and 1 month (n = 19). Compared with control subjects, patients (n = 32) showed lower FMD during AF (8.1 +/- 3.6% vs 12.2 +/- 3.2%, respectively, p <0.001) and similar NMD (17.0 +/- 3.5% vs 15.9 +/- 3.1%, respectively, p = 0.21). In 19 patients who remained in sinus rhythm, FMD increased at both 24 hours (8.0 +/- 3.9% vs 10.6 +/- 4.6%, p = 0.015) and 1 month (8.0 +/- 3.9% vs 13.6 +/- 5.3%, p <0.001). In contrast, NMD was not significantly altered at 24 hours or 1 month after sinus rhythm restoration (17.1 +/- 3.9% vs 17.2 +/- 4.0% vs 16.9 +/- 4.1%). In conclusion, AF is associated with impairment in endothelial function that improves after sinus rhythm restoration.

Atrial fibrillation is associated with increased neurohumoral activation and reduced exercise tolerance in patients with non-ischemic dilated cardiomyopathy.

OBJECTIVES: To assess atrial fibrillation (AF) associated differences in proinflammatory cytokines, natriuretic peptide levels and exercise capacity in patients with heart failure (HF) secondary to non-ischemic dilated cardiomyopathy (NIDC). METHODS: We studied 147 NIDC patients, mean age 58.3+/-12.5 years, left ventricular (LV) ejection fraction 27.8+/-10.9% and NYHA class II-III. Neurohumoral activation was assessed by measurement of interleukin IL-1, IL-6, tumor necrosis factor-a (TNF-a), its soluble receptors sTNFR I and II, N-terminal atrial (NT-ANP) and -brain (NT-BNP) natriuretic peptide levels, and functional class was assessed by cardiopulmonary exercise test. RESULTS: Forty patients (27.5%) had chronic AF and they did not differ in age, LV ejection fraction or HF duration compared to patients in sinus rhythm (SR). AF was associated with increased levels of IL-6 (p=0.001), TNF-a (p=0.002), sTNFRI (p=0.023), NT-ANP (p<0.001) and NT-BNP (p=0.003), decreased exercise duration (p<0.001) and slightly reduced maximal oxygen consumption at peak exercise (p=0.07) compared to SR patients. No significant differences in cytokine and natriuretic peptide levels or exercise tolerance were noted when patients in AF were compared to the subgroup of SR with restrictive LV filling pattern. Multivariate analysis showed that NT-ANP (p=0.003) and IL-6 (p=0.006) plasma levels were independently associated with the presence of AF in our patient population. CONCLUSION: AF is associated with increased inflammatory state, natriuretic peptide levels and reduced exercise capacity in patients with HF secondary to NIDC. These findings suggest that the presence of AF in HF represents a more advanced stage of the syndrome.

Early effects of simvastatin versus atorvastatin on oxidative stress and proinflammatory cytokines in hyperlipidemic subjects.

The authors investigated the time-dependent action of atorvastatin and simvastatin on oxidative stress and cytokine levels immediately after the start of treatment. These factors play a role in endothelial dysfunction. Hyperlipidemic patients (n = 132) were assigned to treatment with 40 mg atorvastatin, 40 mg simvastatin, or placebo. Blood samples were taken before, 2 hours, 24 hours, 7 days, and 3 weeks after the administration of the statin or placebo to evaluate serum concentrations of total peroxides (TP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and soluble intercellular vascular adhesion molecule 1 (sICAM 1). In the atorvastatin group the TP changes were significantly different at 2 hours and 24 hours (p = 0.005), whereas in the simvastatin group there was a gradual, more or less linear decline in TP until 7 days (p = 0.006) and then a plateau. Simvastatin exhibited a faster statistically significant decrease over time in IL-6 and sICAM 1 levels (at 7 days, p = 0.014 and p = 0.001, respectively). TNF-alpha demonstrated a faster linear trend in the simvastatin group, but the significant effect appeared late (p = 0.006). Both simvastatin and atorvastatin exerted early beneficial effects on oxidative stress, proinflammatory cytokines, and endothelial activation in hyperlipidemic subjects. These effects became significant 2 hours following the initiation of therapy.

Late left ventricular color M-mode Doppler in the assessment of diastolic dysfunction in patients with dilated cardiomyopathy.

The ratio of early (Ep) to late (Ap) color M-mode Doppler flow propagation through the left ventricle helps in the differentiation between normal and pseudonormal (PSN) filling pattern in patients with preserved systolic function. We studied the value of this index in the assessment of diastolic dysfunction for patients with reduced left ventricular systolic function. We studied 80 patients with nonischemic dilated cardiomyopathy and 50 control subjects. According to echocardiography 53 patients had abnormal relaxation and 27 had PSN pattern. Patients had reduced Ep (P < .001) and Ep/Ap ratio (P < .001) and increased Ap (P = .001) compared to controls. Binary logistic regression analysis showed that Ep followed by Ep/Ap ratio (both P < .001) were the best determinants for the discrimination of PSN from normal filling pattern. Ep/Ap ratio, this novel echo-index, increases the diagnostic accuracy of color M-mode Doppler in discriminating normal from PSN filling pattern in patients with left ventricular systolic dysfunction.

Association of impaired glucose tolerance with increased heart rate and subclinical inflammation.

INTRODUCTION: This study was designed to assess possible alterations in heart rate (HR), heart rate variability (HRV) and circulating serum levels of proinflammatory cytokines in patients with impaired glucose tolerance (IGT). METHODS: Forty-five patients, aged 34-68 years, with IGT were compared with 28 age-matched healthy controls. Using a 24-hour ambulatory electrocardiogram, we calculated mean HR during daytime (HR-D), night-time (HR-N) and the entire 24-hour period (HR-24h), as well as time domain HRV parameters. From blood samples interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-a) and its soluble receptor (sTNFRII) were also calculated by immunoassay. RESULTS: Patients showed higher mean HR compared to controls and significantly elevated circulating levels of TNF-a, sTNFRII, and IL-6. Pearson correlation analysis showed that TNF-a was positively correlated with mean HR-D (r: 0.304, p=0.042). IL-6 was also positively correlated with mean HR-24h (r: 0.299, p=0.046) and with mean HR-D (r: 0.410, p=0.005). CONCLUSION: IGT patients have an increased HR and elevated cytokine levels. These changes could serve as an index of the primary atherosclerotic process.

Long-term maintenance of normal sinus rhythm in patients with current symptomatic atrial fibrillation: amiodarone vs propafenone, both in low doses.

STUDY OBJECTIVES: To compare the efficacy and safety of amiodarone and propafenone when used for the prevention of atrial fibrillation (AF) and maintenance of normal sinus rhythm in patients with refractory AF. DESIGN: Prospective, randomized, single-blind trial. SETTING: Tertiary cardiac referral center. PATIENTS: One hundred forty-six consecutive patients (72 men; mean age, 63 +/- 10 years [+/- SD]) with recurrent symptomatic AF. INTERVENTIONS: We studied 146 patients after restoration of sinus rhythm; patients were randomized to amiodarone, 200 mg/d, or propafenone, 450 mg/d. Follow-up clinical evaluations were conducted at the first, second, fourth, and sixth months, and at 3-month intervals thereafter. The proportion of patients relapsing to AF and/or experiencing side effects was calculated for each group using the Kaplan-Meier method. End point of the study was recurrence of AF or occurrence of side effects necessitating discontinuation of medication. MEASUREMENTS AND RESULTS: Of 146 patients, 72 received amiodarone and 74 received propafenone. The two groups were clinically similar. Of the 72 patients receiving amiodarone, AF developed in 25 patients, after an average of 9.8 months, compared to 33 of the 74 patients receiving propafenone after an average of 3.8 months. Twelve patients receiving amiodarone and 2 patients receiving propafenone had side effects necessitating withdrawal of medication while still in sinus rhythm. CONCLUSIONS: Amiodarone tends to be more effective than propafenone in maintaining sinus rhythm in patients with AF, but this advantage is offset by a higher incidence of side effects.

Plasma Levels of Nitrites/Nitrates in Patients with Chronic Atrial Fibrillation are Increased after Electrical Restoration of Sinus Rhythm.

INTRODUCTION: Patients with persistent atrial fibrillation (AF) have hemodynamic changes, which impair endothelial cell function resulting in decreased nitric oxide (NO) production. The aim of this work was to assess endothelial function in AF patients before and at various time points after cardioversion. METHODS: Forty-two patients with AF and 21 normal and age-adjusted healthy controls were studied. Nitrites and nitrates (NO(x)) and von Willebrand factor (vWf) concentrations were measured on blood samples taken just before cardioversion and over a 30 day period after the procedure. RESULTS: Plasma levels of NO(x) in AF were significantly lower compared to healthy controls (p < 0.001), but after cardioversion gradually increased to approach to those of the healthy controls by the end of the first month of sustained sinus rhythm (p = 0.004). Interestingly plasma levels of NO(x) were negatively correlated to left atrial volume measured by ultrasonography (r = -0.34, p < 0.05). Plasma levels of vWf in AF patients were significantly higher compared to the healthy controls (p < 0.01) but with sustained sinus rhythm decreased (p = 0.02). CONCLUSION: The parallel normalization of the NO(x) titers and vWf levels suggests that vascular endothelial function improves after 30 days of normal sinus rhythm.