High circulating levels of N-terminal pro-brain natriuretic peptide and interleukin 6 in patients with mixed cryoglobulinemia.

Many patients with mixed cryoglobulinemia and chronic HCV infection experience symptoms, such as dyspnea, which sometimes do not seem to indicate the involvement of the liver but rather the symptoms of heart failure. To our knowledge, there has been no other study evaluating the serum levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and Interleukin 6 (IL-6) in such patients. Serum NTproBNP and IL-6 were assayed in 54 patients with mixed cryoglobulinemia and chronic HCV infection, and in 54 sex- and age-matched controls. Cryoglobulinemic-patients showed significantly higher mean NTproBNP and IL-6 levels than the controls (P = 0.005). By defining a high NTproBNP level as a value higher than 125 pg/ml (the single cut-off point for patients under 75 years of age), 30% of patients with mixed cryoglobulinemia and chronic HCV infection and 7% of controls had high NTproBNP (chi-square; P < 0.003). With a cut-off point of 300 pg/ml (used to rule out heart failure in patients under 75 years of age), 5/49 patients with mixed cryoglobulinemia and chronic HCV infection and 0/54 controls had high NTproBNP (chi-square; P < 0.04). With a cut-off point of 900 pg/ml (used for including heart failure in patients aged between 50 and 75, such as the patients in this study) 3/51 of patients with mixed cryoglobulinemia and chronic HCV infection and 0/54 controls had high NTproBNP (chi-square; P = 0.07). The study revealed high levels of circulating NTproBNP and IL-6 in patients with mixed cryoglobulinemia and chronic HCV infection. The increase in NTproBNP could indicate the presence of a subclinical cardiac dysfunction.

Preserved endothelial-dependent and endothelial-independent skin vasodilator responses in relatives of type 1 diabetes patients.

Since increased plasma and cell levels of oxidative products have been found in non diabetic relatives of type 1 diabetic patients, we hypothesized the occurrence of an endothelial dysfunction in these subjects. To verify this hypothesis we investigated the skin blood flow responses to iontophoresis of both the endothelial-dependent vasodilator acetylcholine (ACh) and the endothelial-independent vasodilator sodium nitroprusside (SNP) in 31 non diabetic healthy relatives (DR) (14 siblings, 17 parents) of 17 type 1 diabetic patients. Twenty healthy control subjects (CS) without a family history of diabetes, matched for age (+/-5 years) and gender, were also investigated. DR and CS did not significantly differ either in basal skin blood flux (6.75+/-0.72 PU and 5.78+/-0.37 PU, respectively) or in skin vasodilator response to both ACh (728+/-53% and 711+/-44%, respectively) and SNP iontophoresis (758+/-71% and 731+/-64%, respectively). This finding is consistent with a preserved skin microvascular endothelial function in the studied subjects. However, since previous data suggest that both nitric oxide (NO) and prostacyclin released form the cutaneous vascular endothelium have an interchanging compensatory role in controlling the skin vasodilator response to ACh iontophoresis, our finding does not allow a defect in NO dependent skin vasodilatation to be excluded in the studied relatives of diabetic patients.

Role of matrix metalloproteinases and their tissue inhibitors as potential biomarkers of left ventricular remodelling in the athlete's heart.

The aim of the present study was to verify whether plasma MMPs (matrix metalloproteinases) and TIMPs (tissue inhibitors of MMPs) could be used as potential markers of paraphysiological remodelling in the athlete's heart, and to correlate these matrix parameters with echocardiographic signs of LV (left ventricular) remodelling. Plasma MMP-2 and MMP-9 were measured by zymography, and TIMP-1 and TIMP-2 were measured by ELISA in 42 veteran marathoners with AH (athlete's heart), and in 25 sedentary healthy subjects (CTL). All subjects were submitted to a clinical examination and two-dimensional colour Doppler echocardiography together with the measurement of circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide); GGT (gamma-glutamyl transpeptidase) was evaluated as a marker of cardiovascular disease. Veteran athletes had a significant elevation in LV dimensions and calculated LV mass index. Diastolic and systolic functions were normal for both groups. MMP-9 levels were significantly lower in AH than in CTL subjects (56.9+/-4.3 compared with 119.4+/-21.5 m-units/l, P<0.01). There were significant differences in MMP-2 between the two groups, with a down-regulation in the AH subjects (182.5+/-16.8 units/ml in CTL compared with 117.1+/-9.1 units/ml in AH, P<0.01). MMP-2 and MMP-2/TIMP-2 were inversely correlated with myocardial indices of hypertrophy in AH and CTL subjects. AH and CTL subjects showed similar TIMP values. The results of the present study indicate that MMPs and TIMPs could represent potential biomarkers of adaptive heart remodelling in the athletes. In addition, the inverse correlation of the MMP-2/TIMP-2 system with echocardiographic signs of myocardial hypertrophy could represent a new diagnostic and prognostic indicator useful in the evaluation of cardiovascular risk in athletes.

Arterial stiffness, intima-media thickness and carotid artery fibrosis in patients with primary aldosteronism.

OBJECTIVES: To evaluate vascular wall structure and conduit artery stiffness in patients with primary aldosteronism. METHODS: This observational study, conducted in a University Hypertension Center, evaluated the carotid wall by 2-D ultrasonography and ultrasonic tissue characterization, and analyzed arterial stiffness by applanation tonometer. Twenty-three consecutive patients with primary aldosteronism, 24 matched patients with essential hypertension and 15 controls were studied. Intima-media thickness and corrected integrated backscatter signal of the carotid arteries were evaluated. Radial and femoral pulse wave velocity and aortic augmentation index were also investigated. RESULTS: Intima-media thickness in patients with essential hypertension (0.69 +/- 0.03 mm) was higher (P < 0.04) than that in controls (0.59 +/- 0.02 mm). This finding was more evident in primary aldosteronism patients (0.84 +/- 0.03 mm), in whom intima-media thickness was greater than that in controls (P < 0.0001) or in patients with essential hypertension (P < 0.01). Similarly, corrected integrated backscatter signal in patients with essential hypertension (-23.6 +/- 0.35 dB) was higher (P < 0.0001) than that in controls (-26.2 +/- 0.44 dB), but it was even more elevated in patients with primary aldosteronism (-22.1 +/- 0.46 dB), who showed greater corrected integrated backscatter signal than was the case in patients with essential hypertension (P < 0.009) or in controls (P < 0.0001). Femoral pulse wave velocity was higher in primary aldosteronism patients (10.8 +/- 0.57 m/s) than in patients with essential hypertension (9.1 +/- 0.34 m/s, P < 0.03) or in controls (7.1 +/- 0.51 m/s, P < 0.0001). Femoral pulse wave velocity was lower in controls than in patients with essential hypertension (P < 0.0001). The same pattern was observed for radial pulse wave velocity. Aortic augmentation index was higher in primary aldosteronism patients (28.2 +/- 2.1%) than in patients with essential hypertension (26.0 +/- 1.8%) or in controls (16.8 +/- 2.0%, P < 0.001). Patients with essential hypertension likewise exhibited higher aortic augmentation index than controls (P < 0.001). CONCLUSION: Aldosterone excess is responsible per se for vascular morphological (wall thickening and carotid artery fibrosis) and functional (central stiffness) damage.

Carotid integrated backscatter analysis in patients with subclinical hypothyroidism.

OBJECTIVE: The aim of the present study was to determine whether integrated backscatter (IBS) analysis combined with conventional ultrasonography could differentiate the tissue characteristics of carotid artery intimal hyperplasia in patients with subclinical hypothyroidism (SH). METHODS: Forty-one patients with SH, as judged by elevated serum TSH levels and free thyroid hormones within the normal range, and 31 sex- and age-matched euthyroid volunteers underwent two-dimensional conventional ultrasonography and IBS analysis of the carotid wall. Carotid intima-media thickness (IMT) and corrected IBS (C-IBS), an index of arterial wall degeneration and fibrosis, were evaluated. RESULTS: Mean IMT as well C-IBS values were higher in SH than in controls (P < 0.0001 for both), whereas the carotid diameter was not significantly different between the two groups. The distribution of C-IBS values in each group showed that regions with higher C-IBS values were found more frequently in SH patients than in control subjects. The percentage of regions that could be considered as fibromatous (C-IBS value from -18 to -21 dB) was 28% in SH and 9% in euthyroid subjects (P < 0.0001). In the SH group, C-IBS values were significantly and positively associated with plasma TSH (r = 0.32, P < 0.05 and r = 0.59, P < 0.0001, respectively) and with both total cholesterol (r = 0.46, P = 0.01) and low density lipoprotein (LDL)-cholesterol (r = 0.55, P = 0.001). CONCLUSIONS: Carotid IMT in subclinically hypothyroid patients is higher than that in euthyroid controls. This is characterized by increased IBS values, which are related to the collagen content of the arterial wall. The severity of this remodelling process seems to be related to TSH and cholesterol levels.

Preclinical cardiac involvement in phaeochromocytoma: a study with integrated backscatter.

OBJECTIVE: It is well known that vascular and cardiac structure may be influenced by circulating neurohormonal factors. Our aim was to study the myocardial wall texture by integrated backscatter (IBS) analysis in patients with phaeochromocytoma (PHEO). DESIGN: Fourteen patients with PHEO, 15 matched high-normal blood pressure (BP) subjects, 15 mild essential hypertensives and 15 normotensive controls underwent two-dimensional conventional ultrasonography and ultrasonic IBS of the myocardial wall. IBS analysis was performed at both interventricular septum and posterior wall levels. IBS values were expressed in decibels and corrected for the IBS values obtained within the pericardium (C-IBS). The systo-diastolic cyclical variations in IBS (CV-IBS), an index of myocardial contractile performance, were also evaluated. RESULTS: Patients with PHEO showed C-IBS values comparable to those of hypertensive patients, and significantly higher than those of high-normal BP subjects and controls at both septum and posterior wall levels (P < 0.001 for all). In PHEO patients, CV-IBS was lower than that of normotensive, high-normal BP subjects and hypertensive patients, at both septum and posterior wall levels (P < 0.001 for all). An inverse relationship was found in the PHEO group between 24-h urinary normetanephrine and CV-IBS of both septum (r(2) = -0.29, P < 0.05) and posterior wall (r(2) = -0.46, P < 0.05). CONCLUSIONS: Our results show that patients with PHEO have myocardial remodelling characterized by increased myocardial fibrosis, confirmed by an increase in the overall myocardial backscatter level measured. The observed decrease in the magnitude of CV-IBS suggests an impairment of myocardial contractile performance. These results may provide insights into the role of catecholamines in left ventricular (LV) structure and function in PHEO.

α-Synuclein Aggregates with ß-Amyloid or Tau in Human Red Blood Cells: Correlation with Antioxidant Capability and Physical Exercise in Human Healthy Subjects.

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), ß-amyloid1-42 (Aß), and tau, in both brain and peripheral tissue. In addition to homo-oligomers, the role of α-syn interactions with Aß or tau has gradually emerged. The altered protein accumulation has been related to both oxidative stress and physical activity; nevertheless, no correlation among the presence of peripheral α-syn hetero-aggregates, antioxidant capacity, and physical exercise has been discovered as of yet. Herein, the content of α-syn, Aß, tau, and of their heterocomplexes was determined in red blood cells (RBCs) of healthy subjects (sedentary and athletes). Such parameters were related to the extent of the antioxidant capability (AOC), a key marker of oxidative stress in aging-related pathologies, and to physical exercise, which is known to play an important preventive role in NDs and to modulate oxidative stress. Tau content and plasma AOC toward hydroxyl radicals were both reduced in older or sedentary subjects; in contrast, α-syn and Aß accumulated in elderly subjects and showed an inverse correlation with both hydroxyl AOC and the level of physical activity. For the first time, α-syn heterocomplexes with Aß or tau were quantified and demonstrated to be inversely related to hydroxyl AOC. Furthermore, α-syn/Aß aggregates were significantly reduced in athletes and inversely correlated with physical activity level, independent of age. The positive correlation between antioxidant capability/physical activity and reduced protein accumulation was confirmed by these data and suggested that peripheral α-syn heterocomplexes may represent new indicators of ND-related protein misfolding.

Carotid vascular remodeling in patients with pheochromocytoma.

CONTEXT: The influence of catecholamines on vascular remodeling in humans was investigated. OBJECTIVE: The objective was to study the carotid vascular wall in patients with pheochromocytoma (PHEO). DESIGN AND SETTING: An observational study was conducted in a university referral center for blood pressure diseases. PATIENTS: Fourteen patients with PHEO, 15 matched high-normal essential hypertensives, 15 mild essential hypertensives, and 15 controls underwent two-dimensional conventional ultrasonography and ultrasonic tissue characterization of the carotid wall. MAIN OUTCOME MEASURES: Intimal media thickness (IMT), diameter, and corrected ultrasonic integrated backscatter signal (C-IBS) of carotid arteries were evaluated. RESULTS: IMT in PHEOs (0.844 +/- 0.18 mm, mean +/- sd) was greater than not only controls (0.596 +/- 0.09 mm, P < 0.0002) but also high-normal (0.710 +/- 0.17 mm, P < 0.03), and even mild (0.727 +/- 0.20 mm, P = 0.06) hypertensives. IMT in the latter was higher than in controls (P < 0.03), without difference in comparison with high-normal hypertensives. C-IBS values in PHEOs (-21.71 +/- 2.0 dB, mean +/- sd) were greater than in controls (-26.20 +/- 1.73 dB, P < 0.0001) but also than in high-normal (-23.84 +/- 1.16 dB, P < 0.002) and mild (-23.37 +/- 1.99 dB, P < 0.01) hypertensives. C-IBS values in controls were lower than in high-normal (P < 0.0005) and mild (P < 0.0001) hypertensives. Carotid diameter was not significantly different in the four groups. In PHEOs, C-IBS was associated with urinary noradrenaline (r = 0.640, P < 0.01) and normethanephrine (r = 0.737, P < 0.009). CONCLUSIONS: Carotid IMT of PHEOs is higher than in controls and matched groups of hypertensives with comparable or even higher blood pressure. This vascular rearrangement is characterized by increased IBS values due to collagen deposition and vascular fibrosis. Therefore, our data show that abnormal catecholamine levels take part per se in carotid wall remodeling of patients with PHEO.

Endothelium-dependent vasodilation and carotid artery wall remodeling in athletes and sedentary subjects.

In this study, the relationship between age, carotid artery remodeling, and endothelium-dependent vasodilation is investigated in sedentary subjects and athletes. Thirty-two young and old healthy sedentary subjects and 32 age-matched endurance athletes underwent ultrasonography of the carotid wall for measuring intima-media thickness (IMT) and corrected integrated backscatter (C-IBS), two early indicators of the atherosclerosis process. Endothelium-dependent vasodilation was assessed by intra-brachial acetylcholine (strain-gauge plethysmography), at baseline and during NO sythase inhibitor NG-monomethyl-L-arginine (L-NMMA), and the antioxidant Vitamin C. Response to sodium nitroprusside (SNP) was also evaluated. Independently of trained status, IMT and C-IBS were higher in older than in young individuals (p<0.0001), while response to acetylcholine, but not to SNP, was lower (p<0.0001). Older athletes showed lower IMT, lower C-IBS (p<0.0001), greater response to acetylcholine (p<0.0001), and greater inhibition of acetylcholine by L-NMMA (p<0.001) than older controls. Only in older sedentary individuals, Vitamin C increased response to acetylcholine (p<0.001) and restored the inhibiting effect of L-NMMA (p<0.01). In the whole population maximal acetylcholine-induced vasodilation was inversely related to IMT (r=-0.60, p<0.0001) and to C-IBS (r=-0.56, p<0.0001). In conclusion, regular physical training can attenuate the age-related impairment of endothelium-dependent vasodilation, which is related to an attenuation of the age-induced remodeling of the carotid wall.

Acute effects of hemodialysis on left ventricular function evaluated by tissue Doppler imaging.

Evidence exists that left ventricular function is impaired in chronic uremic patients. During hemodialysis (HD) treatment, myocardium undergoes electrolyte, hemodynamic and neuro-humoral stress; however, data about the acute changes on ventricular function are controversial. Aim of the present study was to evaluate the effect of a single hemodialysis session on left ventricular (LV) systolic and diastolic function using pulsed tissue Doppler imaging (TDI) sampled by echocardiography. The study group included 20 uremic patients (17 males, aged 51+/-13 yrs) on maintenance HD, free from clinically overt cardiac dysfunction who underwent echocardiography with pulsed TDI 30 min prior and 30 min after a HD session. TDI was performed by placing the sample volume in the center of the basal lateral segment and the basal interventricular septum in the apical four-chamber view. Myocardial systolic wave (S(m)) and early (E(m)) and atrial (A(m)) diastolic waves were measured. On standard sonography examination, no significant changes in LV systolic function parameters were observed after HD, but the indices for LV diastolic function deteriorated significantly (peak E, 75.4+/-11.2 vs. 58.8+/-12.5 cm/s, P<0.01; E/A ratio, 1.0+/-0.3 vs. 0.8+/-0.2, P<0.01). However, regarding TDI measures following HD, the patients exhibited a lower S(m) peak (septum: 7.6+/-1.1 vs. 5.9+/-0.8 cm/s; lateral wall: 7.7+/-1.7 vs. 6.8+/-1.2 cm/s, P<0.001), a lower E(m) peak (septum: 8.3+/-1.6 vs. 6.3+/-1.7 cm/s; lateral wall: 10.2+/-2.4 vs. 7.1+/-1.9 cm/s, P<0.001), and a reduced E(m)/A(m) ratio (septum: 1.0+/-0.4 vs. 0.7+/-0.2; lateral wall: 1.2+/-0.5 vs. 0.7+/-0.2, P<0.001, respectively), as compared to pre-HD parameters. Of interest, peak E(m), and E(m)/A(m) ratio of the lateral wall were negatively related to ultrafiltration rate (r = -0.60, P<0.05 and -0.69, P<0.01, respectively). Our data indicate that a single hemodialysis session is associated with acute deterioration of diastolic and systolic parameters of myocardial function, as assessed by TDI. These reversible changes could be considered as a cardiac stunning that seems to be related to the ultrafiltration rate and then to the interdialysis weight gain. These findings suggest that low ultrafiltration volume and/or limited interdialytic weight gain are cardioprotective measures in hemodialysis patients.

"Effects of recombinant human erythropoietin high mimicking abuse doses on oxidative stress processes in rats".

Although many studies highlight how long-term moderate dose of Recombinant Human Erythropoietin (rHuEPO) treatments result in beneficial and antioxidants effects, few studies take into account the effects that short-term high doses of rHuEPO (mimicking abuse conditions) might have on the oxidative stress processes. Thus, the aim of this study was to investigate the in vivo antioxidant activity of rHuEPO, administered for a short time and at high doses to mimic its sports abuse as doping. Male Wistar healthy rats (n=36) were recruited for the study and were treated with three different concentrations of rHuEPO: 7.5, 15, 30µg/kg. Plasma concentrations of erythropoietin, 8-epi Prostaglandin F2α, plasma and urinary concentrations of NOx were evaluated with specific assay kit, while hematocrit levels were analyzed with an automated cell counter. Antioxidant activity of rHuEPO was assessed analyzing the possible variation of the plasma scavenger capacity against hydroxylic and peroxylic radicals by TOSC (Total Oxyradical Scavenging Capacity) assay. Statistical analyses showed higher hematocrit values, confirmed by a statistically significant increase of plasmatic EPO concentration. An increase in plasma scavenging capacity against peroxyl and hydroxyl radicals, in 8-isoprostane plasmatic concentrations and in plasmatic and urinary levels of NOX were also found in all the treated animals, though not always statistically significant. Our results confirm the literature data regarding the antioxidant action of erythropoietin administered at low doses and for short times, whereas they showed an opposite incremental oxidative stress action when erythropoietin is administered at high doses.

Subclinical cardiac involvement in patients with facioscapulohumeral muscular dystrophy.

Myocardial involvement is a common finding in certain myopathies, while it has not been extensively investigated in facioscapulohumeral muscular dystrophy (FSHD1A). Aim of this study was to assess in FSHD1A patients the electrical and functional properties of the myocardium. Twenty-four patients with FSHD1A (mean age 41.2+/-14.5 years) and 24 matched healthy subjects were studied. Standard- and signal-averaged electrocardiography were recorded to determine QT dispersion and the presence of ventricular late potentials (VLPs). Standard echocardiography with systo-diastolic variations of integrated backscatter signal (CV-IBS) were performed to assess functional properties of the myocardium. Compared with control subjects, patients with FSHD1A had significantly lower CV-IBS and higher QT dispersion. Nine patients had positive VLPs. QT and QTc dispersion were inversely related to CV-IBS at both septum and posterior wall levels. Moreover, septal CV-IBS was inversely related to the Kpnl-BinI4q fragment size. These results suggest a subclinical cardiac involvement in FSHD1A patients, which can represent a substrate for ventricular arrhythmias and heart failure.

Physical activity, plasma antioxidant capacity, and endothelium-dependent vasodilation in young and older men.

BACKGROUND: Sedentary aging is associated with oxidative stress and endothelial dysfunction. The aim of this study was to evaluate the relationship between long-term physical activity, plasma antioxidant status, and conduit artery endothelial function in young and older healthy men. METHODS: In young (n = 16) and older athletes (n = 16) and in matched healthy sedentary subjects, endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent response to glyceryl trinitrate (GTN), 400 microg, were measured in the brachial artery from high-resolution ultrasonography. Plasma malondialdehyde (MDA) and antioxidant capacity as total oxyradical scavenging capacity (TOSC) were also evaluated. RESULTS: We found that FMD was lower (< or =0.01) in sedentary older subjects (2.3% +/- 1.0%) as compared with older athletes (5.3% +/- 3.2%) and both sedentary (5.4% +/- 2.0%) and athletically trained (6.1% +/- 3.2%) young subjects. Sedentary older subjects showed higher (P < or = .05) MDA levels and lower (P < .0001) plasma antioxidant capacity as compared with the other subgroups, whereas in older athletes MDA levels and antioxidant capacity were similar to those observed in the young subgroups. In the whole group, FMD, but not GTN, was negatively related to age (r = -0.31, P < .05) and directly related (P < or = .01) to VO2max (r = 0.49) and TOSC against peroxyl (r = 0.69) and hydroxyl radicals (r = 0.53). In the multivariate analysis, TOSC against peroxyl radicals resulted as the most significant predictor of FMD (R2 = 0.60; P = .003). CONCLUSIONS: These results suggest that regular physical activity is associated with preserved antioxidant defenses and endothelial function in older individuals.

Effect of epirubicin-based chemotherapy and dexrazoxane supplementation on QT dispersion in non-Hodgkin lymphoma patients.

BACKGROUND AND OBJECTIVE: Aim of the present study was to assess the effect of epirubicin-based chemotherapy on QT interval dispersion in patients with aggressive non-Hodgkin lymphoma (NHL), and the effect of dexrazoxane supplementation. Prolongation of QT dispersion may not only represent a sensitive tool in identifying the first sign of anthracycline-induced cardiotoxicity, but it may serve also in identifying patients who are at risk of arrhythmic events. METHODS: Twenty untreated patients,

Early detection of cardiac dysfunction in patients with anorexia nervosa by tissue Doppler imaging.

BACKGROUND: Cardiac damage is a major complication of chronic starvation. The aim of this study was to evaluate the changes of left ventricular function in patients with anorexia nervosa by means of pulsed tissue Doppler imaging. METHODS: A total of 20 females (age 22.4+/-4.3 years) with overt anorexia nervosa, 20 matched healthy thin females with body mass index < 19 kg/m2 and 20 matched healthy normal-weight females underwent both standard echocardiography and tissue Doppler imaging. Myocardial systolic wave (Sm) and early (Em) and atrial (Am) diastolic waves were measured on the basal lateral segment and the basal interventricular septum from the apical four-chamber view. RESULTS: When compared with control groups, the anorexia nervosa group showed lower left ventricular mass (p < 0.0001), lower Sm peak of both lateral wall (6.5+/-0.9 vs. 9.4+/-2.1 and vs. 9.5+/-1.9 cm/sec, p < 0.001) and septum (5.6+/-1.5 vs. 8.6+/-1.6 and vs. 8.8+/-1.5 cm/sec, p < 0.001), and comparable Em, Am and Em/Am ratio. The ratio between transmitral peak E and Em was significantly greater in anorexic patients than in controls (lateral wall: 8.1+/-0.1 vs. 6.8+/-0.2 and vs. 6.9+/-0.2, p < 0.001; septum: 10.8+/-0.4 vs. 8.8+/-0.5 and vs. 8.8+/-0.3, p < 0.001). No differences were observed between thin and normal-weight females. In the anorexia nervosa group, S(m) peak was significantly related to left ventricular mass indexed, at both septum (r = 0.55, p < 0.02) and lateral wall (r = 0.49, p < 0.03) levels. CONCLUSIONS: These results show that anorexia nervosa is associated with left ventricular systolic dysfunction, which is related with the reduction of cardiac mass. Tissue Doppler imaging can give useful information in the identification of regional left ventricular dysfunction, in addition to traditional parameters.

ß2-Microglobulin and TIMP1 Are Linked Together in Cardiorenal Remodeling and Failure.

BACKGROUND/AIMS: The cardiorenal syndrome is a complication in patients hospitalized with chronic heart failure (CHF). The ß2-microglobulin (b2M) level is an index of decreased glomerular filtration rate (GFR), tissue turnover and inflammation. It is an emerging new predictive marker of cardiovascular events and mortality, but its role as a biomarker of cardiorenal remodeling and failure is still unknown. TIMP1, an endogenous tissue inhibitor of activated matrix metalloproteinases, is a biomarker of heart remodeling and failure. We aimed to evaluate the circulating profile of b2M and TIMP1 in CHF patients, in sedentary controls with no tissue remodeling and in veteran athletes with physiological cardiorenal remodeling and athlete's heart (AH). METHODS: We investigated the plasma levels of b2M and TIMP1 in 24 subjects with CHF without primitive renal disease, in 25 sedentary controls and in 30 veteran marathoners with AH over 50 years. RESULTS: The b2M and TIMP1 levels were higher in CHF patients, and there was a correlation between them (r = 0.5287, p < 0.0095). The b2M level correlated with the severity of cardiorenal impairment: with proBNP (r = 0.66, p > 0.0007), percent ejection fraction (r = -0.56, p = 0.0162) and GFR (r = 0.83, p < 0.0001). b2M was also correlated with TIMP1 in AH subjects (r = 0.7548, p < 0.0001) but not in controls. This correlation was independent from GFR in both CHF patients and sedentary controls. CONCLUSIONS: In CHF patients, the plasma levels of b2M and TIMP1 were linked together and correlated with the severity of cardiorenal failure. Moreover, a strong correlation between b2M and TIMP1 characterized cardiovascular remodeling not only in CHF patients but also in AH subjects. These findings suggest that clinicians should use b2M and TIMP1 as associated biomarkers of cardiorenal remodeling and failure.

Skin vasoreactivity to insulin iontophoresis is reduced in elderly subjects and is absent in treated non-insulin-dependent diabetes patients.

We investigated the skin vasoreactivity to insulin in normal subjects and in treated non-insulin-dependent diabetes mellitus (NIDDM) patients. We measured cutaneous perfusion by laser-Doppler flowmetry (LDF) at rest and during skin cathodal iontophoresis (six pulses of 0.1 mA each for 20 s, with 40 s interval between stimulations) of insulin (0.1 ml Humulin R 100 IU/ml diluted 1/10 with of 0.9% saline solution) in 45 healthy subjects (HS), (25 males, 20 females, aged 45 +/- 18 years), and in 15 treated NIDDM patients (13 males), aged 66 +/- 8 years. Fifteen of the HS were used as controls. In these 15 sex- and age-matched HS and in the patients, we assessed also the skin postischemic hyperemia by LDF. In HS cutaneous blood flux response (CBF) to iontophoresis of insulin in saline (expressed as percent changes from baseline) was significantly higher than CBF response to iontophoresis of pure saline (maximum response: 360 +/- 51% versus 172 +/- 42%, respectively; P < 0.001, ANOVA for repeated measures). The maximum "net" CBF response to insulin (response to insulin minus response to saline) showed a negative correlation (r = -0.361; P < 0.01) with age in HS, and resulted significantly lower in the oldest than in the youngest HS (105 +/- 40% versus 307 +/- 45%, respectively; P < 0.01). No significant correlation was observed between the maximum CBF response to saline and the age of subjects. In NIDDM patients the "net" CBF response to insulin iontophoresis resulted significantly lower than in 15 sex- and age-matched control subjects (maximum response: -50 +/- 89% versus 201 +/- 81%, respectively; P < 0.001, ANOVA for repeated measures). No significant difference was observed between diabetics and controls, nor in basal perfusion (6.5 +/- 1.3 IU versus 6.8 +/- 1.7 IU, respectively) neither in the skin postischemic hyperemia (250 +/-14% versus 258 +/- 27%, respectively). These results confirm that insulin iontophoresis induces a skin vasodilatatory effect in normal subjects and show that this effect is reduced by aging and is absent in treated NIDDM patients. The local skin vasodilatatory effect induced by insulin seems to involve mechanisms different from those underlying the skin postischemic hyperemia.

An in vitro study of the peroxyl and hydroxyl radical scavenging capacity of the calcium antagonist amlodipine.

Amlodipine has been reported to improve endothelial function in patients with arterial hypertension and to significantly limit the progression of carotid atherosclerosis. The aim of this study was to assess the total antioxidant activity of amlodipine. We measured the in vitro antioxidant activity of amlodipine as its ability to antagonize the oxidation of alpha-keto-gamma-methiolbutyric acid by both hydroxyl and peroxyl radicals. The results are expressed as Total Oxyradical Scavenging Capacity (TOSC) units. Reduced glutathione, uric acid and trolox were used as the reference antioxidants. Amlodipine showed an efficiency as scavenger of peroxyl radicals (TOSC: 5945 +/- 544 units/mg) significantly higher (>50%, P <0.001) than that of GSH (2733 +/- 636 units/mg), and 70% lower (P < 0.0001) than the value obtained with uric acid (18144 +/- 696 units/mg) and trolox (17522 +/- 734 units/mg). Of interest, the scavenging capacity of amlodipine towards hydroxyl radicals (1455 +/- 154 units/mg) was 320% higher (P < 0.00001) than that of GSH (358 +/- 112 units/mg), 20% higher than that of uric acid (1198 +/- 121 units/mg), and 100% higher than that of trolox (759 +/- 143 units/mg). Amlodipine has intrinsic antioxidant activity with both anti-hydroxyl and anti-peroxyl radicals activity.

Left ventricular diastolic function and carotid artery wall in elderly athletes and sedentary controls.

Advancing age is characterized by structural and functional change of left ventricle (LV) and large elastic arteries. Recent advances in tissue Doppler imaging (TDI) and integrated backscatter (IBS), new ultrasound tools, have allowed non-invasive assessment of structural and functional characterization of myocardium and artery wall. Our aim was to compare LV diastolic function and carotid artery remodeling in elderly athletes and sedentary controls. Twenty-five elderly athletes (males, aged 68.6 +/- 4.2 years) were compared to 25 age-sex-matched sedentary controls. All the subjects underwent either conventional Doppler echocardiography with pulsed TDI to evaluate LV diastolic function, and conventional ultrasonography and integrated backscatter (IBS) analysis to evaluate the carotid wall. Corrected IBS values (C-IBS) were obtained by subtracting the IBS value of the adventitia. Body mass index and blood pressure were not different in the two groups; athletes showed lower heart rate (P < 0.0001) and, as expected, higher LV mass than sedentary subjects (P < 0.0001). Transmitral Doppler analysis showed in trained subjects a significantly lower peak A and a higher E/A ratio (P < 0.001). On regards to TDI measurements, athletes exhibited a higher Em, a lower Am, and, subsequently, an increased Em/Am ratio of both lateral wall and septum (P < 0.0001). The IVRTm was shorter in trained subjects (P < 0.001). Athletes showed a lower C-IBS (-26.8 +/- 2.9 vs. -23.4 +/- 3.8 dB, P < 0.001) and a smaller intima-media thickness (IMT: 0.66 +/- 0.14 vs. 0.80 +/- 0.18 mm, P < 0.001) respect to sedentary controls. Moreover, a significant direct correlation was found between Em/Am of LV septal and lateral wall and C-IBS values (respectively, r = 0.62 and r = 0.56, P < 0.001). Thus the aging heart manifests structural and functional changes in response to physical activity. The expected pattern of cardiac and arterial alterations normally seen in response to age is modified in the older athletes, suggesting the exercise training is an effective stimulus in shaping arterial structure and left ventricular function in older heart. It would appear that pulsed TDI and IBS analysis may play an important role in detecting training-induced LV and carotid artery structural and functional modifications.

Responses to Tilt test in young and elderly patients with syncope of unknown origin.

The aim of the present study was to assess the cardiovascular autonomic function and responses to tilt test in young and elderly patients with syncope of unknown origin. We evaluated two groups of patients with previous unexplained syncope: 192 older subjects (112 males, 80 females, mean age 67.2 +/- 6.8 years) and 188 young subjects (102 males, 86 females, mean age 25 +/- 9 years). All patients underwent ambulatory electrocardiogram (ECG) monitoring, to evaluate time domain indices of heart rate variability (HRV), and head-up tilt test in the morning after an overnight fast. The responses of positive tilt test were classified using the VAsovagal Syncope International Study (VASIS) criteria: mixed (VASIS-1), cardioinhibition (VASIS-2A), severe cardioinhibition/asystole (VASIS-2B), pure vasodepression (VASIS-3). All the time-domain HRV indexes were lower in the older than in young subjects. The rate of positive responses was not different in the two groups. In elderly group the positive head-up tilt test responses showed: a pure vasodepressive response (VASIS 3) in 126 patients (65%), a mixed (VASIS-1) response in 25 patients (13%), a cardioinhibitory (VASIS-2A) response in 13 patients (7%). Only 28 (14.6%) of elderly group patients had negative head-up tilt test response. In contrast, in young group the positive head-up tilt test responses showed: 114 patients (61.2%) a mixed (VASIS-1) vasovagal response, 40 patients (22.3%) a cardioinhibitory (VASIS-2A) response, four (2.1%) patients a severe cardioinhibitory (VASIS-2B) and four (2.1%) patients a pure vasodepression (VASIS-3) response, respectively. The tilt test was negative in response in 26 young patients (12.2%). Our results confirm that the head-up tilt test may be useful in assessing unexplained syncope, since it is seen to be positive in 85% of elderly patients and 86% in young patients. In our subjects, vasodepressive response was the most frequent cause of syncope in older subjects, while vasovagal response is the commonest cause of syncope of young patients. This different behaviour in the elderly may be is explained with physiological aging, which is associated with a reduction of sympathetic-parasympathetic control on the cardiac rhythm, demonstrated by reduction in all the time domain HRV indices.