Guido Arcaro

Noninvasive Detection of Functional Alterations of the Arterial Wall in IDDM Patients With and Without Microalbuminuria

OBJECTIVE To test endothelial function in a group of 10 normoalbuminuric and eight microalbuminuric insulin-dependent diabetes mellitus patients (ages 28 ± 3 [mean ± SE] and 28 ± 1 years, respectively), in comparison with 16 control subjects (age 35 ± 2 years, normal subjects vs. diabetic subjects P = NS), to identify prestructural abnormalities of the arterial wall. An early stage of vascular involvement seems in fact to be characterized by functional alterations of endothelial control on vascular tone and wall interaction with circulating cells. Furthermore, many recent studies suggest the importance of microalbuminuria as an early marker not only of nephropathy but also of retinopathy and macroangiopathy. RESEARCH DESIGN AND METHODS Endothelium-mediated flow-dependent vasodilation and endothelium-independent vasodilation (induced by glyceryl trinitrate administration) were evaluated in the right common femoral artery by echo-Doppler ultrasound. Arterial wall distensibility was evaluated at the common femoral artery by an echo-tracking system. RESULTS In spite of a comparable increase in flow velocity, endothelium-mediated vasodilation was significantly reduced in diabetic subjects, particularly in microalbuminuric patients. Endothelium-independent vasodilation was also significantly impaired in diabetic subjects, particularly in microalbuminuric subjects; whereas arterial wall distensibility, an index of the viscoelastic properties of the wall, was similar in the three groups. CONCLUSIONS These results confirm a reduced vasodilatory capacity in diabetes mellitus, with a more marked alteration in microalbuminuric diabetic subjects. This reliable, noninvasive evaluation of arterial function is particularly useful for early diagnosis of vascular involvement.

Ultrasound evaluation of ulnar neuropathy at the elbow: correlation with electrophysiological studies

OBJECTIVES To evaluate, in patients with ulnar neuropathy at the elbow (UNE), if ultrasonographic differences in ulnar nerve size correlate with severity score determined by electrodiagnostic studies. METHODS We examined prospectively 38 patients (50 elbows) with UNE. Patients were classified into mild, moderate and severe groups according to electrodiagnostic studies. Cross-sectional areas (CSAs) of the ulnar nerve were measured 4 cm proximal to the medial epicondyle (CSA-prox), 4 cm distal to the epicondyle (CSA-dist) and at the maximum CSA (CSA-max) of the ulnar nerve found between these points. We used a control group of 50 normal elbows. RESULTS The CSA-max in the patient group was highly correlated with the severity score obtained by electrodiagnostic studies: mild: 11.1 +/- 3.4 mm(2), moderate: 15.8 +/- 3.8 mm(2), severe: 18.3 +/- 5.1 mm(2) (P < 0.001). Patients with UNE had larger ulnar nerve CSAs than controls at all three levels (P = 0.012 for CSA-prox, P < 0.001 for CSA-max, P = 0.003 for CSA-dist). A cut-off point of > or =10 mm(2) for CSA-max yields both sensitivity and specificity of 88%. CONCLUSIONS Ultrasonography can have a role not only in the diagnosis, but also in the severity stratification of patients with UNE.

Stiffness of the common carotid artery in treated hypertensive patients.

Antihypertensive treatment, by lowering blood pressure and correcting functional and/or structural abnormalities of the arterial wall, may prevent the arterial damage due to the accelerated ageing process. The objective of the present study was to determine, using a cross-sectional approach, whether arterial distensibility of patients whose blood pressure had been normalized for several months by antihypertensive treatment, was significantly higher than that of untreated hypertensive patients. The properties of the vessel wall of the common carotid artery (CCA) were studied non-invasively, using an original pulsed ultrasound echo-tracking system based on Doppler shift, during a study comparing 46 normotensive subjects and 81 age-matched hypertensive patients. The latter group included 25 patients well controlled by antihypertensive treatment for at least 3 months and 56 untreated hypertensives. The three groups did not differ with respect to age, total and high-density lipoprotein cholesterol, blood glucose and smoking. In each group, there were significant relationships between age and CCA dimensional and functional data, including end-diastolic diameter, absolute and relative stroke changes in diameter and Peterson modulus, indicating a widening of the CCA with advancing age and a decrease in its buffering function. When compared with untreated hypertensives, well controlled hypertensives had significantly lower blood pressure and Peterson elastic modulus according to age. However, although blood pressure of well controlled hypertensives was not significantly different from that of normotensive subjects, their arterial distensibility remained altered compared with that of normotensive subjects (significant increase in Peterson elastic modulus). These results suggest that long-term antihypertensive treatment may not fully reverse arterial lesions due to the hypertensive disease.

Mechanism of nitrate-induced improvement on arterial compliance depends on vascular territory

The link between arterial caliber and distensibility has been studied extensively, with conflicting results. As have other researchers, we previously showed evidence of an increase in arterial diameter and a decrease in arterial stiffness with use of nitrates at the site of the brachial artery (BA) and the aorta. Whether these results would apply to other large superficial arteries remained to be established. In the present study, by means of an original pulsed ultrasound echo-tracking system based on Doppler shift, we measured internal diastolic diameter and stroke change in diameter of the common carotid artery (CCA), the femoral artery, and the BA in patients with essential hypertension and determined the acute effects of administration of isosorbide dinitrate (ISDN 20 mg). Twenty untreated hypertensive patients entered this randomized, placebo-controlled, double-blind, parallel study. No significant change occurred during placebo. During ISDN therapy, blood pressure (BP) decreased significantly; cross-sectional compliance increased at the site of the CCA, the BA, and the common femoral artery (CFA). The increase in cross-sectional compliance was mainly due to an increase in internal diameter for CCA and to an increase in distensibility coefficient (DC) for BA. The pattern of cross-sectional compliance was intermediate for CFA. During ISDN therapy, the augmentation index of the CCA distension waveform was significantly reduced, whereas no change occurred during placebo, suggesting a reduction in wave reflection by nitrates. These results indicate a heterogeneous response of arterial territories to ISDN therapy and suggest that arterial dilation is not necessarily associated with improvement in the DC. In addition, analysis of the carotid artery distension waveform may provide information not only on the local vasodilating effect of the drug but also on arterial wave reflection, i.e., on the peripheral vasodilating effect of the drug.

Non-invasive detection of early endothelial dysfunction in hypercholesterolaemic subjects

Hypercholesterolaemia is associated with accelerated atherogenesis. Before the evidence of morphological lesions or plaques, endothelial dysfunctions, such as impairment in endothelium-dependent vascular tone regulation, may occur. We studied 32 subjects, 16 with primary hypercholesterolaemia and 16 normocholesterolaemic controls. Flow-dependent vasodilation, an endothelium-dependent phenomenon, was evaluated by measuring femoral artery diameter and flow velocity in basal conditions and during distal post-ischemic hyperaemia, using a high resolution echo-Doppler. Arterial distensibility and compliance were evaluated for the common carotid and femoral arteries, using a pulsed echo-tracking system and measuring the absolute and relative stroke change in arterial diameter. In the hypercholesterolaemic group there was no flow-dependent arterial relaxation, indicated by the area under the curve of percentage diameter variation as a function of time. This parameter was inversely correlated with both total and LDL-cholesterol values in all population subjects. No difference was observed between the two groups in endothelium-independent vasodilation induced by glyceryl trinitrate administration or arterial wall distensibility and compliance, confirming the hypothesis of a functional defect.

Plasma PAI-1 Levels Are Increased in Patients With Nonalcoholic Steatohepatitis

Recent data suggest that nonalcoholic fatty liver disease (NAFLD) is linked to increased cardiovascular disease (CVD) risk independently of the metabolic syndrome (MetS) (1–7), although the possible molecular mediators linking NAFLD and CVD are poorly known (8). Increased plasma plasminogen activator inhibitor-1 (PAI-1) concentrations, responsible for reduced fibrinolytic activity, play a key role in atherothrombosis (9). Since limited information is available about the relations among NAFLD, MetS, and PAI-1, we assessed whether PAI-1 correlates with liver histopathology among NAFLD patients independent of MetS features. Plasma PAI-1 activity concentrations (Spectrolyse/PL; Biopool) were measured in 85 consecutive NAFLD outpatients (50/35 male/female, mean ± SD age 45 ± 2 years, and BMI …

Increased protein nitration in mitochondrial diseases: evidence for vessel wall involvement.

Mitochondrial diseases (MD) are heterogeneous disorders because of impairment of respiratory chain function leading to oxidative stress. We hypothesized that in MD the vascular endothelium may be affected by increased oxidative/nitrative stress causing a reduction of nitric oxide availability. We therefore, investigated the pathobiology of vasculature in MD patients by assaying the presence of 3-nitrotyrosine in muscle biopsies followed by the proteomic identification of proteins which undergo tyrosine nitration. We then measured the flow-mediated vasodilatation as a proof of altered nitric oxide generation/bioactivity. Here, we show that 3-nitrotyrosine staining is specifically located in the small vessels of muscle tissue and that the reaction is stronger and more evident in a significant percentage of vessels from MD patients as compared with controls. Eleven specific proteins which are nitrated under pathological conditions were identified; most of them are involved in energy metabolism and are located mainly in mitochondria. In MD patients the flow-mediated vasodilatation was reduced whereas baseline arterial diameters, blood flow velocity and endothelium-independent vasodilatation were similar to controls. The present results provide evidence that in MD the vessel wall is a target of increased oxidative/nitrative stress.

Retinopathy Predicts Future Cardiovascular Events Among Type 2 Diabetic Patients: The Valpolicella Heart Diabetes Study

We read with interest the recent article by van Hecke et al. (1) showing that diabetic retinopathy is associated with an increased risk of mortality and cardiovascular disease (CVD) incidence among type 1 diabetic patients. Because the available data on associations between retinopathy and incident CVD in large population samples of type 2 diabetic patients are limited and conflicting (2–4), we would like to offer recent findings from our large observational study. We carried out a prospective, nested, case-control study in 2,103 …

Ultrasound differentiation of two types of de Quervain’s disease, the role of retinaculum

de Quervains disease (dQD) is a stenosing tenosynovitis of the first extensor compartment of the wrist which is formed by the tendons of the abductor pollicis longus (APL) and extensor pollicis brevis (EPB).1,–,3 Thirty-three consecutive patients with a clinical diagnosis of dQD underwent ultrasound (US). The inclusion criteria were (1) a history of pain over the radial aspect of the wrist aggravated by excessive use of the thumb; (2) an orthopaedic diagnosis of dQD; and (3) a positive Finkelstein test. The control group consisted of 24 healthy subjects and was matched for age and sex. All studies were performed using a Vivid 7 machine (General Electric, Milwaukee, Wisconsin, USA) with a 12 MHz matrix linear array transducer. The sonographer was not blinded to the identity of the control subjects. Statistical analysis was performed using the Student …

Regression of cardiac hypertrophy after antihypertensive therapy with nifedipine and captopril.

The effects of two antihypertensive agents, nifedipine (N) and captopril (C), on left ventricular (LV) mass and volume were studied in 16 patients with essential hypertension (8 treated with N and 8 with C for 6 months) by means of a complete M-mode echocardiogram monitored by two-dimensional echocardiography. Both N and C induced a significant reduction in end-diastolic, but not systolic, posterior wall and septum thickness and an increase in end-diastolic volume, but not in end-systolic volume. A significant increase in the contribution of rapid filling together with a simultaneous reduction in the contribution of atrial systole to end diastolic volume were also observed. The reduction in LV wall thickness and mass after both C and N might be attributed to an improvement in diastolic function and to a reduction in wall tension, rather than to an effective regression of LV hypertrophy.