The effect of angiotensin receptor blockers on C-reactive protein and other circulating inflammatory indices in man

Anti-inflammatory properties may contribute to the pharmacological effects of angiotensin II receptor blockers (ARBs), a leading therapeutic class in the management of hypertension and related cardiovascular and renal diseases. That possibility, supported by consistent evidence from in-vitro and animal studies showing pro-inflammatory properties of angiotensin II, has been evaluated clinically by measuring the effect of ARBs on C-reactive protein and other circulating indices of inflammation (e-selectin, adhesion molecules, interleukin-6, tissue necrosis factor-alpha, monocyte chemoattractant protein-1) of potential clinical relevance, a body of evidence that this paper aims to review

Lack of a relationship between circulating gamma-glutamyltransferase levels and carotid intima media thickness in hypertensive and diabetic patients

Marco Nuti, Paolo Spontoni, Chrysanthos Grigoratos, Giulia Dell'Omo, Alberto Balbarini, Roberto PedrinelliDipartimento Cardio Toracico e Vascolare, Università di Pisa, Pisa, ItalyBackground: By increasing the intracellular prooxidant burden, gamma-glutamyltransferase (GGT) may accelerate atherosclerotic vascular disease. That noxious influence may be reflected by circulating enzyme levels, a correlate of cardiovascular risk factors, and a predictor of incident events. To evaluate this hypothesis, we tested the association between circulating GGT and common carotid intima-media thickness (CIMT), a surrogate index of systemic atherosclerotic involvement, in a large and well-characterized group of patients at risk of cardiovascular disease (CVD).Patients: This study analyzed 548 patients with hypertension and/or diabetes and a widely prevalent history of CVD. Subjects with known hepatic disease and abnormal GGT values were excluded.Methods: CIMT (B-mode ultrasonography) values were the mean of four far-wall measurements at both common carotids. Metabolic syndrome (MetS) was diagnosed according to National Cholesterol Education Program-Adult Treatment Panel III criteria. Due to inherent sex-related differences in GGT levels, the data were analyzed separately in males and females in samples dichotomized by the median.Results: The age-adjusted CIMT values did not differ by GGT levels in males or females. In contrast, the carotid wall was consistently thicker in patients with a history of CVD and MetS independent of age and concurrent GGT values. In both sexes, GGT was associated with key components of the MetS such as triglycerides, fasting plasma glucose, and body mass index.Conclusion: The data collected in this mixed group of hypertensive and/or diabetic patients with widely prevalent history of CVD do not support the concept of a direct pathophysiological link between GGT levels within reference limits and atherosclerotic involvement.Keywords: gamma-glutamyltransferase, carotid intima-media thickness, atherosclerosis, metabolic syndrom

Microperimetric evaluation and predictive factors of visual recovery after successful inverted internal limiting membrane-flap technique for macular hole in high myopic eyes

IntroductionInverted Internal Limiting Membrane (ILM)-flap technique demonstrated its effectiveness, in terms of anatomical closure rate and visual acuity recovery for high myopic macular holes. We evaluated macular function after a successful inverted ILM-flap for macular holes in high myopic eyes (hMMH) using microperimetry to predict visual prognosis.MethodsA retrospective study on 23 eyes of 23 patients after surgical closure of hMMH, was performed. All patients underwent inverted ILM-flap and gas tamponade. Cataract surgery was performed in phakic eyes. Study outcomes including best-corrected visual acuity (BCVA), retinal sensitivity (RS) at central 12°, central retinal sensitivity (CRS) at central 4° and mean deviation (MD), and fixation behavior as bivariate contour ellipse area (BCEA, degrees2) measured by microperimetry, were evaluated over 6 months. A mixed-effects model was used to evaluate and compare the repeated measurements of outcomes between phakic and pseudophakic eyes. A regression model was performed to assess the relationship between BCVA at 6 months and independent variables.ResultsOverall mean BCVA improved from 0.98 ± 0.21 logMAR at baseline to 0.47 ± 0.31 logMAR at the last follow-up (p < 0.001). Over 6 months, overall sensitivity measurements improved (RS, p = 0.001; CRS, p < 0.0001; MD, p = 0.03), and the BCEA decreased in dimension, although not significantly (p ≥ 0.05). The mixed model revealed a significantly better effect of inverted ILM-flap combined with cataract surgery on BCVA and CRS in phakic eyes than inverted ILM-flap alone in pseudophakic ones. The regression model revealed a relationship of 6-month BCVA with pre-operative BCVA (β = 0.60, p = 0.02) and RS (β = −0.03, p = 0.01).ConclusionThe inverted ILM-flap technique significantly improved visual acuity and retinal sensitivity after the hMMH closure, particularly when combined with cataract extraction. Pre-operative visual acuity and retinal sensitivity at central 12° may predict post-surgical visual acuity

Multimodal Imaging of Lamellar Macular Holes

Evolution of imaging techniques has renewed interest in the diagnosis of lamellar macular hole (LMH) and greatly implemented the possibilities of gaining more detailed insights into its pathogenesis. Among noninvasive techniques, optical coherence tomography (OCT) is considered the primary examination modality to study LMHs, given its ability to image foveal structure and its widespread availability. OCT also allows to resolve the epiretinal materials associated with LMH, i.e., tractional epiretinal membranes (ERMs) and epiretinal proliferation (EP). En face OCT reconstructions are useful to confirm the foveal abnormalities shown by the eyes with LMH, whereas OCT angiography may reveal alterations of the size and shape of the foveal avascular zone and alterations of the density of the superficial and deep vascular plexuses. On slit-lamp biomicroscopy or fundus camera examination, LMH appears as a round or oval, reddish lesion at the center of the macula, slightly darker than the surrounding retina. The associated tractional ERM, causing wrinkling and glistening of the retinal surface, is usually readily appreciable, whereas EP is hardly apparent on biomicroscopy or fundus photography since the retina surface appears smooth. When imaged with blue fundus autofluorescence (B-FAF) imaging, LMHs are characterized by an increased autofluorescent signal, the intensity of which does not correlate with the thickness of the residual outer retinal tissue. Green reflectance and blue reflectance (BR) images clearly show the increased reflection and wrinkling of the retinal surface caused by tractional ERM associated with LMH. BR and multicolor imaging enable the visualization of EP associated with LMH in the form of a sharply demarcated dark area and in the form of a yellowish area surrounding the hole, respectively. Scarce data regarding invasive imaging techniques, such as fluorescein angiography, for the study of LMH are available in the literature. The aim of this review is to evaluate the contribution that each imaging modality can provide to study the morphologic characteristics of LMH

Restoration of foveal thickness and architecture after macula-off retinal detachment repair

PURPOSE. To investigate the foveal changes after repair of macula-off rhegmatogenous retinal detachment (RRD). METHODS. Prospective comparative case series. Twenty-four eyes of 24 patients with maculaoff/ fovea-on detachment (n ¼ 9) and fovea-off detachment (n ¼ 15) were studied. Serial optical coherence tomography (OCT) images taken at the same location were recorded at months 1, 3, 6, and 12 after operation. Fellow eyes were used as controls. RESULTS. No significant changes of the central foveal thickness (CFT) were recorded in the fovea-on group over the follow-up. From month 1 to month 12, CFT increased significantly in the fovea-off group (P < 0.00001). In this group, a significant increase of the Henle fiber and outer nuclear layer (HFL þ ONL, P ¼ 0.007), external limiting membrane (ELM)-ellipsoid zone (EZ; P ¼ 0.03), and EZ-retinal pigment epithelium (RPE) thicknesses (P < 0.00001) was recorded. Significant restoration of the integrity of the ELM in the fovea-off group (P < 0.001) and of the EZ and cone interdigitation zone in the fovea-on group and the fovea-off group was observed (P ¼ 0.02 and P < 0.001, and P ¼ 0.002 and P < 0.001, respectively). Twelve months after operation the foveal bulge restored in 8 of 15 eyes of the fovea-off group. Multiple regression analysis showed that in the fovea-off group BCVA correlated with EZ-RPE thickness at months 1 and 12, whereas the improvement of BCVA during the 12 months follow-up correlated with the increase of ELM-RPE thickness. CONCLUSIONS. Optical coherence tomography scans taken serially at the same location showed a progressive increase of HNLþONL, ELM-EZ, and EZ-RPE thicknesses and restoration of the integrity of outer retinal bands after repair of fovea-off RRD. The use of software able to rescan at exactly the same area is crucial to correctly follow and interpret the reconstitution of the retinal bands and to correlate them to BCVA recovery

P-60: Dihydropiridine calcium channel blockers and dependent edema: a comparison between amlodipine and lercanidipine in essential hypertensive patients

Background: Dependent leg edema complicates treatment with amlodipine (AMLO) and other dihydropiridine (DHP) calcium channel blocker (CCB)s and frequently obliges to interrupt an otherwise highly effective therapeutic regimen. Among other possible explanations, DHP CCBs may alter the balance between pre- and post-capillary pressures by dilating preferentially precapillary arterioles of the cutaneous microcirculation, thus increasing capillary pressure and promoting fluid extravasation. In contrast, DHP CCBs such as lercanidipine (LERCA), which may relax both pre- and post-capillary vessels in in-vitro studies, may induce a lesser degree of dependent edema. However, this hypothesis has never been tested in man. Methods: We compared the leg edema-forming potential of AMLO and LERCA according to a cross-over, sequence-randomized experimental design carried out in 22 never treated mild-moderate uncomplicated essential hypertensive (EH) males (age: 48±5 yrs). Drugs were administered at doses (AMLO: 10 vs LERCA: 20 mg o.d.) equipotent on the basis of published titration studies. Active treatment was given for 2 weeks preceded and followed by 2 week wash-outs to allow the recovery of study variables to baseline. Leg weight (LW) was used as a surrogate measure of dependent edema; the parameter was measured by water plethysmography (accuracy within 5 grams; variation coefficient: 0.8%) at both legs and the data were averaged. Systolic and diastolic blood pressure (BP, the mean of at least 10 determinations) was recorded by an automated oscillometric device. Results: (means±SD): AMLO (from 147±8/94±12 to 137±14/83±9 mmHg, p<.002) and LERCA (from 145±18/92±12 to 137±9/83±8 mmHg, p<0.01) decreased BP to a similar extent. Both drugs increased LW (AMLO: from 3244±306 to 3324±293 grams, p<0.001; LERCA: from 3256±279 to 3293±258 grams, p<0.04), but the increase was greater during AMLO (80±91 vs 37±74 grams, p<0.03). Conclusions: These data, consistent with pharmacological differences previously reported at the in-vitro microvascular level, show for the first time in man that, for a similar drop in BP, the edema-forming potential of AMLO and LERCA, two CCBs belonging to the same DHP class, is not equivalent

Valutazione dell’innervazione simpatica cardiaca nella pratica clinica: tra mito o realtà

Il sistema nervoso simpatico (SNS) riveste un ruolo fondamentale nel controllo omeostatico delle principali funzioni cardiovascolari e nello sviluppo di patologie come lo scompenso cardiaco e l’ipertensione arteriosa. Per questo motivo, la valutazione del tono simpatico ha guadagnato, negli ultimi decenni, un interesse rilevante, con possibili importanti ripercussioni cliniche. Ad oggi, tuttavia, nessuna delle metodiche in qui proposte per la valutazione del grado di attivazione del SNS cardiaco ha guadagnato l’interesse clinico, né prevede di farlo nell’immediato futuro. Questo lavoro si propone di sintetizzare le evidenze esistenti sul ruolo isiopatologico della disfunzione del SNS nella genesi di alcune delle più rilevanti affezioni cardiovascolari (scompenso cardiaco, cardiopatia ischemica, ipertensione arteriosa), descrivendo al contempo le caratteristiche principali e le limitazioni più rilevanti degli strumenti attualmente disponibili per la sua valutazione