Massimiliano Morreale

Synergistic effect of glycolic acid on the antioxidant activity of α‐tocopherol and melatonin in lipid bilayers and in human skin homogenates

Considerable interest has been raised concerning the use of natural compounds in preventing skin aging and photoaging. In the idea that the combined action of agents increasing epidermal turnover with antioxidants could be advantageous in cosmetic and therapeuthic treatments, we first investigated if α‐glycolic acid affected or prevented the antioxidant activity of vitamin E and of melatonin, two compounds found beneficial as topical photoprotectant. Assays were carried out in vitro either in a biomimetic liposomal system, or in human skin homogenates. Lipid peroxidation was monitored spectrophotometrically by the time course of lipid hydroperoxide production in liposomes and by formation of TBA reactive substances (TBARS) in skin homogenates. Glycolic acid. at 25 μM to 1 mM, showed a mild, concentration‐dependent antioxidant effect in liposomes, as evaluated by a slight decrease of the peroxidation rate, while, at 1 mM, reduced TBARS production in skin homogenates by 14 %. Combinations of either vitamin E or melatonin with glycolic acid, in a 1:5 to 1:200 molar ratio, resulted in a clear synergistic protection of liposomes, more evident for the combination of glycolic acid with vitamin E. An amount of synergism up to 250% and up to 80% was evahmted with vitamin E and melatonin, respectively. Consumption rate of vitamin E during peroxidation of liposomes, in the absence or in the presence of glycolic acid, suggests that regeneration of vitamin E may in part explain the observed synergism. Synergistic antioxidant activity between vitamin E and glycolic acid was also observed in skin homogenates, whereas the effect of glycolic acid on the antioxidant activity of melatonin appeared additive. However, the combination of these three compounds inhibited TBARS production almost completely.

Association of renal resistive index with aortic pulse wave velocity in hypertensive patients.

Background Recent data suggest that renal haemodynamic parameters obtained by duplex Doppler sonography, especially the intrarenal resistive index (RI), may be associated with systemic vascular changes. However, conflicting data exist about the independent relationship between aortic stiffness and RI. The aim of this study was to evaluate the relationship between RI and arterial stiffness, assessed by aortic pulse wave velocity (aPWV), in hypertensive patients. Design Cross-sectional study. Methods We enrolled 264 hypertensive subjects aged between 30 and 70 years. They were divided into two groups, either with normal renal function (n = 140) or with chronic kidney disease (CKD) (n = 124). Each patient underwent assessment of ultrasonographic renal RI and measurement of aPWV through oscillometric device. Results Patients with renal RI>0.7 showed higher values of aPWV, both in the overall population (p < 0.001) and in the subgroups with (p < 0.01) and without CKD (p < 0.01). Moreover, statistically significant correlations were observed between aPWV and RI in the whole population (r = 0.38, p < 0.001) and in the subgroups with (r = 0.35, p < 0.001) and without CKD (r = 0.31, p < 0.001). These correlations held even after adjustment for several confounding factors in multivariate analyses. Conclusions Our results seem to corroborate the concept that the RI may be considered as a marker of systemic vascular changes and therefore a predictor of cardiovascular risk.

Relationship between aortic root size and glomerular filtration rate in hypertensive patients.

Objective: Recent studies suggest that enlarged aortic root diameter (ARD) may predict cardiovascular events in absence of aneurysmatic alterations. Little is known about the influence of renal function on ARD. Our study was aimed to assess the relationships between glomerular filtration rate (GFR) and ARD in hypertensive subjects. Methods: We enrolled 611 hypertensive individuals (mean age: 52 ± 15 years; men 63%). ARD was measured by echocardiography at the level of Valsalvas sinuses using M-mode tracings. It was considered as absolute measure, normalized to body surface area (ARD/BSA) and indexed to height (ARD/H). GFR was estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. The study population was categorized into seven groups: subjects without chronic kidney disease (no CKD) and subjects with increasing severity of CKD (1, 2, 3a, 3b, 4, 5), as proposed by the 2012 Kidney Disease: Improving Global Outcomes guidelines. Results: ARD/BSA and ARD/H showed a stepwise increase from the group with normal renal function to the groups with increasing severity of CKD. GFR correlated significantly with ARD (r = –0.17), ARD/BSA (r = –0.43) and ARD/H (r = –0.35; all P < 0.001). The associations of GFR with ARD/BSA (&bgr; = –0.26; P < 0.001) and ARD/H (&bgr; = –0.13; P = 0.01) held in linear multiple regression analyses, after adjustment for various confounding factors. Conclusion: Our study seems to suggest that a reduced renal function may adversely influence ARD. This may contribute to explain the enhanced cardiovascular risk associated with renal insufficiency.

Average real variability of 24-h systolic blood pressure is associated with microalbuminuria in patients with primary hypertension

Limited and conflicting data are available about the association between short-term blood pressure (BP) variability and urinary albumin excretion rate (uAER). The objective of our study was to analyze the relationships between microalbuminuria (MAU), defined as an uAER between 20 and 200 μg min−1, and short-term BP variability (BPV), assessed as average real variability (ARV), weighted s.d. of 24-h BP and as s.d. of daytime and night-time BP. The study population consisted of 315 untreated essential hypertensives with normal estimated glomerular filtration rate (>60 ml min−1 per 1.73 m2), who underwent 24-h ambulatory BP monitoring and 24-h uAER determination. MAU was detected in 82 (26%) patients. ARV of 24-h systolic BP (SBP) was significantly higher in patients with MAU (9.8 (8.5–11.1) mm Hg) when compared with those without it (9.1 (8–10.2) mm Hg; P=0.007). This difference held (P=0.026) after adjustment for age, mean levels of BP and other potential confounders by analysis of covariance. A statistically significant correlation was also found between ARV of 24-h SBP and uAER (r=0.17; P=0.003). This association remained significant (β=0.15; P=0.01), also taking into account the effect of 24-h average systolic and diastolic BP, age, gender, diabetes, serum uric acid, triglycerides, estimated glomerular filtration rate in multiple regression analyses. All the other indices of short-term BPV tested were not independently associated with MAU. Our results seem to suggest that in essential hypertension, short-term BPV, only when estimated by ARV of 24-h SBP, is independently associated with MAU.

The renal resistive index: is it a misnomer?

Progress in digital ultrasound technology and diffusion of Doppler ultrasound evaluation of the kidney enable a widespread non-invasive evaluation of renal haemodynamics. Initially most attention has been paid to the study of extraparenchymal renal arteries, mainly to detect renovascular disease. However, this approach has low reproducibility and accuracy. Therefore, interest has gradually moved towards the duplex evaluation of intrarenal anatomy, where the best and most reliable signals are obtained from the large segmental or interlobar arteries that run directly towards the transducer [1]. Among the sonographic parameters used in the last decade, great emphasis has been placed on the intrarenal resistive index (RRI), which is defined as the dimensionless ratio of the difference between maximum and minimum (end-diastolic) flow velocity to maximum flow velocity [1, 2]. It has been used for a long time for the diagnostic and prognostic assessment of renovascular disease [2, 3]. One of the earliest prospective uses of the RRI was in the prediction of kidney function outcomes following intervention for renal artery stenosis. In the pioneering study of Radermacher et al., an RRI[0.80 is associated with poorer outcomes, when surgery or angioplasty is used to correct renal artery stenosis [3]. Subsequently, RRI has been more widely used to detect changes in transplanted kidney perfusion, and to predict the rate of decline in renal function in chronic kidney diseases (CKD) of different etiologies [2, 4, 5]. Despite these promising data, most clinicians currently rely on measurements of traditional predictors of the progression of CKD (blood pressure, proteinuria, baseline renal function) rather than on ultrasound indices in individual patients. The current reluctance to use RRI as prognostic marker partly results from some uncertainty about the physiological factors that influence it. In the current issue of Internal and Emergency Medicine, Boddi and co-workers publish an exhaustive review of the literature on this topic, excellently summarizing the available information on the role or RRI in cardiovascular and renal medicine [6]. As discussed in this interesting paper, increased RRI may indicate remodelling of the microcirculation with a reduction of the cross-sectional area of vessels, and an increase of the total peripheral resistance of the kidney [2, 5, 6]. It is suggested that this index directly reflects intrarenal vascular resistance, which results in its denomination as ‘resistance index’. However, accumulating evidence indicates that the RRI provides important information about the systemic vasculature as well [2, 5– 10]. Indeed, recent data suggest that this parameter is not only an expression of parenchymal perfusion, but may also be influenced by upstream vascular factors, and indeed these factors appear to play a more important role than intrarenal resistance [2, 5–10]. In this regard, in a large group of hypertensive patients with and without impaired renal function, we describe a close and positive association between RRI and large arteries stiffness, determined by measuring aortic pulse wave velocity (aPWV), a strong independent predictor of cardiovascular morbidity and mortality [7, 11]. This close association remains statistically significant even after adjustment for age, blood pressure (BP) (either when & Giuseppe Mulè giuseppe.mule@unipa.it

Association of Renal Resistive Index with Markers of Extrarenal Vascular Changes in Patients with Systemic Lupus Erythematosus

Recent data suggest that renal hemodynamic parameters obtained by duplex Doppler sonography, especially the intrarenal resistive index (RRI), may be associated with systemic vascular changes. We evaluated the relationships between RRI and arterial stiffness, assessed by aortic pulse wave velocity, and between RRI and subclinical atherosclerosis, assessed by measuring carotid intima-media thickness in patients with systemic lupus erythematosus. We enrolled 39 patients with systemic lupus erythematosus (mean age 39 y) compared with 19 healthy controls, matched for age and sex. Each participant underwent 24 h of ambulatory blood pressure, aortic pulse wave velocity, carotid intima-media thickness and RRI measurements. RRI correlated significantly with aortic pulse wave velocity (r = 0.44, p = 0.006), and with carotid intima-media thickness (r = 0.46, p = 0.003). Both correlations held (p = 0.01), even after correction for age, mean arterial pressure and glomerular filtration rate. Our results suggest that the RRI may be considered a marker of systemic vascular changes and probably a predictor of cardiovascular risk in patients with systemic lupus erythematosus.

[OP.7B.08] INFLUENCE OF GENDER ON THE RELATIONSHIPS BETWEEN NEW INDICES OF ADIPOSITY AND LEFT VENTRICULAR MASS AND HYPERTROPHY IN HYPERTENSIVE PATIENTS

Objective: The unfavourable effects of the association of obesity with hypertension on cardiac structure and function have been extensively studied. However, controversy still exists about the influence of gender on the relationship between obesity and left ventricular mass (LVM) and hypertrophy (LVH). Even if body mass index (BMI) and waist circumference (WC) are widely used as anthropometric predictors for cardiovascular diseases (CVD), their validity has been questioned. Recently, Body Shape Index (ABSI) and Body Roundness Index (BRI) were proposed as alternative measures of adiposity that may better reflect health status (1–2). Our study was aimed to assess the ability of ABSI and BRI in identifying LVH and to determine whether they are superior to BMI and WC. Moreover, the influence of gender on the relationships between all these indices of adiposity and LVM was also evaluated. Design and method: We enrolled 724 subjects with EH (mean age 45 ± 12 years, 63 % men) without cardiovascular complications. In all subjects the anthropometric indices (weight, height and waist circumference) and the routine biochemical parameters were determined. BMI, ABSI and BRI were calculated. Furthermore, all patients underwent a 24-h blood pressure monitoring and an echocardiogram. LVM was indexed for body surface area (LVMI) and for height2.7 (LVMH2.7). Results: The univariate correlations of LVMI and LVMH2.7 with the measures of adiposity evaluated are shown in the table 1. ROC curves analysis revealed that in overall population (table 2) and in men BRI has a greater ability to identify LVH defined as LVMH2.7 > 51 g/m2.7. Figure. No caption available. Conclusions: Our results seems to suggest that in men, but not in women, the BRI has a greater sensitivity to detect LVH than ABSI and the traditional measures of adiposity.

[PP.36.02] ASSOCIATION BETWEEN URIC ACID AND RENAL FUNCTION IN HYPERTENSIVE PATIENTS: WHICH ROLE FOR SYSTEMIC VASCULAR INVOLVEMENT?

Objective: The role of systemic vascular involvement in mediating the association between serum uric acid (SUA) and renal function in hypertension and chronic kidney disease (CKD) has not been fully explored. The purposes of our study were: (1) to investigate the relationship between SUA with both carotid intima-media thickness (cIMT) and aortic pulse wave velocity (aPWV) in hypertensive subjects; (2) to assess the influence of renal function on these relationships; (3) to study whether systemic vascular changes may mediate the association between SUA and renal function in this population. Design and method: We enrolled 523 hypertensive subjects with (n = 263) or without CKD (n = 260). The study was also conducted in the population divided into tertiles of SUA based on sex-specific cut-off values. cIMT was assessed by Duplex-Doppler ultrasonography and aPWV through oscillometric device. Results: cIMT and aPWV were higher, and eGFR lower, in uppermost SUA-tertile patients when compared to those in the lowest ones (all p < 0.001) (Figure 1). Figure. No caption available. Uricemia strongly correlated with eGFR, cIMT and aPWV at univariate analysis (p < 0.001) in all subjects, and with eGFR and cIMT after adjustment for confounders (p < 0.001). The relationships between SUA and cIMT were significant in both patients with or without CKD, in absence of significant differences between groups. Moreover, the adjustment of SUA for cIMT attenuated the relationship between SUA and eGFR (p = 0.019). Conclusions: Systemic vascular changes related with SUA seem in part to mediate the association between SUA and renal function in hypertensive patients, regardless of kidney function.

[PP.07.17] VITAMIN D RECEPTOR GENE POLYMORPHISMS, FGF-23 AND FETUIN-A IN ESSENTIAL HYPERTENSION

Objective: The association between FokI and BsmI vitamin D receptor gene (VDR) polymorphisms and cardiovascular risk was analyzed with contrasting results. Low plasmatic concentrations of fetuin-A, a negative regulator of vascular calcification, and high levels of fibroblast growth factor 23 (FGF-23), a calcium and phosphate metabolism regulator, seem to be associated with higher cardiovascular mortality. Our aim was to evaluate possible association between FokI and BsmI VDR polymorphisms and plasma concentrations of fetuin-A and FGF-23 in essential hypertension. Design and method: Seventy-one patients with essential hypertension underwent clinical blood pressure evaluation, 24-hour ambulatory blood pressure monitoring, assays of 25-hydroxyvitamin D (25[OH]D), FGF-23 and fetuin-A serum levels, and FokI and BsmI VDR polymorphisms analysis. Results: No significant correlations were found either between 25[OH]D and FGF-23, or between 25[OH]D and fetuin-A. When patients were divided according to FokI and BsmI genotypes, we did not observe any significant difference in 25[OH]D, fetuin-A and FGF23 values among different subgroups. Considering FGF-23 median value (79 pg/ml), we did not find any association between a genotype or allele and FGF-23 serum level higher than cut-off. A similar result was obtained by evaluating the association between FokI and BsmI genotypes or alleles, and fetuin-A levels lower than median value (1,2 g/L). Conclusions: In essential hypertension FokI and BsmI VDR polymorphisms does not seem to be associated either with high FGF-23 serum levels, or with low fetuin-A plasma concentrations.

[OP.4B.03] CIRCULATING ALDOSTERONE LEVELS ARE ASSOCIATED WITH CONCENTRIC LEFT VENTRICULAR GEOMETRY IN ESSENTIAL HYPERTENSIVE PATIENTS

Objective: Sound evidence indicates that aldosterone has a fundamental role in determining functional and structural changes in the heart. Moreover, it has been observed that high plasma aldosterone concentration (PAC) is related to the development of congestive heart failure and to cardiovascular mortality. However, previous studies on the association between circulating aldosterone levels and left ventricular (LV) mass (LVM) and LV geometry, in subjects without primary aldosteronism yielded conflicting results. The aim of our study was to evaluate in patients with essential hypertension the relationships of PAC with LV mass and geometry, and to asses the influence of gender on these relationships. Design and method: A total of 478 subjects (men: 63%; mean age 44 ± 12 years) with untreated essential hypertension were enrolled. The measurements included 24-h blood pressure (BP) readings, plasma renin activity (PRA) and PAC, obtained by radioimmunoassay and an echocardiogram. For its skewed distribution PAC was log transformed and expressed as median value and interquartile range. Results: PAC was significantly lower (p < 0.01) in subjects with normal LVM indexed for body surface area (BSA) (n = 272) [7.5 (5.3–12.4)], as compared to those with concentric remodeling (n = 61) [10.2 [7.95–14.5)], to the patients with eccentric LV hypertrophy (LVH) (n = 90) [9.8 (6.9–12.9)], and to the subjects with concentric LVH (n = 61) [11.3 (7.7–16.6 ng/ml)]. Significant correlations of Log (PAC) with LVM, either indexed for BSA (r = 0.20; p < 0.0001), or for height 2.7 (r = 0.21; p < 0.0001) and with relative wall thickness (RWT) (r = 0.18; p < 0.0001) were found. These correlations were similar in men and in women and remained statistically significant in multiple regression analyses, even after adjustment for potential confounding factors (all p < 0.01). Conclusions: Our results seem to suggest that in essential hypertensive patients circulating aldosterone levels are independently associated with concentric LV geometry, without gender-related differences.