Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register.

BACKGROUND: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. METHODS: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000-2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers' characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. RESULTS: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. DISCUSSION: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers' characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.

Serum uric acid is not independently associated with plasma renin activity and plasma aldosterone in hypertensive adults.

BACKGROUND AND AIMS: In experimental investigations conducted in rats, raising serum uric acid (SUA) levels resulted in the stimulation of intrarenal renin expression. Studies in humans exploring the association of SUA with plasma renin activity (PRA) yielded conflicting results. Moreover, little is known about the relationship of SUA with plasma aldosterone concentration (PAC). The study aimed to assess the relationship between SUA levels, PRA, and PAC and the influence of age, gender, body mass index (BMI), and hyperuricemia on these relationships in subjects with essential hypertension (EH). METHODS AND RESULTS: We enrolled 372 hypertensive patients (mean age 45 ± 12 years, men 67%) with uncomplicated EH that was not pharmacologically treated. The study population was divided in tertiles according to SUA levels. While PRA did not differ significantly across the three tertiles, PAC was higher in subjects belonging to the uppermost tertile of SUA than those in the lower ones (p = 0.0429); however, this difference lost statistical significance after adjustment for age, sex, BMI, and serum creatinine. Univariate correlation analyses showed significant associations of SUA with PRA (r = 0.137; p = 0.008) and PAC (r = 0.179; p < 0.001). However, these relationships were not significant after correcting for confounding factors in multiple linear regression analyses. We did not observe statistically significant effect modification by gender, age, BMI, and hyperuricemia. CONCLUSION: SUA levels are weakly associated with PRA and PAC in adults with untreated EH. These relationships were lost after adjustment for age, sex, BMI, and serum creatinine.

Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity.

BACKGROUND: The approval of 9-δ-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex) for the management of treatment-resistant multiple sclerosis (MS) spasticity opened a new opportunity for many patients. The aim of our study was to describe Sativex effectiveness and adverse events profile in a large population of Italian patients with MS in the daily practice setting. METHODS: We collected data of all patients starting Sativex between January 2014 and February 2015 from the mandatory Italian medicines agency (AIFA) e-registry. Spasticity assessment by the 0-10 numerical rating scale (NRS) scale is available at baseline, after 1 month of treatment (trial period), and at 3 and 6 months. RESULTS: A total of 1615 patients were recruited from 30 MS centres across Italy. After one treatment month (trial period), we found 70.5% of patients reaching a ≥20% improvement (initial response, IR) and 28.2% who had already reached a ≥30% improvement (clinically relevant response, CRR), with a mean NRS score reduction of 22.6% (from 7.5 to 5.8). After a multivariate analysis, we found an increased probability to reach IR at the first month among patients with primary and secondary progressive MS, (n=1169, OR 1.4 95% CI 1.04 to 1.9, p=0.025) and among patients with >8 NRS score at baseline (OR 1.8 95% CI 1.3-2.4 p<0.001). During the 6 months observation period, 631(39.5%) patients discontinued treatment. The main reasons for discontinuation were lack of effectiveness (n=375, 26.2%) and/or adverse events (n=268, 18.7%). CONCLUSIONS: Sativex can be a useful and safe option for patients with MS with moderate to severe spasticity resistant to common antispastic drugs.

Renal haemodynamics and severity of carotid atherosclerosis in hypertensive patients with and without impaired renal function.

BACKGROUND AND AIM: Renal resistance index (RRI), assessed by Duplex-Doppler sonography, has been classically considered as a mere expression of intrarenal vascular resistance. Recent studies, however, have showed that RRI is also influenced by upstream factors, especially arterial compliance, confirming its possible role as a marker of systemic vascular alterations. Several studies have shown that carotid intima-media thickness (cIMT) and carotid plaques (cP), assessed by ultrasonography, are documented markers of subclinical organ damage as well as expression of progressive atherosclerotic disease, and that they get worse with the progressive deterioration of renal function. The study was aimed to evaluate the relationship between RRI and severity of carotid atherosclerosis in hypertensive subjects with and without impaired renal function. METHODS AND RESULTS: The study population, including 263 hypertensive patients (30-70 years), was split into 3 groups based on cIMT and presence of cP (cIMT ≤ 0.9 mm and no cP; cIMT > 0.9 mm and no cP; cP). All patients were also divided into 2 subgroups (normal renal function; CKD stage I-IV). A stepwise increase in RRI corresponding to the groups of progressive severity of carotid atherosclerosis was observed (respectively 0.61 ± 0.07, 0.65 ± 0.06, 0.68 ± 0.06; p < 0.001). A strong positive correlation was observed between RRI and cIMT in the whole population (r = 0.43; p < 0.001) and in the subgroups with (r = 0.42; p < 0.001) and without (r = 0.39; p < 0.001) CKD. These associations remained statistically significant even after adjustment for various confounding factors. CONCLUSION: Showing a close association between RRI and severity of carotid atherosclerosis, our results strengthen the concept that RRI is a marker of systemic vascular changes.

Relationships between mild hyperuricaemia and aortic stiffness in untreated hypertensive patients.

BACKGROUND AND AIMS: Clinical studies exploring the relationship between serum uric acid (SUA) and arterial stiffness yielded conflicting results. Only in a few of these studies, arterial distensibility was examined by measuring aortic pulse wave velocity (PWV), which is considered the gold standard for evaluating arterial stiffness. In none of the previous investigations was the influence of SUA on aortic distensibility assessed, taking into account the effect of albuminuria. The purpose of our study was to comprehensively analyse the relationships between SUA and aortic PWV in a group of essential hypertensive patients. METHODS AND RESULTS: We enrolled 222 untreated and uncomplicated hypertensive subjects (mean age: 44 ± 10 years; 60% males), without gout. In all patients, SUA and urinary albumin excretion rate (AER) were determined. Moreover, carotid-femoral (c-f) PWV was measured. C-f PWV was significantly higher in hypertensive patients belonging to the uppermost tertile of SUA distribution, compared to subjects of the lowest tertiles (10.9 ± 2.2 vs. 10 ± 1.8 vs. 9.9 ± 1.7 m s(-1); p = 0.001). In univariate analysis, SUA correlated with c-f PWV (r = 0.24; p < 0.001). This association disappeared when AER was added in a multiple regression model, including SUA, age, mean arterial pressure, gender, metabolic syndrome components and glomerular filtration rate. CONCLUSION: The results of our study showed that, in essential hypertensive subjects, there is a positive relationship between mild hyperuricaemia and aortic stiffness. This association weakened after adjustment for covariates and lost statistical significance after further correction for albuminuria.

Absence of an independent association between serum uric acid and left ventricular mass in Caucasian hypertensive women and men.

BACKGROUND AND AIM: Experimentally uric acid may induce cardiomyocyte growth and interstitial fibrosis of the heart. However, clinical studies exploring the relationship between serum uric acid (SUA) and left ventricular (LV) mass yielded conflicting results. The aim of our study was to evaluate the relationships between SUA and LV mass in a large group of Caucasian essential hypertensive subjects. METHODS AND RESULTS: We enrolled 534 hypertensive patients free of cardiovascular complications and without severe renal insufficiency. In all subjects routine blood chemistry, including SUA determination, echocardiographic examination and 24 h ambulatory blood pressure (BP) monitoring were obtained. In the overall population we observed no significant correlation of SUA with LV mass indexed for height(2.7) (LVMH(2.7)) (r = 0.074). When the same relationship was analysed separately in men and women, we found a statistically significant correlation in female gender (r = 0.27; p < 0.001), but not in males (r = -0.042; p = NS). When we grouped the study population in sex-specific tertiles of SUA, an increase in LVMH(2.7) was observed in the highest tertiles in women (44.5 ± 15.6 vs 47.5 ± 16 vs 55.9 ± 22.2 g/m(2.7); p < 0.001), but not in men. The association between SUA and LVMH(2.7) in women lost statistical significance in multiple regression analyses, after adjustment for age, 24 h systolic BP, body mass index, serum creatinine and other potential confounders. CONCLUSIONS: Our findings do not support an independent association between SUA and LV mass in Caucasian men and women with arterial hypertension.

Gut-oriented interventions in patients with multiple sclerosis: fact or fiction?

OBJECTIVE: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS. PATIENTS AND METHODS: We reviewed all available studies in PubMed concerning gut-directed interventions and MS. This research was conducted using different combinations of pertinent keywords (multiple sclerosis, immune-mediated inflammatory diseases, autoimmune diseases, first demyelinating event, neurocognition, neurological disorders, neurology practice, risk factors, taxonomic biomarkers, nutrition, diet, dietary additives, complementary treatment, gut bacteria, gut microbiome, microbiome, gut-brain axis, epidemiology, alpha-linolenic acid, fermentative metabolites, fat, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 fatty acids, calorie restricted diet, fasting, fecal microbiome, fecal microbiota transplantation, animal testing). RESULTS: There is an emerging evidence that alterations in the gut microbiome and increased intestinal permeability may be causative factors in the complex interplay between nutrition, metabolic status and the immune-inflammatory response in patients with MS. This suggests the possibility that modification of lifestyle and the microbiome, for example by specific diets or fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers, may positively influence the pathogenesis of MS. CONCLUSIONS: Although the role of nutritional factors in the pathogenesis of MS remains to be established, there is evidence that appropriate gut-directed interventions such as diet, nutritional supplementation or fecal transplantation may modulate the inflammatory response and improve the course of MS as a complementary treatment in the disease.

Quality of life, depression and fatigue in mildly disabled patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta-1a: 3-year results from the COGIMUS (COGnitive Impairment in MUltiple Sclerosis) study.

BACKGROUND: The precise relationships among quality of life, depression, fatigue and cognitive impairment in multiple sclerosis (MS) are complex and poorly understood. OBJECTIVE: To assess the effects of subcutaneous interferon beta-1a on quality of life, depression and fatigue over 3 years in the COGIMUS study, and to examine the relationship between these outcomes and baseline cognitive status. METHODS: COGIMUS was an observational 3-year trial assessing cognitive function in 459 patients with relapsing-remitting MS treated with subcutaneous interferon beta-1a. RESULTS: In total, 331 patients completed the study (168 received interferon beta-1a, 44 µg subcutaneously three times weekly, and 163 received interferon beta-1a, 22 µg subcutaneously three times weekly). Mean MS Quality of Life-54 (MSQoL-54) composite scores did not change over time. There were no significant differences between groups in MSQoL-54 composite scores when patients were grouped by treatment dose and baseline cognitive status. Mean (standard deviation) Hamilton Depression Rating Scale score decreased from 6.8 (4.9) at baseline to 5.8 (5.9) at year 3. Mean total Fatigue Impact Scale scores were low (<30) at all time points. CONCLUSION: Quality of life, depression and fatigue remained largely stable over 3 years; no effects of treatment dose or baseline cognitive status were found.

Natalizumab therapy of multiple sclerosis: recommendations of the Multiple Sclerosis Study Group--Italian Neurological Society.

Three years after the introduction of natalizumab (NA) therapy for the second line treatment of relapsing-remitting multiple sclerosis (MS), Italian MS centers critically reviewed the scientific literature and their own clinical experience. Natalizumab was shown to be highly efficacious in the treatment of MS. However, the risk of progressive multifocal leukoencephalopathy was confirmed and defined better. This article summarizes the MS-SIN Study Group recommendations on the use of NA in MS, with particular reference to the appropriate selection and monitoring of patients as well as to the management of adverse events.

Effects of hypocaloric very-low-carbohydrate diet vs. Mediterranean diet on endothelial function in obese women*.

Obesity is a cardiovascular risk factor associated with endothelial dysfunction, but the effect of different weight loss strategies on endothelial function is not known. The effect of diet on endothelial function in two hypocaloric diets, a very-low-carbohydrate diet (A) and a Mediterranean diet (M), was measured by brachial artery flow-mediated dilation (FMD). Design Using a longitudinal, randomized, open study design, subjects were engaged in a 2-month weight loss diet. FMD, inflammatory cytokines [interleukin-6 (IL-6) and tumour necrosis factor-alpha] and a marker of oxidative stress [8-iso-prostaglandin F2alpha (8-iso-PGF2alpha)] were measured in subjects on three occasions: before initiating the diet (T0), after 5-7 days of dieting (T5) and after 2 months of dieting (T60). The very short- and medium-term time points were established to discriminate respectively the effect of the diet itself (T5) from that of weight loss (T60). Twenty overweight/obese but otherwise healthy women (BMI: 27-34.9 kg m(-2); age 30-50 years) completed the study. Results Group A lost more weight (mean +/- SEM; -7.6 +/- 0.8 kg) than group M (-4.9 +/- 0.6 kg, P = 0.014) at T60. The FMD was not significantly different between the two groups at T0 (group A: 12.2 +/- 2.9% vs. group B: 10.3 +/- 2.3%, P = ns). In group A, FMD was significantly reduced at T5 and returned to baseline at T60; in group M, FMD increased at T5 and returned to baseline at T60 (P = 0.007 for diet x time interaction). Serum concentrations of IL-6 and 8-iso-PGF2alpha were not significantly different between the two groups at T0 and increased significantly at T5 only in group A (P < 0.001 and P < 0.005 respectively). Conclusion As endothelial dysfunction is known to be associated with acute cardiovascular events, this study suggests that the cardiovascular risk might be increased in the first days of a very-low-carbohydrate diet.

[Inflammation, oxidative stress and kidney function in arterial hypertension]. / Infiammazione, stress ossidativo e funzione renale nell'ipertensione arteriosa.

Traditional risk factors such as hypertension, diabetes, dyslipidemia, obesity and metabolic syndrome, as well as additional nontraditional risk factors, can damage the kidney directly and by promoting intrarenal atherogenesis. Evidence indicates that increased oxidative stress and inflammation may mediate most of the effects of risk factors on the kidney. An early sign of impending nephropathy is microalbuminuria, defined as urinary excretion of albumin at a rate of 20-200 mg/min. Patients with microalbuminuria, especially in diabetes, may progress along the renal continuum to chronic kidney disease (CKD) (indicated by macroalbuminuria or proteinuria), increased serum creatinine concentration and decreased glomerular filtration rate. Microalbuminuria is now recognized as an important marker not only for renal disease, but above all for cardiovascular risk. Clinical studies have demonstrated a relationship between oxidative stress and inflammatory biomarkers, and a few studies indicate an inverse correlation of oxidative stress biomarkers, assessed by 8-isoprostaglandin F2 alpha, with estimated glomerular filtration rate (eGFR). Moreover, plasma concentrations of high-sensitivity C-reactive protein have been shown to be increased and related to left ventricular mass in CKD individuals having left ventricular hypertrophy. Further, surrogate indexes of atherosclerosis such as intima-media thickness and aortic pulse wave velocity have been demonstrated to be related to plasma concentrations of markers of endothelial activation, inflammation and fibrosis in patients with different stages of CKD. In conclusion, current evidence supports a central role for inflammation in all phases of the atherosclerotic process. On the other hand, in arterial hypertension experimental and clinical data suggest a possible interplay of inflammatory molecules with both oxidative stress and endothelial activation markers. The identification of novel biomarkers and cardiovascular risk factors is needed for prognostic evaluation, cardiovascular and renal prevention, and slowing renal function decline.

Discontinuation of teriflunomide and dimethyl fumarate in a large Italian multicentre population: a 24-month real-world experience.

BACKGROUND: Teriflunomide (TRF) and Dimethyl fumarate (DMF) are licensed drugs for relapsing-remitting Multiple Sclerosis (RRMS). OBJECTIVES: We aimed to compare the rate and the time to discontinuation among persons with RRMS (pwRRMS), newly treated with TRF and DMF. MATERIALS AND METHODS: A retrospective study on prospectively collected data was performed in nine tertiary MS centers, in Italy. The 24-month discontinuation rate in the two cohorts was the primary study outcome. We also assessed the time to discontinuation and reasons of therapy withdrawn. Discontinuation of TRF and DMF was defined as a gap of treatment ≥ 60 days. RESULTS: A cohort of 903 pwRRMS (316 on TRF and 587 on DMF) was analyzed. During 24 months of follow-up, pwRRMS on TRF and DMF showed similar discontinuation rates. The analysis of predictors with Cox regression model showed differences between the two groups (p for log-rank test = 0.007); male gender [HR 2.21 (1.00-4.90); p = 0.01] and the number of previous switches [HR 1.47 (1.16-1.86); p = 0.01] were associated with higher hazard of discontinuation in the DMF group. CONCLUSIONS: In a real-world setting, pwRRMS on TRF and DMF had similar discontinuation rates over 24 months. Male pwRRMS on DMF with a previous history of therapeutic failure are at more risk of discontinuation therapy.

Relationships between metabolic syndrome and left ventricular mass in hypertensive patients: does sex matter?

Several studies documented an association between metabolic syndrome (MetS) and left ventricular (LV) hypertrophy. However, only in a few of these studies the impact of MetS on left ventricular mass (LVM) was separately analysed by gender, with conflicting results. The aim of our study was to verify, in a wide sample of essential hypertensive patients, the influence of gender, if any, on the relationship between MetS and LVM. We enrolled 475 non-diabetic subjects (mean age: 46 +/- 11 years), with mild-to-moderate essential hypertension, of whom 40% had MetS, defined on the basis of Adult Treatment Panel III (ATPIII) criteria. All the patients underwent a 24-h ambulatory blood pressure monitoring and an echocardiogram. LVM indexed for height (2.7) (LVMH (2.7)) was significantly (P < 0.001) higher in women with MetS (n=83) than in those without it (n=97; 54+/-17 vs 42+/-11 g m(-2.7)). An equally significant difference in LVMH (2.7) was documented also in male gender between the two groups with (n=105) and without MetS (n=190; 51+/-14 vs 43+/-11 g m(-2.7); P < 0.001). The relationship between MetS and LVMH (2.7) remained statistically significant (P < 0.001) in both sexes, in multiple regression analyses, even after adjustment for potential confounding factors. Our results seem to suggest that the relationship between MetS and LVM is not significantly affected by gender, being LVM increased in both hypertensive women and men with MetS.

Metabolic syndrome in subjects with white-coat hypertension: impact on left ventricular structure and function.

Some reports have suggested that white-coat hypertension (WCH) is associated with some features of the metabolic syndrome (MetS). These metabolic disturbances, instead of WCH per se, may potentially explain the greater extent of end-organ damage sometimes observed in WCH subjects (WCHs) when compared to normotensive individuals (NTs). The aim of the present cross-sectional study was to compare left ventricular (LV) structure and function in three groups of subjects: WCHs with MetS, WCHs without MetS and NTs. A total of 145 WCHs, 35% of whom had MetS, were enrolled. As controls, 35 NTs were also studied. In all subjects, routine blood chemistry, echocardiographic examination and 24-h ambulatory blood pressure monitoring were performed. When compared with WCHs without MetS, those with MetS showed higher LV mass indexed by height elevated by a power of 2.7 (LVMH(2.7)) (49.6+/-14.8 vs 38.9+/-9.8 g/m(2.7); P<0.0001). The same parameter was greater in WCHs without MetS than in NTs (32+/-8 g/m(2.7); P=0.004). Moreover, the E-wave deceleration time was longer in WCHs with MetS than in those without it (236.2+/-66.4 vs 200.5+/-30.8 ms; P<0.0001). The relationship of MetS with LVMH(2.7) was confirmed in multivariate regression models. Our results seem to suggest that MetS may have a deleterious influence on LV structure and function in WCH. However, WCH, being associated with an increased LV mass, also in subjects without MetS, may not be considered as an innocuous phenomenon.

Microalbuminuria and early endothelial activation in essential hypertension.

We hypothesized that in essential hypertensive patients (EHs), plasma levels of pro-atherogenic adhesion molecules would be increased and related with urine albumin excretion (UAE). Thus, this study was aimed at evaluating biochemical markers of endothelial activation and their relationship with UAE in a group of patients with uncomplicated EH. In basal condition soluble forms of adhesion molecules intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, as well as 24-h UAE were assayed. One hundred patients with essential hypertension and no diabetes or ultrasonographic evidence of atherosclerosis were included in the study. Seventy normotensive healthy subjects served as controls. EHs were first studied overall, than were divided into two subgroups: those with UAE > or =20 mcg/min MAUs and those with UAE <20 mcg/min (non-MAUs). ICAM-1 (P<0.001) and VCAM-1 (P<0.0001) plasma concentrations were higher in EHs than in controls. Microalbuminuric EHs had greater levels of adhesion molecules than non-MAUs (ICAM-1 P=0.04; VCAM-1 P=0.02, respectively). In EHs UAE was correlated with ICAM-1 (r=0.29, P=0.003), and VCAM-1 (r=0.30, P=0.002). These associations were confirmed in multiple regression models (P=0.02 for both ICAM-1 and VCAM-1) including, along with adhesion molecules, age, body mass index and blood pressures. Our findings show that in essential hypertension there is a very early activation of endothelial adhesion molecules favouring atherosclerosis.

Association between biomarkers of inflammation and left ventricular hypertrophy in moderate chronic kidney disease.

AIMS: Left ventricular hypertrophy (LVH) is a predictor for cardiovascular mortality, and it is considered to be a surrogate marker of preclinical cardiovascular disease. This study aimed at evaluating whether fetuin-A plasma levels are decreased in patients with moderate chronic kidney disease (CKD) and their linkage to plasma concentrations of hs-C-reactive protein (CRP), cardiotrophyn-1 (CT-1), tumor necrosis factor-ac (TNF-alpha), propeptide of collagen Type I (PIP) and to LVH. MATERIAL AND METHODS: We enrolled 64 moderate CKD and 55 essential hypertensives (EH) with normal renal function as controls. All the patients underwent an echocardiographic examination; plasma samples were obtained to measure routine clinical parameters and the molecules listed above (measured by ELISA). RESULTS: Among CKD there were 30/64 patients with LVH, and in EH group 14/55 subjects had LVH. Fetuin A was reduced in CKD when compared with EH (p < 0.0001). The comparison between CKD having LVH with those without LVH showed significant differences in plasma levels of fetuin-A (p < 0.002), TNF-alpha (p < 0.01) and hs-CRP (p < 0.001), CT-1 and PIP (p < 0.002). CKD with LVH had lower values of fetuin-A (p < 0.001), and higher values of hs-CRP (p < 0.001) TNF-alpha (p < 0.001), CT-1 (p < 0.001) and PIP (p < 0.001) than EH with LVH. The multivariate analysis of correlation demonstrated that in CKD patients hs-CRP (beta 0.42, p < 0.00006), and systolic blood pressure (beta 0.29, p < 0.02) were independent predictors of LV mass index. The relationship between LV mass index and fetuin-A did not reach statistical significance. CONCLUSIONS: For the first time in moderate CKD patients, we demonstrate that fetuin-A is decreased and relates to LVH depending on C-reactive protein.

Favorable clinical heart and bone effects of anti-thyroid drug therapy in endogenous subclinical hyperthyroidism.

Although subclinical hyperthyroidism (SCH) has been associated with increased risk of osteoporosis and cardiac arrhythmias, its treatment is still controversial. This study was designed as a prospective, randomized, intervention, control-study with a 1-year follow-up in order to investigate whether normalization of serum TSH in SCH using methimazole has favorable bone and heart clinical effects. Fourteen patients with endogenous SCH (not Graves' disease) were enrolled, 7 (5 women/2 men; group T) were treated with methimazole (2.5-7.5 mg/day), and 7 (5 women/2 men; group C) were followed without treatment; 10 healthy subjects were also included in the study as controls. Serum free-T3 (FT3), free-T4 (FT4) and TSH, thyroid echography, bone stiffness index (SI), as measured by heel ultrasonometry, and 24-h electrocardiography monitoring were obtained. SCH patients exhibited higher systolic and diastolic blood pressure than control subjects. They also had a significantly higher number of both ventricular premature beats (VPB) (mean+/-SEM: 681+/-238 vs 6+/-2 beats/24 h; p<0.02) and atrial premature beats (APB) (mean+/-SEM: 495+/-331 vs 7+/-2 beats/24 h; p<0.0001), and a lower SI (66+/-5 vs 96+/-3; p<0.001). Twelve months after normalization of TSH with the use of methimazole, the number of VPB decreased significantly (947+/-443 vs 214+/-109 beats/24 h; p<0.05) while it remained unchanged in untreated SCH patients (414+/-163 vs 487+/-152 beats/24 h; p=ns). An insignificant therapy effect was observed as far as APB were concerned (826+/-660 vs 144+/-75 beats/24 h; p=ns), however their number increased significantly in the untreated group (463+/-49 vs 215+/-46 beats/24 h; p<0.05). The SI increased significantly as a result of therapy in group T (64.1+/-4.8 vs 70.0+/-5.3; p<0.02) and was further reduced in group C at the end of the study (69.1+/-7.3 vs 62.9+/-7.1; p<0.001). No adverse effect was observed in group T. In conclusion, anti-thyroid therapy seems to have favor-able bone and heart clinical effects in subjects with endogenous SCH.

Oxidative stress and inflammation in long-term renal transplanted hypertensives.

INTRODUCTION: Several studies have shown that chronic renal failure (CRF) is characterized by "accelerated atherosclerosis". More recent studies emphasize that inflammation and oxidative stress play a central role in atherosclerosis, and it is well-established that C-reactive protein (CRP) is a cardiovascular risk marker in the general population, in end-stage renal disease (ESRD) patients and in allograft recipients. METHODS: We measured the serum concentration of high sensitivity CRP, TNFalpha, 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha, an in vivo oxidative stress marker) in 15 CRF patients and in 15 transplant recipients. Exclusion criteria were age < 30 and > 65 years, smoking, diabetes mellitus and history of cardiovascular diseases. Immunosuppressive therapy was not withdrawn, and antihypertensive treatment was the same for both groups. Systolic (SBP) and diastolic blood pressure (DBP), serum creatinine (sCr) and estimated glomerular filtration rate (GFR) were also evaluated. 15 healthy subjects were enrolled as controls. RESULTS: The transplanted group showed significantly higher values than controls of CRP (p < 0.05), TNFalpha (p < 0.05), 8-iso-PGF2alpha (p < 0.05). The CRF group as well exhibited, in comparison with controls significantly higher concentrations of CRP (p < 0.05), TNFalpha (p < 0.05), and 8-iso-PGF2alpha (p < 0.05). SBP, DBP and sCr were not different between transplanted and CRF patients. CRP was higher in transplant recipients than in CRF patients (p < 0.05). No difference in TNFalpha levels between the 2 groups was found. 8-iso-PGF2alpha was significantly higher in CRF than in the transplanted group (p < 0.05). In this latter, 8-iso-PGF2alpha showed a positive correlation with TNFalpha (p < 0.001), sCr (p < 0.001), SBP (p < 0.05) and DBP (p < 0.05). In the same group both 8-iso-PGF2alpha and TNFalpha were negatively correlated with GFR (r = -0.873 and -0.912, respectively, p < 0.001 for both). CONCLUSION: Our data have shown the coexistence of an increased oxidative stress and an inflammatory state in long-term renal graft recipients.