Renal function is impaired in normotensive chronic HCV patients: role of insulin resistance

Renal dysfunction is an independent predictor for cardiovascular morbidity and mortality. We investigated whether chronic hepatitis C virus (HCV) infection and the related insulin resistance/hyperinsulinemia influence renal function in comparison with a group of healthy subjects and with another group with metabolic syndrome. We enrolled 130 newly diagnosed HCV outpatients matched for age and gender with 130 patients with metabolic syndrome and 130 healthy subjects. Renal function was evaluated by calculation of glomerular filtration rate (e-GFR, mL/min/1.73 m2) using the CKD-EPI equation. The following laboratory parameters were measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, and HOMA to evaluate insulin sensitivity. HCV patients with respect to both healthy subjects and metabolic syndrome patients have a decreased e-GFR: 86.6 ± 16.1 vs 120.2 ± 23.1 mL/min/1.73 m2 (P < 0.0001) and 94.9 ± 22.6 mL/min/1.73 m2 (P = 0.003), respectively. Regarding biochemical variables, HCV patients, in comparison with healthy subjects, have a higher triglyceride level, creatinine, fasting insulin and HOMA (3.4 ± 1.4 vs 2.6 ± 1.3; P < 0.0001). At linear regression analysis, the correlation between e-GFR and HOMA is similar in the metabolic syndrome (r = -0.555, P < 0.0001) and HCV (r = -0.527, P < 0.0001) groups. At multiple regression analysis, HOMA is the major determinant of e-GFR in both groups, accounting for, respectively, 30.8 and 27.8 % of its variation in the metabolic syndrome and HCV. In conclusion, we demonstrate that HCV patients have a significant reduction of e-GFR and that insulin resistance is the major predictor of renal dysfunction

Sympathovagal balance and 1-h postload plasma glucose in normoglucose tolerant hypertensive patients.

AIMS: Normoglucose tolerant (NGT) subjects with a 1-h postload plasma glucose (PLPG) value ≥155 mg/dL have an increased risk of type-2 diabetes and subclinical organ damage. Heart rate variability (HRV) reflects cardiac autonomic balance, frequently impaired in course of diabetes. At this time, no data support the association between 1-h PLPG and HRV; thus, we investigated the possible association between 1-h PLPG and HRV. METHODS: We enrolled 92 never-treated hypertensive subjects (56 women, 36 men), aged 55 ± 9.8 years. During OGTT, the patients underwent electrocardiographic recordings to evaluate HRV in the time domain (SDNN). Insulin sensitivity was assessed by Matsuda index. RESULTS: Among participants, 56 were NGT, 20 had impaired glucose tolerance (IGT), and 16 had type-2 diabetes. According to the 1-h PLPG cutoff point of 155 mg/dL, we divided NGT subjects into: NGT < 155 (n = 38) and NGT ≥ 155 (n = 18). Glucose tolerance status was associated with a significant (P < 0.0001) increase in PLPG and insulin and the reduction in Matsuda index. In all groups, the SDNN values significantly (P < 0.0001) decreased during the first hour of OGTT. A complete recovery in NGT groups was observed at the end of the second hour; in IGT and type-2 diabetes, SDNN remained significantly lower with respect to baseline values. At multiple regression analysis, Matsuda index resulted in the only determinant of SDNN modification, explaining the 12.3 % of its variability. CONCLUSIONS: Our data demonstrate that during OGTT, sympathovagal balance is acutely affected by both glucose and insulin modifications. Particularly, NGT ≥ 155 subjects behave in the same way of IGT and type-2 diabetes patients

MicroRNA-277 Modulates the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats

Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder, has been recognized in older male fragile X premutation carriers and is uncoupled from fragile X syndrome. Using a Drosophila model of FXTAS, we previously showed that transcribed premutation repeats alone are sufficient to cause neurodegeneration. MiRNAs are sequence-specific regulators of post-transcriptional gene expression. To determine the role of miRNAs in rCGG repeat-mediated neurodegeneration, we profiled miRNA expression and identified selective miRNAs, including miR-277, that are altered specifically in Drosophila brains expressing rCGG repeats. We tested their genetic interactions with rCGG repeats and found that miR-277 can modulate rCGG repeat-mediated neurodegeneration. Furthermore, we identified Drep-2 and Vimar as functional targets of miR-277 that could modulate rCGG repeat-mediated neurodegeneration. Finally, we found that hnRNP A2/B1, an rCGG repeat-binding protein, can directly regulate the expression of miR-277. These results suggest that sequestration of specific rCGG repeat-binding proteins could lead to aberrant expression of selective miRNAs, which may modulate the pathogenesis of FXTAS by post-transcriptionally regulating the expression of specific mRNAs involved in FXTAS

Uric acid is an independent predictor of cardiovascular events in post-menopausal women

BACKGROUND: Uric acid (UA) is a risk factor for cardiovascular (CV) disease. In post-menopause UA levels are increased and strongly associated with subclinical organ damage. We investigated the prognostic significance of UA levels in predicting CV morbidity and mortality in post-menopausal women. METHODS: We considered 645 post-menopausal outpatients not taking hormone replacement therapy or any drugs interfering with UA levels. We evaluated major adverse cardiovascular events (MACE) as primary endpoint, with coronary, stroke or total events as secondary endpoint. Survival curves for tertiles of UA were obtained by using the Kaplan-Meier and Mantel methods. Effect of prognostic factors on survival was evaluated by multivariable Cox regression model, considering P<0.05 as statistically significant. RESULTS: During a mean (SD) follow-up at 72.5 (23.5) months, there were 90 new CV events (2.31%): 62 coronary and 28 cerebrovascular events. The rate of nonfatal CV events (3.15% versus 2.03% and 1.52%, P=0.009) as well as that of MACE (3.23% versus 2.11% and 1.59%, P=0.011) were significantly higher in the third tertile than in the other two groups. Interestingly, cerebrovascular (1.15% versus 0.62% and 0.30%, P=0.027) but not coronary events were significantly different among the three groups. In the Cox regression model, UA was independently and strongly associated with the incident risk of MACE (HR=1.248, P=0.001), cerebrovascular (HR=1.657, P<0.0001) and total events (HR=1.391, P<0.0001). CONCLUSIONS: In post-menopause, independently of other CV risk factors and menopause duration, UA levels are associated with increased risk of death and MACE, in particular cerebrovascular but not coronary events

CHADS2 and CHA2DS 2-VASc scores are independently associated with incident atrial fibrillation: the Catanzaro Atrial Fibrillation Project

No data exist concerning a possible association between CHADS2 or CHA2DS2-VASc scores and atrial fibrillation (AF). In this prospective observational study, we tested the hypothesis whether thromboembolic risk scores predict AF. We investigated 3549 subjects, 1829 men and 1720 women, aged 60.7 ± 10.6 years, without baseline AF. Patients with thyroid disorders were excluded. CHADS2 and CHA2DS2-VASc scores were evaluated as categorical variables. To test the effect of some clinical confounders on incident AF, we constructed different models including clinical and laboratory parameters. During follow-up (53.3 ± 18.1 months), 546 subjects developed AF (4.5 events/100 patient-years). Progressors to AF are older, have a higher body mass index (BMI), blood pressure, LDL-cholesterol, and glucose. Hypertension, metabolic syndrome, diabetes and carotid wall thickening were more common among AF cases than among control subjects. In the final Cox-regression model, variables that remained significantly associated with incident AF were BMI (HR = 1.022, 95% CI = 1.008-1.037), LDL-cholesterol (HR = 1.032, 95% CI = 1.008-1.056), CHA2DS2-VASc score (HR = 1.914, 95% CI = 1.439-2.546), and CHADS2 score (HR = 2.077, 95% CI = 1.712-2.521). In conclusion, CHADS2 and CHA2DS2-VASc scores are independent predictors of AF

Multiplicative effect of serum phosphorus levels and insulin resistance on hypertensive vascular stiffness

No abstract available

One-hour post-load plasma glucose and IGF-1 in hypertensive patients

In normoglucose-tolerant subjects (NGT), 1-h post-load plasma glucose value ≥155 mg/dL, during an oral glucose tolerance test (OGTT), is associated with an increased risk of type-2 diabetes (T2D) and subclinical organ damage. Insulin-like growth factor-1 (IGF-1) is involved in the pathogenesis of insulin resistance (IR) and T2D. Moreover, hypertensives have different degrees of IR and different levels of IGF-1. Actually, there are no data supporting the association between post-load glucose and IGF-1; thus, the aim of the study was to investigate this relationship. MATERIALS AND METHODS: We enrolled 1126 never-treated hypertensive subjects who underwent an OGTT and clinical characterization. Insulin sensitivity was assessed by the Matsuda index. IGF-1 was measured by a sensitive immunoradiometric assay. RESULTS: Among participants, 764 had NGT, 263 had impaired glucose tolerance (IGT) and 99 had T2D. According to the 1-h post-load plasma glucose cut-off point of 155 mg/dL, we divided NGT subjects into NGT < 155 mg/dL and NGT ≥ 155 mg/dL. NGT ≥ 155 in comparison with NGT < 155 had significantly reduced insulin sensitivity and IGF-1 levels. At multiple regression analysis, IGF-1 was the major determinant of 1-h post-load glucose in NGT ≥ 155 subjects, IGT and diabetics, accounting for 20·9%, 17·7% and 15·5% of its variation in the respective models. CONCLUSIONS: In hypertensive NGT ≥ 155 subjects, IGF-1 results strongly associated with 1-h post-load glucose, similarly to that observed in IGT and diabetics. This finding has clinical relevance because both low IGF-1 levels and 1-h post-load glucose in NGT subjects are associated with subclinical organ damage, an independent predictor of cardiovascular events

Low dose of acetylsalicylic acid and oxidative stress-mediated endothelial dysfunction in diabetes: a short-term evaluation

Current guidelines suggest the use of low doses of acetylsalicylic acid (ASA) for patients with diabetes mellitus (DM) in primary prevention. However, the evidences demonstrating the beneficial effect of ASA in primary prevention are conflicting. In this pilot study, we evaluated in a group of diabetic patients, in primary prevention, the impact of ASA treatment on oxidative stress and vascular function. We enrolled 22 newly diagnosed diabetic patients, without any previous clinical evidence of cardiovascular disease, to receive, in primary prevention, ASA (100 mg/daily). We tested, in basal condition, after 4 weeks of ASA administration and after 4 weeks of pharmacological washout, the impact of ASA treatment on endothelial function, assessed by a semipletysmographic method, measuring the main oxidative stress parameters related to it. As expected, after 4 weeks of treatment, ASA induced a significant reduction of plasma thromboxane-A2, as a consequence of cyclooxygenase-1 inhibition. By contrast, ASA significantly increased the plasma and urine 8-iso-PGF2α, a well-known prothrombotic molecule, parallel to an increase of plasma NOX2 levels. The enhancement of this oxidative pathway is associated with a significant impairment of endothelial vasodilation, assessed by reactive hyperemia index (RHI). The pharmacological washout reverted all parameters to basal condition. Our findings suggest that ASA utilization for primary prevention in diabetic patients causes a significant increase of oxidative stress burden impairing the vascular function. Present data, if confirmed on a larger population, could permanently discourage the use of the ASA for the primary prevention in patients with DM