Impruneta, Italy
Impruneta, Italy

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Leishear K.,University of Pittsburgh | Ferrucci L.,U.S. National Institute on Aging | Lauretani F.,University of Parma | Boudreau R.M.,University of Pittsburgh | And 11 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2012

Background: Low vitamin B12 and high homocysteine (Hcy) levels are common in older adults and may be associated with worse neurological function. The aim of this study is to determine whether changes in B12 or Hcy levels are associated with longitudinal changes in peripheral nerve function and clinical neurological signs and symptoms. Methods: Participants aged 60 years and older at baseline (n = 678; 72.2 ± 6.2 years; 43.5% male) were from the InCHIANTI Study. Low B12 (<260 pmol/L) and high Hcy (≥13 μmol/L) were measured at baseline and 3-year follow-up. Neurological function was assessed by peroneal nerve conduction amplitude (compound motor action potential) and velocity, neurological examination, and peripheral neuropathy symptoms at baseline, 3-year, and 6-year follow-up.Results:At baseline, 43.8% had low B12 levels and 58.6% had high Hcy levels. Over 6 years, 12.4% declined to poor compound motor action potential (<1 mV) and 42.1% declined to poor nerve conduction velocity (<40 m/s). In mixed models analyses, sustained high Hcy was associated with worse compound motor action potential compared with sustained normal Hcy (p =. 04), adjusting for demographics, diabetes, and folate level. Participants whose Hcy level became high at follow-up were more likely to become unable to detect monofilament at 6-year follow-up compared with those with sustained normal Hcy (odds ratio: 5.4; 95% CI: 1.5-19.0), adjusting for demographics, diabetes, body mass index, and peripheral arterial disease. There was no association with vitamin B12 level or with symptoms. Conclusions: High Hcy may be associated with worse sensory and motor peripheral nerve function. Because poor nerve function has been associated with lower strength and physical performance, these results have important implications for disability in older adults. © 2011 The Author.

Da Vico L.,Servizio Tecnico Sanitario | Biffi B.,Centro S Maria Agli Ulivi | Agostini S.,Servizio di Dietetica | Brazzo S.,Fondazione Salvatore Maugeri | And 3 more authors.
Monaldi Archives for Chest Disease - Cardiac Series | Year: 2010

Background and aims. A series of validation studies was performed on the Moynihan questionnaire to obtain data on nutrition knowledge, translated and adapted to Italian eating habits. Higher scores mean lower knowledge. Methods. Test-retest reliability was assessed administering the questionnaire at a 15-day interval in 52 inpatients. Factor structure and correlation with demographic and anthropometric characteristics were studied on a larger sample, which included a number of health professionals. Finally, sensitivity to change induced by an educational program was verified in a sample of 11 patients with type 1 diabetes. Results. Test-retest reliability was satisfactory; factor structure suggested one single principal component. Test scores were inversely correlated with age (r=0.24; p=0.02), but not with body mass index or waist circumference. Patients with higher education show a greater degree of nutrition knowledge. Among type 1 diabetic patients, an educational program induces a significant improvement of test scores (from 20.6 [18.6-22.8] to 16.6 [15.5-17.7], p=0.003). Conclusions. The Italian version of the questionnaire appears to be psychometrically adequate for its use in clinical research.

Marcucci R.,University of Florence | Gori A.M.,University of Florence | Gori A.M.,Centro S Maria Agli Ulivi | Paniccia R.,University of Florence | And 8 more authors.
Thrombosis and Haemostasis | Year: 2010

There is some data available on the role of high on-treatment platelet reactivity by ADP whereas, as regards arachidonic acid or other agonists, there is no proof of the best cut-off for identifying populations with a different cardiovascular outcome by the construction of appropriate receiver-operator characteristics (ROC) curves. We enrolled 1,108 acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) with stent implantation and followed them up for 12 months. Platelet reactivity was assessed by light transmission aggregometry (LTA) using 10 μM ADP, 1 mM arachidonic acid (AA) and 2 μg/ml collagen. At a 12-month follow-up, we found 37 cardiovascular deaths (3.3%), 54 non-fatal myocardial infarctions (MI) (4.8%) and 154 target vessel revascularisations (TVR) (13.8%). ROC analysis demonstrated that 10 μM ADP LTA, 1 mM AA and 2 μg/ml collagen LTA were able to distinguish between patients with and without subsequent cardiovascular death and non-fatal MI (area under the curve for 10 μM ADP 0.63 (0.55-0.71), p<0.001; for 1 mM AA 0.68 (0.61-0.76), p<0.0001; for 2 μg/ml collagen 0.62 (0.52-0.73), p<0.0111), whereas no association was demonstrated with the occurrence of TVR. Ten μM ADP LTA ≥55%, 1 mM AA LTA ≥15% and 2 μg/ml collagen LTA ≥31% were identified as the optimal cut-off to predict cardiovascular death and non-fatal MI at 12-month follow-up. The contemporary platelet hyperreactivity to more than one agonist was associated with a higher risk of 12-month cardiovascular death and MI, whereas isolated platelet hyperreactivity to only one agonist had not a predictive value [10 μM ADP LTA ≥55% + 1 mM AA LTA ≥15%: odds ratio [OR]=3.6(2.4-6.1), p<0.0001; ADP LTA ≥55% + 1 mM AA LTA ≥15% + 2 μg/ml collagen LTA ≥31%: OR=4.7(2.9-7.7), p<0.0001]. In this prospective study on a large number of acute coronary syndrome patients undergoing stent implantation, we have found that high on-treatment platelet reactivity measured by LTA induced by more than one agonist - AA, ADP, collagen - is an independent risk factor for 12-month cardiovascular death and non-fatal MI. Isolated platelet hyperreactivity to only one agonist has not a predictive value for clinical recurrences. © Schattauer 2010.

Cesari F.,University of Florence | Marcucci R.,University of Florence | Gori A.M.,University of Florence | Gori A.M.,Centro S Maria Agli Ulivi | And 8 more authors.
International Journal of Cardiology | Year: 2013

Background: Among the benefits of a cardiac rehabilitation (CR) program for patients after an acute coronary syndrome (ACS) is the mobilization of endothelial progenitor cells (EPCs). However not all patients respond to CR with an increase of EPC. We performed this study to identify the characteristics of patients who will not benefit from an increase of EPCs at the end of a CR program. Methods: 112 ACS patients were admitted to a four-week CR program. EPCs, high sensitivity C-reactive protein (hsCRP) and NT-ProBNP levels were determined at the beginning (T1) and at the end (T2) of the CR program. All patients performed a cardiopulmonary exercise test at T1 and at T2. EPCs were defined as CD34+KDR+, CD133+KDR+ and CD34+CD133+KDR+. hsCRP and NT-ProBNP were measured by nephelometric and immunometric method, respectively. Results: At T2, we observed a significant increase of EPCs (p = 0.001), VO2 peak, Watt max HDL-cholesterol (p < 0.0001) and a significant decrease (p < 0.001) of hsCRP and NT-ProBNP, triglycerides, HbA1c, systolic blood pressure and waist circumference. Variations of VO2 peak were significantly correlated with the variations of EPCs. Patients with increased EPCs showed significantly (p = 0.01) lower baseline levels of CRP and higher basal Watt max (p = 0.04). In a multivariate logistic regression analysis, the lowest tertile of baseline hsCRP significantly affected the likelihood of having an increase of EPCs at the end of the CR program. Conclusions: A CR program determines an increase of EPCs with a decrease of CRP and NT-ProBNP. A different trend for EPCs can be detected among patients correlated to CRP levels and exercise tolerance. © 2012 Elsevier Ireland Ltd.

Saracini C.,University of Florence | Bolli P.,University of Florence | Sticchi E.,University of Florence | Sticchi E.,Centro S Maria Agli Ulivi | And 8 more authors.
Journal of Vascular Surgery | Year: 2012

Abdominal aortic aneurysm (AAA) has a multifactorial etiology and the relevance of genetic factors is getting increasing interest, in particular those related to the destructive remodeling of extracellular matrix. We performed a candidate gene association study of polymorphisms in genes coding matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), and elastin (ELN) in AAA. DNA samples from 423 AAA patients and 423 controls were genotyped for 12 polymorphisms in 10 genes: MMP1 (-1607G/GG), MMP2 (-735C/T; -1306C/T; -1575 G/A), MMP3 (5A/6A), MMP9 (-1562C/T), MMP10 (A180G), MMP-12 (-82A/G), MMP-13 (-77A/G), TIMP1 (C434T), TIMP3 (-1296T/C), and ELN (G1355A). Genotype distribution was significantly different between patients and controls for the following polymorphisms: -1306C/T MMP2; 5A/6A MMP3; -77A/G MMP-13; G1355A ELN; and C434T TIMP1. In a multivariable logistic regression analysis adjusted for traditional cardiovascular risk factors and chronic obstructive pulmonary disease, -1306C/T MMP2 (odds ratios [OR] = 0.55 [95% confidence interval, CI.34-.85], P <.007) and G1355A ELN (OR = 0.64 ([95% CI.41-.99], P =.046) polymorphisms resulted in independent protective factors for abdominal aortic aneurysm (AAA), whereas 5A/6A MMP3 (OR = 1.82 [95% CI 1.04-3.12], P =.034) and -77 A/G MMP-13 (OR = 2.14 [95% CI 1.18-3.86], P =.012) polymorphisms resulted in independent risk factors for AAA. In a multivariable logistic regression analysis adjusted for traditional cardiovascular factors and chronic obstructive pulmonary disease, the prevalence of the contemporary presence of three or four genetic risk conditions was a strong and independent determinant of AAA disease (OR = 2.96, 95% CI 1.67-5.24, P <.0001). For those polymorphisms independently associated with AAA in this study (-1306C/T MMP2, 5A/6A MMP3, -77A/G MMP-13, and G1355A ELN polymorphisms), we performed a meta-analysis of the available data (this paper and literature data). We found a significant association with an increased risk of AAA for MMP3 (AAA patients n = 1258, controls n = 1406: OR = 1.48 [95% CI = 1.23-1.78], I 2 = 0%) and MMP-13 (AAA patients n = 800, controls n = 843: OR = 1.37 [95% CI = 1.04-1.82], I 2 = 25%) polymorphisms and a trend that did not reach the statistical significance, toward a decreased risk of AAA for MMP2 (AAA patients n = 1090, controls n = 1077: OR = 0.83 [95% CI =.60-1.15], I 2 =7 1%) and ELN (AAA patients n = 904, controls n = 1069: OR = 0.79 [95% CI =.53-1.18], I 2 = 72%) polymorphisms. These findings suggest that polymorphisms in MMP2, MMP3, MMP-13, and ELN genes may independently contribute to the pathogenesis of AAA. © 2012 Society for Vascular Surgery.

Evangelisti L.,University of Florence | Lucarini L.,University of Florence | Attanasio M.,University of Florence | Lapini I.,University of Florence | And 6 more authors.
European Journal of Medical Genetics | Year: 2010

The Fibrillin-1 gene (FBN1; chromosome 15q21.1) encodes a major glycoprotein component of the extracellular matrix. Mutations in FBN1, TGFBR1, TGFBR2 are known to cause Marfan syndrome (MIM .154700), a pleiotropic disorder. In the present study, we describe five novel missense .FBN1 mutations in five Marfan patients that have the peculiarity to activate two contemporary mutational mechanisms: a missense mutation and exon skipping. © 2010 Elsevier Masson SAS.

Marcucci R.,University of Florence | Giusti B.,University of Florence | Paniccia R.,University of Florence | Gori A.M.,University of Florence | And 8 more authors.
Platelets | Year: 2012

High on-treatment platelet reactivity (HPR) by ADP, which primarily reflects the effect of thienopyridines, has been found to be an independent predictor of ischemic events in patients with acute coronary syndrome (ACS) on dual antiplatelet therapy. CYP2C19*2 is associated with HPR by ADP. The aim of our study was to evaluate if high on-clopidogrel platelet reactivity (HPR) by ADP is associated with an increased risk of major adverse coronary events (MACE) after ACS independent of CYP2C19*2 allele, i.e. whether genotyping patients for CYP2C19*2 polymorphism is sufficient to identify those to be switched to novel antiplatelets. A total of 1187 patients were included (CYP2C19 *1/*1 n892; *1/*2 n264; *2/*2 n31); 76 MACE (CV death and non-fatal MI) were recorded in non-carriers of CYP2C19*2 (8.5) and 39 in carriers of CYP2C19*2 (13.2). At the landmark analysis in the first 6 months, HPR by ADP and CYP2C19*2 allele were both significantly and independently associated with MACE [HPR by ADP: HR2.0 (95 CI 1.23.4), p0.01; CYP2C19*2 allele: HR2.3 (95 CI 1.33.9), p0.003]. At the land mark analysis from 7 to 12 months, only HPR by ADP remained significantly associated with the risk of MACE [HPR by ADP: HR2.7 (95 CI 1.45.3), p0.003; CYP2C19*2: HR0.8 (95 CI 0.21.1), pns]. CYP2C19*2 allele and HPR by ADP are both independently associated with an increased risk of MACE in the first 6 months after ACS. HPR by ADP is associated with an increased risk until 12 months of follow-up. Therefore, both phenotype and genotype are clinically relevant for the evaluation of the antiplatelet effect of clopidogrel and for the prognostic stratification of ACS patients. Copyright © 2012 Informa UK Ltd.

Cesari F.,University of Florence | Marcucci R.,University of Florence | Gori A.M.,Centro S Maria Agli Ulivi | Caporale R.,Central Laboratory | And 8 more authors.
Thrombosis and Haemostasis | Year: 2010

Renal transplant recipients (RTRs) patients are at increased risk of cardiovascular morbidity and mortality. We aimed this study to assess reticulated platelets (RP), platelet reactivity and von Willebrand factor (vWF) levels in RTRs patients. In 150 RTRs patients [84 (56%) not on acetylsalicylic acid (ASA) treatment, group A; 66 (44%) on ASA 100 mg treatment, group B] and in 60 healthy control subjects, RP were measured by a Sysmex XE-2100 and were expressed as the percentage of RP of the total optical platelet count (immature platelet fraction; IPF), as the percentage of RP highly fluorescent (H-IPF) and as the absolute number of RP (IPF#). Platelet function was assessed by optical aggregometry (PA) induced by 1 mmol arachidonic acid (AA-PA), 2 and 10 μM ADP (ADP2-PA and ADP10-PA) and 2 μg/ml collagen (Coll-PA). vWF levels were measured by using a miniVidas analyser. Group A and group B showed significant higher values of RP than controls. At a multiple linear regression analysis IPF and IPF# were significantly and positively related to collagen-PA. By analysing group B according to residual platelet reactivity (RPR), we observed a significant higher number of RP among patients with RPR by collagen. Moreover at a multiple logistic regression analysis, IPF# significantly affected the risk of having a RPR by collagen. With regard to vWF, RTRs patients showed higher levels than control subjects. We documented a higher platelet turn-over in both groups of RTRs patients and increased platelet reactivity in RTRs patients not on ASA therapy than controls. © Schattauer 2010.

Zanazzi M.,The Surgical Center | Cesari F.,The Surgical Center | Rosso G.,The Surgical Center | Farsetti S.,The Surgical Center | And 7 more authors.
Transplantation Proceedings | Year: 2010

Introduction: Renal transplant recipients are at increased risk of cardiovascular morbidity and mortality. We assessed platelet reactivity and reticulated platelets (RPs) in 90 recipients, 51 (56.6%) of whom were not receiving acetylsalicylic acid (ASA) therapy (group A) and 39 (43.3%) who were receiving ASA therapy, 100 mg (group B), and in 60 healthy controls (group C). Methods: Reticulated platelets were measured using a hematology automated analyzer (XE-2100; Sysmex Corp, Kobe, Japan) and were expressed as the percentage of RPs in the total optical platelet count (immature platelet fraction [IPF]), as the percentage of highly fluorescent RPs, and as the absolute number of RPs (IPF#). Platelet function was assessed using optical aggregometry (platelet aggregation) induced using 1 mmol/L of arachidonic acid, 2 or 10 μmol/L of adenosine diphosphate, or 2 μg/mL of collagen. Results: Group A demonstrated significantly higher values of RP compared with group B or group C. Group B demonstrated a substantially higher percentage of RPs compared with group C, which was significant only for the IPF parameter. Multiple regression analysis demonstrated that IPF and IPF# were significantly and positively related to collagen-induced platelet aggregation. Conclusion: We documented the presence of higher concentrations of RPs in transplant recipients compared with a control population, and a significant association between RPs and platelet function. © 2010 Elsevier Inc. All rights reserved.

Grippo A.,SOD Neurofisiopatologia DAI Science Neurologiche AOU Careggi | Grippo A.,NeuroLogica | Carrai R.,SOD Neurofisiopatologia DAI Science Neurologiche AOU Careggi | Carrai R.,Centro S Maria Agli Ulivi | And 4 more authors.
Clinical Neurophysiology | Year: 2011

Objective: Respiratory-related evoked potentials (RREP) elicited by transmural pressure in obstructive sleep apnoea (OSA) subjects have reported conflicting data. Different features of pressure stimuli and/or in the timing of stimuli application seem to account for these contradictory results. The negative expiratory pressure (NEP) technique, highly reproducible in terms of rise time and pressure values, allows to minimize the methodological confounding factors. We determined whether the afferent activity from the upper airway (UA) is altered in OSA subjects. Methods: RREP potentials were examined in 10 OSA and in 12 non-apnoeic awake subjects by means of the NEP technique. Results: All controls showed a cortical response to all pressure stimuli. All OSA subjects showed responses to -5 and -10cmH2O whereas six of them showed no responses to -1cmH2O. The amplitude of the P22, N45 and P85 components of the RREP was significantly reduced in OSA with respect to the controls in response to both the -5 and -10cmH2O stimuli. We found no significant differences in latencies. Conclusions: Awake OSA subjects had a raised threshold to pressure stimuli and blunted respiratory-related evoked potentials. Significance: These data indicate a deficit in afferent activity in the UA. © 2011 International Federation of Clinical Neurophysiology.

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