Publications by authors named "Silvia Maffei"

51 Publications

The Gynogram: A Multicentric Validation of a New Psychometric Tool to Assess Coital Pain Associated With VVA and Its Impact on Sexual Quality of Life in Menopausal Women.

J Sex Med 2021 Apr 23. Epub 2021 Apr 23.

Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, Tor Vergata University of Rome, Rome, Italy. Electronic address:

Background: Vulvo-Vaginal Atrophy (VVA) affects about fifty percent of postmenopausal women, contributing more vulnerable sexual and psycho-relational equilibrium. To date, no psychometric instruments have been designed to assess the impact of coital pain associated with VVA on sexual quality of life.

Aim: To validate a new psychometric tool, the Gynogram, able to investigate coital pain and to quantify its impact on sexual well-being in menopause.

Methods: 214 sexually active postmenopausal women were enrolled in the study during clinical consultations in gynecological outpatient clinics in Italy. After gynecological examination and evaluation of the presence of VVA, the study sample was divided in a clinical group (103 women with certified diagnosis of VVA) and in a control group (111 women without certified diagnosis of VVA) according to the Vaginal Health Index (VHI) cut-off. Factor, Reliability and Receiving Operating Characteristics (ROC) analysis were performed in order to validate our newly created Gynogram.

Outcomes: A structured questionnaire, named Gynogram, to assess coital pain and its impact, and the Female Sexual Function Index (FSFI).

Results: The factor analysis performed on the original form (80 items) reduced the Gynogram to 24 items. Reliability analysis conducted with Cronbach's Alpha coefficients showed high values in all the components (ranging from .813 to .972), both in the long and in the short form. The sensitivity analysis demonstrated that the Gynogram, with a cut-off ≤93, is able to recognize a clinically significant coital pain. With respect to the FSFI, statistically significant differences were found for all the domains. In addition, statistically significant differences were found for all the twelve factors of the Gynogram, showing that VVA profoundly affects the sexual quality of life of women in post-menopause.

Clinical Translation: The utility of this tool consists in the possibility to improve prognosis, compliance/adherence and treatment outcomes.

Strengths And Limitations: The Gynogram is able to evaluate and to quantify the impact of coital pain associated with VVA. Moreover, it can also recognize the areas of biopsychosocial functioning being more affected by this clinical condition. The main limit of the study is the impossibility to evaluate both mental health and partner's general and sexual health.

Conclusions: The Gynogram is a new and validated psychometric tool able to detect the impact of symptomatic VVA on sexual quality of life among post-menopausal women, with a specific focus on the different areas of sexual functioning. Nappi RE, Graziottin A, Mollaioli A, et al. The Gynogram: A Multicentric Validation of a New Psychometric Tool to Assess Coital Pain Associated With VVA and Its Impact on Sexual Quality of Life in Menopausal Women. J Sex Med 2021;xxx:xxx-xxx.
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http://dx.doi.org/10.1016/j.jsxm.2021.02.011DOI Listing
April 2021

What women think about menopause: An Italian survey.

Maturitas 2021 May 15;147:47-52. Epub 2021 Mar 15.

Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Introduction: Menopause is a critical period for most women who experience associated symptoms while they are still socially and individually active.

Objectives: The objective of this study is to report how Italian women perceive and approach menopause.

Materials And Methods: A survey of 1028 Italian women aged 45-65 years was conducted by the Italian Center for Studies of Social Investments (CENSIS) through anonymous interviews using two methods: CATI (Computer Assisted Telephone Interviewing) and CAWI (Computer Assisted Web Interviewing).

Principal Outcome Measures: Principal outcome measures were women's perceptions and experiences of menopause and its treatments.

Results: The global consciousness and understanding of menopause was common (82.8 %) among Italian women and it was usually considered a physiological condition (77 %). Overall, 74.6 % of the sample were postmenopausal. Hot flushes were reported to be the most frequent (37.9 %) and bothersome symptoms (43.1 %) while 12.9 % of the women were asymptomatic. As for menopausal therapies, 24.5 % were on treatment; herbal medications were the most common remedy (63.3 %) whereas 7.6 % of the women took hormone replacement therapy (HRT). About half of the sample (50.4 %) had not sought help from the Italian National Health System (INHS). Medical expertise in the field of menopause was thought to be moderately satisfactory by 54.5 % of the sample.

Conclusions: Italian women consider menopause a physiological condition. Most postmenopausal women had experienced symptoms but relied on non-hormonal treatments. The median women's satisfaction with the role of the INHS and medical competence suggests the need to improve current knowledge and awareness concerning menopause.
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http://dx.doi.org/10.1016/j.maturitas.2021.03.007DOI Listing
May 2021

Progestogens as a component of menopausal hormone therapy: the right molecule makes the difference.

Drugs Context 2020 2;9. Epub 2020 Dec 2.

Department of Obstetrics and Gynecology, Evangelisches Klinikum Weyertal gGmbH, Academic Hospital, University of Cologne, Germany.

Optimizing menopausal hormone therapy (MHT) requires an awareness of the benefits and risks associated with the available treatments. This narrative review, which is based on the proceedings of an Advisory Board meeting and supplemented by relevant articles identified in literature searches, examines the role of progestogens in MHT, with the aim of providing practical recommendations for prescribing physicians. Progestogens are an essential component of MHT in menopausal women with a uterus to prevent endometrial hyperplasia and reduce the risk of cancer associated with using unopposed estrogen. Progestogens include natural progesterone, dydrogesterone (a stereoisomer of progesterone), and a range of synthetic compounds. Structural differences and varying affinities for other steroid receptors (androgen, glucocorticoid, and mineralocorticoid) confer a unique biological and clinical profile to each progestogen that must be considered during treatment selection. MHT, including the progestogen component, should be tailored to each woman, starting with an estrogen and a progestogen that has the safest profile with respect to breast cancer and cardiovascular effects, while addressing patient-specific needs, risk factors, and treatment goals. Micronized progesterone and dydrogesterone appear to be the safest options, with lower associated cardiovascular, thromboembolic, and breast cancer risks compared with other progestogens, and are the first-choice options for use in 'special situations,' such as in women with high-density breast tissue, diabetes, obesity, smoking, and risk factors for venous thromboembolism, among others.
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http://dx.doi.org/10.7573/dic.2020-10-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716720PMC
December 2020

Quarantine during COVID-19 outbreak: Changes in diet and physical activity increase the risk of cardiovascular disease.

Nutr Metab Cardiovasc Dis 2020 08 30;30(9):1409-1417. Epub 2020 May 30.

Department of Neuroscience, Imaging and Clinical Sciences, University of Chieti-Pescara, Chieti, Italy.

Aims: CoV-19/SARS-CoV-2 is a highly pathogenic virus that is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of infection, several governments have enforced restrictions on outdoor activities or even collective quarantine on the population. The present commentary briefly analyzes the effects of quarantine on lifestyle, including nutrition and physical activity and the impact of new technologies in dealing with this situation.

Data Synthesis: Quarantine is associated with stress and depression leading to unhealthy diet and reduced physical activity. A diet poor in fruit and vegetables is frequent during isolation, with a consequent low intake of antioxidants and vitamins. However, vitamins have recently been identified as a principal weapon in the fight against the Cov-19 virus. Some reports suggest that Vitamin D could exert a protective effect on such infection. During quarantine, strategies to further increase home-based physical activity and to encourage adherence to a healthy diet should be implemented. The WHO has just released guidance for people in self-quarantine, those without any symptoms or diagnosis of acute respiratory illness, which provides practical advice on how to stay active and reduce sedentary behavior while at home.

Conclusion: Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety. Following quarantine, a global action supporting healthy diet and physical activity is mandatory to encourage people to return to a good lifestyle routine.
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http://dx.doi.org/10.1016/j.numecd.2020.05.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260516PMC
August 2020

Cardiovascular prevention in women: a narrative review from the Italian Society of Cardiology working groups on 'Cardiovascular Prevention, Hypertension and peripheral circulation' and on 'Women Disease'.

J Cardiovasc Med (Hagerstown) 2019 Sep;20(9):575-583

Cardiovascular and Gynaecological Endocrinology Unit, Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy.

: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in women.Some authors highlighted that the female risk profile consists of traditional and emerging risk factors. Despite the lower prevalence of type 2 diabetes, years of life lost owing to the disease for women are substantially higher compared with men. In addition, pregnancy complicated by gestational diabetes represents a risk factor for CVD. Women with gestational diabetes have a higher prevalence of coronary artery disease that occur at a younger age and are independent of T2DM.Hypertension is an important cardiovascular risk factor in women. Estrogens and progesterone, known to have an impact on blood pressure levels, have also been proposed to be protective against sleep-disordered breathing. It is very difficult to understand whereas obstructive sleep apnea in women is independently associated with hypertension or if many confounders acting at different stages of the woman lifespan mediate this relation.The cardioprotective effect of physical activity in women of all ages is well known. Women are generally more physically inactive than men. During and after menopause, most women tend to reduce their physical activity levels and together with the reduction in basal metabolic rate, women experience loss of skeletal muscle mass with a negative change in the ratio of fat-to-lean mass.In conclusion, sex differences in the cardiovascular system are because of dissimilarities in gene expression and sex hormones; these result in variations in prevalence and presentation of CVD and associated conditions, such as diabetes, hypertension and vascular and cardiac remodeling.Changes in lifestyle and increase in physical activity could help in prevention of cardiovascular disease in women.
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http://dx.doi.org/10.2459/JCM.0000000000000831DOI Listing
September 2019

Depression and cardiovascular disease: The deep blue sea of women's heart.

Trends Cardiovasc Med 2020 04 11;30(3):170-176. Epub 2019 May 11.

Department of Neuroscience, Imaging and Clinical Sciences, ``G. d'Annunzio'', University of Chieti, Italy.

Cardiovascular disease (CVD) constitutes a leading worldwide health problem, with increasing evidence of differences between women and men both in epidemiology, pathophysiology, clinical management, and outcomes. Data from the literature suggest that women experience a doubled incidence of CVD related deaths, while angina, heart failure and stroke are increasingly prevalent in females. About 20-25% of women go through depression during their life, and depressive symptoms have been considered a relevant emergent, non-traditional risk factor for CVD in this part of the general population. Underlying mechanisms explaining the link between depression and CVD may range from behavioral to biological risk factors, including sympathetic nervous system hyperactivity and impairment in hypothalamic-pituitary-adrenal function. However, the neuroendocrine-driven background could only partially explain the differences mentioned above for chronic systemic inflammation, altered hemostasis and modulation of cardiac autonomic control. In addition, some evidence also suggests the existence of gender-specific differences in biological responses to mental stress. Given these premises, we here summarize the current knowledge about depression and CVD relationship in women, highlighting the sex differences in physiopathology, clinical presentation and treatments.
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http://dx.doi.org/10.1016/j.tcm.2019.05.001DOI Listing
April 2020

Women-specific predictors of cardiovascular disease risk - new paradigms.

Int J Cardiol 2019 07 15;286:190-197. Epub 2019 Feb 15.

Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, United Kingdom.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality in women in spite of the overall reduction in age-adjusted CVD mortality in the past few years. Although traditional risk factors for CVD are predictors of increased risk in both men and women, risk factors that are unique to women and related to their reproductive history have recently been considered to be important. The development of CVD in women may correlate with specific events taking place throughout a woman's obstetric and gynaecological history. Gynaecological conditions such as polycystic ovary syndrome, premature ovarian failure, surgical and spontaneous menopause, and conditions related to pregnancy, i.e. gestational diabetes, preeclampsia, intrauterine growth restriction, miscarriages, and preterm birth, may affect the onset, clinical features, and prognosis of CVD later in women's lives. These pathological conditions that develop during the fertile period of life or peri-menopause have been suggested to be early markers of future CVD; their presence presents a unique opportunity for the early identification of women who may be at an increased risk of CVD. The assessment of CV risk in women should not just focus on conventional risk factors but also on different aspects of the gynaecological history to allow specific preventive and therapeutic strategies to be established. This paper reviews the various pathological conditions occurring in women during their fertile period of life and peri-menopause, which have been identified to potentially increase CVD risk.
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http://dx.doi.org/10.1016/j.ijcard.2019.02.005DOI Listing
July 2019

IGENDA protocol: gender differences in awareness, knowledge and perception of cardiovascular risk: an Italian multicenter study.

J Cardiovasc Med (Hagerstown) 2019 May;20(5):278-283

Department of Medical Sciences and Public Health, University of Cagliari, Cagliari.

Aims: Recent reports evidenced gender differences in the knowledge, perception and awareness of cardiovascular risk factors (CVRFs) and cardiovascular diseases (CVDs). Despite the number of high-quality trials that attempted to establish the efficacy of different preventive interventions on CVDs, in the Italian scenario the differences by gender in awareness, knowledge and perception of CVD have not been addressed yet. So, the aims of this cross-sectional, observational and multicenter study will be to evaluate the gender differences in the awareness and perception of CVD risk, to assess the knowledge of CVD symptoms and preventive behaviors/barriers in men and women participating in this study, and to provide a national primary care approach for gender-oriented cardiovascular prevention strategies and therapy.

Methods: A self-administered questionnaire will be completed by 5000 consecutive Italian women and men aged 18-70 years. Moreover, a health questionnaire will be completed by the physicians.

Results: The present study will be the largest to be conducted in Italy, and probably in the European countries, to comprehensively demonstrate the current level of the knowledge, awareness and perception of CVRFs and CVD in both men and women.

Conclusion: The present project could shed new light on the knowledge, awareness and perception of CVRFs and CVDs. If substantial differences will be detected by gender, the findings of this study may contribute to ultimately provide a new gender-oriented primary care approach inside the Italian healthcare system related to cardiovascular prevention and therapy strategies.
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http://dx.doi.org/10.2459/JCM.0000000000000761DOI Listing
May 2019

Sex-specific echocardiographic reference values: the women's point of view.

J Cardiovasc Med (Hagerstown) 2018 Oct;19(10):527-535

Department of Cardiology and Cardiovascular Surgery, Heart Valve Clinic, GIGA Cardiovascular Sciences, University of Liège Hospital, CHU Sart Tilman, Liège, Belgium.

: Clinical presentation, diagnosis and outcomes of cardiac diseases are influenced by the activity of sex steroid hormones. These hormonal differences explain the later development of heart diseases in women in comparison with men and the different clinical picture, management and prognosis. Echocardiography is a noninvasive and easily available technique for the analysis of cardiac structure and function. The aim of the present review is to underline the most important echocardiographic differences between sexes. Several echocardiographic studies have found differences in healthy populations between women and men. Sex-specific difference of some of these parameters, such as left ventricular (LV) linear dimensions and left atrial volume, can be explained on the grounds of smaller body size of women, but other parameters (LV volumes, stroke volume and ejection fraction, right ventricular size and systolic function) are specifically lower in women, even after adjusting for body size and age. Sex-specific differences of standard Doppler and Tissue Doppler diastolic indices remain controversial, but it is likely for aging to affect LV diastolic function more in women than in men. Global longitudinal strain appears to be higher in women during the childbearing age - a finding that also highlights a possible hormonal influence in women. All these findings have practical implications, and sex-specific reference values are necessary for the majority of echocardiographic parameters in order to distinguish normalcy from disease. Careful attention on specific cut-off points in women could avoid misinterpretation, inappropriate management and delayed treatment of cardiac diseases such as valvular disease and heart failure.
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http://dx.doi.org/10.2459/JCM.0000000000000696DOI Listing
October 2018

Gender differences in the development of cardiac complications: a multicentre study in a large cohort of thalassaemia major patients to optimize the timing of cardiac follow-up.

Br J Haematol 2018 03 7;180(6):879-888. Epub 2018 Feb 7.

Magnetic Resonance Imaging Unit, Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy.

We assessed whether male gender was associated with a higher risk of cardiac iron accumulation and fibrosis, heart dysfunction and complications in a large, multicentre cohort of thalassaemia major (TM) patients, in order to optimize the timing in cardiac follow-up. We considered 1711 TM patients (899 females, 31·09 ± 9·08 years), enrolled in the Myocardial Iron Overload in Thalassaemia Network. Clinical/instrumental data are recorded from birth to the first Cardiovascular Magnetic Resonance Imaging scan. Although having a similar risk of accumulating iron, males showed a significantly higher risk of developing cardiac dysfunction, heart failure, arrhythmias and cardiac complications overall, when compared to females (P < 0·0001). Up to 20-30 years of follow-up, the Kaplan-Meier curves for the outcomes for which the male sex was a significant prognosticator almost overlapped, whereas they clearly diverged after this period. In patients with follow-up longer than 20 years, males exhibited a significantly higher risk of ventricular dysfunction, heart failure, arrhythmias, and cardiac complications. Female patients may have an intrinsically better tolerance for iron toxicity. International guidelines suggest annual cardiac evaluation for thalassaemia patients. It is possible that female patients can be evaluated at longer intervals, thus reducing health costs.
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http://dx.doi.org/10.1111/bjh.15125DOI Listing
March 2018

Sex-related differences in chronic heart failure.

Int J Cardiol 2018 Mar;255:145-151

Scuola Superiore Sant'Anna, Pisa, Italy; Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

The prevalence of chronic heart failure (CHF) is steadily increasing. Both sexes are affected, with significant differences in etiology, epidemiology and clinical presentation, prognosis, comorbidities, and response to treatment. Women tend to develop CHF at a more advanced age, present more often with HF with preserved ejection fraction, are more symptomatic, and have a worse quality of life than men, but also a better prognosis. In women, CHF has more frequently a non-ischemic etiology, and arterial hypertension and diabetes mellitus are leading comorbidities. Furthermore, many sex-related differences have been detected in the response to treatment, for example a greater prognostic benefit from angiotensin-receptor blockers in women, a higher incidence of complications after defibrillator implantation, and a greater response to cardiac resynchronization therapy. Furthermore, women are less likely to receive defibrillator therapy or heart transplantation. The significant underrepresentation of women in clinical trials limits our capacity to evaluate the extent of sex-related differences in CHF, although their characterization seems crucial in order to achieve the ultimate goal of a tailored therapy for this condition.
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http://dx.doi.org/10.1016/j.ijcard.2017.10.068DOI Listing
March 2018

Relationship between Bone Health Biomarkers and Cardiovascular Risk in a General Adult Population.

Diseases 2017 Oct 24;5(4). Epub 2017 Oct 24.

Fondazione CNR-Regione Toscana G Monasterio and Istituto di Fisiologia Clinica, CNR via Moruzzi 1, I-56124 Pisa, Italy.

Purpose/Introduction: Osteoporosis (OP) and cardiovascular (CV) disease emerge as closely related conditions, showing common risk factors and/or pathophysiological mechanisms. The aim of this study was to evaluate the association between bone health markers (BHM) and individual CV risk factors and overall CV risk (FRAMINGHAM-FRS, and PROCAM scores) in a general adult population.

Methods: In 103 subjects (21 males; age: 56 ± 12 years), vitamin D (25(OH)D), osteocalcin (OC), bone alkaline phospatase (BALP), procollagen I aminoterminal propeptide (P1NP), CTx-telopeptide, as well clinical history and life style were evaluated.

Results: Aging ( < 0.001) and glycemia ( < 0.05) emerged as independent 25(OH)D predictors. Aging ( < 0.001), male sex ( < 0.05), and obesity ( < 0.05) represented independent OC determinants. Aging ( < 0.05) was the only independent BALP determinant. After multivariate adjustment, low 25(OH)D (<20 ng/mL) (Odds ratio OR (95% confidence intervals CI)) (5 (1.4-18) < 0.05) and elevated OC (>75th percentile-16.6 ng/mL) (6.7 (1.9-23.8) < 0.01) were found to be significant FRS predictors, while subjects with elevated OC and/or BALP (>75th percentile-9.8 μg/L) showed a higher CV risk as estimated by PROCAM (3.6 (1.2-10.7) < 0.05). CTx and P1NP did not significantly correlate with CV risk factors or scores.

Conclusion: As we go further into bone and CV physiology, it is evident that a close relationship exists between these diseases. Further studies are needed to investigate mechanisms by which bone turnover markers are related to metabolic risk and could modulate CV risk. This knowledge may help to develop possible multiple-purpose strategies for both CV disease and OP prevention and treatment.
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http://dx.doi.org/10.3390/diseases5040024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750535PMC
October 2017

Effect of Sex on Reverse Remodeling in Chronic Systolic Heart Failure.

JACC Heart Fail 2017 10;5(10):735-742

Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy; Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy. Electronic address:

Objectives: This study sought to investigate sex-related differences in reverse remodeling (RR).

Background: RR, that is, the recovery from left ventricular (LV) dilation and dysfunction in response to treatment for heart failure (HF), is associated with improved prognosis.

Methods: Data from patients with stable systolic HF (LV ejection fraction [LVEF] of <50%) undergoing 2 transthoracic echocardiograms within 12 ± 2 months were analyzed. Reverse remodeling was defined as a ≥15% reduction in LV end-systolic volume index.

Results: A total of 927 patients were evaluated (68 ± 12 years; median LVEF = 35% [interquartile range: 30% to 43%]; 27% women). Ischemic HF was less often encountered in women (33% vs. 60%, respectively; p < 0.001), whereas most characteristics did not differ with regard to sex. Women showed a higher incidence of RR (41% vs. 27%, respectively; p < 0.001), despite similar baseline LV volume and function. RR was more frequent among women in the subgroups with either ischemic or nonischemic HF, as well as in all categories of systolic dysfunction (LVEF ≤35% or >35%, according to current indication for device implantation, and LVEF <40% or 40% to 50% according to the definition of HF with reduced or mid-range EF). In the whole population, female sex was an independent predictor of RR (hazard ratio: 1.54; 95% confidence interval: 1.11 to 2.14; p = 0.011), together with cause of HF, disease duration, and left bundle branch block. Female sex was again an independent predictor of RR in all LVEF categories.

Conclusions: Reverse remodeling is more frequent among women, regardless of cause and severity of LV dysfunction. Female sex is an independent predictor of RR in all categories of LV systolic dysfunction.
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http://dx.doi.org/10.1016/j.jchf.2017.07.011DOI Listing
October 2017

Evaluation of the Effects of the Metha® Short Stem on Periprosthetic Bone Remodelling in Total Hip Arthroplasties: Results at 48 Months.

Surg Technol Int 2017 Jul;30:346-351

1st Orthopedic Division, Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.

Introduction: Total hip arthroplasty is one of the most performed procedures in orthopaedic surgery. Implantation of a prosthesis determines changes in the distribution of loads on the host bone, and this phenomenon, known as stress shielding, is related to the biomechanical characteristics of the implant. Usually stress shielding involves the proximal portion of the femur by reducing the mechanical strength and ability to withstand the transmitted loads. The aim of our study is to demonstrate how the use of a short hip stem reduces the stress shielding phenomenon to the proximal femur.

Materials And Methods: The study analyzed 20 patients undergoing hip prosthesis surgery with a short stem (Metha<, B. Braun Medical, Inc., Bethlehem, Pennsylvania) at the Ist Orthopaedic Division of Pisa University (between December 2008 and January 2010). Each patient was subjected to analysis of periprosthetic bone mineral density by a bone densitometry (dual emission X-ray absorptiometry [DEXA] with the metal removal software) at 0, 6, 12, 18, 24, and 36 months, following a protocol based on the evaluation of the changes of bone density in the seven Gruen zones.

Results: We recorded minimal changes in bone mineral density (BMD) at the level of the greater trochanter (-1.44%) and at the level of the calcar (-3.7%). BMD increased significantly after four years at the level of the lateral distal regions (R2 +9.6% - R3 + 12.4%) and at the level of the distal medial regions (R5 + 8.2% - R6 + 13.1%). We compared the results obtained with the literature data at 12 and 24 months with the same stem (Metha<). At 12 months follow up, we did not see a significant difference between our data and the data published in the literature. However, after 48 months of follow-up, we recorded significant differences in the curves of periprosthetic bone reabsorption at the level of the greater trochanter (Zone 1) and at the level of the calcar (Zone 7).

Discussion: The data obtained from our study are in agreement with other studies in the literature, which demonstrates how the use of short stems preserves the metaphyseal bone stock at the level of the proximal femur, reducing the stress shielding phenomenon. From our data, obtained at 24 months and confirmed at 36, stress shielding seems to minimally occur at the level of the calcar. At the level of the great trochanter, we saw a good load distribution that maintained the baseline BMD; these data are in opposition to the literature data that showed a high increase of BMD at the level of the calcar (+12.9%) and a decrease at the level of the great trochanter. From the analysis of the radiographic images of our cases, and of the cases published with the same stem, these differences in load transfer encountered between the great trochanter and the calcar seems to be related to the level of the femoral neck osteotomy and the consequent stem position (varus/valgus).

Conclusion: We conclude that the amount of periprostetic bone reabsorption around the Metha< stem seems to be strictly related to the surgical technique and the final implant position.
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July 2017

Significance of the ionized calcium measurement to assess calcium status in osteopenic/osteoporosis postmenopausal outpatients.

Gynecol Endocrinol 2017 May 19;33(5):383-388. Epub 2017 Jan 19.

b Fondazione CNR-Regione Toscana G Monasterio , Pisa , Italy.

Introduction: Evaluation of calcium status is important in the osteoporotic risk assessment. Although guidelines indicate total calcium (tCa) as first-line measurement, directly measured ionized calcium (m-iCa), considered as the gold standard, is more and more often required. Aim of this study is to evaluate the agreement between m-iCa, tCa and iCa calculated from a formula based on total calcium and albumin (c-iCa) in osteopenic/osteoporotic postmenopausal outpatients.

Methods: A total of 140 postmenopausal outpatients, 41 osteopenic (OPN) and 99 osteoporotic (OP) were enrolled. Levels of tCa, m-iCa, c-iCa, total protein and albumin, vitamin D (25-OHD), parathyroid hormone 1-84 (PTH), bone alkaline phosphatase, osteocalcin and serum collagen type 1 cross-linked C-telopeptide (CTX) were also measured.

Results: There were no statistically significant differences between OPN and OP groups regarding values of tCa, m-iCa, and c-iCa, 25-OHD and PTH. However, OP women had lower levels of CTX (p < 0.05). A significant direct correlation between m-iCa and tCa (r = 0.60, p < 0.001) and c-iCa (r = 0.61, p < 0.001) was found. Women with isolated hyper-m-iCa had similar DEXA parameter levels respect to the other patients. However, one patient with confirmed primary hyperparathyroidism presented hyper-m-iCa versus normal tCa and c-iCa values.

Conclusions: The use of tCa could be sufficient to characterize the calcium status in postmenopausal outpatients, but reflexive calcium testing strategy for m-iCa test is necessary to women presenting the low or high extremes of tCa levels, or in women with suspected PHPT.
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http://dx.doi.org/10.1080/09513590.2016.1270932DOI Listing
May 2017

Atrial chamber remodelling in healthy pre-adolescent athletes engaged in endurance sports: A study with a longitudinal design. The CHILD study.

Int J Cardiol 2016 Nov 14;223:325-330. Epub 2016 Aug 14.

Department of Public Health and Clinical Medicine, Umeå University, and Heart Centre, Umeå, Sweden.

Aims: Previous studies investigated the exercise-induced adaptation of left (LA) and right atrium (RA) in adults, but little is known about respective changes in the growing heart of children. We aimed to longitudinally investigate the effects of endurance training on biatrial remodelling in preadolescent athletes.

Methods And Results: Ninety-four children (57 endurance athletes, 37 sedentary controls; mean age 10.8±0.2 and 10.2±0.2years, respectively) were evaluated at baseline and after 5months by ECG and by two-dimensional, three-dimensional (3D) and speckle-tracking echocardiography. Athletes were trained at least 10h/week. The resting heart rate was lower in athletes (p=0.046) and decreased further after training (p<0.0001). Neither athletes nor controls had ECG evidence for LA or RA enlargement. At baseline, indexed LA volumes did not differ between groups (p=0.14) but indexed RA dimensions were larger in athletes (p=0.007). After 5months, indexed LA volumes increased in athletes but not in controls (p<0.0001, p=0.29; respectively) while indexed RA volumes increased in both groups (p<0.0001, p=0.018; respectively). At the same time, slight differences in biatrial reservoir and contractile function were found either in athletes, as demonstrated by speckle-tracking echocardiography, but 3D-derived LA and RA ejection fraction remained stable in both groups.

Conclusion: Endurance training influences the growing heart of preadolescent athletes with an additive increase in biatrial size, suggesting that morphological adaptations can occur also in the early phases of the sports career. Training-induced remodelling was associated with a preserved biatrial function, supporting the hypothesis of a physiological remodelling.
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http://dx.doi.org/10.1016/j.ijcard.2016.08.231DOI Listing
November 2016

Age at menopause: A fundamental data of interest to acquire in female patients' anamnesis.

Int J Cardiol 2016 Jul 26;215:358-9. Epub 2016 Apr 26.

Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy; Institute of Clinical Physiology, CNR, Pisa, Italy.

Although menopause is a universal phenomenon among women, the timing of the onset and the duration of the menopausal transition and the timing of the final menstrual period are not so codified. Compelling evidence supports the idea that the different impact of cardiovascular disease and the differences in vascular biology in men and women may be, at least in part, related to the cardiovascular and metabolic effects of sex steroid hormones. Indeed, androgens and estrogens influence a multitude of vascular biological processes and their cardiovascular effects are multifaceted. Gender pharmacology has proven that men and women have tiny but not paltry different effects to the same drug. Estrogens exert potential beneficial effects on the cardiovascular system in both sexes. It is evident that there is a need for the physician who approaches the female patient, to stress the main anamnestic data concerning her hormonal life starting from menarche, through pregnancy, until menopause. Thus it will be not only a formality becoming a cornerstone of the first doctor-patient relationship, both for in- and outpatient, we will have a clear and complete representation of the etiology and evolution of cardiovascular diseases that increasingly afflict the female gender.
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http://dx.doi.org/10.1016/j.ijcard.2016.04.107DOI Listing
July 2016

Gender differences for uric acid as predictor of hard events in patients referred for coronary angiography.

Biomark Med 2016 14;10(4):349-55. Epub 2016 Mar 14.

Fondazione G Monasterio CNR-Regione Toscana & Istituto di Fisiologia Clinica-CNR Via Moruzzi 1, I-56124 Pisa, Italy.

Aim: To assess gender differences in uric acid (UA) as predictor for hard events (HE, mortality and nonfatal myocardial infarction) in a large cohort of patients referred for coronary angiography. Design & patients: 3020 inpatients (2177 males, age: 68 ± 9 years, mean ± SD) were retrospectively studied, collecting data from the Institute electronic databank which included demographic, clinical, instrumental and follow-up data.

Results: Although the Kaplan-Meier survival estimates showed a significantly worst outcome in female patients, high UA did not remained a significant predictor for HE after adjustment. Moreover, UA correlated with antioxidant capacity in both sexes.

Conclusion: Hyperuricemia was not an independent risk for HE, and being correlated with antioxidant capacity, its elevation appears more likely compensatory than causative for HE.
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http://dx.doi.org/10.2217/bmm.16.5DOI Listing
December 2016

Arterial hypertension in the female world: pathophysiology and therapy.

J Cardiovasc Med (Hagerstown) 2016 Apr;17(4):229-36

aDepartment of Medical Sciences 'M. Aresu', University of Cagliari bDepartment of Biomedical Sciences, University of Sassari cCardiology Complex Unit, Marino Hospital - ASL Cagliari Marino - ASL Cagliari dDepartment of Biomedical Sciences, University of Sassari; National Laboratory of Gender Medicine of the National Institute of Biostructures and Biosystems, Osilo, Sassari eCMR Unit, Fondazione G. Monasterio CNR-Regione Toscana fFondazione G. Monasterio CNR-Regione Toscana and Institute of Clinical Physiology-CNR, Pisa gDepartment of Neuroscience, Imaging and Clinical Sciences, University of Chieti, Pescara hDepartment of Cardiovascular and Respiratory Sciences, University of Rome 'La Sapienza', Italy.

Hypertension is a major risk factor for cardiovascular disease and outcomes in women, and antihypertensive therapy is not always successful in achieving control over the blood pressure (BP). Nonoptimal control of BP remains a crucial risk factor for cardiovascular mortality, and in women, it could be related to sex-specific factors. Historically, women have been under-represented in clinical trials; therefore, the benefits of clinical outcomes and the safety profiles of antihypertensive therapies have been studied less extensively in women. The reasons for the sex differences in BP levels are multifactorial, implying different roles of the sex hormones, the renin-angiotensin system, sympathetic activity, and arterial stiffness. A complete understanding of the pathophysiological features of these differences requires further investigation.Nevertheless, the prevalence of the use of antihypertensive agents is higher among middle-aged women than among men. Notably, in the United States, hypertensive women use more diuretics and angiotensin receptor blockers than men, whereas hypertensive men more often receive beta-blockers, calcium channel antagonists, or inhibitors of angiotensin-converting enzyme. To date, the explanations for these sex differences in the consumption of antihypertensive drugs remain unknown.
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http://dx.doi.org/10.2459/JCM.0000000000000315DOI Listing
April 2016

The different role of sex hormones on female cardiovascular physiology and function: not only oestrogens.

Eur J Clin Invest 2015 Jun 10;45(6):634-45. Epub 2015 May 10.

Department of Neuroimaging, University of Chieti, Chieti, Italy.

Human response to different physiologic stimuli and cardiovascular (CV) adaptation to various pathologies seem to be gender specific. Sex-steroid hormones have been postulated as the major contributors towards these sex-related differences. This review will discuss current evidence on gender differences in CV function and remodelling, and will present the different role of the principal sex-steroid hormones on female heart. Starting from a review of sex hormones synthesis, receptors and CV signalling, we will summarize the current knowledge concerning the role of sex hormones on the regulation of our daily activities throughout the life, via the modulation of autonomic nervous system, excitation-contraction coupling pathway and ion channels activity. Many unresolved questions remain even if oestrogen effects on myocardial remodelling and function have been extensively studied. So this work will focus attention also on the controversial and complex relationship existing between androgens, progesterone and female heart.
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http://dx.doi.org/10.1111/eci.12447DOI Listing
June 2015

Effects of ω-3 PUFAs supplementation on myocardial function and oxidative stress markers in typical Rett syndrome.

Mediators Inflamm 2014 12;2014:983178. Epub 2014 Jan 12.

Child Neuropsychiatry Unit, University Hospital AOUS, Viale M. Bracci 16, 53100 Siena, Italy.

Rett syndrome (RTT) is a devastating neurodevelopmental disorder with a 300-fold increased risk rate for sudden cardiac death. A subclinical myocardial biventricular dysfunction has been recently reported in RTT by our group and found to be associated with an enhanced oxidative stress (OS) status. Here, we tested the effects of the naturally occurring antioxidants ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on echocardiographic parameters and systemic OS markers in a population of RTT patients with the typical clinical form. A total of 66 RTT girls were evaluated, half of whom being treated for 12 months with a dietary supplementation of ω-3 PUFAs at high dosage (docosahexaenoic acid ~71.9 ± 13.9 mg/kg b.w./day plus eicosapentaenoic acid ~115.5 ± 22.4 mg/kg b.w./day) versus the remaining half untreated population. Echocardiographic systolic longitudinal parameters of both ventricles, but not biventricular diastolic measures, improved following ω-3 PUFAs supplementation, with a parallel decrease in the OS markers levels. No significant changes in the examined echocardiographic parameters nor in the OS markers were detectable in the untreated RTT population. Our data indicate that ω-3 PUFAs are able to improve the biventricular myocardial systolic function in RTT and that this functional gain is partially mediated through a regulation of the redox balance.
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http://dx.doi.org/10.1155/2014/983178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913460PMC
October 2014

A biomarker of oxidative stress as a nontraditional risk factor in obese subjects.

Biomark Med 2013 Aug;7(4):633-9

Fondazione G Monasterio CNR Regione Toscana, Pisa, Italy.

Background: Oxidative stress has been postulated as an additive factor linking obesity to cardiovascular disease.

Materials & Methods: Derivatives of reactive oxygen species metabolites (d-ROMs) were measured in 136 obese (42 males, 94 females; mean age: 47 ± 12 years; BMI: 36 ± 5 kg/m(2)) and in 306 over- and normal-weight subjects (112 males, 194 females; age: 47 ± 12 years; BMI: 24 ± 3 kg/m(2)).

Results: d-ROMs levels were higher in obese than in over- and normal-weight subjects (395 ± 104 vs 362 ± 102 and 351 ± 84 arbitrary units (AU); p < 0.001), in women than males (390 ± 104 vs 327 ± 68 AU; p < 0.001), in subjects with than those without hypertension (390 ± 103 vs 360 ± 95 AU; p < 0.01) and in smokers than former and nonsmokers (380 ± 97 vs 358 ± 97 AU; p < 0.05). A positive correlation was found between d-ROMs and BMI (r = 0.25; p < 0.001) and age (r = 0.13; p < 0.01). Levels of d-ROM (>75th percentile: 420 AU) remained as an independent obesity predictor (odds ratio: 2.5; p < 0.001) in women. Continuous variables are reported as mean ± standard deviation.

Conclusion: d-ROMs are a powerful obesity predictor, and could represent a reliable tool in obesity and cardiovascular risk evaluation, especially in women.
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http://dx.doi.org/10.2217/bmm.13.49DOI Listing
August 2013

Association between high sensitivity C-reactive protein, heart rate variability and corrected QT interval in patients with chronic inflammatory arthritis.

Eur J Intern Med 2013 Jun 19;24(4):368-74. Epub 2013 Mar 19.

Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.

Background: The risk of sudden cardiac death is increased in chronic inflammatory arthritis, particularly rheumatoid arthritis (RA). To evaluate the putative effect of systemic inflammation on heart rate variability (HRV) and ventricular repolarization in chronic inflammatory arthritis, we analyzed in these patients the possible relationship among HRV parameters, QT interval, and high sensitivity C-reactive protein (hsCRP).

Methods: One hundred-one patients with chronic inflammatory arthritis underwent a 15-minute ambulatory twelve-channel electrocardiogram-recording, to evaluate HRV and QT interval, as well as a venous withdrawal for hsCRP as an estimation of ongoing systemic inflammation.

Results: In patients with chronic inflammatory arthritis, hsCRP is inversely correlated with HRV and directly with QTc duration, but while hsCRP is associated with HRV independently from any other investigated factor, the association between hsCRP and QTc seems to be an indirect consequence of the autonomic dysfunction itself. Within the whole cohort of patients, those subjects having elevated hsCRP levels displayed both a significant reduction in HRV and a prolongation of QTc with respect to patients with a normal hsCRP value. A similar, although less marked, degree of HRV depression and QTc prolongation was found in RA patients when compared to subjects with spondyloarthritis (SpA) and healthy controls.

Conclusions: These data provide evidence of a link between systemic inflammation and the arrhythmic risk in patients with chronic inflammatory arthritis, also putatively explaining, at least in part, how the different inflammatory load characterizing RA and SpA parallels the different risks of cardiovascular death in these two conditions.
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http://dx.doi.org/10.1016/j.ejim.2013.02.009DOI Listing
June 2013

Preanalytical, analytical (DiaSorin LIAISON) and clinical variables potentially affecting the 25-OH vitamin D estimation.

Clin Biochem 2012 Dec 11;45(18):1652-7. Epub 2012 Aug 11.

Fondazione G.Monasterio CNR-Regione Toscana, Pisa, Italy.

Background: Vitamin D (25-OHD) physiological functions have been expanded beyond traditional bone health, increasing the importance of its estimation in Laboratory Medicine, which renders validation of available methods mandatory.

Aims And Methods: We evaluated some preanalytical and analytical aspects of 25-OHD determination and the effects of potentially confounding clinical variables by using the DiaSorin "LIAISON 25-OH Vitamin D TOTAL".

Results: 25-OHD samples were extremely stable, at least in the short term, without requiring special transport or storage. Precision intervals (CV%) were: within run (7-11%) and total precision (8-11.5%). Mean (SD) recovery was 96 (2)%. The assay was linear on dilution. Comparison with radioimmunoassay (RIA) yielded acceptable correlation (Inter-rater agreement/kappa coefficient=0.94) and clinical equivalence in the interval from 6 to 55 ng/mL. The assay was evaluated on a general population (N=476, age: 60±14 years, 65 males). The status of 25-OHD resulted inversely related to parathyroid hormone levels (r=-0.21, p<0.001), and aging (r=-0.17, p<0.001), but not to sex. Levels of 25-OHD were found to be sufficient (≥30 ng/mL) only in 54 samples (12%). Marked seasonal 25-OHD variations were observed in 13 subjects (p<0.05). Moreover, a marked seasonal fluctuation was seen in samples collected during the period of February 2010-October 2011 (p≤0.01). Lower 25-OHD concentration was observed in subjects with diabetes (19±9 vs 14±7 ng/mL, p<0.01) and hypertension (20±9 vs 17±9 ng/mL, p<0.01). Moreover, 25-OHD inversely correlated with BMI (r=-0.25, p<0.001). Conversely, no difference in 25-OHD levels was observed between subjects due to smoking habits and dyslipidemia. In multiple logistic regression models, aging is the only significant independent risk factor for low 25-OHD levels (Odds ratio, 95% confidence intervals: 3.1, 1.3-7.3; p≤0.01).

Conclusions: Results confirm the LIAISON 25-OHD assay as a useful tool for 25-OHD estimation in the clinical practice. Lack of vitamin D is common among Italian adults, and appears associated with several cardiovascular risk factors.
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http://dx.doi.org/10.1016/j.clinbiochem.2012.08.003DOI Listing
December 2012

Sex-related differences in association of oxidative stress status with coronary artery disease.

Fertil Steril 2012 Feb 22;97(2):414-9. Epub 2011 Dec 22.

Fondazione G. Monasterio CNR-Regione Toscana and Institute of Clinical Physiology-CNR, Pisa, Italy.

Objective: To assess oxidative stress status in coronary artery disease (CAD) patients according to gender.

Design: Case-controlled, observational, retrospective study.

Setting: Clinical and research center.

Patient(s): A total of 55 postmenopausal women and 108 men (mean age: 66 ± 9 years), including 72 patients with angiographically proven CAD (CAD(+), 19 women) and a group of 91 age-matched controls (CAD(-), 36 women).

Intervention(s): None.

Main Outcome Measure(s): Oxidant/antioxidant balance as a global index (oxidative index) obtained using two commercial assays (d-ROMs and OXY Adsorbent Test, respectively) for estimation of levels of reactive oxygen metabolites and total antioxidant status.

Result(s): There was a statistically significant difference in oxidative stress status between men and women who were CAD(-) (-0.424 ± 1.3 vs. 0.64 ± 1.1 arbitrary units, respectively), but the CAD(+) women had oxidative stress levels almost three times those of the CAD(+) men (2.45 ± 2.5 vs. 0.9 ± 1.6 arbitrary units, respectively). After adjustment in the multivariate model, age and oxidative stress status in women and diabetes and age in men remained as statistically significant predictors of positive CAD findings.

Conclusion(s): Oxidative stress status was a powerful predictor of CAD in women. This result may have important implications for the differences between sexes in CAD physiopathology.
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http://dx.doi.org/10.1016/j.fertnstert.2011.11.045DOI Listing
February 2012

Subclinical myocardial dysfunction in Rett syndrome.

Eur Heart J Cardiovasc Imaging 2012 Apr 23;13(4):339-45. Epub 2011 Nov 23.

Neonatal Intensive Care Unit, University General Hospital, Azienda Ospedaliera Universitaria Senese, Viale M. Bracci 16, Siena, Italy.

Aims: Rett syndrome (RTT) is a rare neurodevelopmental disorder frequently linked to methyl-CpG-binding protein 2 (MeCP2) gene mutations. RTT is associated with a 300-fold increased risk of sudden cardiac death. Rhythm abnormalities and cardiac dysautonomia do not to fully account for cardiac mortality. Conversely, heart function in RTT has not been explored to date. Recent data indicate a previously unrecognized role of MeCP2 in cardiomyocytes development. Besides, increased oxidative stress markers (OS) have been found in RTT. We hypothesized that (i) RTT patients present a subclinical biventricular dysfunction and (ii) the myocardial dysfunction correlate with OS.

Methods And Results: We evaluated typical (n = 72) and atypical (n = 20) RTT female and healthy controls (n = 92). Main outcome measurements were (i) echocardiographic biventricular systo-diastolic parameters; (ii) correlation between echocardiographic measures and OS levels, i.e. plasma and intra-erythrocyte non-protein-bound iron (NPBI) and plasma F2-Isoprostanes (F2-IsoPs). A significant reduction in longitudinal biventricular function (tricuspid annular plane systolic excursion, mitral annular plane systolic excursion, S' of lateral and septal mitral annulus, S' of tricuspidal annulus) was evidenced in RTT patients vs. controls. No significant changes in the LV ejection fraction were found. Peak-early filling parameters (E, E' of lateral mitral annulus, E' of tricuspidal annulus) and right ventricular systolic pressure were reduced. A-wave, E/A, and E/E' were normal. OS markers were increased, but only F2-IsoPs correlated to LV systolic dysfunction.

Conclusion: These data indicate a previously unrecognized subclinical systo-diastolic biventricular myocardial dysfunction in typical and atypical RTT patients. A reduced preload is evidenced. The biventricular dysfunction is partially related to OS damage.
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http://dx.doi.org/10.1093/ejechocard/jer256DOI Listing
April 2012

Effects of levosimendan without loading dose on systolic and diastolic function in patients with end-stage heart failure.

Cardiol J 2011 ;18(5):532-7

Department of Cardiology, University of Siena, Italy.

Background: Levosimendan (L) is used in clinical practice for the treatment of severe heart failure (HF); it has inotropic and vasodilatory effects, without increasing myocardial oxygen consumption. In acute HF, levosimendan improves hemodynamic parameters; previous studies have demonstrated that it has favorable effects on left ventricular (LV) diastolic function. The aim of our study was to evaluate the effect of on LV long-axis function that represents the earlier marker of diastolic dysfunction.

Methods: We enrolled 41 patients (age 62 ± 12 years) admitted to our Department for acute HF, NYHA class IV and severe LV dysfunction. Twenty-six patients were treated with L (0.1 μg/kg/min ev for 24 h without loading dose) and 15 patients were treated with standard therapy (C). We evaluated clinical, blood exams and echocardiographic parameters at baseline and one week after L or C treatment.

Results: Baseline demographic, clinical and biochemical data were similar in both groups. After one week, the L group had shown a significant improvement in NYHA class and a reduction of pro-B-type natriuretic peptide (pro-BNP). In echocardiographic study, we observed an improvement in LV longitudinal function (p 〈 0.05) and LV ejection fraction (p 〈 0.05) with a reduction of E/E' (p 〈 0.05) in the L group. We divided the L group into ischemic and non- -ischemic patients and we demonstrated a significant increase in systolic function in the former. No differences were found between subgroups in diastolic function.

Conclusions: L therapy, without loading dose, improves NYHA class and ventricular function in patients with acute HF; we believe that these prolonged hemodynamic effects are due to active metabolities of L.
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http://dx.doi.org/10.5603/cj.2011.0009DOI Listing
January 2012

Determinants of oxidative stress related to gender: relevance of age and smoking habit.

Clin Chem Lab Med 2011 Sep 17;49(9):1509-13. Epub 2011 Jun 17.

Fondazione G. Monasterio CNR-Regione Toscana and Institute of Clinical Physiology-CNR, Pisa, Italy.

Background: Magnitude and major causes of oxidative stress may be different between sexes, although limitedly addressed in clinical studies with controversial results. The present study aimed to determine whether any gender-related difference exists concerning oxidative stress in a population of 332 subjects of both sexes, in a wide age range, with and without cigarette smoking habit.

Methods: The Oxidative-INDEX was calculated after evaluation of serum hydroperoxides (ROMs) and total antioxidant capacity (OXY) by means of commercial kits (d-ROMs and Oxy-adsorbent Tests, Diacron, Italy) subtracting the OXY standardized variable from the ROMs standardized variable.

Results: The Oxidative-INDEX resulted higher in women with respect to men (p<0.001), in smokers (p<0.01) than in non-smokers, and correlated with cigarette number (p<0.01), age (p<0.001), and post-menopausal status (p<0.001). The multivariate analysis identified age, high blood pressure, and smoking habit as factors independently associated with the Oxidative-INDEX in men, whereas cigarette smoking and age represented the independent risk factors for an elevated oxidative stress status in women.

Conclusions: Gender-based differences in oxidative stress levels may provide a biochemical basis for the epidemiologic differences in the disease susceptibility between sexes, and suggest different strategies for risk assessment, diagnosis, and treatment specifically targeted to men and women.
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http://dx.doi.org/10.1515/CCLM.2011.622DOI Listing
September 2011