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Objective To compare the antihypertensive efficacy and tolerability of a once-daily fixed valsartan/hydrochlorothiazide (HCTZ) combination and amlodipine in subjects with mild-to-moderate hypertension. Subjects and setting In this multicentre, double-blind, randomized, comparative trial, 690 patients with sitting systolic blood pressure (BP) > or = 160 mmHg and sitting diastolic BP > or = 95 mmHg at the end of a 2-week placebo wash-out period were randomized to valsartan-based treatment (n = 342) or amlodipine (n = 348). Methods The patients received valsartan 80 mg o.d. or amlodipine 5 mg o.d for 4 weeks; in the case of an unsatisfactory blood pressure response, the treatments could be respectively changed to the fixed combination of valsartan 80 mg + HCTZ 12.5 mg o.d. or amlodipine 10 mg o.d. for a further 8 weeks. Results Both treatment approaches decreased systolic blood pressure and diastolic blood pressure to the same extent. The rate of responders to treatment at the end of fourth week (before up-titration) was 57.4% among the valsartan-treated patients and 61.9% among the amlodipine-treated patients (ns). At the end of the study, the rate of responders was not significantly different between the two groups (74.9 versus 72.1%). Valsartan-based treatment had a slightly lower incidence of adverse events (1.5 versus 5.5%; P = 0.006). Conclusions The results of this trial demonstrate that the valsartan/hydrochlorothiazide combination and amlodipine are equally effective in lowering BP, and that the combination is better tolerated.

Aims The aim of this study was to investigate prospectively the effect of sacubitril/valsartan in advanced heart failure (HF) patients in waiting list for heart transplantation (HT) and the effect on physical frailty (PF). Methods and results We treated 37 consecutive patients with advanced HF with sacubitril/valsartan. Patients were followed up until HT, device implant, or last follow‐up visit after 2 years of follow‐up. At baseline, mean New York Heart Association (NYHA) class was 3.1 ± 0.4, with 64.9% in NYHA III and 35.1% NYHA IIIB. Left ventricular ejection fraction was 23.5 ± 5.8%, VO2 max was 10.3 ± 2.3 mL/kg/min, cardiac index was 2.3 ± 0.5 L/min/m2, and N‐terminal pro‐brain natriuretic peptide (NT‐pro‐BNP) was 4943.0 ± 5326.8 pg/mL. After a mean follow‐up of 17.1 ± 4.4 months, no deaths were observed, but NYHA class improved significantly with 56.8% in NYHA II, 40.5% in NYHA III, and 2.7% in NYHA IIIB (P < 0.001). VO2 max and 6 min walk test (6MWT) increased, whereas pulmonary systolic blood pressure, E/E′, VE/VCO2 slope, and NT‐pro‐BNP decreased. At right heart catheterization performed after 1 year of follow‐up, cardiac index and pulmonary vascular resistance remained stable, while a decrease in systolic pulmonary artery pressure and pulmonary capillary wedge pressure is observed. Furosemide dosage decrease from 102.7 ± 69.4 to 78.7 ± 66.3 mg (P = 0.040). PF decreased from 3.35 ± 1.0 at baseline to 1.57 ± 1.3 at the end of follow‐up (P < 0.001), with a reduction in all PF domains. Conclusions Our study showed a rapid improvement in PF in HT waiting list patients treated with sacubitril/valsartan. The improvement in all PF domains was paralleled by VO2 and 6MWT increase and together with an NT‐pro‐BNP reduction constant over the follow‐up.

Background Although individuals with diabetes mellitus frequently have dyslipidaemias and high blood pressure, much of the increased risk for coronary heart disease is not explained by these and other classical risk factors. Thus, other less widely recognized risk factors, including increased susceptibility of low-density lipoprotein (LDL) to oxidation, might enhance vascular dysfunction and atherogenesis in diabetes. Aims We compared both the rate and extent of LDL oxidation ex vivo between 78 poorly controlled individuals with type 1 diabetes and 78 age- and sex-matched non-diabetic controls. We then initiated intensive insulin therapy for 3 months to determine the impact of improved glucose control on LDL composition and oxidation. Results Diabetic and non-diabetic individuals did not have significantly different body weights, dietary intake, blood pressure, renal function or plasma lipid levels. LDL composition was also similar in both groups. In contrast, vitamin E content in LDL was significantly lower in diabetic patients. Measures of LDL lipid oxidation, including conjugated diene, lipid peroxide and thiobarbituric acid reactive substances formation, as well as measures of LDL protein modification, were significantly greater in diabetic patients. Levels of hyperglycaemia correlated strongly with each measure of LDL lipid oxidation (r ranges from 0·60–0·81, P

Purpose of Review: Immune checkpoint inhibitors, such as monoclonal antibodies targeting CTLA-4, PD-1, and PD-L1, have improved the outcome of many malignancies, but serious immune-related cardiovascular adverse events have been observed. Patients’ risk factors for these toxicities are currently being investigated. Recent Findings: Interfering with the CTLA-4 and PD-1 axes can bring to several immune-related adverse events, including cardiotoxic events such as autoimmune myocarditis, pericarditis, and vasculitis, suggesting that these molecules play an important role in preventing autoimmunity. Summary: Risk factors (such as pre-existing cardiovascular conditions, previous and concomitant cardiotoxic treatments, underlying autoimmune diseases, tumor-related factors, simultaneous immune-related toxic effects, and genetic factors) should be always recognized for the correct management of these toxicities.

Aims The assessment of frailty in older adults with heart failure (HF) is still debated. Here, we compare the predictive role and the diagnostic accuracy of physical vs. multidimensional frailty assessment on mortality, disability, and hospitalization in older adults with and without HF. Methods and results A total of 1077 elderly (≥65 years) outpatients were evaluated with the physical (phy‐Fi) and multidimensional (m‐Fi) frailty scores and according to the presence or the absence of HF. Mortality, disability, and hospitalizations were assessed at baseline and after a 24 month follow‐up. Cox regression analysis demonstrated that, compared with phy‐Fi score, m‐Fi score was more predictive of mortality [hazard ratio (HR) = 1.05 vs. 0.66], disability (HR = 1.02 vs. 0.89), and hospitalization (HR = 1.03 vs. 0.96) in the absence and even more in the presence of HF (HR = 1.11 vs. 0.63, 1.06 vs. 0.98, and 1.14 vs. 1.03, respectively). The area under the curve indicated a better diagnostic accuracy with m‐Fi score than with phy‐Fi score for mortality, disability, and hospitalizations, both in absence (0.782 vs. 0.649, 0.763 vs. 0.695, and 0.732 vs. 0.666, respectively) and in presence of HF (0.824 vs. 0.625, 0.886 vs. 0.793, and 0.812 vs. 0.688, respectively). Conclusions The m‐Fi score is able to predict mortality, disability, and hospitalizations better than the phy‐Fi score, not only in absence but also in presence of HF. Our data also demonstrate that the m‐Fi score has better diagnostic accuracy than the phy‐Fi score. Thus, the use of the m‐FI score should be considered for the assessment of frailty in older HF adults.

Modifications of lean mass are a frequent critical determinant in the pathophysiology and progression of heart failure (HF). Sarcopenia may be considered one of the most important causes of low physical performance and reduced cardiorespiratory fitness in older patients with HF. Sarcopenia is frequently misdiagnosed as cachexia. However, muscle wasting in HF has different pathogenetic features in sarcopenic and cachectic conditions. HF may induce sarcopenia through common pathogenetic pathways such as hormonal changes, malnutrition, and physical inactivity; mechanisms that influence each other. In the opposite way, sarcopenia may favor HF development by different mechanisms, including pathological ergoreflex. Paradoxically, sarcopenia is not associated with a sarcopenic cardiac muscle, but the cardiac muscle shows a hypertrophy which seems to be “not-functional.” First-line agents for the treatment of HF, physical activity and nutritional interventions, may offer a therapeutic advantage in sarcopenic patients irrespective of HF. Thus, sarcopenia is highly prevalent in patients with HF, contributing to its poor prognosis, and both conditions could benefit from common treatment strategies based on pharmacological, physical activity, and nutritional approaches.

BACKGROUND AND AIM: Permanent Atrial Fibrillation (pAF) is associated with increased risk of embolic complications. The relationship between pAF and pulmonary embolism (PE) has not been extensively investigated in elderly patients. Here, we aim at verifying whether pAF is associated to an increased risk of PE in a cohort of elderly patients with and without Deep Vein Thrombosis (DVT). METHODS: 235 patients older than 65 years with PE with or without pAF were retrospectively enrolled and stratified by the absence or presence of DVT. The diagnosis of PE was performed by computed tomography angiography (CTA). Right echocardiographic parameters were monitored. The severity of PE was evaluated by CTA quantization (PE score = 1, involvement of main branches of pulmonary artery) and by dimer-D (> 3000 µg/L). RESULTS: DVT was identified only in 51 cases of PE (21.7%). pAF prevalence was higher in PE without than in those with DVT (64.9% vs. 35.1%, p 3000 µg/L). CONCLUSIONS: We conclude that in elderly patients with PE, the prevalence of pFA was doubled, in the absence of DVT, and it is associated with a more severe PE in the absence than in the presence of DVT. Thus, in the absence of DVT, pFA should be considered as cause of PE.

BACKGROUND: Depression is highly prevalent in Heart Failure (HF). Treatment with sacubitril/valsartan improved quality of life and survival in HF patients. Aim of the study was to investigate prospectively the effect of sacubitril/valsartan on depression in advanced HF patients in waiting list for heart transplant (HT). METHODS: 37 consecutive patients with advanced HF in waiting list for HT were treated with sacubitril/valsartan. We analyzed data derived from the assessment performed the year before the beginning of sacubitril/valsartan, at study entry, and at one year of follow-up. Depression was assessed with Beck Depression Inventory II (BDI) scale. Cognitive function were assessed with Mini-Mental State Examination (MMSE). Functioning was evaluated measuring meters at 6 Minute Walking Test (6MWT) and maximum rate of oxygen consumption (VO2 max). RESULTS: At baseline, 64.9% of HF patients were in NYHA III and 35.1% NYHA IIIB, BDI was 15.2 ± 5.2 with 59.5% of patients with a score > 13. MMSE was 27.8 ± 2.6. After one year of follow-up NYHA class improved significantly, with 56.8% in NYHA II, 40.5% in NYHA III and 2.7% NYHA in IIIB (p 13. MMSE remain stable (28.2 ± 2.1) (p = 0.104). No statistical differences are observed between data collected in the evaluation 1-year before and soon before treatment with sacubitril/valsartan. Multivariate regression analysis demonstrate a relationship between reduction in BDI-II score and improvement in six-minute walking test independently by the effect of sex, age, selective serotonin reuptake inhibitors, VO2 max, NT-proBNP, PAPs, NYHA class differences evaluated at follow-up versus baseline. CONCLUSIONS: Our study showed a reduction in depressive symptomatology in heart transplant waiting list patients treated with sacubitril/valsartan. The improvement in depressive symptomatology was paralleled by 6MWT increase in the follow-up.

In the last years, guidelines for the treatment of hypertension recommended individualized blood pressure goals for geriatric population because of elderly susceptibility to adverse outcomes and higher mortality rate deriving from the excessive blood pressure lowering, especially in "frail" elderly. Recent findings from the SPRINT study, which demonstrated that intensive blood pressure lowering was associated with lower rates of cardiovascular events and mortality in both hypertensive fit and frail elderly subjects compared to standard treatment, heavily influenced the recent US guidelines. In SPRINT sub-study analysis of adults aged ≥75 years, the most controversial issue appears the method of blood pressure measurement, the selection of patients and related-frailty degree that appears to be very light. Accordingly, it has been described that light frailty is related to good outcomes in older adults. SPRINT findings in "frail elderly patients" cannot be applied to the clinical practice because this condition has been clearly under-estimated. Thus, frailty status should be routinely and correctly quantified in order to identify the frailty degree and to find the best harms-benefits balance of antihypertensive drug treatment in frail older adults.

Ilaria Liguori,1 Gennaro Russo,1 Luisa Aran,1 Giulia Bulli,1 Francesco Curcio,1 David Della-Morte,2,3 Gaetano Gargiulo,4 Gianluca Testa,1,5 Francesco Cacciatore,1,6 Domenico Bonaduce,1 Pasquale Abete1 1Department of Translational Medical Sciences, University of Naples “Federico II”, Naples, Italy; 2Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 3Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, Rome, Italy; 4Division of Internal Medicine, AOU San Giovanni di Dio e Ruggi di Aragona, Salerno, Italy; 5Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy; 6Azienda Ospedaliera dei Colli, Monaldi Hospital, Heart Transplantation Unit, Naples, Italy Abstract: Life expectancy is increasing worldwide, with a resultant increase in the elderly population. Aging is characterized by the progressive loss of skeletal muscle mass and strength – a phenomenon called sarcopenia. Sarcopenia has a complex multifactorial pathogenesis, which involves not only age-related changes in neuromuscular function, muscle protein turnover, and hormone levels and sensitivity, but also a chronic pro-inflammatory state, oxidative stress, and behavioral factors – in particular, nutritional status and degree of physical activity. According to the operational definition by the European Working Group on Sarcopenia in Older People (EWGSOP), the diagnosis of sarcopenia requires the presence of both low muscle mass and low muscle function, which can be defined by low muscle strength or low physical performance. Moreover, biomarkers of sarcopenia have been identified for its early detection and for a detailed identification of the main pathophysiological mechanisms involved in its development. Because sarcopenia is associated with important adverse health outcomes, such as frailty, hospitalization, and mortality, several therapeutic strategies have been identified that involve exercise training, nutritional supplementation, hormonal therapies, and novel strategies and are still under investigation. At the present time, only physical exercise has showed a positive effect in managing and preventing sarcopenia and its adverse health outcomes. Thus, further well-designed and well-conducted studies on sarcopenia are needed. Keywords: sarcopenia, elderly, assessment, therapy

Ilaria Liguori,1 Gennaro Russo,1 Francesco Curcio,1 Giulia Bulli,1 Luisa Aran,1 David Della-Morte,2,3 Gaetano Gargiulo,4 Gianluca Testa,1,5 Francesco Cacciatore,1,6 Domenico Bonaduce,1 Pasquale Abete1 1Department of Translational Medical Sciences, University of Naples “Federico II”, Naples, Italy; 2Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 3San Raffaele Roma Open University, Rome, Italy; 4Division of Internal Medicine, AOU San Giovanni di Dio e Ruggi di Aragona, Salerno, Italy; 5Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy; 6Azienda Ospedaliera dei Colli, Monaldi Hospital, Heart Transplantation Unit, Naples, Italy Abstract: Reactive oxygen and nitrogen species (RONS) are produced by several endogenous and exogenous processes, and their negative effects are neutralized by antioxidant defenses. Oxidative stress occurs from the imbalance between RONS production and these antioxidant defenses. Aging is a process characterized by the progressive loss of tissue and organ function. The oxidative stress theory of aging is based on the hypothesis that age-associated functional losses are due to the accumulation of RONS-induced damages. At the same time, oxidative stress is involved in several age-related conditions (ie, cardiovascular diseases [CVDs], chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases, and cancer), including sarcopenia and frailty. Different types of oxidative stress biomarkers have been identified and may provide important information about the efficacy of the treatment, guiding the selection of the most effective drugs/dose regimens for patients and, if particularly relevant from a pathophysiological point of view, acting on a specific therapeutic target. Given the important role of oxidative stress in the pathogenesis of many clinical conditions and aging, antioxidant therapy could positively affect the natural history of several diseases, but further investigation is needed to evaluate the real efficacy of these therapeutic interventions. The purpose of this paper is to provide a review of literature on this complex topic of ever increasing interest. Keywords: elderly, reactive oxygen species, reactive nitrogen species, antioxidants

Type 2 myocardial infarctions (T2-MI) is a type of necrosis that results from reduced oxygen supply and/or increased demand secondary to other causes unrelated to acute coronary atherothrombosis. The development and implementation of sensitive and high-sensitivity cardiac necrosis marker and the age-related increase of comorbidity lead to a boost of the frequency of T2-MI. T2-MI is often a complication of a high degree of clinical frailty in older adults, emerging as a "geriatric syndrome". Age-related non-cardiovascular causes may be the triggering factors and are strongly associated with the diagnosis, treatment, and prognosis of T2-MI. To date, there are no guidelines on management of this pathology in advancing age. Patient-centered approach and comprehensive geriatric assessment play a key role in the diagnosis, therapy and prognosis of geriatric patients with T2-MI.

The development of therapeutic approaches based on direct cardiac reprogramming of fibroblasts into induced-cardiomyocytes (iCM) has emerged as an attractive strategy to repair the injured myocardium. The identification of the mechanisms driving lineage conversion represents a crucial step toward the development of new and more efficient regenerative strategies. To this aim, here we show that pre-treatment with the Bmi1 inhibitor PTC-209 is sufficient to increase the efficiency of Chemical-induced Direct Cardiac Reprogramming both in mouse embryonic fibroblasts and adult cardiac fibroblasts. PTC-209 induces an overall increase of spontaneously beating iCM at end-stage of reprogramming, expressing high levels of late cardiac markers Troponin T and myosin muscle light chain-2v. The inhibition of Bmi1 expression occurring upon PTC-209 pre-treatment was maintained throughout the reprogramming protocol, contributing to a significant gene expression de-regulation. RNA profiling revealed that, upon Bmi1 inhibition a significant down-regulation of genes associated with immune and inflammatory signalling pathways occurred, with repression of different genes involved in interleukin, cytokine and chemokine pathways. Accordingly, we observed the down-regulation of both JAK/STAT3 and MAPK/ERK1-2 pathway activation, highlighting the crucial role of these pathways as a barrier for cardiac reprogramming. These findings have significant implications for the development of new cardiac regenerative therapies.

Increased left ventricular mass (LVM) is often present in metabolic syndrome (MS), also in the setting of well-controlled blood pressure (BP). Aim of the present study was to evaluate the efficacy of a nutraceutical combination of berberine, red yeast rice extract and policosanol (Armolipid Plus™, AP) in reducing LVM in patients with MS and left ventricular hypertrophy (LVH).In this multicenter, randomized, double-blind, placebo-controlled trial, 158 patients with MS (IDF criteria) and LVH (LVM48 g/mOne-hundred-and-forty-five patients (AP n = 74, placebo n = 71) completed the study. A significant percentage reduction in LVM was observed in AP group vs baseline (-2.7%, p 0.0001), and compared to placebo (-4.1%, p 0.0001), and remained significant after adjustment for age, sex, baseline systolic BP and BMI and their changes during the study period. The proportion of subjects showing LVM reduction was higher in AP group than in the placebo group (57% vs 28%, adjusted p = 0.007). Treatment with AP was associated with improvement of lipid profile.24-week of treatment with AP is associated with a significant reduction in LVM in subjects with MS and LVH, in addition to favourable effects on lipid profile, and could represent an effective strategy aiming at reducing the associated cardiovascular risk. The trial was registered at clinicaltrials.gov with ID NCT02295176.

Chronic heart failure (CHF) is frequently linked to clinical frailty, a complex geriatric condition associated with negative outcomes. However, the full characterization of frailty is still debated. Fried and colleagues focused on a ‘physical phenotype’ of frailty based on the assessment of unintentional weight loss, muscle weakness, slow walking speed, low physical activity, and exhaustion,1 while Rockwood and colleagues fostered a multidimensional concept involving, besides physical impairments, comorbidity, disability, mental, nutritional, and social components (known as the ‘Canadian frailty index’).

Background Nutraceuticals represent a new therapeutic frontier in the treatment of metabolic syndrom (MetS) and related cardiovascular risk factors. The aim of this study was to evaluate the potential beneficial effects of Armolipid Plus (AP) (berberine 500 mg, red yest rice, monacolin K 3 mg and policosanol 10 mg) on insulin resistance, lipid profile, particularly on small and dense LDL cholesterol (sdLDL-C), representing the most atherogenic components, as well as its effects on high sensitivity C-reactive protein, a notable marker of cardiovascular risk, blood pressure and cardiac remodeling in subjects affected by MetS, with left ventricular hypertrophy. Methods The study was a prospective, multi-center, randomized, double blind, placebo-controlled trial. One hundred and fifty eight patients, aged between 28 and 76 years old, were enrolled and randomized to receive either one tablet of AP or placebo (PL) once daily for 24 weeks. Anthropometric and vital parameters, total cholesterol (tot-C), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceridemia (TG), non-HDL cholesterol (NHDL-C) and sdLDL-C were evaluated. Results After 24 weeks of treatment, the analysis performed on 141 subjects (71 in AP arm and 70 in PL arm), showed a significant improvement of lipid profile in the AP group, with reduction in tot-C (− 13.2 mg/dl), LDL-C (− 13.9 mg/dl) and NHDL-C (− 15.3 mg/dl) and increase in HDL-C (+ 2.0 mg/dl). These changes were equally significant compared with placebo (tot-C: AP − 13.2 mg/dL vs PL + 2.7 mg/dL, p

BACKGROUND: Orthostatic hypotension (OH) has high prevalence in frail older adults. However, its effect on mortality, disability, and hospitalization in frail older adults is poorly investigated. Thus, we assessed the relationship between the prevalence of OH and its effect on mortality, disability, and hospitalization in noninstitutionalized older adults stratified by frailty degree. METHODS: Prospective, observational study of 510 older participants (≥65 years of age) consecutively admitted to a geriatric evaluation unit to perform a geriatric comprehensive assessment. MEASUREMENTS: Clinical frailty was assessed using the Italian frailty index (40 items). Systolic blood pressure (mm Hg), diastolic blood pressure (mm Hg), and heart rate (bpm) were evaluated in clinostatic position and after 1, 3, and 5 minutes of orthostatic position. OH was defined with a decrease of 20 mm Hg in systolic blood pressure and/or a decrease of 10 mm Hg in diastolic blood pressure. RESULTS: OH prevalence was 22%, and it increased from 9.0% to 66.0% according to frailty degree (P for trend

BACKGROUND: Malnutrition indices and muscle mass and strength in the elderly are poorly investigated. Moreover, malnutrition seems to be 1 of the more important factors in the cause of sarcopenia. The presence of sarcopenia and its relationship with malnutrition indices were studied in noninstitutionalized elderly people who underwent Comprehensive Geriatric Assessment (CGA). METHODS: A total of 473 elderly subjects (mean age, 80.9 ± 6.6 years) admitted to CGA were studied. Malnutrition risk was evaluated with Mini Nutritional Assessment (MNA) score, whereas muscle mass and muscle strength were evaluated by bioimpedentiometry and hand grip, respectively. Sarcopenia was assessed as indicated in the European Working Group on Sarcopenia in Older People (EWGSOP) consensus. RESULTS: Overall prevalence of sarcopenia was 13.1%, and it increased from 6.1% to 31.4% as MNA decreased (P < .001). MNA score was lower in elderly subjects with sarcopenia (15.4 ± 4.2) than without sarcopenia (22.0 ± 4.0) (P = .024). Linear regression analysis showed that MNA score is linearly related both with muscle mass (r = 0.72; P < .001) and strength (r = 0.42; P < .001). Multivariate analysis, adjusted for several confounding variables including comorbidity and disability, confirmed these results. CONCLUSIONS: MNA score is low in noninstitutionalized elderly subjects with sarcopenia, and it is linearly related to muscle mass and muscle strength. These data indicate that MNA score, when evaluated with muscle mass and strength, may recognize elderly subjects with sarcopenia.

The traditional model of care is based on "disease-centered" management that requires the organization of the hospital in specialized wards, to which the patient is assigned for the main disease. The growing need to optimize economical and human resources and to promote a global approach to the patient has led to the setting up of the intensity of care model. It is a health system based on a "patient-centered" approach, where the hospital is organized in departments dedicated to patients with homogenous needs of care. In Italy, intensity of care model is currently being tested in the hospital organization, where three levels of intensity are proposed: low, medium and high. The purpose of the following review is to describe the role and importance of the Geriatrician in each of these care settings and to highlight the contradiction of a National Health System which promotes the geriatric approach to all types of patients, but does not invest in the formation and integration of the figure of the Geriatrician in clinical practice, condemning it to marginalization or even extinction.

Traditional risk factors of cardiovascular death in the general population, including body mass index (BMI), serum cholesterol, and blood pressure are also found to relate to outcomes in the geriatric population, but in a differing direction. A higher body mass index, hypercholesterolemia and hypertension are not harmful but even permit better survival at advancing age. This phenomenon is called "reverse epidemiology" or "risk factor paradox" and is also detected in a variety of chronic disease states such as chronic heart failure. Accordingly, a low BMI, blood pressure and cholesterol values are associated with a worse prognosis. Several possible causes are hypothesized to explain this elderly paradox, but this phenomenon remains controversial and its underlying reasons are poorly understood. The aim of this review is to recognize the factors behind this intriguing phenomenon and analyse the consequences that it can bring in the management of the cardiovascular therapy in elderly patient. Finally, a new phenotype identified as "catabolic syndrome" has been postulated.

Background and Purpose: Sarcopenia, a loss of muscle mass and strength accompanying aging, is common in older adults who are not physically active. Nevertheless, the association between physical activity and sarcopenia has not been extensively studied. Therefore, we examined the relationship of both muscle mass and muscle strength with physical activity as quantified using the Physical Activity Scale for Elderly (PASE). Methods: PASE score, muscle mass by bioimpendiometry, and muscle strength by handgrip were evaluated in a cohort study of 420 older adult participants (mean age 82.4 [5.9] years), admitted to the Comprehensive Geriatric Assessment Center. Sarcopenia was assessed as indicated in the European Working Group on Sarcopenia in Older People (EWGSOP) consensus. Results: PASE score was lower in sarcopenic (40.2 [89.0]) than in non-sarcopenic (92.0 [52.4]) older adults (P < .001). Curvilinear regression analysis demonstrated that PASE score is related with muscle mass (R-2 = 0.63; P < .001) and strength (R-2 = 0.51; P < .001). Conclusions: The present study indicates that PASE score is curvilinearly related to muscle mass and strength and that low PASE score identifies sarcopenic noninstitutionalized older adults. This evidence suggests that PASE score evaluated together with muscle mass and strength may identify older adults at high risk of sarcopenia.

The aging population is increasing and, therefore, a higher prevalence of cardiac disease is emerging; including hypertension, coronary artery disease, atrial fibrillation and chronic heart failure. Large cohort studies have revealed a relationship among increased risk for cognitive impairment and dementia in cardiovascular diseases probably due to embolic stroke or chronic cerebral hypoperfusion. Thus, the aim of the present review is to overview the studies that investigate the presence and/or the development of cognitive impairments and dementia in patients with varied types of cardiovascular disease. Finally, a continuum among hypertension, coronary artery disease, atrial fibrillation and chronic heart failure with to the development of cognitive impairment and progression to dementia has been hypothesized. © 2014 Elsevier B.V.

Restenosis after percutaneous transluminal coronary angioplasty is caused by neointimal hyperplasia, which involves impairment of nitric oxide (NO)-dependent pathways, and may be further exacerbated by a concomitant aging process. We compared the effects of NO-releasing-aspirin (NCX-4016) and aspirin (ASA) on experimental restenosis in both adult and elderly rats. Moreover, to ascertain the efficacy of NCX-4016 during vascular aging, we fully characterized the release of bioactive NO by the drug. Sprague–Dawley rats aged 6 and 24 months were treated with NO releasing-aspirin (55 mg/kg) or ASA (30 mg/kg) for 7 days before and 21 days after standard carotid balloon injury. Histological examination and immunohistochemical double-staining were used to evaluate restenosis. Plasma nitrite and nitrate and S -nitrosothiols were determined by a chemiluminescence-based assay. Electron spin resonance was used for determining nitrosylhemoglobin. Treatment of aged rats with NCX-4016 was associated with increased bioactive NO, compared with ASA. NO aspirin, but not ASA, reduced experimental restenosis in old rats, an effect associated with reduced vascular smooth muscle cell proliferation. NCX-4016, but not ASA, was well tolerated and virtually devoid of gastric damage in either adult or old rats. Thus, impairment of NO-dependent mechanisms may be involved in the development of restenosis in old rats. We suggest that an NCX-4016 derivative could be an effective drug in reducing restenosis, especially in the presence of aging and/or gastrointestinal damage.

The effects of chronic treatment with the new sulfhydryl angiotensin-converting enzyme (ACE)-inhibitor, zofenopril, in comparison with the classical sulfhydryl ACE-inhibitor captopril or enalapril or placebo on the development of atherosclerosis were determined in apolipoprotein-E knockout (apoE(-/-)) mice. Groups of 2-month-old male mice received either placebo (N=10), 0.05 mg/kg/day of zofenopril (N=10), 1 mg/kg/day of zofenopril (N=10), 5 mg/kg/day of captopril (N=10) or 0.5 mg/kg/day of enalapril (N=8). After 29 weeks of treatment, computer-assisted imaging analysis revealed that zofenopril reduced the aortic cumulative lesion area by 78% at 0.05 mg/kg/day and by 89% at 1 mg/ml/day of zofenopril compared to that of the placebo (P

This study assesses whether administration of recombinant tissue-type plasminogen activator (rt-PA) up to 8 hours after onset of symptoms of acute myocardial infarction (AMI) may result in a significant improvement in left ventricular function. Sixty patients were classified into 3 groups: group A (n = 21) received rt-PA within 4 hours from symptom onset; the remaining 39 patients, admitted between 4 and 8 hours, were randomized into 2 groups--group B (n = 19) received rt-PA, and group C (n = 21) was treated with conventional therapy. Coronary and left ventricular angiograms were recorded 8 to 10 days after rt-PA administration. The patency rate of the infarct-related artery was 76% in group A, and 63 and 35% in group B and C, respectively. The Thrombolysis in Myocardial Infarction trial perfusion grade was higher in group A and B than in group C (A vs C: p less than 0.005; B vs C: p less than 0.01). Left ventricular ejection fraction was significantly higher in group A (60.2 +/- 10%) and B (54.7 +/- 12%) compared with group C (44.2 +/- 12%) (A vs C: p less than 0.01; B vs C: p less than 0.05). Regional wall motion of the entire ischemic zone was better in group A and B than in group C (A vs C: p less than 0.001; B vs C: p less than 0.01). In contrast, the kinesis of the central ischemic zone was significantly better in group A than in both group B and C (A vs B: p less than 0.05; A vs C: p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVES: Advancing age is an independent predictor of increased mortality after acute myocardial infarction (AMI). Several hypotheses have been developed to try to explain this phenomenon, but data available about the efficacy of thrombolytic therapy in older patients are still not conclusive. The goal of this study was to investigate the efficacy of thromholysis in adult and older patients who suffered their first AMI. DESIGN: Retrospective cohort study. SETTING: A coronary care unit. PARTICIPANTS: The sample included 244 younger (aged

Cardiovascular disease is the most severe complication of acromegaly accounting for the increased mortality of these patients. Recently, the slow-release form of octreotide (OCT; Sandostatin LAR, OCT-LAR), for im injection every 28 days, was reported to induce suppression of GH levels below 7.5 mU/L (2.5 μg/L) in 39–75% of patients, and normalization of insulin-like growth factor (IGF)-I levels for age in 64–88% of patients, with an excellent patients’ compliance. The aim of the present study was to investigate the early effect of OCT-LAR treatment on the left ventricular (LV) structure and performance in 15 somatostatin analog-naive patients with acromegaly (GH, 94.8 ± 24.9 mU/L; IGF-I, 757.9 ± 66.6 μg/L), focusing on the early effect of GH and IGF-I suppression on the heart. Cardiac structure was investigated by echocardiography, whereas LV performance was investigated by gated-blood-pool scintigraphy, before and after 3 and 6 months of treatment with OCT-LAR. OCT-LAR was initially administered im, at a dose of 20 mg every 28 days, for 3 months. In six patients, the dose was then increased to 30 mg every 28 days to achieve disease control, which was considered when fasting and/or glucose-suppressed GH values were below 7.5 and 3.0 mU/L, respectively, together with IGF-I values within the normal range for age. The treatment with OCT-LAR for 6 months induced a significant decrease of GH (to 12.9 ± 3.0 mU/L) and IGF-I levels (to 340.3 ± 40.2 μg/L) in all 15 patients. After 6 months of treatment, the percent IGF-I suppression was 52.8 ± 4.4%, and serum GH/IGF-I levels were normalized in 9 patients. A significant decrease of LV mass index (LVMi), interventricular septum thickness, and LV posterior wall thickness was observed in all 15 patients after 3 and 6 months of OCT-LAR treatment: LVMi was decreased by 19.1 ± 2.0% without any difference in patients with (19.9 ± 2.7%) or without disease control (17.8 ± 3.3%). Among the 11 patients with LV hypertrophy, 6 normalized their LVMi after treatment. At study entry, an inadequate LV ejection fraction (LVEF) at rest ( In conclusion, the results of the present study demonstrate that OCT-LAR im injections every 28 days induces a sustained suppression of GH levels and IGF-I levels in all acromegalic patients, allowing achievement of disease control in 60% of patients after 6 months of treatment. The sustained suppression of IGF-I levels was followed by a significant reduction of LVMi in all patients already after 3 months of treatment, with recovery of LV hypertrophy in 6 of 11 patients. In contrast, LV performance was significantly improved only in patients achieving normalization of their hormone levels. These data suggest that the treatment with OCT-LAR, by inducing a rapid suppression of circulating GH and IGF-I levels, could produce an early improvement of the cardiac abnormalities of acromegaly, thus contributing to reversal of the poor prognosis for cardiovascular diseases of these patients.

Myocardial asynergies detected by two-dimensional echocardiography during intravenous administration of Dipyridamole (0.75 mg/kg) were evaluated in 54 patients referred for angiographic evaluation of chest pain. Technically adequate two-dimensional echocardiograms suitable for analysis were recorded in 42 of 54 (77.7%) patients studied. Thallium-201 myocardial perfusion scintigraphy, during dipyridamole test was performed in the same patients. Thirty of the 42 patients studied showed significant coronary narrowing at cardiac catheterization. Dipyridamole-induced wall motion abnormalities and myocardial perfusion defects were detected, respectively, in 19 (63.3%) and 21 (70%) of 30 patients with significant coronary artery disease. Wall by wall comparison of the distribution of dipyridamole-induced echocardiographic asynergy with reversible thallium-201 (/sup 201/Tl) perfusion defects demonstrated complete correlation in 42 segments examined. Three segments with perfusion defects at thallium scanning did not show asynergy during the test while two segments showing wall motion abnormalities during dipyridamole infusion did not manifest perfusion defects. Our study demonstrates that two-dimensional echocardiography during dipyridamole testing is useful in detecting patients with coronary artery disease. Furthermore, ventricular asynergies detected during the test show a high correspondence with site of myocardial perfusion defects at thallium scanning.