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Background:Gender differences for incidence of dementia among elderly people have been usually investigated considering gender as a predictor and not as a stratification variable.Methods:Analyses were based on data collected by the Italian Longitudinal Study on Aging (ILSA), which enrolled 5,632 participants aged 65–84 years between 1992 and 2000. During a median follow-up of 7.8 years, there were 194 cases of incident dementia in the participants with complete data. Cox proportional hazard models for competing risks, stratified by sex, were defined to determine risk factors in relation to developing dementia.Results:The incidence rate of dementia increased from 5.57/1,000 person-years at 65–69 years of age to 30.06/1,000 person-years at 80–84 years. Cox proportional hazard models for competing risks of incidence of dementia and death revealed that, among men, significant risk factors were heart failure, Parkinson's disease, family history of dementia, mild depressive symptomatology and age, while triglycerides were associated with a lower risk of developing dementia. Significant risk factors in women were age, both mild and severe depressive symptomatology, glycemia ≥109 mg/dL, and a BMI < 24.1 kg/m2. Even as little as three years of schooling was found to be a significant protective factor against the incidence of dementia only for women.Conclusions:Our results suggest that there is an effect modification by gender in our study population in relation to the association between low education level, lipid profile, BMI, and glycemia and dementia.

Background Frailty is a clinical syndrome generally associated with a greater risk for adverse outcomes such as falls, disability, institutionalization, and death. Cognition and dementia have already been considered as components of frailty, but the role of frailty as a possible determinant of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) has been poorly investigated. We estimated the predictive role of frailty syndrome on incident dementia and its subtypes in a nondemented, Italian, older population. Methods We evaluated 2581 individuals recruited from the Italian Longitudinal Study on Aging sample population consisting of 5632 subjects aged 65 to 84 years and with a 3.9-year median follow-up. A phenotype of frailty according to a modified measurement of Cardiovascular Health Study criteria was operationalized. Dementia, AD, and VaD were classified using current published criteria. Results Over a 3.5-year follow-up, 65 of 2581 (2.5%) older subjects, 16 among 252 frail individuals (6.3%), of which 9 were affected by VaD (3.6%), developed overall dementia. In a proportional hazards model, frailty syndrome was associated with a significantly increased risk of overall dementia (adjusted hazard ratio: 1.85; 95% confidence interval: 1.01–3.40) and, in particular, VaD (adjusted hazard ratio: 2.68; 95% confidence interval: 1.16–7.17). The risk of AD or other types of dementia did not significantly change in frail individuals in comparison with subjects without frailty syndrome. Conclusion In our large population-based sample, frailty syndrome was a short-term predictor of overall dementia and VaD.

ACKGROUND: Preclinical cognitive changes may predict an increased risk of dementia, allowing selection of subgroups as possible targets for preventive or therapeutic interventions. OBJECTIVE: To evaluate the predictive effect of daily functioning and motor performance (MP) on the progression to dementia in normal cognition, cognitive impairment, no dementia (CIND), and mild cognitive impairment (MCI). METHODS: The Italian Longitudinal Study on Aging is a large population-based survey on age-related diseases of the cardiovascular and nervous systems. After the baseline assessment, to detect prevalent cases of cognitive impairment and dementia, participants were re-examined at 4-year and 8-year follow-ups. Functional independence was evaluated using the Index of Activities of Daily Living (ADL) and the Instrumental Activities of Daily Living (IADL) Scale. A six-test battery was used to assess MP. RESULTS: Overall, 2,386 individuals were included, for a total of 16,545 person-years. Eight-year incidence of dementia (per 1,000 person-years) was 12.69 in total sample, 9.86 in subjects with normal cognition at baseline, 22.99 in CIND, and 21.43 in MCI. Progression to dementia was significantly higher with increasing baseline ADL and IADL impairment, and with a worse MP. In Cox regression analyses controlled for demographics and major age-related conditions, increased IADL impairment was the stronger predictor of progression to dementia (p

Midlife elevated blood pressure and hypertension contribute to the development of Alzheimer's disease (AD) and overall dementia. We sought to estimate whether angiotensin-converting enzyme inhibitors (ACE-Is) reduced the risk of developing mild cognitive impairment (MCI) in cognitively normal individuals. In the Italian Longitudinal Study on Aging, we evaluated 1,445 cognitively normal individuals treated for hypertension but without congestive heart failure from a population-based sample from eight Italian municipalities with a 3.5-year follow-up. MCI was diagnosed with current clinical criteria. Dementia, AD, and vascular dementia were diagnosed based on DSM-IIIR criteria, NINCDS–ADRDA criteria, and ICD-10 codes. Among 873 hypertension-treated cognitively normal subjects, there was no significant association between continuous exposure to all ACE-Is and risk of incident MCI compared with other antihypertensive drugs [hazard ratio (HR), 0.45, 95% confidence interval (CI), 0.16–1.28]. Captopril exposure alone did not significantly modify the risk of incident MCI (HR, 1.80, 95% CI, 0.39–8.37). However, the enalapril sub-group alone (HR, 0.17, 95% CI, 0.04 –0.84) or combined with the lisinopril sub-group (HR, 0.27, 95% CI, 0.08–0.96), another ACE-I structurally related to enalapril and with similar potency, were associated with a reduced risk of incident MCI. Study duration exposure to ACE-Is as a “class” was not associated with incident MCI in older hypertensive adults. However, within-class differences linked to different chemical structures and/or drug potencies may exist, with a possible effect of the enalapril and lisinopril sub-groups in reducing the risk of incident MCI.

We investigated the relationship of metabolic syndrome (MetS) and its individual components with incidence of mild cognitive impairment (MCI) and its progression to dementia in a large longitudinal Italian population-based sample with a 3.5-year follow-up. A total of 2097 participants from a sample of 5632 65-84-year-old subjects from the Italian Longitudinal Study on Aging were evaluated. MetS was defined according to the Third Adults Treatment Panel of the National Cholesterol Education Program criteria. MCI, dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were classified using current published criteria. Among MCI patients those with MetS (N=49) had a higher risk of progression to dementia (HR, 4.40; 95% CI, 1.30-14.82) compared with those without MetS (N=72). After a multivariate adjustment, the risk in MCI patients with MetS approximately doubled (multivariate adjusted HR, 7.80, 95% CI 1.29-47.20) compared with those MCI without MetS. Finally, among non-cognitively impaired individuals there were no significant differences in risks of developing MCI in those who were affected by MetS (N=608) in comparison with those without MetS (N=837), as well as excluding those individuals with undernutrition or low inflammatory status with or without undernutrition. In our population, among MCI patients the presence of MetS independently predicted an increased risk of progression to dementia over 3.5 years of follow-up.

OBJECTIVES: To evaluate the prevalence of diarrhea and its association with drug use in elderly outpatients. METHODS: The study was carried out by 133 general practitioners (GPs) who referred to 24 geriatric units in Italy. The demographic data, disability, gastrointestinal symptoms, and current medications were evaluated using a structured interview, including the evaluation of the activities of daily living (ADL), the instrumental activities of daily living (IADL), and the gastrointestinal symptoms rating scale (GSRS). RESULTS: The study included 5,387 elderly subjects who regularly completed the structured interview. In total, 488 patients (9.1% of the whole population, 210 men and 278 women, mean age 75.6 6.2 yr, range 65–100 yr) reported diarrhea, that is, items 11 and 12 of the GSRS, during the 7-day period before the interview. The prevalence of diarrhea significantly increased with older age (P= 0.025), the severity of ADL (P < 0.0001) and IADL disability (P < 0.0001), and the number of drugs taken (P= 0.0002). A multivariate analysis demonstrated that the presence of diarrhea was significantly associated with the use of antibiotics (odds ratio [OR] 4.58, 95% confidence interval [CI] 1.95–10.73), proton pump inhibitors (OR 2.97, 95% CI 2.03–4.35), allopurinol (OR 2.19, 95% CI 1.26–3.81), psycholeptics (OR 1.82, 95% CI 1.26–2.61), selective serotonin reuptake inhibitors (OR 1.71, 95% CI 1.01–2.89), and angiotensin II receptor blockers (OR 1.46, 95% CI 1.08–1.99), also accounting for sex, age, and the use of antidiarrheal agents and drugs for functional gastrointestinal disorders. CONCLUSION: Diarrhea is a common problem in elderly outpatients. Its prevalence increases with old age, the severity of disability, and the number of drugs. Monitoring the presence of diarrhea and its complications in elderly patients who need treatments with drugs significantly associated with diarrhea may be clinically useful.

Objective To evaluate the prevalence of drug use by elderly outpatients in Italy and to identify the association between drug use and gastrointestinal symptoms. Study design and setting The study was carried out by 133 general practitioners (GPs) who referred to 24 geriatric units in Italy. All consenting elderly patients seen at the GPs’ offices were evaluated for gender, age, disability, current medications, and upper gastrointestinal symptoms. Results The study included 5,515 elderly subjects. The prevalence of drug use was 91.6%, and the mean number of drugs taken was 2.86 per person. Both the prevalence and the mean number of drugs significantly increased with advancing age. Regarding gastrointestinal symptoms, 32.7% of patients reported at least one upper gastrointestinal symptom: 25% with indigestion syndrome, 16.2% with abdominal pain, and 14.2% with reflux symptoms. A significantly higher prevalence of symptoms was observed in females, patients who were taking a higher number of drugs, and those who had higher disability. Adjusted multivariate analysis demonstrated that the use of nonsteroidal antiinflammatory drugs, steroids, psycholeptics, diuretics, selective β2 adrenoreceptor agonists or adrenergics, and antiplatelet drugs was significantly associated with upper gastrointestinal symptoms. Conclusion The prevalence of drug use is very high in this elderly outpatient population. The number of drugs and the use of some specific drug classes are significantly associated with the presence of upper gastrointestinal symptoms.

Summary Background: The association between coxib or non-steroidal anti-inflammatory drug use with gastrointestinal symptoms and drug prescriptions in ambulatory elderly patients is not well defined. Aim: To evaluate the association between non-steroidal anti-inflammatory drug NSAID and coxib use with gastrointestinal symptoms and therapies in elderly subjects managed by their general practitioner. Materials: The study was carried out by 133 general practitioners in Italy. By using a structured interview, sex, age, physical function, current medications, new drug prescriptions and upper gastrointestinal symptoms were registered from all elderly subjects who were referred to their general practitioners during a 2-week period. The numbers of hospitalizations, gastrointestinal bleeding events and gastrointestinal diagnostic procedures occurring during the last 6-month period were recorded. Results: Included in this study were 5515 elderly subjects. The overall prevalence of drug use was 92%. Musculo-skeletal drugs were taken by 15% of patients; NSAIDs were taken by 6%, and coxibs by 3% of patients. A significantly higher prevalence of upper gastrointestinal symptoms was observed in elderly NSAID users compared with coxib users and non-users of musculo-skeletal drugs (44% vs. 33% vs. 32% respectively, P = 0.001). The prescriptions of drugs for acid-related disorders were significantly higher in patients who were concomitantly taking NSAID rather than coxibs (13% vs. 6%, P

Background:Clinical studies have shown that hippocampal atrophy is present before dementia in people with memory deficits and can predict dementia development. The question remains whether this association holds in the general population. This is of interest for the possible use of hippocampal atrophy to screen population for preventive interventions. The aim of this study was to assess hippocampal volume and shape abnormalities in elderly adults with memory deficits in a cross-sectional population-based study.Methods:We included individuals participating in the Italian Project on the Epidemiology of Alzheimer Disease (IPREA) study: 75 cognitively normal individuals (HC), 31 individuals with memory deficits (MEM), and 31 individuals with memory deficits not otherwise specified (MEMnos). Hippocampal volumes and shape were extracted through manual tracing and the growing and adaptive meshes (GAMEs) shape-modeling algorithm. We investigated between-group differences in hippocampal volume and shape, and correlations with memory deficits.Results:In MEM participants, hippocampal volumes were significantly smaller than in HC and were mildly associated with worse memory scores. Memory-associated shape changes mapped to the anterior hippocampus. Shape-based analysis detected no significant difference between MEM and HC, while MEMnos showed shape changes in the posterior hippocampus compared with HC and MEM groups.Conclusions:These findings support the discriminant validity of hippocampal volumetry as a biomarker of memory impairment in the general population. The detection of shape changes in MEMnos but not in MEM participants suggests that shape-based biomarkers might lack sensitivity to detect Alzheimer's-like pathology in the general population.

We prospectively examined whether vascularfactors are related to an increased incidence of ChronicIdiopathic Distal Symmetric Neuropathy (CI-DSN) in anon-diabetic elderly population. In 8 Italian municipalities,2,512 men and women without both diabetes and CI-DSNat baseline are examined. Potential effect of vascular fac-tors was estimated by regressing new onset CI-DSN on theoccurrence of several vascular diseases and risk factors.Multivariate relative risks of CI-DSN were estimated byCox proportional hazards models. After 3.8 (±2.4) years offollow-up, we documented 51 incident CI-DSN cases. Atunivariate analysis, age, comorbidity, waist circumference,leg length, peripheral artery disease, and coronary heartdisease proved to increase the risk of developing CI-DSN.By multivariate analyses, only age (RR=1.08; 95 % CI,1.02–1.14), leg length (RR=1.05; 95 % CI, 1.01–1.1) andperipheral artery disease (RR=2.75; 95 % CI, 1.15–6.56)proved significant predictors of CI-DSN. Separate analysesby gender show that age is an independent predictor of CI-DSN both in men and in women, while PAD predicts thedisease only in men, together with body height. Incidenceof CI-DSN is higher in individuals carrying vascular con-ditions. In men, the presence at baseline of peripheralartery disease is associated with a threefold increase in therisk of developing CI-DSN. The incidence of neuropathy innon-diabetic individuals is associated with potentiallymodifiable vascular factors.

BackgroundDepression is recognized as being associated with increased mortality. However, there has been little previous research on the impact of longitudinal changes in late-life depressive symptoms on mortality, and of their remission in particular.MethodAs part of a prospective, population-based study on a random sample of 5632 subjects aged 65–84 years, with a 10-year follow-up of vital status, depressive symptoms were assessed by the 30-item Italian version of the Geriatric Depression Scale (GDS). The number of participants in the GDS measurements was 3214 at baseline and 2070 at the second survey, 3 years later. Longitudinal changes in depressive symptoms (stable, remitted, worsened) were examined in participants in both evaluations (n=1941). Mortality hazard ratios (MHRs) according to severity of symptoms and their changes over time were obtained by means of Cox proportional hazards regression models, adjusting for age and other potentially confounding factors.ResultsSeverity is significantly associated with excess mortality in both genders. Compared to the stability of depressive symptoms, a worsened condition shows a higher 7-year mortality risk [MHR 1.46, 95% confidence interval (CI) 1.15–1.84], whereas remission reduces by about 40% the risk of mortality in both genders (women MHR 0.55, 95% CI 0.32–0.95; men MHR 0.59, 95% CI 0.37–0.93). Neither sociodemographic nor medical confounders significantly modified these associations.ConclusionsConsistent with previous reports, the severity and persistence of depression are associated with higher mortality risks. Our findings extend the magnitude of the association demonstrating that remission of symptoms is related to a significant reduction in mortality, highlighting the need to enhance case-finding and successful treatment of late-life depression.

Congestive heart failure (CHF) has been proposed as a possible cause of cognitive dysfunction but only a few studies have directly assessed cognitive performance in CHF. The aim of the present study was to compare the cognitive patterns of patients with CHF and patients having cardiovascular diseases uncomplicated by CHF (no-CHF group). In a multicenter observational case-control study, we studied 149 hospitalized elderly CHF patients in the New York Heart Association (NYHA) class II (CHFm, m: moderate), 159 CHF patients in NYHA class III-IV (CHFs, s: severe), and 207 no-CHF patients. Patients underwent a multidimensional assessment and neuropsychological tests for the following cognitive domains: attention, visual-spatial intelligence, verbal attainment, verbal and visuo-spatial memory. Neuropsychological performances of groups were compared by multivariate analysis. Correlates of an abnormal performance on at least three neuropsychological tests were assessed by logistic regression analysis. CHFs performed worse than no-CHF patients on 4 of the 7 neuropsychological measures, the largest difference being in tests of attention and verbal learning (p < 0.001). Prevalence of abnormal performance on at least 3 tests was 57.9 % in CHFs, 43% in CHFm and 34.3 % in no-CHF groups (chi square = 17.3, p < 0.0001). The following qualified as independent correlates of the outcome at logistic regression analysis: CHFs group membership (Odds Ratio-OR = 2.56, 95% Confidence Interval-CI = 1.49-4.40), depression (OR = 2.37, 95% CI = 1.54-3.66), hypertension (OR = 1.88, 95% CI = 1.18-2.99). Our results demonstrate that cognitive impairment is common among CHF patients and seems to be causally related to CHF severity, depression and hypertension. The cognitive dysfunction also characterizes a relevant fraction of patients with cardiovascular diseases uncomplicated by CHF.

Objectives To investigate whether amnestic mild cognitive impairment (aMCI) is characterised by restriction in instrumental activities of daily living (IADL). Further, to examine the role of comorbidity and cognitive performance on IADL changes in aMCI subjects. Methods The study included 132 subjects with aMCI and 249 subjects with no cognitive impairment (NCI), consecutively enrolled as outpatients in a multicentric Italian clinical-based study, the ReGAl Project. All subjects underwent a comprehensive evaluation including clinical examination, laboratory screening, neuroimaging and cognitive and behavioral assessments. Functional status was evaluated by the Lawton's Instrumental Activities of Daily Living (IADL) scale. Comorbidity was evaluated by the Cumulative Illness Rating Scale (CIRS). Cognitive evaluation included tests assessing episodic memory, language, attention/executive functioning and praxis, as well as the the Mini-Mental State Examination (MMSE) as a measure of global cogniton. Results Subjects with aMCI had higher IADL changes than NCI. Among IADL items, aMCI subjects showed a significant impairment in shopping, taking drugs, and handling economy; however also NCI had minor IADL changes regarding cooking, washing and cleaning. IADL restriction in aMCI subjects was significantly associated with cognitive performance, mainly related to executive functioning, but not with comorbidity. On the contrary, in NCI sensory impairment accounts for slight IADL changes. Conclusion In aMCI subjects a mild degree of cognitive deterioration has a stronger impact on IADL than somatic comorbidity. Current diagnostic criteria for MCI should include a mild impairment in IADL. Copyright © 2007 John Wiley & Sons, Ltd.

Eleven insulin-dependent diabetes mellitus (IDDM) patients with angiographically normal coronary arteries and a normal hemodynamic response to an echocardiographic-dipyridamole test and 12 normal controls were studied at rest and after atrial pacing simultaneously sampling arterial and coronary sinus blood. In IDDM patients, despite hyperglycemia [10.0 +/- 2.0 (SE) mmol/l], myocardial glucose uptake was slightly lower than in controls. This process was significantly activated in both groups during atrial pacing. The isotopically calculated net flux of lactate across myocardium, in agreement with the net balance value based on unlabeled lactate-pyruvate arteriovenous differences, showed a net uptake in controls (3.5 +/- 0.6 mumol.min-1.1.73 m-2) and a net release in IDDM (12.4 +/- 2.6; P less than 0.01). Atrial pacing stimulated lactate uptake in both groups. Myocardial uptake of ketone bodies was significantly higher in IDDM (37.0 +/- 6.3 mumol.min-1.1.73 m-2) than in controls (10.1 +/- 3.4 mumol.min-1.1.73 m-2; P less than 0.01). Free fatty acid uptake was also significantly greater in IDDM than in controls (44.1 +/- 7.0 vs. 24.1 +/- 5.1 mumol.min-1.1.73 m-2; P less than 0.01). Alanine and branched amino acids were released by diabetic but not by control hearts at rest. The normalization of blood glucose concentrations restored normal patterns of lactate and ketone body kinetics across diabetic myocardium. In conclusion, 1) at rest, myocardial lactate and amino acid uptake is markedly impaired in IDDM without coronary artery disease, and 2) the metabolic abnormalities of the diabetic myocardium are not a primary phenomenon but rather a consequence of hypoinsulinemia and hyperglycemia because insulin administration, resulting in euglycemia, restored normal patterns of cardiac metabolism.

Oxygen radical-mediated injury has been implicated in the process of cardiac aging. We investigated the tolerance to oxidative stress of hearts from rats of different age. Langendorff-perfused hearts from 3-12-month-old rats received a 30 min infusion of the reactive oxygen specie hydrogen peroxide (H2O2, 60 microM), followed by a 15 min wash-out. H2O2 infusion resulted in a significantly larger increase in end-diastolic pressure in hearts of 6- and 12-month-old rats than 3 months (P

Background Regular physical activity has been shown to improve outcome of acute myocardial infarction (AMI) in the elderly population. The aim of this study was to evaluate whether the positive role of an active lifestyle on cardiac prognosis extends to elderly patients with AMI who undergo primary percutaneous transluminal coronary angioplasty (PTCA). Methods We prospectively studied 180 patients with AMI aged ≥70 years and treated with primary PTCA. In all patients, physical activity levels before AMI were quantified by a score derived from the Physical Activity Scale for the Elderly (PASE). Cardiac deaths and nonfatal cardiac events were evaluated within 30 days and 1-year from primary PTCA. Results A high PASE score was significantly associated with a strong reduction of 30-day cardiac deaths (from 23.1% to 4%; P for trend=.021) and overall nonfatal events (from 21.1% to 10%; P for trend=.01). Accordingly, at 1 year of follow-up, the incidence of cardiac mortality and nonfatal events significantly decreased with increasing PASE score (from 28.8% to 8% and from 55.7% to 14.5%, respectively). Logistic regression analysis indicated that physical activity before AMI was an independent predictor of increased survival in those patients that showed the highest PASE scores. In addition, at 6 months of follow-up, although low ejection fraction and recurrent angina strongly predicted 1-year mortality, high PASE scores still predicted a better outcome. Conclusions Our data indicate that an active lifestyle may favorably affect early and late outcomes of primary PTCA in the elderly population.

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

Several aspects of congestive heart failure are discussed in the light of international literature and of recent findings of our group. The annual incidence of heart failure in elderly subjects, agedor=75y, is 13 to 50/1000, while it is 1.6/1000 in people aged 45-54 y. The prevalence of heart failure is about 3% in subjects aged 45-64% in subjects aged more than 65 y and 10% in subjects aged more than 75 y. These data are confirmed by our population based study in elderly subjects. The etiology of congestive heart failure is similar in elderly and middle-aged patients. However, several anatomo-functional, hormonal and autonomic nervous system changes, typical of congestive heart failure, occur during physiologic ageing processes also. These findings may explain the dramatic evolution of congestive heart failure in elderly patients. Moreover, some features of the elderly - e.g. comorbidity, atypical clinical presentations, loss of autonomy, increased iatrogen risk should be considered. No specific drugs exist for the pharmacologic treatment of heart failure in the elderly, so that the geriatric specificity in the treatment of heart failure can be recognized in the art of drug choice and dosage, to obtain the best results with the least side effects. The multiple etiology of congestive heart failure, the comorbidity, the loss of autonomy and the deterioration of cognitive functions suggest the need for multidimensional approach and continuative intervention in elderly patients with heart disease, and in particular with congestive heart failure. Further studies on disease- and age-related changes are necessary to develop new and more potent strategies to secure 'successful ageing'.

The pathophysiological basis for the use of metabolic therapy in the treatment of heart failure is analyzed. Bioenergetical processes related to ATP bioavailability play a central role in regulating myocardial contractility at rest and on effort. Furthermore, a significant correlation has been demonstrated in diseased heart between ATP content, revealed at endomyocardial biopsy, and systolic and diastolic left ventricular indexes evaluated with invasive and noninvasive methods. Several international investigations demonstrate the beneficial effects of ubiquinone (coenzyme Q10) in the treatment of heart failure. Here the results of a study are reported that was conducted on patients with heart failure treated with ubiquinone. After 7 months of oral drug administration (100 mg/day), a significant improvement was observed in echocardiographic indexes of systolic function, cardiothoracic ratio, and clinical signs and symptoms of congestive heart failure. In conclusion, the introduction of metabolic drugs, such as ubiquinone, in the treatment of heart failure opens new horizons in the therapeutic approach to an ailment that entails substantial human and social costs.

Objectives Cognitive frailty, a condition describing the simultaneous presence of physical frailty and mild cognitive impairment, has been recently defined by an international consensus group. We estimated the predictive role of a “reversible” cognitive frailty model on incident dementia, its subtypes, and all-cause mortality in nondemented older individuals. We verified if vascular risk factors or depressive symptoms could modify this predictive role. Design Longitudinal population-based study with 3.5- and 7-year of median follow-up. Setting Eight Italian municipalities included in the Italian Longitudinal Study on Aging. Participants In 2150 older individuals from the Italian Longitudinal Study on Aging, we operationalized reversible cognitive frailty with the presence of physical frailty and pre-mild cognitive impairment subjective cognitive decline, diagnosed with a self-report measure based on item 14 of the Geriatric Depression Scale. Measurements Incidence of dementia, its subtypes, and all-cause mortality. Results Over a 3.5-year follow-up, participants with reversible cognitive frailty showed an increased risk of overall dementia [hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.02–5.18], particularly vascular dementia (VaD), and all-cause mortality (HR 1.74, 95% CI 1.07–2.83). Over a 7-year follow-up, participants with reversible cognitive frailty showed an increased risk of overall dementia (HR 2.12, 95% CI 1.12–4.03), particularly VaD, and all-cause mortality (HR 1.39, 95% CI 1.03–2.00). Vascular risk factors and depressive symptoms did not have any effect modifier on the relationship between reversible cognitive frailty and incident dementia and all-cause mortality. Conclusions A model of reversible cognitive frailty was a short- and long-term predictor of all-cause mortality and overall dementia, particularly VaD. The absence of vascular risk factors and depressive symptoms did not modify the predictive role of reversible cognitive frailty on these outcomes.

Objective Cognitive frailty is a condition recently defined by operationalized criteria describing the simultaneous presence of physical frailty and mild cognitive impairment (MCI). Two subtypes for this clinical construct have been proposed: "potentially reversible" cognitive frailty (physical frailty plus MCI) and "reversible" cognitive frailty (physical frailty plus pre-MCI subjective cognitive decline). Here the prevalence of a potentially reversible cognitive frailty model was estimated. It was also evaluated if introducing a diagnosis of MCI in older subjects with physical frailty could have an additive role on the risk of dementia, disability, and all-cause mortality in comparison with frailty state or MCI condition alone, with analyses separately performed for inflammatory state. Methods In 2,373 individuals from the population-based Italian Longitudinal Study on Aging with a 3.5-year-follow-up, we operationally categorized older individuals without dementia into four groups: non-frail/non-MCI, non-frail/MCI, frail/non-MCI, and frail/MCI. Results The prevalence of potentially reversible cognitive frailty was 1%, increasing with age and more represented in women than in men, and all groups were associated with significant increased incident rate ratios of dementia, disability, and mortality. A significant difference in rates of disability has been found between the MCI and non-MCI groups (contrasts of adjusted predictions: 0.461; 95% confidence interval: 0.187–0.735) in frail individuals with high inflammatory states (fibrinogen >339 mg/dL). Conclusion In older individuals without dementia and with elevated inflammation, a potentially reversible cognitive frailty model could have a significant additional predictive effect on the risk of disability than the single conditions of frailty or MCI.

OBJECTIVE Elderly subjects are characterized by a high prevalence of OA and clinical frailty. This study aimed to examine the predictive role of clinical frailty on long-term mortality in elderly subjects with and without OA. METHODS Mortality was evaluated after a 12-year follow-up in 698 subjects with and 590 subjects without OA recruited in 1992. Clinical frailty was assessed according to the Frailty Staging System and stratified in tertiles. RESULTS After a 12-year follow-up, mortality was 42.2% in subjects without and 55.8% in subjects with OA (P = 0.256). With increasing frailty, mortality increased by 30.5% (P for trend < 0.001) in subjects without and by 45.6% in subjects with OA (P for trend < 0.001). Multivariate analysis showed that frailty [hazard ratio (HR) = 1.49 for each unit of increase, 95% CI 1.32, 1.94, P < 0.001) but not OA (HR = 1.28, 95% CI 0.987, 1.39, P = 0.412) was predictive of long-term mortality. Moreover, when Cox regression analysis was performed, frailty enhanced the risk of long-term mortality for each unit of increase by 32% (HR = 1.32, 95% CI 1.06, 1.65, P = 0.03) in the absence of OA and by 98% in the presence (HR = 1.98, 95% CI 1.63, 2.95, P < 0.01) of OA. CONCLUSION Clinical frailty significantly predicts mortality in subjects without OA and even more in those with OA. Thus clinical frailty may be considered a new prognostic factor to identify subjects with OA at high risk of mortality.

Permanent AF is characterized by an increased mortality in elderly subjects with CHF. Moreover, AF increased the risk of mortality also in elderly subjects without CHF. Thus, we examined long-term mortality in community-dwelling elderly people with and without CHF. A total of 1332 subjects aged 65 and older were selected from the electoral rolls of Campania, a region of southern Italy. The relationship between AF and mortality during a 12-year follow-up in 125 subjects with CHF and in 1.143 subjects without CHF were studied. Elderly subjects showed a higher mortality in those with respect to those without AF (72.1% vs. 51.8%; p< 0.01). Similarly, elderly subjects without CHF showed a higher mortality in those with respect to those without AF (61.8% vs. 49.8%; p< 0.05). In contrast, elderly subjects with CHF showed a similar mortality in those with respect to those without AF (74.7% vs. 82.4%; p=. 0.234). Multivariate analysis shows that AF was predictive of mortality in all elderly subjects (Hazard Risk = HR = 1.39, 95% confidence interval (CI) = 1.25-2.82; p< 0.001). When the analysis was conducted considering the presence and the absence of CHF, AF was strongly predictive of mortality in elderly subjects without CHF (HR = 1.95, 95%CI = 1.25-4.51; p< 0.001) but not in those with CHF (HR = 1.12, 95%CI = 0.97-3.69; p=. 0.321). We concluded that AF is able to predict long-term mortality in elderly subjects. Moreover, AF is strongly predictive of long-term mortality in the absence but not in the presence of CHF. © 2011 Elsevier Ireland Ltd.

Background: Age-related effects on the ability of 6-min walking test (6MWT) and ejection fraction (EF) to predict mortality in coronary artery bypass grafting (CABG) patients undergoing cardiac rehabilitation (CR) is still debated. Design and methods: In order to verify the role of 6MWT and EF on all-cause mortality in patients undergoing CR following CABG, 882 CABG patients undergoing CR stratified in adults (

Background. an active lifestyle is associated with a reduced cardiovascular risk in middle-aged as well as in elderly patients. In the present study, we investigated the association between physical activity habits of elderly participants prior to coronary artery bypass grafting (CaBG) and survival free from both all-cause and cardiac death. Methods and Results. Study population consisted of 587 elderly patients ( ≥70 years) CaBG patients stratified, ac - cording to the Physical activity Scale for the Elderly (P aSE), into less active (low P aSE) and exercised (high P aSE) groups. at follow-up (mean: 44.3 ± 21.0 months), 33 (37.1%) of 89 total deaths occurred for cardiac causes. Sixty-month survival rate was 65% and 96% for low-P aSE and high-P aSE groups, respectively (log rank = 49.460, p < .0001). Cox survival analysis indicated a significant ( p < .0001) nonlinear association between P aSE score increments and improved survival with the most evident differences in the lowest score categories. a robust association was also found between low PaSE score and increased cardiac-related mortality ( p < .0001). Conclusions. our data indicate that a more active lifestyle is significantly associated with improved survival in elderly CaBG patients. The nonlinearity of the relation suggests that more sedentary patients could have the most benefit on survival by increasing their exercise lifestyle habits. The improved outcome is explained by both cardiac and overall mortality reduction.

Cognitive impairment is highly prevalent in chronic obstructive pulmonary disease (COPD) complicated by chronic hypoxemia, but the effect of cognitive training in patients with COPD has not been studied. The aim of the present study was to verify whether cognitive training can preserve cognitive abilities of patients with hypoxemic COPD. Our series consisted of 105 COPD patients with at rest (n = 36) or effort (n = 69) hypoxemia and free from concurrent dementing diseases. Neuropsychologic assessment included a screening test, the Mini Mental State Examination (MMSE), and a standardized confirmatory battery of neuropsychological tests, the Mental Deterioration Battery (MDB). After baseline assessment, patients were randomized to receive standardized multidimensional care (standardization of pharmacological therapy, health education, selection of inhalers according to patient's ability, respiratory rehabilitation, nutritional counseling, oxygen therapy, and control visits) with (n = 53) or without (n = 52) cognitive training aimed at stimulating attention, learning, and logical-deductive thinking. Cognitive performance was reassessed after 1.5, 4, and 6 months. The analysis of variance for repeated measures (ANOVA) having the group membership (study vs. control) as grouping factor was used to assess changes in cognitive performance. Both intervention and control groups showed no significant changes in cognitive performance except for a trend toward improvement in verbal fluency and verbal memory, but cognitive intervention had no significant effect. In conclusion, cognitive training seems ineffective in COPD. However, a multidimensional standardized therapeutic approach, as it was indistinctly provided to all patients, could help to slow or prevent cognitive decline.

OBJECTIVE: To assess the effectiveness of rehabilitation in a group of patients with active ankylosing spondylitis (AS) by the Assessment in Ankylosing Spondylitis (ASAS) Working Group response criteria. METHODS: Fifty-two active AS patients consecutively admitted to a rehabilitation inpatient clinic were enrolled. Patients underwent a 3-week intensive rehabilitation programme and were then discharged with home exercises. The primary outcome measure was the proportion of patients achieving a response based on ASAS 20 at discharge, and at 6 and 12 weeks after. Secondary outcome measures included an improvement in the Revised Leeds Disability Questionnaire (RLDQ) and function expressed as anthropometric measures. RESULTS: The ASAS 20 was achieved in 46 patients (88.5%) at the end of the rehabilitation, in 31 (59.6%) and in 17 (32.7%) patients at 6 and 12 weeks follow-up, respectively. The percentage of ASAS 20 responders statistically declined over time measured from the end of rehabilitation compared with 6 (P < 0.001) and 12 weeks follow-up (P < 0.001). Conclusion: The present study shows the effectiveness of rehabilitation as assessed by the ASAS 20, a validated instrument for treatment response, suggesting its usage in rehabilitation settings. Moreover, the results obtained show that the effectiveness of the intensive inpatient rehabilitation declined over time.

Low-to-high frequency ratio (LF/HF) is an indirect index of sympathovagal balance derived by heart rate spectral analysis. We investigated the effect of glucose ingestion on LF/HF in 17 healthy, normotensive young subjects (9 male, 8 female) with a wide body fat content range (body fat = 29 +/- 5.9%; range = 19-42%) and a normal thyroid hormone status. Before and after an oral glucose tolerance test (OGTT), the Holter technique and indirect calorimetry allowed us to determine heart rate and substrate oxidation in all subjects. At baseline, LF/HF correlated with body fat (r = 0.60, P < 0.005), waist-to-hip ratio (r = 0.57, P < 0.01), fasting plasma insulin (r = 0.55, P < 0.04), leptin (r = 0.56, P < 0.01), and norepinephrine (r = 0.58, P < 0.009) concentrations. Age-, body fat-, content-, and fat-free mass-adjusted respiratory quotient (r = 0.59, P < 0.007) and basal metabolic rate (r = 0.61, P < 0.001) were also correlated with basal LF/HF. Along with OGTT plasma glucose, insulin and norepinephrine concentrations and basal LF/HF significantly rose at 60 min and then declined throughout the test. Area under the curve (AUC) for LF/HF correlated with body fat (r = -0.66, P < 0.004), fasting plasma leptin concentration (r = -0.57, P < 0.01), glucose induced thermogenesis (r = 0.62, P < 0.001), glucose uptake (r = 0.59, P < 0.007), and AUC for plasma norepinephrine concentration (r = 0.63, P < 0.001). Water instead of glucose ingestion does not significantly affect LF/HF (n = 8). In conclusion, our study supports the hypothesis that glucose ingestion affects LF/HF and that such change is related to the amount of body fat.

SUMMARY 1. The actions of lidocaine on cardiac pacemaker rhythms were studied in anaesthetized dogs and in Purkinje fibres from hearts of the same animals. 2. In vivo, lidocaine (1 mg/ kg, intravenously) slowed the sino-atrial (SA) node rhythm (– 5.0%), and (during vagal stimulation) prolonged ventricular standstill by + 25.1% and slowed the idioventricular rhythm (– 16.7%). A higher dose (4 mg/kg) had more pronounced effects. 3. Propranolol also slowed sinus (– 26.2%) and idioventricular (– 27.2%) rhythms, and prolonged ventricular standstill (+ 36.8%). In the presence of propranolol, the effects of lidocaine on idioventricular rhythm were exaggerated. 4. In Purkinje fibres driven in vitro, lidocaine (10 μmol/L) decreased contractile force (– 47.9%) and (during the interruption of drive) prolonged the suppression of (+ 53.2%) and slowed the escape rhythm (– 67.0%). 5. In the presence of lidocaine the threshold potential was shifted to less negative values and diastolic depolarization slope was decreased (– 23.6%). 6. Lidocaine slowed spontaneously active Purkinje fibres, abolished early afterdepolarizations in low [K]0 and slow responses in high [K]0 (by shifting the threshold to less negative values), and antagonized strophanthidin arrhythmias. 7. TTX reduced the hyperpolarization by lidocaine in low [K]0 and vice versa. 8. We conclude that lidocaine enhances vagally-induced ventricular standstill by depressing the idioventricular rhythm far more than the sinus rhythm, an action enhanced by beta-blockade. Furthermore, lidocaine depresses normal and different types of abnormal automaticity through direct and indirect effects of the blockade of the fast sodium channel.

Cognitive impairment frequently occurs in elderly COPD patients, but little is known about its prognostic implications. We aimed at evaluating the prognostic role of cognitive impairment in patients with severe COPD.Our series consisted of 149 stable patients (mean [+/- SD] age, 68.7 +/- 8.5 years) with COPD and a Pao(2) of57 mm Hg at rest (n = 97) or at the end of the 6-min walking test (n = 37) who were enrolled in a prospective observational study. After a multidimensional baseline assessment, patients were followed up by telephone calls for a mean duration of 32.5 +/- 9.2 months (minimal follow-up duration, 24 months); 134 patients were successfully tracked. We used multivariable Cox proportional hazard analysis to identify predictors of death among clinical/functional variables that previously were shown to have prognostic implications and among neuropsychological indexes selected on the basis of univariate analysis.We observed 29 deaths over a median follow-up time of 32 months. Only the two following variables were independently associated with the outcome: an abnormal score on the copy with landmark test (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.34 to 6.39); and a 6-min walk distance of300 m (HR, 3.46; 95% CI, 1.15 to 10.5). A Pao(2) of57 mm Hg at rest (HR, 2.19; 95% CI, 0.93 to 5.18) and an FEV(1) of40% predicted (HR, 2.74; 95% CI, 0.99 to 7.57) were nearly significantly associated with the outcome, while Paco(2), body mass index, physical dependence, comorbid diseases, and the impairment of cognitive domains other than drawing impairment were unrelated to the outcome.Drawing impairment is a risk factor for mortality and might improve the assessment of hypoxemic COPD patients.

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have been promulgated to improve the management of chronic obstructive pulmonary disorder (COPD). Objective: To evaluate the extent to which the current therapeutic approach to COPD conforms to GOLD guidelines. Methods: This was a multicentre observational study of elderly COPD patients enrolled for acute care in general medicine or geriatric wards in tertiary hospitals in Italy in April 2002. Our series consisted of 471 patients >64 years of age consecutively admitted for acute exacerbations of COPD to wards participating in the study. Data describing drugs used prior to exacerbation and prescribed at discharge were collected using a standardised protocol. Changes in prescription at discharge were then compared with home therapy. Demographic variables and indices of COPD severity and co-morbidity were tested as potential correlates for the main outcome measure 'variant prescription', i.e. prescription of a drug considered as a third-line treatment (e.g. methylxanthines) or not recommended (e.g. mucolytics) by GOLD guidelines. The correlation was assessed first by univariate analysis and then by logistic regression analysis. Results: At discharge, prescription of short-acting β2-adrenoceptor agonists had decreased from 26.3% to 14.0%. Conversely, increases in prescription of long-acting β2- adrenoceptor agonists (from 43.1% to 68.4%), inhaled corticosteroids (50.7% to 69.6%) and anticholinergics (17.2% to 22.3%) were seen. The rate of use of methylxanthines was 49.7% before admission and 44.8% at discharge, with previous use being the main correlate of discharge prescription for this class of drugs (odds ratio [OR] = 4.35; 95% CI 2.88, 6.54). The rate of use of mucolytics was 26.3% before admission and 26.8% at discharge, with use of mucolytics prior to admission being the only correlate of discharge prescription (OR = 4.10; 95% CI 2.47, 6.82). Conclusions: Hospitalisation resulted in increased adherence to GOLD guidelines in patients with COPD, but the rate of use of anticholinergics was distinctly low and that of methylxanthines and mucolytics surprisingly high. A carry-over effect (i.e. of therapy prescribed by general practitioners on that prescribed by hospital-based physicians) likely accounts for most of the 'variant prescriptions' seen at discharge from the acute care hospital

Ischemic preconditioning (IP) has been proposed as an endogenous form of protection against ischemia reperfusion injury. IP, however, does not prevent post-ischemic dysfunction in the aging heart but may be partially corrected by exercise training and food restriction. We investigated the role of exercise training combined with food restriction on restoring IP in the aging heart. Effects of IP against ischemia-reperfusion injury in isolated hearts from adult (A, 6 months old), sedentary 'ad libitum' fed (SL), trained ad libitum fed (TL), sedentary food-restricted (SR), trained- and food-restricted senescent rats (TR) (24 months old) were investigated. Norepinephrine release in coronary effluent was determined by high performance liquid cromatography. IP significantly improved final recovery of percent developed pressure in hearts from A (p

Summary Orthostatic hypotension (OH) is a debilitating condition very common in the elderly that may leads to syncope. There is no single drug able to limit the fall in blood pressure in patients affected by OH when standing. In addition, the presence of hyperkinetic arrhythmias may worsen the fall in orthostatic blood pressure especially in elderly patients affected by OH. Unfortunately most of antiarrhythmic therapies lead to a decrease in blood pressure contrasting the effect of OH treatment. By contrast, disopyramide seems to have an anticholinergic effect that could play an important role in limiting the fall in blood pressure in participants with hyperkinetic arrhythmias and OH. We report a case of successful combination therapy of fludrocortisone, disopyramide and nonpharmacologic treatment in an elderly participant affected by neurogenic orthostatic OH and hyperkinetic arrhythmias with a poor quality of life and frequent syncope episodes.

We evaluated the antiischemic action and the effects on left ventricular response to exercise of lercanidipine, a long-acting dihydropyridine calcium antagonist, in 23 patients with stable effort angina in a randomized, double-blind, parallel trial. Left ventricular function was assessed during upright bicycle exercise using an ambulatory radionuclide detector for continuous noninvasive monitoring of cardiac function. Exercise was performed under control conditions before (run-in placebo period) and after 2-week treatment with lercanidipine 10 or 20 mg once daily. During the placebo run-in period and at the study end, patients underwent clinical examination, ECG, exercise tests, ambulatory ventricular scintigraphic monitoring (VEST). Results showed that both drug doses increased time to onset of ST segment depression >/=1 mm and peak ST segment depression, with improvement of total exercise duration. Heart rate, blood pressure, and the rate-pressure product did not significantly change with respect to pretreatment value. The left ventricular ejection fraction, indicating contractility state of myocardium, was unchanged at rest and during exercise after both lercanidipine doses. In conclusion, lercanidipine is safe and effective in reducing ischemia in patients with stable effort angina without any deterioration of cardiac function.

The purpose of this study was to assess whether different stages of chronic obstructive pulmonary disease (COPD) severity defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria correlate with meaningful differences in health status. A total of 381 COPD patients, aged 73+/-6 yrs, were classified in the five GOLD stages. Disease-specific (St George Respiratory Questionnaire (SGRQ)) and generic indexes of health status were measured in all patients. Multivariate analysis of covariance or Kruskal Wallis tests were used to compare health status indexes across the spectrum of GOLD stages of COPD severity. GOLD stages of COPD severity significantly differed in SGRQ components and Barthel's index, but not in the indexes assessing cognitive and affective status and quality of sleep. The largest variation in health status was observed at the transition from stage IIa to stage IIb, while there were no other significant differences between consecutive stages. Both female sex and comorbidity were associated with a greater impact of COPD on the health status. In conclusion, the upper limit of stage IIb (forced expiratory volume in one second of 49%) marks a threshold for dramatic worsening of health status. Progression of chronic obstructive pulmonary disease severity from stage 0 to stage IIa does not correspond to any meaningful difference in health status.

Background: Spirometry is more and more frequently used for the diagnosis of respiratory diseases in the elderly people. Unfortunately, reliable predictive values for the spirometric variables in the elderly are lacking. Objectives: Data obtained from 429 subjects participating in the multicenter Italian study SARA on respiratory health in the elderly were analyzed in order to derive reference values for spirometry in the age range of 65–85 years. The second aim of this study was to assess the influence of variables describing many dimensions of the health status on the prediction of spirometric variables in that age range. Methods: Subjects were recruited as consecutive outpatients referred during the study period to 24 geriatric or respiratory institutions distributed throughout Italy. Spirometries were performed using the same equipment by specifically trained and certified personnel supervised by a real-time quality control program. In addition to the standard anthropometric variables, covariates describing the affective, mental, and general health conditions were investigated through standardized questionnaires, to improve the modeling of spirometric outcomes. Results: Reliable predictive values for forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were produced (coefficient of determination, for FVC: R2 = 0.64; for FEV1: R2 = 0.54). The effect of general health conditions on spirometric outcomes accounted for the most part of the between-gender difference in the ageing-dependent decrease in lung function. Conclusions: We suggest that a multidimensional approach to health problems should be used for a better interpretation of spirometric results in the elderly.

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.

Background: The pharmacokinetics, efficacy, and safety of calcium channel blockers have rarely been investigated in the elderly. Gallopamil, a methoxy derivative of verapamil with calcium antagonistic properties, has been shown to be effective in the treatment of angina pectoris. Objective: The aim of this study was to assess the anti-ischemic action of gallopamil, its effects on left ventricular and autonomic function, and its pharmacodynamics and safety in elderly patients. Methods: We studied immediate-release (IR) and sustained-release (SR) formulations of gallopamil in 12 sedentary elderly patients with stable effort angina and angiographically documented coronary artery disease in a randomized, placebo-controlled, cross-over, double-blind trial. Following a run-in period, patients received either IR gallopamil 50 mg TID or SR gallopamil 100 mg BID for 28 days, after which patients crossed over to the alternate regimen. A washout period of 4 days was incorporated between the 2 treatment phases. Antianginal efficacy was assessed by monitoring the number of angina episodes per week and the amount of sublingual nitroglycerin consumed per week as well as sequential cycloergometer exercise testing 2 and 6 hours postdose. Patients underwent clinical examination, electrocardiography (ECG), echocardiography, 24-hour Holter ECG monitoring, and blood testing at the beginning of the study and at the end of each phase. On the last day of the active treatment period, sequential blood samples were collected to determine plasma levels of gallopamil. Results: Both IR and SR gallopamil reduced the number of angina episodes and the amount of nitroglycerin consumed per week. Gallopamil also reduced the number of ECG signs of ischemia at peak exercise testing, as well as symptomatic and asymptomatic ischemic episodes on 24-hour Holter ECG monitoring. IR and SR gallopamil did not affect left ventricular diameters, ejection fraction, and average heart rate, nor did they cause significant changes in heart rate variability. Peak plasma levels of gallopamil were reached rapidly after ingestion of the IR and SR formulations. The plasma concentrations of gallopamil and the norgallopamil metabolite were similar during the first 2 hours after administration of IR and SR gallopamil. Thereafter, patients who received the SR formulation showed significantly higher gallopamil (P < 0.05) and norgallopamil (P < 0.05) plasma concentrations than patients who received the IR formulation. The area under the concentration-time curve for SR gallopamil was significantly larger than for IR gallopamil; however, half-life, clearance, and peak plasma concentration were similar after IR and SR gallopamil treatment. Adverse effects, which were observed in 25% of patients, were minor and were not related to plasma levels of gallopamil; no patient suffered hemodynamic or major cardiac conduction abnormalities attributable to gallopamil. Conclusions: Our data suggest that both IR and SR gallopamil were effective in reducing signs and symptoms of ischemia in elderly patients with stable effort angina, with few adverse effects.

Objective: The aim of this double-blind, placebo-controlled, parallel- group, dose-response, pilot study was to assess the acute hemodynamic and therapeutic effects of a single dose of lercanidipine in patients with angina pectoris. Background: The calcium channel blocker lercanidipine is a new lipophilic, vasoselective dihydropyridine derivative with a slow onset and long duration of action that has been shown to be effective in hypertensive patients at a dosage of 10 to 20 mg/d. Methods: Forty-five patients (42 males, 3 females) with chronic stable angina pectoris and angiographically documented coronary artery disease received a single oral dose of lercanidipine 5 mg (n = 7), 10 mg (n = 8), 20 mg (n = 7), 30 mg (n = 7), or 40 mg (n = 8) or of placebo (n = 8). Anti-ischemic and antianginal efficacy was assessed by a bicycle exercise test 3 and 8 hours after dosing. Systolic and diastolic blood pressures and heart rate were assessed both at rest and during exercise. Results: Because of the small number of patients and high variability between the groups, no significant difference was seen compared with placebo. Nevertheless, a significant (P < 0.05) improvement in total exercise duration was observed 3 and 8 hours after dosing compared with baseline in patients receiving lercanidipine 10 mg and 40 mg. A significant improvement in time to ST-segment depression was also observed with all lercanidipine doses compared with baseline, and the maximal ST:segment depression decreased significantly in the 20- and 30-mg lercanidipine groups. An improvement in time to angina was observed with all lercanidipine doses except the 5-mg dose. Heart rate, systolic blood pressure, and rate pressure product remained unchanged at rest and during exercise after active treatment (all doses). No adverse effects caused by reflex tachycardia or acute hypotension were reported. Conclusions: Our data indicated that the acute administration of lercanidipine 10 mg to 40 mg in patients with stable exercise-induced angina pectoris caused no unfavorable change in myocardial oxygen consumption and was well tolerated.

Background. A reduction of exercise-induced ischemia in patients with coronary artery disease by means of brief period of exercise followed by resting is called the “warm-up” phenomenon. This phenomenon may represent a clinical counterpart of “ischemic preconditioning.” We studied the warm-up phenomenon in both adult and elderly patients with similar angiographic evidence of coronary artery disease, using three exercise tests after excluding the “training effect.” Methods. In order to verify the presence of “training effect,” three exercise tests were performed in days 1, 2, and 3 (“training” tests). The third test was used as baseline for a successive test, performed after a recovery period of 10 minutes to reestablish baseline electrocardiographic conditions. A third exercise test was performed 30 minutes later (“warm-up” tests). Results. “Training” tests did not differ in all parameters in both adult and elderly patients. “Warm-up” tests showed that time to onset 1-mm ST depression was significantly higher ( p , .001), whereas ST depression and time to recovery was significantly lower in the second and third test in adult but not in elderly patients ( p , .001). Difference (in seconds) in the time at which 1-mm ST depression occurred on first warm-up exercise compared with the second was inversely correlated with age ( p , .001). Conclusions. Previous exercise followed by resting is able to reduce the successive exercise-induced ischemia (“warm-up” phenomenon) in adult but not in elderly patients with coronary artery disease. This is independent of a greater age-related severity of coronary disease and of “training effect.” These results confirm the hypothetical agerelated reduction of “ischemic preconditioning” in aging heart.

It is known that platelet-derived serotonin at the site of coronary angioplasty induces an increase in coronary tone and plays a role in vasoconstriction after balloon angioplasty. The goal of the present investigation was to compare local release of serotonin with changes in coronary tone after coronary stenting and coronary angioplasty. Twenty patients with significant stenosis (> or =50% diameter narrowing) of the left anterior descending coronary artery were referred to traditional coronary angioplasty (10 patients; group 1) or high-pressure coronary stenting (10 patients; group 2). An additional 16 patients with similar angiographic characteristics were referred to the coronary angioplasty group (8 patients; group 1a) or stenting group (8 patients; group 2a) after pretreatment with ketanserin. Serotonin plasma levels in coronary sinus and coronary cross-sectional area distal to the site of dilatation were measured before and after bath revascularization procedures. In groups 1 and 1a, plasma serotonin levels in coronary sinus increased from basal values of 3.2+/-0.8 and 3.2+/-0.5 ng/ml to 29.5+/-13 and 25.6+/-9 ng/ml after ballooning (p

The aging heart appears to be more susceptible to ischemia-reperfusion injury than the adult heart. There is no evidence of an age-related difference in the threshold of myocardial ischemia and myocardial stunning. We studied the effects on mechanical, hemodynamic, and metabolic parameters of graded reduction of coronary perfusion pressure from 66 to 29 mmHg in isolated and perfused hearts from adult and senescent rats. Cardiac function was also assessed during recovery following ischemic period. In both adult and senescent hearts developed pressure and +dP/dt linearly decreased and end-diastolic pressure linearly increased with decreasing perfusion pressure. However, all mechanical parameters were more severely impaired in senescent than in adult hearts at 37 mmHg and 29 mmHg perfusion pressure, respectively (p < 0.01 vs. adult). At 29 mmHg, in both adult and senescent hearts lactate production similarly increased whereas creatine kinase leakage did not differ from controls. Developed pressure recovered more slowly in senescent than in adult hearts (p < 0.001) in the absence of cellular damage and in the presence of restoration of coronary flow. Lactate production observed at the same step of coronary perfusion pressure suggests that the ischemic threshold is similar in adult and senescent hearts. The slow recovery of myocardial contractility after the ischemic period observed in senescent hearts suggests an age-related increase in myocardial stunning.

OBJECTIVE: Inducing tolerance to myocardial ischemia by repeated brief episodes of ischemia has been called “ischemic preconditioning.” “Warm-up” phenomenon refers to patients with coronary heart disease improving performance after a first exertion and may represent a clinical counterpart to ischemic preconditioning. The goal of this study was to assess whether the severity of myocardial ischemia would be attenuated by two repeated walking-induced ischemic episodes in adult and older patients. SUBJECTS: Thirty-eight adults (51 ± 5 years) and 39 older patients (76 ± 4 years) with stable angina and angiographic evidence of coronary stenosis. MEASUREMENTS: Holter monitoring was performed in adult and older patients walking on two consecutive occasions, with a 5-minute rest between walks, a distance known to have previously caused myocardial ischemia. RESULTS:Computer-assisted analysis recorded by ambulatory Holter monitoring revealed that the mean maximal ST-segment depression (P < .001) and ischemia duration decreased (P < .001), whereas the ischemic threshold increased (P < .001), from the first to the second walk in the adult but not in the older group. CONCLUSIONS: Myocardial ischemia is attenuated and ischemic threshold is increased between two brief ischemic episodes in adult but not in older patients. These results indicate that the “warm-up” phenomenon, involved in increasing myocardial ischemic tolerance, is absent in the aging heart. J Am Geriatr Soc 47:1114–1117,1999.

Objective: Moderate alcohol consumption is related to a reduction of mortality. However, this phenomenon is not well established in the elderly, especially in the presence of chronic heart failure (CHF). The aim of the study was to verify the effect of moderate alcohol consumption on 12-year mortality in elderly community-dwelling with and without CHF. Settings: community-dwelling from 5 regions of Italy. Participants: A cohort of 1332 subjects aged 65 and older. Measurement: Mortality after 12-year follow-up in elderly subjects (≥65 years old) with and without CHF was studied. Moderate alcohol consumption was considered ≤250 ml/day (drinkers). Results: In the absence of CHF (n=947), mortality was 42.2% in drinkers vs. 53.7% in non-drinker elderly subjects (p=0.021). In contrast, in the presence of CHF (n=117), mortality was 86.5% in drinkers vs. 69.7% in non-drinker elderly subjects (p=0.004). Accordingly, Cox regression analysis shows that a moderate alcohol consumption is protective of mortality in the absence (HR=0.79; CI 95% 0.66-0.95; p

Elderly subjects are characterized by a high prevalence of diabetes and clinical frailty. This study aimed to examine the predictive role of clinical frailty on long-term mortality in elderly subjects with and without diabetes. The study evaluated mortality after 12-year follow-up in 188 subjects with diabetes and 1,100 subjects without diabetes selected in 1992. Clinical frailty was assessed according to the “Frailty Staging System” and stratified in tertiles. After 12-year follow-up, mortality was 50.5 % in subjects without and 66.5 % in subjects with diabetes (p < 0.001). With increasing frailty, mortality increases from 57.9 to 79.0 % (p for trend

In the present paper we discuss two issues about relationships between congestive heart failure and the brain. First, major acute cerebrovascular events are very frequent among elderly people, but stroke does not appear to be frequently associated with congestive heart failure. Second, some cardiovascular conditions may determine progressive damage of cerebral tissue, with consequent impairment of cognitive functions. The association of cognitive impairment and cardiovascular diseases may dramatically increase morbility and mortality risks in the elderly. Recent studies seem to show that hypotension and congestive heart failure are risk factors for dementia in elderly people. In view of this data, an Italian multicentric study on congestive heart failure in hospitalized elderly patients (CHF Italian Study I) included a brief screening of cognitive abilities (MMSE). The presence of congestive heart failure induced a significant decrease of MMSE scores: mean MMSE score after statistical adjustment for the other variables was about one point lower in patients with congestive heart failure respect to elderly patients affected by heart disease but without congestive heart failure. A novel multicentric study (CHF Italian Study II) has been performed to identify cognitive functions more specifically impaired during congestive heart failure in the elderly. Preliminary data relative to 385 patients, confirmed that congestive heart failure may induce a generalized impairment of cognitive functions. These data have relevant clinical implications because they demonstrate that a multidisciplinary approach is necessary in these patients, both for prevention and rehabilitation therapy.

A multicenter, double-blind, randomized, placebo-controlled trial was conducted to assess the effects of verapamil on total mortality, cardiac mortality, reinfarction, and angina after an acute myocardial infarction. All patients, aged 30 to 75 years, consecutively admitted for acute myocardial infarction between 1985 and 1987 to the participating centers, and without contraindications to verapamil or history of severe heart failure were enrolled. Seven to 21 days (mean 13.8) after myocardial infarction, 531 patients were randomized to verapamil retard 360 mg/day, and 542 patients to placebo. At baseline, the 2 groups of patients had similar characteristics. Mean age was 55.5 years and 91% were men. During a mean follow-up of 23.5 months, 5.5% of the patients died. No differences between verapamil and placebo were observed in total mortality (n = 30 and 29, respectively) and cardiac death (n = 21 and 22, respectively). The verapamil group had nonsignificant lower reinfarction rates (n =39 vs 49). The number of patients developing angina was significantly less in the verapamil group (n = 100 vs 132, RR = 0.8, 95% confidence interval 0.5 to 0.9). There were no differences in discontinuation of therapy caused by adverse reactions. This trial showed no effect of verapamil on mortality. The lower reinfarction rates found in the verapamil group are in agreement with the results of other studies.

Background Experimentally induced myocardial ischemia in animals causes tissue modifications that alter characteristics of the ultrasonic beam backscattered from the myocardial muscle. Alterations of backscatter parameters have been evidenced in human subjects with acute or remote myocardial infarction and during ischemia induced by angioplasty balloon occlusion or pharmacological stimuli. The effects of transient effort ischemia in humans have not been reported. The purpose of this study is to assess ultrasonic backscatter parameter changes induced by transient effort myocardial ischemia in human subjects. Methods and Results Nineteen patients with single left anterior descending coronary stenosis and 15 healthy subjects underwent ultrasonic backscatter analysis (parasternal long-axis view) at rest, immediately after a supine stress test, and 30 minutes later. Two windows were selected in each ultrasonic study: one encompassing the septum; the other, the posterior wall. Integrated backscatter was computed throughout the cardiac cycle, yielding a power curve relative to the midmyocardial region of the myocardial wall (excluding pericardial and endocardial borders). Five parameters were computed from the backscatter power curve: the maximum−minimum difference, amplitude and phase of the first harmonic Fourier fitting, phase-weighted amplitude, and time-averaged integrated backscatter difference from rest (an index of overall myocardial reflectivity). This protocol allowed comparison of the backscatter data from a region at risk of ischemia (the septum) with that from a region normally perfused (posterior wall) and a comparison with the same regions of the control group during the three ultrasonic studies. All backscatter indexes in the septum were altered significantly by exercise compared with rest values, whereas no changes were found in the normally perfused posterior wall or in the septum of the control group. All modified parameters returned to baseline values at the time of the recovery study. Conclusions These data indicate that transient, exercise-induced ischemia is associated with reduction of the cardiac cycle–dependent variation of the integrated backscatter power curve, a temporal shift in the nadir of the power curve with respect to the R wave (phase increase), and a small but detectable increase of myocardial reflectivity. These changes may be detected noninvasively in humans with ultrasonic backscatter analysis.

Fifteen patients with angiographic evidence of significant coronary artery disease, exertional myocardial ischemia, and positive dipyridamole echocardiographic test results at basal conditions and after 7 days of placebo treatment were prospectively studied to see whether captopril (containing sulfhydryl) and enalapril (nonsulfhydryl) modify myocardial ischemia induced by exercise testing and the effects of dipyridamole echocardiographic testing on regional myocardial contractility. Patients were randomized to captopril (150 mg/day in 3 separate doses) or enalapril (20 mg/day) for 1 week. At the end of this period each patient crossed over to the alternate regimen after a washout period of 7 days. Exercise stress testing and dipyridamole echocardiographic testing were repeated at the end of each treatment period. Neither captopril nor enalapril had a significantly greater anti-ischemic effect than placebo in any patient. Exercise duration, time to onset of ST-segment depression, maximal workload, degree of ST-segment depression, and rate-pressure product were not affected by either drug. Neither captopril nor enalapril improved dipyridamole-induced mechanical dysfunction or ST-segment depression.

It has been suggested that aging may enhance the deleterious effects of myocardial ischemia-reperfusion. This study evaluates the relationship between oxygen consumption and functional impairment during reperfusion following myocardial ischemia in adult and senescent rat hearts. Global ischemia induced a marked impairment of contractile function which was significantly higher in senescent than in adult hearts. During reperfusion postischemic dysfunction was more evident in senescent hearts: at the 10th minute, the developed pressure recovered less (p0.05) and end-diastolic pressure increased more (p0.05) in senescent than in adult hearts. However, oxygen consumption per unit of work was significantly higher throughout 60 min of reperfusion when compared to controls with no significant difference between adult and senescent hearts. This study demonstrates that following ischemia and reperfusion depression of function and inappropriately high oxygen consumption were observed in both adult and senescent hearts. However, aging was associated with greater contractile impairment, which occurred in the absence of further deterioration of metabolic efficiency of contraction.