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To evaluate the incidence of unexplained falls in elderly patients affected by fall-related fractures admitted to orthopaedic wards, we recruited 246 consecutive patients older than 65 (mean age years, range 65–101). Falls were defined “accidental” (fall explained by a definite accidental cause), “medical” (fall caused directly by a specific medical disease), “dementia-related” (fall in patients affected by moderate-severe dementia), and “unexplained” (nonaccidental falls, not related to a clear medical or drug-induced cause or with no apparent cause). According to the anamnestic features of the event, older patients had a lower tendency to remember the fall. Patients with accidental fall remember more often the event. Unexplained falls were frequent in both groups of age. Accidental falls were more frequent in younger patients, while dementia-related falls were more common in the older ones. Patients with unexplained falls showed a higher number of depressive symptoms. In a multivariate analysis a higher GDS and syncopal spells were independent predictors of unexplained falls. In conclusion, more than one third of all falls in patients hospitalized in orthopaedic wards were unexplained, particularly in patients with depressive symptoms and syncopal spells. The identification of fall causes must be evaluated in older patients with a fall-related injury.

BACKGROUND: Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are associated with high rates of mortality in elderly subjects. Concurrent CHF and COPD frequently occur, especially in with advancing age. This study examines long-term mortality in community-dwelling elderly subjects affected by CHF alone, COPD alone, and coexistent CHF and COPD. METHODS: The study evaluated 12-years mortality in 1288 subjects stratified for the presence or absence of CHF or COPD alone, and for coexistence of CHF and COPD. RESULTS: Mortality, at 12 year follow-up, was 46.7% overall, 68.6% in the presence of CHF alone (p

Background Several studies suggest transient ischemic attack (TIA) may be neuroprotective against ischemic stroke analogous to preinfarction angina's protection against acute myocardial infarction. However, this protective ischemic preconditioning-like effect may not be present in all ages, especially among the elderly. The purpose of this study was to determine the neuroprotective effect of TIAs (clinical equivalent of cerebral ischemic preconditioning) to neurologic damage after cerebral ischemic injury in patients over 65 years of age. Methods We reviewed the medical charts of patients with ischemic stroke for presence of TIAs within 72 hours before stroke onset. Stroke severity was evaluated by the National Institutes of Health Stroke Scale and disability by a modified Rankin scale. Results We evaluated 203 patients (≥65 years) with diagnosis of acute ischemic stroke and categorized them according to the presence (n = 42, 21%) or absence (n = 161, 79%) of TIAs within 72 hours of stroke onset. Patients were monitored until discharged from the hospital (length of hospital stay 14.5 ± 4.8 days). No significant differences in the National Institutes of Health Stroke Scale and modified Rankin scale scores were observed between those patients with TIAs and those without TIAs present before stroke onset at admission or discharge. Conclusion These results suggest that the neuroprotective mechanism of cerebral ischemic preconditioning may not be present or functional in the elderly.

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.

Because no controlled clinical studies are available about the possible role of angiotensin II receptor blockers in preventing effort myocardial ischemia, we evaluated the effect of angiotensin II receptor blocker/losartan in preventing exercise-induced myocardial ischemia in patients with coronary artery disease. Twenty-four sedentary patients with chronic stable ischemia were prospectively randomized to 28 days (double blind) of losartan 100 mg or losartan placebo in 2 divided doses. In each patient the treatment was crossed over to the alternative regimen (28 days, double blind) after a 1-week placebo period (single blind). At the end of each phase a new exercise stress test was performed. At baseline, systolic blood pressure was significantly decreased after losartan 100 mg compared with losartan placebo. At submaximal exercise, systolic blood pressure and rate-pressure product were lower after losartan 100 mg administration compared with losartan placebo, and these findings remained significant at 1-mm ST depression and at peak exercise. Losartan 100 mg administration versus losartan placebo significantly delayed the time to 1-mm ST-depression onset and decreased ST-segment depression at peak exercise and time to recovery of ST-segment depression. Losartan 100 mg administration compared with losartan placebo was able to significantly increase exercise duration and maximal workload during exercise stress testing. In conclusion, in our study, losartan decreased electrocardiographic parameters of myocardial ischemia in patients with coronary artery disease, suggesting a possible role of this drug in treatment of patients with effort myocardial ischemia.

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.

Downregulation of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) are shown to be involved in age-dependent impairment of angiogenesis. In this study, we explore whether prior exercise is able to affect these molecular patterns favorably and to enhance neoangiogenesis in old Wistar rats with hind-limb ischemia. At day 7 after surgery, HIF-1alpha and VEGF expression increased in the ischemic muscle of trained animals. Exercise increased capillary density and limb perfusion as revealed by histologic, angiographic, and dyed bead techniques. Furthermore, exercise capacity and limb trophism have significantly improved in trained aged rats. In these animals, the reduction of VEGF serum levels has reflected the comprehensive improvement in local ischemia evoked by exercise. In conclusion, prior exercise represents a valid tool to counteract age-related molecular alterations resulting in impaired angiogenesis in response to ischemia.

Mortality related to heart rate (HR) increase in the elderly has not yet been well established. To ascertain the relationships among cognitive impairment (CI), mortality, and HR increase, the authors prospectively studied a random sample of elderly subjects stratified according to presence or absence of CI. Elderly subjects randomly selected in 1991 (n = 1332) were followed up for 12 years. Mortality was established in 98.1% of the subjects. When HR was stratified in quartiles (69, 70-75, 76-80, and80 bpm), mortality was linearly associated with increased HR in all (from 47.7 to 57.0; r2 = .43, p = .019) and in subjects without (from 41.7 to 51.1%; r2 = .50, p = .043) but not in those with CI (from 57.5 to 66.1; r2 = .20, p = .363). Cox regression analysis, adjusted for several variables, shows that HR doesn't predict mortality in all subjects (RR 0.69; 95% CI = 0.27-1.73) or in those with CI (RR 0.91; 95% CI = 0.81-1.02). In contrast, HR predicts mortality in subjects without CI (RR 1.10; 95% CI = 1.00-1.22). Hence, HR increase is a predictor of mortality in elderly subjects without CI. However, when considering all elderly subjects and those with CI, HR increase seems to have no effect on mortality. Thus, CI should be considered when focusing on HR increase as risk factor for mortality in the elderly.

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 Heart rate recovery (HRR), defined as the fall in HR during the first minute after exercise, is a marker of vagal tone, which is a powerful predictor of mortality in patients with coronary artery disease and in older patients. Whether exercise training (ET) modifies HRR in elderly patients recovering from acute myocardial infarction (AMI) is still unknown. Therefore, this study aims at evaluating the effect of ET on HRR in elderly AMI patients. METHODS This was a prospective observational study including 268 older patients after AMI (217 men, 51 women), subdivided in two groups: Group A (n = 104), enrolled in an ET program; Group B (n = 164), discharged with generic instructions to continue physical activity. At baseline and at 3-month follow-up, all Group A and 54/164 Group B patients underwent a cardiopulmonary exercise stress test, whereas 110/164 Group B patients underwent an exercise stress test. RESULTS After completion of the ET program, in Group A we observed an improvement in oxygen consumption at peak exercise (VO2peak; from 14.7 +/- 1.3 to 17.6 +/- 1.9 mL/kg/min, p < .001), in the rate of increase of ventilation per unit of increase of carbon dioxide production (VE/VCO2slope; from 34.2 +/- 3.8 to 30.4 +/- 3.0, p < .001), and in HRR (from 13.5 +/- 3.7 to 18.7 +/- 3.5 beats/min, p < .001). The changes in VO2peak and in VE/VCO2slope after ET were correlated with the improvement of HRR (r = -0.865, p < .01; r = -0.594, p < .01, respectively). No changes in these parameters were observed in Group B patients. CONCLUSIONS In older AMI patients, ET results in HRR improvement, which was correlated to the improvement in cardiopulmonary parameters. These findings may shed additional light on the possible mechanisms of the beneficial prognostic effects of ET in this patient population.

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

Background: Controversial data are available on the association between mortality, blood pressure and cognitive impairment in the elderly. Objective: To verify the role of blood pressure on mortality in an elderly population with and without cognitive impairment. Methods: A cross-sectional survey with a 6-year mortality evaluation was conducted in a region of southern Italy in elderly subjects with and without cognitive impairment. Subjects were divided into 4 groups on the basis of systolic, diastolic, mean and pulse blood pressure values. Results: Mortality shows a linear relationship with pulse blood pressure and a U-curve shape for diastolic blood pressure. This phenomenon was more evident in subjects with cognitive impairment showing the greatest risk of mortality at the lowest and highest levels of diastolic blood pressure. Conclusion: The study shows that mortality increases linearly with increasing blood pressure in the elderly. In contrast, mortality shows a U-shape curve for diastolic blood pressure; cognitively impaired patients with the lowest and highest diastolic blood pressures show the greatest relative risk of mortality.

Whether chronic obstructive pulmonary disease (COPD) carries a risk of cognitive dysfunction prior to the onset of arterial hypoxemia is not known. Our objective was to assess both the prevalence and main correlates of subclinical cognitive dysfunction in older patients with non-hypoxemic COPD.Home-dwelling non-demented subjects over 64 years of age consecutively attending 24 outpatient Departments of Respiratory Medicine or Geriatrics because of COPD (N = 233), asthma (N = 203), non-obstructive bronchitis (N = 92) or chronic non-respiratory and non-dementing diseases (controls, N = 1080) underwent a multidimensional assessment. Cognitive status was assessed by the Mini-Mental State Examination (MMSE). Independent correlates of MMSE24 were identified by logistic regression analysis. In order to limit the confounding effect of collinearity between COPD group membership and the 6' walked distance, a properly designed multivariate analysis was performed.Prevalence of MMSE24 ranged from 16.7% (controls) to 21.9% (COPD). Education9 years (Odds Ratio = 1.56, Confidence Intervals = 1.22-1.98), a score6 on the 15-item Geriatric Depression Scale (OR = 1.37, CI = 1.16-1.62). a 6' walked distance242 m (OR = 1.22, CI = 1.02-1.45), a Barthel Index greater than 80 (OR = 1.48, CI = 1.03-2.14) and a Forced Vital Capacity inferior to 80% of the predicted value (OR = 1.17, CI = 1.09-1.38) qualified as independent correlates of MMSE24. The multivariate analysis confirmed that groups had comparable MMSE scores.Non-hypoxemic COPD did not increase the risk of subclinical cognitive dysfunction in an older population.

Background Diabetes mellitus (DM) is associated with impaired prognosis in patients with heart failure (HF), but pathogenic mechanisms are unclear. In the failing heart, elevated β-adrenergic receptor (β-AR) activation by catecholamines causes G-protein-coupled receptor kinase-2 (GRK2) upregulation which is responsible for β-AR signalling dysfunction. Importantly, GRK2 expression, measured in peripheral lymphocytes of HF patients, correlates with levels of this kinase in the failing myocardium reflecting the loss of hemodynamic function. Moreover, HF-related GRK2 protein overexpression promotes insulin resistance by interfering with insulin signalling. The aim of this study was to assess lymphocyte GRK2 protein levels in HF patients with and without DM. Methods and materials Patients with a diagnosis of HF were enrolled in the study. All subjects underwent a complete clinical examination (including NYHA functional class assessment and echocardiography) and blood draw for serum N-terminal pro-brain natriuretic peptide (NT-proBNP), lymphocyte GRK2 and plasma norepinephrine (NE) levels. Demographic data including age, sex, medications, cardiovascular risk factors and presence of comorbidities were also collected. Results Two hundred and sixty-eight patients with HF (left ventricular ejection fraction [LVEF] 30·6 ± 7·6%) with and without DM were enrolled. No differences between the two groups were found in terms of demography, HF aetiology, LVEF, NYHA class, NE and NT-proBNP. GRK2 was significantly higher in patients with DM compared to non-DM. At multivariate linear regression analysis, LVEF, NE, NT-proBNP and diabetes came out to be independent predictors of GRK2 levels in the overall study population. Conclusion In HF patients, DM is associated with significantly more elevated lymphocyte GRK2 protein levels, likely reflecting more compromised cardiac β-AR signalling/function, despite similar hemodynamic status and neuro-hormonal activation compared to patients without DM. These findings contribute to explain the negative prognostic impact of DM in patients with HF.

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.

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.

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

The time course of the effects of intravenous or intracoronary administration of peptide leukotrienes on metabolic parameters and on systemic and coronary hemodynamics was evaluated in 15 patients with normal coronary arteries. Peptide leukotriene C4 (2 nmol given as a bolus intravenous injection) induced an early fall (at 2 min) in mean arterial pressure (P

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.

To determine which of the many clinical parameters routinely collected influence mortality in patients with low left ventricular ejection fraction (LVEF) (45% at radionuclide ventriculography), 128 elderly patients (mean age 79 +/- 3 years) with various heart diseases were prospectively followed for 3 years. Twenty-eight-percent had coronary heart disease, 16% hypertensive heart disease, 7% valvular heart disease. The remaining 62 patients (48%) made up a group comprising patients with primitive cardiomyopathy, cor pulmonary with no evidence of coronary heart disease, valvular disease or hypertensive heart disease. Thirty-four-percent of all patients were classified as having congestive heart failure (CHF). Age, sex and 37 clinical variables were analyzed using a Cox proportional model. Forty-four patients died, 36 (82%) of sudden cardiac death. Ten characteristics at study entry predicted an increased mortality risk: S3 gallop, number of clinical signsor= 3, LVEFor= 25%, New York Heart Association (NYHA) classor= III, dyspnea, digoxin treatment, rales, number of symptomsor= 4, asthenia, associated pulmonary disease. Long-term survival of very elderly patients with low ejection fraction is related to the functional capacity, the severity of symptoms and the number of clinical signs. Moreover a LVEFor= 25% selects a subgroup of patients at higher risk. Our results suggest that these variables may influence the long-term survival of elderly patients with heart disease. Further studies with a greater number of patients are necessary to better delineate the prognostic value of the clinical and instrumental variables routinely collected in these patients.

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.

We evaluated left ventricular (LV) mechanical efficiency in 23 elderly patients (mean age 67 +/- 2) with coronary artery disease (CAD) and in 22 patients younger than 65 years (mean age 49 +/- 8) with similar severity of CAD (2.4 +/- 0.8 and 2.2 +/- 0.8 vessels per patient, respectively) and history of myocardial infarction (34% and 41%, respectively). LV mechanical efficiency was calculated as the ratio of LV work per minute and myocardial O2 consumption. LV stroke volume was calculated from left ventriculography. Coronary blood flow was measured by thermodilution. Older patients had lower values of LV stroke volume (49 +/- 16 vs 73 +/- 16 mL, p < 0.005), ejection fraction (41 +/- 17 vs 58 +/- 17%, p < 0.05), LV stroke work (93 +/- 26 vs 131 +/- 41 g.m., p < 0.02) and LV work per minute (6.7 +/- 2.6 vs 9.3 +/- 2.7 kg.m./min, p < 0.05). Since myocardial O2 consumption was similar in the two groups, LV mechanical efficiency was lower in older CAD patients (16.2 +/- 15 vs 23.8 +/- 12%, p < 0.05). Thus, elderly patients with CAD show a reduced LV mechanical pump performance and efficiency, compared with younger patients with similar disease severity and history of myocardial infarction. These observations may contribute to understanding the higher frequency of congestive heart failure in elderly patients with CAD.

Background The evaluation of surgical risk is crucial in elderly patients. At present, there is little evidence of the usefulness of comprehensive geriatric assessment (CGA) as a part of the overall assessment of surgical elderly patients. Methods We verified whether CGA associated with established surgical risk assessment tools is able to improve the prediction of postoperative morbidity and mortality in 377 elderly patients undergoing elective surgery. Results Overall mortality and morbidity were 2.4% and 19.9%, respectively. Multivariate analysis showed that impaired cognitive function (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.15 to 4.22; P < .02) and higher Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (OR, 1.11; 95% CI, 1.00 to 1.23; P < .04) are predictive of mortality. Higher comorbidity is predictive of morbidity (OR, 2.12; 95% CI, 1.06 to 4.22; P < .03) and higher American Society of Anesthesiologists (OR, 2.18; 95% CI, 1.31 to 3.63; P < .001) and National Confidential Enquiry into Patient Outcome of Death score (OR, 2.03; 95% CI, 1.03 to 4.00; P < .04). Conclusions In elective surgical elderly patients, the morbidity and mortality are low. The use of CGA improves the identification of elderly patients at higher risk of adverse events, independent of the surgical prognostic indices.

Background and aims: Elderly subjects are characterized by a high prevalence of chronic obstructive pulmonary disease (COPD) and frailty. This study examined the predictive role of frailty on long-term mortality in elderly subjects with and without COPD. Methods: The study assessed mortality after a 12-year follow-up in 489 subjects with COPD and 799 subjects without COPD, selected in 1992. Frailty was assessed according to the Frailty Staging System scores ranging from 1 to 7. Results: After 12 years’ follow-up, mortality was 48.1% in subjects without and 60.7% in subjects with COPD (p

Background syncope is a common cause of hospitalisation in the elderly. However, morbidity and mortality in elderly patients with syncope is not well established. Methods two-hundred and forty-two patients older than 65 years consecutively referred to the participating centres for evaluation of transient loss of consciousness were enrolled in a multicentre 2-year longitudinal observational study. Mortality and syncope recurrences were recorded and multidimensionally evaluated at 6, 12, 18 and 24 months. Findings at 24 months, total mortality was 17.2% and syncope recurrence was 32.5%. Cardiac syncope was more frequent in deceased than in survivor patients (21.7 versus 12.3%; P = 0.03), whereas neuro-mediated (62.1 versus 66.2%; P = 0.357) and unexplained syncope (10.8 versus 11.8%; P = 0.397) did not differ between the two groups. Drug-induced and/or multifactorial syncope was less frequent in patients with syncope recurrence (5.7 versus 10.7%; P = 0.02). Kaplan-Meyer curves indicated that mortality and syncope recurrence increased significantly with age (P = 0.006 and P = 0.008, respectively). At multivariate analysis, mortality was significantly predicted by age and comorbidity (hazard ratios: 1.17 and 1.39, and 95% confidence interval 1.01-1.37 and 1.01-1.93, respectively), and syncope recurrence by age and disability (hazard ratio: 1.13 and 1.04, 95% confidence interval 1.01-1.25 and 1.04-2.25, respectively). Depression increased from baseline to the end of follow-up (from 28.3 to 41.4%; P = 0.001). Conclusions in our patients, mortality was related to increasing age and comorbidity, whereas recurrence was related to increasing age and disability. Cardiac syncope was more frequent in deceased than in survivor patients, and syncope recurrence was high despite a low incidence of unexplained syncope.

To evaluate and quantify the relationship between premature ventricular contractions (PVCs) and heart rate (HR), 57 patients (48 men and 8 women, mean age 59.8 ± 7.9 years) with severe PVCs (Lown-Wolf grade ≥3a) over 24 hours of Holter monitoring were studied. Twenty had no coronary artery disease (CAD), 25 had angiographically documented CAD, and 12 had acute myocardial infarction. All parameters of the 24-hour recordings from two ECG leads were measured by a Holter analyzer designed in our laboratory, based on fast microprocessors and controlled by a microcomputer. Scatter diagrams of the number of PVCs per minute as a function of HR and correlation coefficient were computed for various HR values corresponding to a total number of minutes greater than five. A positive correlation ( r ≥ 0.35) was found in most patients without CAD (85%); there was a complex relationship between the strength of the correlation and the presence of CAD or acute myocardial infarction because of a greater variability in the results of correlation coefficient analysis (coefficient of variation 62%, 208%, and 145% in patients without CAD, with CAD, and with acute myocardial infarction, respectively). The incidence of a positive correlation was similar in patients with Lown-Wolf grade III (63%), IVa (82%), or ≥IVb (67%) arrhythmias. The reproducibility of the correlation coefficient of the relationship between PVC frequency and HR was tested in 15 patients. The mean value of the correlation coefficient was 0.801 ± 0.169 for the first test and 0.805 ± 0.22 ( p = NS) for the second test. Results of our study show a positive correlation between PVCs and HR in patients without CAD but not in those with CAD or acute myocardial infarction. This is because of a greater variability in coefficient of correlation analysis in the latter patients, even though our mathematical model shows good short-term reproducibility.

Background— Multidimensional impairment of older patients may influence the clinical outcome of diseases. The aim of this study was to evaluate whether a Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment predicts short-term mortality in older patients with heart failure. Methods and Results— In this prospective study with a 1-month follow-up, 376 patients aged 65 and older with a diagnosis of heart failure were enrolled. A standardized comprehensive geriatric assessment that included information on functional (activities of daily living and instrumental activities of daily living), cognitive (Short Portable Mental Status Questionnaire), and nutritional status (Mini Nutritional Assessment), as well as on risk of pressure sore (Exton-Smith Scale), comorbidities (Cumulative Illness Rating Scale Index), medications, and social support network, was used to calculate the MPI for mortality using a previously validated algorithm. The New York Heart Association, the Enhanced Feedback for Effective Cardiac Treatment, and the Acute Decompensated Heart Failure National Registry regression model scores were also calculated. Higher MPI values were significantly associated with higher 30-day mortality, both in men (MPI-1, 2.8%; MPI-2, 15.3%; MPI-3, 47.4%; P =0.000) and women (MPI-1, 0%; MPI-2, 6.5%; MPI-3, 14.6%; P =0.011). The discrimination of the MPI was also good, with areas under the receiver operating characteristic curves (men: 0.83; 95% CI, 0.75 to 0.90; women: 0.80; 95% CI, 0.71 to 0.89) greater than receiver operating characteristic areas of New York Heart Association (men: 0.63; 95% CI, 0.57 to 0.69; P =0.015; women: 0.65; 95% CI, 0.55 to 0.75; P =0.064), Enhanced Feedback for Effective Cardiac Treatment (men: 0.69; 95% CI, 0.58 to 0.79; P =0.045; women: 0.71; 95% CI, 0.55 to 0.87; P =0.443), and Acute Decompensated Heart Failure National Registry scores (men: 0.65; 95% CI, 0.52 to 0.78; P =0.023; women: 0.67; 95% CI, 0.49 to 0.83, P =0.171). Conclusions— The MPI, calculated from information collected in a standardized comprehensive geriatric assessment, is useful to estimate the risk of 1-month mortality in older patients with heart failure.

A mild stress such as brief ischemic episodes may protect the heart from a successive and more prolonged myocardial ischemia (ischemic preconditioning). This phenomenon is considered a typical “hormetic mechanism” by which the heart is immunized from pathological insults such as myocardial ischemia. This mechanism is reduced with aging and it may be restored and/or preserved by drugs such as adenosine or nicorandil, a mitochondrial KATP channels, and lifestyle interventions such as physical activity and/or hypocaloric diet. Moreover, since the mechanisms involved in cardiac ischemic preconditioning have been established basic and clinical investigators are encouraged to test several drug in well-controlled animal and human studies in order to prevent and/or restore the age-related reduction of ischemic preconditioning.

Background Preinfarction angina (PrA), clinical equivalent of ischemic preconditioning, confers protection against inhospital mortality for acute myocardial infarction (AMI) in adult but not in elderly patients. This study aims to examine the interaction between physical activity and body mass index (BMI) in preserving the cardioprotective effect of PrA in elderly patients with AMI. Design Elderly patients (Z65 years old) with AMI admitted to Coronary Care Unit. Methods Elderly patients with AMI were retrospectively stratified for the presence and absence of PrA, and for quartiles of BMI and physical activity. In-hospital outcomes (death, cardiogenic shock, and reinfarction and creatine kinase-MB peak) were evaluated. Results In-hospital mortality of 1014 elderly patients with AMI was 19.2% in those with PrA and 22.7% in those without (P = 0.18, NS). Mortality further decreased with increased physical activity and reduced BMI, a trend that was not observed in patients without PrA. When physical activity and BMI were considered together, lowest in-hospital mortality was observed in patients with highest physical activity and normal BMI (from 18.2 to 9.6%; P < 0.01) with the greatest reduction observed in patients with PrA (from 18.3 to 5.1%; P =0.02). Multivariate analysis showed that PrA did not exert a protective effect in all patients irrespective of physical activity and BMI. A protective role was, however, observed in patients with highest physical activity or normal BMI and reached a maximum protective role in patients who showed both highest physical activity and normal BMI [odds ratio =0.08; 95% confidence interval = 0.02–0.72; P < 0.01]. Conclusion The cardioprotective effect of PrA was preserved in elderly patients who showed the highest physical activity and a normal BMI.

We studied 54 patients with hypoxemic chronic obstructive pulmonary disease (COPD). The Mini Mental State Examination and the Mental Deterioration Battery were used for neuropsychological assessment. Heart rate variability (HRV) was assessed based on 24-h Holter ECG recording. Mann-Whitney test was used to compare HRV parameters of patients performing normally or abnormally on individual neuropsychological tasks. Spearman's rho was used to investigate the correlations between HRV parameters and neuropsychological scores, indexes of health status or COPD severity. Patients with defective performance at copying drawings with landmarks (CDL) test (N = 23) had lower very low frequency (VLF) power with respect to patients with normal performance (N = 31) (24 h: median 213; interquartile range 120-282 vs. 309; 188-431 ms2, p = 0.043; daytime: 202; 111-292 vs. 342; 194-397 ms2, p = 0.039). The CDL score correlated with the VLF power (24 h: rho = 0.27, p = 0.049; daytime: rho = 0.30, p = 0.028), and the normalized low frequency/high frequency (LF/HF) ratio (24 h: rho = 0.27, p = 0.05; daytime: rho = 0.33, p = 0.015). Sympathetic modulation decreased for increasing severity of COPD. In conclusion, drawing impairment correlates with depressed sympathetic modulation in patients with COPD, and both might be indexes of COPD severity.

Background: comorbidity plays a critical role in the high mortality for chronic heart failure (CHF) in the elderly. Charlson Comorbidity Index (CCI) is the most extensively studied comorbidity index. No studies are available on the ability of CCI to predict mortality in CHF elderly subjects. The aim of the present study was to assess if CCI was able to predict long-term mortality in a random sample of elderly CHF subjects. Methods: long-term mortality after 12-year follow-up in 125 subjects with CHF and 1,143 subjects without CHF was studied. Comorbidity was evaluated using CCI. Findings: in elderly subjects stratified for CCI (1‐3 and ≥4), mortality was higher in non-CHF subjects with CCI ≥4 (52.4% versus 70%, P < 0.002) but not in those with CHF (75.9% versus 77.6%, P = 0.498, NS). Cox regression analysis on 12 years mortality indicated that both CCI (HR = 1.15; 95% CI = 1.01‐1.31; P = 0.035) and CHF (HR = 1.27; 95% CI = 1.04‐8.83; P = 0.003) were predictive of mortality. When Cox analysis was performed by selecting the presence and the absence of CHF, CCI was predictive of mortality in the absence but not in the presence of CHF. Conclusion: CCI does not predict long-term mortality in elderly subjects with CHF.

Falls in the elderly are commonly and often wrongly identified as "accidental". We report a case of an elderly woman admitted to first aid for a trauma due to an accidental fall. Geriatric multidisciplinary evaluation revealed mild cognitive impairment associated with depressive symptoms; both findings made the anamnesis uncertain. Syncope algorithm was applied and "tachy-brady form of sick sinus syndrome" was diagnosed. Differential diagnosis between "accidental" and "apparently accidental" falls in elderly patients is very difficult but a multidisciplinary geriatric evaluation can clarify the correct diagnosis.

Aims: We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated beta-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise.Methods and results: Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 +/- 5%), increased LV end diastolic pressure (20.9 +/- 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac beta-adrenergic receptor downregulation and desensitization.Conclusions: Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.

We studied 149 patients with stable chronic obstructive pulmonary disease (COPD). Three clusters were generated (high, mid, and low level of cognitive function) based on 11 neuropsychologic scores; personal independence in basic/instrumental activities of daily living (BADL/IADL) of clusters was compared by discriminant analysis. Pattern of BADL/IADL was cluster-specific in 79.2% of high and 54.9% of low clusters, but only 20.8% of mid cluster. Self-administering drugs, continence, managing money, and dressing items had the greatest discriminatory capacity. Clusters had comparable respiratory function. In older COPD patients, dependence parallels cognitive impairment only to some extent. Indices of COPD severity are poor correlates of dependence.

Alterations in signal transduction pathway of G-protein-coupled receptors (GPCRs) have been found in the cerebrocortex and in the peripheral cultured tissues of patients with Alzheimer's disease (AD). The G-protein-coupled receptor kinase-2 (GRK2) plays an important role in regulating the GPCRs signaling: its increased expression is associated with receptor desensitization. The aim of this study was to explore GRK2 levels in peripheral lymphocytes of AD patients and to establish a correlation between lymphocyte protein concentrations and the degree of cognitive impairment. GRK2 mRNA and protein expression were evaluated in the lymphocytes of AD patients with mild or moderate/severe cognitive impairment and in age-matched healthy subjects. Both GRK2 mRNA and protein expression were higher in AD patients lymphocytes compared to controls. Furthermore, lymphocyte GRK2 levels were significantly correlated to the degree of cognitive decline. Our preliminary data suggest that GRK2 is involved in GPCRs coupling dysfunction observed in AD patients. Further studies are needed in order to verify whether the lymphocyte GRK2 might be utilized as a novel biomarker in AD diagnosis and clinical monitoring.

Exercise training and beta-blocker treatment ameliorate age-dependent impairment of beta-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation. Am J Physiol Heart Circ Physiol 293: H1596–H1603, 2007. First published June 8, 2007; doi:10.1152/ajpheart.00308.2007.— Cardiac beta-adrenergic receptor (*-AR) signaling and left ventricular (LV) responses to beta-AR stimulation are impaired with aging. It is shown that exercise and beta-AR blockade have a favorable effect on cardiac and vascular *-AR signaling in several cardiovascular diseases. In the present study, we examined the effects of these two different strategies on *-AR dysregulation and LV inotropic reserve in the aging heart. Forty male Wistar-Kyoto aged rats were randomized to sedentary, exercise (12 wk treadmill training), metoprolol (250 mg kg-1 day-1 for 4 wk), and exercise plus metoprolol treatment protocols. Ten male Wistar- Kyoto sedentary young rats were also used as a control group. Old trained, old metoprolol-treated, and old trained plus metoprololtreated rats showed significantly improved LV maximal and minimal first derivative of the pressure rise responses to beta-AR stimulation (isoproterenol) compared with old untrained animals. We found a significant reduction in cardiac sarcolemmal membrane beta-AR density and adenylyl cyclase activity in old untrained animals compared with young controls. Exercise training and metoprolol, alone or combined, restored cardiac beta-AR density and G-protein-dependent adenylyl cyclase activation in old rats. Although cardiac membrane G-proteinreceptor kinase 2 levels were not upregulated in untrained old compared with young control rats, both exercise and metoprolol treatment resulted in a dramatic reduction of G-protein-receptor kinase 2 protein levels, which is a further indication of beta-AR signaling amelioration in the aged heart induced by these treatment modalities. In conclusion, we demonstrate for the first time that exercise and beta-AR blockade can similarly ameliorate beta-AR signaling in the aged heart, leading to improved beta-AR responsiveness and corresponding LV inotropic reserve.

Cognitive dysfunction is common and clinically important in severe chronic obstructive pulmonary disease (COPD). We investigated the diagnostic accuracy of the Mini Mental State Examination (MMSE) and Instrumental Activities of Daily Living (IADL) scale in screening severe cognitive dysfunction in 149 patients with COPD, mean age 69.3 ± 8.5 years, forced expiratory volume in 1 s = 36.6 ± 17.8% of the predicted. Patients underwent the MMSE and an in-depth neuropsychological assessment based upon the Mental Deterioration Battery (MDB). The 5-item IADL scale was assessed. The sample was randomly divided into a training (n = 73) and a testing (n = 76) population. The diagnostic accuracy of MMSE, IADL scale or both versus cognitive dysfunction corresponding to abnormal performance in 3 or more MDB tests was assessed in the training population and the model obtained was tested in the testing population. The combination of MMSE

In Western countries, the aging and improving survival of patients with coronary heart disease are responsible for an increasing number of older adults (65 years of age and older) who are eligible for cardiac rehabilitation. The elderly with coronary heart disease represent a special population with changes induced by aging and lifestyle, comorbidity, cognitive dysfunction, and high risk of disability. Although the elderly account for the majority of cardiac admissions and procedures, studies on cardiac rehabilitation have traditionally focused on younger patients. In aged experimental animals, there is evidence that exercise training is able to improve hemodynamic parameters and biologic markers. Moreover, in older patients, exercise improves functional capacity and reduces myocardial work, similar to that seen in younger patients. As for younger patients, cardiac rehabilitation requires a multidisciplinary approach, including comprehensive assessment, treatment of risk factors and comorbidity, and psychosocial assessment. Cardiac rehabilitation is safe and helpful for elderly coronary patients. Physicians must be encouraged to prescribe cardiac rehabilitation programs for the elderly following major coronary events and coronary revascularization procedures.

Background The elderly are characterized by a high prevalence of chronic heart failure (CHF) and frailty, which is a complex interaction of physical, psychological and social impairment. This study aimed to examine the predictive role of frailty on long-term mortality in elderly subjects with CHF. Materials and methods The study assessed long-term mortality after 12-year follow up in 120 subjects with CHF and 1139 subjects without CHF, selected in 1992, from a random sample of the elderly population in the Campania region of Italy. Frailty was assessed according to a ‘Frailty Staging System’. Results Subjects with CHF were prevalently female (60%) and older than 75 years (mean 75·9 ± 6·7); subjects without CHF were prevalently female (56·4%) and younger than 75 years (mean 74·0 ± 6·3). In subjects with and without CHF stratified into classes of frailty there was a statistically significant increase in age, comorbidity, disability and low social support, and a decrease in MMSE score. Moreover, death progressively increased more with frailty in subjects (70·0% to 94·4%, P

The study evaluated the effect of Losartan in preventing nitrate tolerance during continuous transdermal nitroglycerin (TD-GTN) therapy in patients with coronary disease. Fifteen subjects with chronic stable ischemia evaluated by exercise test, were randomized to 28 days of TD-GTN 20 mg once a day without free interval plus Losartan 100 mg or Losartan-placebo with a double blind crossover design. Myocardial ischemic parameters during stress test were evaluated after each test period and results of Losartan therapy were compared to those with placebo. Time to onset 1 mm ST-depression was significantly higher after acute TD-GTN 20 mg with respect to placebo run-in, sustained TD-GTN 20 mg plus Losartan 100 mg or Losartan-placebo (p < 0.001). ST-depression at peak exercise and time to recovery of ST segment were markedly lower after acute TD-GTN 20 mg compared to placebo run-in (p < 0.05), sustained TD-GTN 20 mg plus Losartan 100 mg (p < 0.001) or Losartan-placebo (p < 0.05). At 1 mm-ST depression and at peak exercise, systolic blood pressure and rate-pressure product significantly decreased after sustained TD-GTN 20 mg plus Losartan 100 mg (p < 0.001, p < 0.05 respectively) with respect to placebo run-in, acute and sustained TD-GTN 20 mg plus Losartan-placebo. Moreover at peak exercise, these data were also observed after acute TD-GTN 20 mg compared to placebo run-in and sustained TD-GTN 20 mg plus Losartan-placebo (p < 0.001). The AT(1) antagonist Losartan administration does not prevent the development of nitrate tolerance during continuous TD-GTN therapy.

Many older patients, because of their high prevalence of coronary artery disease, are candidates for percutaneous coronary interventions (PCI), but the effects of vascular aging on restenosis after PCI are not yet well understood. Balloon injury to the right carotid artery was performed in adult and old rats. Vascular smooth muscle cell (VSMC) proliferation, apoptotic cell death, together with Akt induction, telomerase activity, p27kip1, and endothelial nitric oxide synthase (eNOS) expression was assessed in isolated arteries. Neointima hyperplasia and vascular remodeling along with endothelial cell regeneration were also measured after balloon injury. Arteries isolated from old rats exhibited a significant reduction of VSMC proliferation and an increase in apoptotic death after balloon injury when compared with adult rats. In the vascular wall of adult rats, balloon dilation induced Akt phosphorylation, and this was barely present in old rats. In arteries from old rats, Akt-modulated cell cycle check points like telomerase activity and p27kip1 expression were decreased and increased, respectively, compared with adults. After balloon injury, old rats showed a significant reduction of neointima formation and an increased vascular negative remodeling compared with adults. These results were coupled by a marked delay in endothelial regeneration in aged rats, partially mediated by a decreased eNOS expression and phosphorylation. Interestingly, chronic administration of l-arginine prevented negative remodeling and improved reendothelialization after balloon injury in aged animals. A decreased neointimal proliferation, an impaired endothelial regeneration, and an increase in vascular remodeling after balloon injury were observed in aged animals. The molecular mechanisms underlying these responses seem to be a reduced Akt and eNOS activity.

M agneslum sulfate (MgSO4) has been widely used in the last decades as treatment for supraventrlcular or ventricular arrhythmias, l,2 particularly in patients with coronary artery disease 3-6 Because a sustmned increase In heart rate during tachyarrhythmlas may provoke symptomatic or asymptomatic myocardial ~schemla in these patients, we thought it would be of interest to investigate whether this drug could also prevent myocardml ischemm associated with increased myocardial oxygen requirements. This is also in light of previous observations showing that MgSO 4 may beneficially affect myocardial oxygen supply/demand ratio by coronary vasodilatatlon, 7-1° probably due to its calcium antagonist effects. H Thus, we investigated whether MgSO 4 can reduce myocardial ischemia in response to atrial pacing m patients with fixed coronary artery disease and stable angma

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: Our objectives were to test the hypothesis that, in the geriatric population, chronic airway obstruction is associated with a higher prevalence of sleep disturbances; to identify the main correlates of sleep disturbances, and to verify whether asthma and COPD patients have different patterns of sleep disturbances. Methods: The EPESE questionnaire was administered to 734 patients aged 65 years and over with asthma or chronic obstructive pulmonary disease (cases) and 1237 individuals of comparable age who were free of respiratory disease but not of other chronic conditions (controls). Four sleep disturbances were quantified: difficulty in falling asleep, nocturnal awakening, morning tiredness, and early awakening. Multidimensional assessment of demographic data, personal history, clinical, and functional status was performed. Independent correlates of sleep disturbances were identified by logistic regression analysis. Results: One or more sleep disturbances were reported by 445 cases and 697 controls (60.6% vs. 56.4%, ns). Morning tiredness and early awakenings were more prevalent among cases (38% vs. 27.8%, p

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

We evaluated the anti-ischemic action and the effects on autonomic function of lercanidipine, a long-acting dihydropyridine calcium antagonist, in 25 patients with stable effort angina in a randomized, double-blind, parallel trial. After a 2-week placebo run-in period, patients entered a 2-week treatment period with 10 or 20 mg of lercanidipine once daily. During the placebo run-in period and at the study end, the patients underwent clinical examination, electrocardiography, exercise tests, 24-hour Holter electrocardiography for long-term heart rate variability evaluation, and short-term spectral analysis of heart rate and systolic blood pressure variability and plasma epinephrine and norepinephrine levels at rest and during tilting. Results showed that time to onset of ST segment depression > or =1 mm was significantly increased by both drug doses. No significant change was recorded in the average hourly heart rate after treatment with both 10 and 20 mg of lercanidipine. During the 24-hour recordings, no significant change was observed in low-frequency power, high-frequency power, or low frequency/high frequency. In the standing position, there was a significant increase in plasma norepinephrine and epinephrine concentration in both groups, and no change in the supine position after 10 and 20 mg of lercanidipine. When considering short-term heart rate variability, no significant difference was observed in either treatment group in low frequency, high frequency, or their ratio on electrocardiographic R-R spectra. The blood pressure spectral component was also unchanged. In conclusion, lercanidipine is effective in reducing ischemia in patients with stable effort angina. Moreover, lercanidipine does not cause adrenergic activation, which is the main mechanism hypothesized to explain the negative effect on cardiovascular mortality assigned to short-acting dihydropyridine calcium antagonists.

Background A reduction in the relative lymphocyte count is a marker of the stress response; however, its prognostic value remains undetermined. The objective of this study was to investigate the predictive value of the relative lymphocyte count for survival in elderly patients with congestive heart failure (CHF). Methods and Results One thousand two hundred seventy-four consecutive patients above the age of 65 years hospitalized with heart disease were enrolled in the CHF Italian Study and followed up for 3 years. Of these, 413 patients were excluded because of factors that could affect the lymphocyte count. Of the remaining 861 patients, 423 (49%) met the criteria for the diagnosis of CHF (mean age 76 ± 7 years, 51% men), of whom 162 patients (38%) had a relative lymphocyte count ≤20%. The 3-year all-cause mortality in patients with CHF and a relative lymphocyte count ≤20% was 64% compared with 40% in patients with a relative lymphocyte count >20% (P

OBJECTIVES The study investigated the effects of physical activity on preinfarction angina, a clinical equivalent of ischemic preconditioning (PC), in adult and elderly patients with acute myocardial infarction (AMI). BACKGROUND Preinfarction angina seems to confer protection against in-hospital mortality in adult but not in elderly patients. However, it has been experimentally demonstrated that exercise training restores the protective effect of PC in the aging heart. METHODS We retrospectively verified whether physical activity preserved the protective effect of preinfarction angina against in-hospital mortality in 557 elderly patients with AMI. Physical activity was quantified according to the Physical Activity Scale for the Elderly (PASE). RESULTS In-hospital mortality was 22.2% in elderly patients with preinfarction angina and 27.2% in those without (p = 0.20). When the PASE score was stratified in quartiles (0 to 40, 41 to 56, 57 to 90, >90), a high score was strongly associated with reduced in-hospital mortality (30.8%, 32.2%, 17.2% and 15.3%, respectively, p < 0.001 for trend). Interestingly, a high level of physical activity reduced in-hospital mortality in elderly patients with preinfarction angina (35.7%, 35.4%, 12.3% and 4.23%, respectively, p < 0.001 for trend) but not in those without (23.0%, 27.2%, 26.0% and 35.0%, respectively, p = 0.35 for trend). Accordingly, the protective role of preinfarction angina on in-hospital mortality was present only in elderly patients showing a high level of physical activity (adjusted odds ratio, 0.09; 95% confidence interval, 0.01 to 0.57; p < 0.05). CONCLUSIONS Physical activity and not preinfarction angina protects against in-hospital mortality in elderly patients with myocardial infarction. Nevertheless, the protective effect of preinfarction angina is preserved in elderly patients with a high level of physical activity.

Background: Hearing impairment (HI) is a very common condition in elderly people and the epidemiology together with hearing-related problems is still poorly investigated. Moreover, the cognitive status may be impaired in relation to hearing function. Objective: The goal of the study was to evaluate: (a) the prevalence of HI in a random sample of elderly people aged 65 and over (n = 1,750) living in Campania, a region of southern Italy; (b) the cross-sectional relationship between hearing function and cognitive status and also depressive symptomatology and disability, and (c) to assess the role of hearing aids on depressive symptomatology. Methods: Cross-sectional study on a random sample of elderly population. Results: The overall participation rate in the study was 74.8% (n = 1,332, mean age was 74.2 ± 6.4 years). The prevalence rate of HI (evaluated by questionnaire) was 27.2%, cognitive impairment prevalence (evaluated by the Mini-Mental State Examination (MMSE)) was 27.9%, mean depressive symptomatology score (evaluated by Geriatric Depression Scale (GDS)) was 11.4 ± 6.6, while disability assessed by Activity of Daily Living (ADL) was present in 7.0% of the whole population. A strong relationship was found between both decreasing hearing function and MMSE decline, independently by the effect of age and education (r = 0.97; p < 0.01). A positive relationship (r = 0.85; p < 0.01) between GDS score and hearing function was also found. Moreover, at an increased level of hearing loss, a lower ADL score was recorded (r = 0.98; p < 0.01). Finally, the use of hearing aids reduced GDS score. In logistic regression analysis, gender, age and educational level indicate that hearing loss risk increased with age (odds ratio 1.60; 95% confidence interval 1.53–1.71), whereas education plays a protective role (odds ratio 0.75; 95% confidence interval 0.72–0.80). Conclusion: HI is very prevalent among elderly people and is associated with either cognitive impairment and/or depression and reduction of functional status. This study suggests that hearing aids may protect against cognitive impairment and disability, improving quality of life of aged people.