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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.

Background: Preinfarction angina, a clinical equivalent of ischemic preconditioning, seems to protect against in-hospital death, cardiogenic shock, and the combined endpoints in adult but not in elderly patients with acute myocardial infarction. Experimental evidence indicates that caloric restriction may restore ischemic preconditioning in aged animals., Objective: The objective was to verify whether body mass index (BMI) influences the cardioprotective effect of preinfarction angina in the elderly., Design: We retrospectively studied 820 patients aged >/= 65 y with acute myocardial infarction by evaluating BMI and major (death and cardiogenic shock) and minor in-hospital outcomes., Results: In-hospital death, cardiogenic shock, and the combined endpoints were not significantly different between elderly patients with and without preinfarction angina. Interestingly, in-hospital death, cardiogenic shock, and the combined endpoints were significantly fewer in elderly patients with than without preinfarction angina in the subset of patients with the lowest BMI (P < 0.01, < 0.01, and < 0.01, respectively). Regression analysis showed that preinfarction angina did not protect against in-hospital death when analyzed in all patients independently of BMI, whereas it was protective in the subset of patients with the lowest BMI (odds ratio: 0.06; 95% CI: 0.00, 0.54)., Conclusions: Preinfarction angina does not protect against in-hospital death, cardiogenic shock, or the combined endpoints in elderly patients with acute myocardial infarction. With stratification by quartiles of BMI, the protective effect of preinfarction angina is preserved in elderly patients with the lowest BMI.

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., (Copyright 2003 S. Karger AG, Basel)

Aging is associated with alterations in beta-adrenergic receptor (beta-AR) signaling and reduction in cardiovascular responses to beta-AR stimulation. Because exercise can attenuate age-related impairment in myocardial beta-AR signaling and function, we tested whether training could also exert favorable effects on vascular beta-AR responses. We evaluated common carotid artery responsiveness in isolated vessel ring preparations from 8 aged male Wistar-Kyoto (WKY) rats trained for 6 wk in a 5 days/wk swimming protocol, 10 untrained age-matched rats, and 10 young WKY rats. Vessels were preconstricted with phenylephrine (10-6 M), and vasodilation was assessed in response to the beta-AR agonist isoproterenol (10-10-3 x 10-8 M), the alpha2-AR agonist UK-14304 (10-9-10-6 M), the muscarinic receptor agonist ACh (10-9-10-6 M), and nitroprusside (10-8-10-5 M). beta-AR density and cytoplasmic beta-AR kinase (beta-ARK) activity were tested on pooled carotid arteries. beta-ARK expression was assessed in two endothelial cell lines from bovine aorta and aorta isolated from a 12-wk WKY rat. beta-AR, alpha2-AR, and muscarinic responses, but not that to nitroprusside, were depressed in untrained aged vs. young animals. Exercise training restored beta-AR and muscarinic responses but did not affect vasodilation induced by UK-14304 and nitroprusside. Aged carotid arteries showed reduced beta-AR number and increased beta-ARK activity. Training counterbalanced these phenomena and restored beta-AR density and beta-ARK activity to levels observed in young rat carotids. Our data indicate that age impairs beta-AR vasorelaxation in rat carotid arteries through beta-AR downregulation and desensitization. Exercise restores this response and reverts age-related modification in beta-ARs and beta-ARK. Our data support an important role for beta-ARK in vascular beta-AR vasorelaxation.

Objective: 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 < 0.001, and 35.1% vs. 28%, p < 0.001, respectively). Depression, as assessed by the 15-item Geriatric Depression Scale, was the most significant independent correlate for all sleep scores. Both being a case and having arthritis were independent correlates of three out of the four sleep disturbances., Conclusions: Selected sleep disturbances are more common among elderly patients with chronic airway diseases than in those with chronic non-respiratory diseases. Depressed mood and coexisting arthritis are the most relevant independent correlates of sleep disturbances.

Study Objectives: This study investigated to what extent a diagnosis of COPD is erroneously made or the disease remains unrecognized in elderly asthmatic patients, and identified factors leading to misdiagnosis and underdiagnosis of asthma in such patients., Design: A multicenter study involving 24 Italian pulmonary or geriatric institutions., Patients: One hundred twenty-eight asthmatic patients (98 women, 76.6%) aged 73 +/- 6.4 years (mean +/- SD) were selected from the cohort of the Salute Respiratoria nell'Anziano (respiratory health in the elderly) study., Methods: All patients underwent a clinical evaluation that included clinical history and spirometry with a bronchodilator test. A diagnosis of asthma was based on criteria proposed by international guidelines adapted to the elderly population. A multidimensional geriatric assessment was performed to estimate physical and cognitive impairments and mood state. Finally, the diagnosis of respiratory disease previously made by a doctor, if any, was recorded., Results: Of asthmatic patients, COPD had been improperly diagnosed in 19.5%, whereas 27.3% of asthmatic patients did not report any previous diagnosis of asthma. The main correlates of misdiagnosis were older age and disability. Conversely, underdiagnosis was associated with better functional conditions, expressed by spirometry, even when wheezing or a significant response to the bronchodilator test occurred., Conclusions: Asthma in the elderly is frequently confused with COPD. Misdiagnosis can be related to older age and to greater degree of disability. Asthma in patients with mild functional impairment may be underdiagnosed in spite of overt respiratory symptoms suggestive of asthma.

Nitrate tolerance remains a problem despite an enormous number of studies on this phenomenon. The aim of the present study was to compare the efficacy of nitroglycerin transdermal patches intermittently or continuously administered to patients with myocardial ischemia evaluated by the echocardiography dipyridamole stress test. We prospectively studied 34 coronary patients with stable myocardial ischemia. A double-blind, randomized, crossover study technique was used. After a run-in period (1 week) they underwent a dipyridamole stress test to evaluate nitrate responsiveness and then were randomized to 1 week of transdermal nitroglycerine 20 mg/24 h (two patches of 10 mg/24) administered either intermittently or continuously for 1 week. During the following week all patients were given placebo. In the final week, therapy was crossed over the alternate regimen. No significant changes in heart rate, systolic and diastolic blood pressure and rate-pressure product were observed at basal conditions and at peak of dipyridamole infusion among patients after placebo run-in period, after acute, 1 week of intermittent and 1 week of continuous nitroglycerine administration. At peak of dipyridamole infusion after acute administration of nitrate we observed a significant decrease in wall motion score index with respect to placebo. This pattern was similar during intermittent, but not continuous, patch therapy (p < 0.001). Our results suggest that transdermal nitroglycerin patches are an effective anti-ischemic medication, in reducing transient myocardial ischemia induced by dipyridamole. This anti-ischemic effect is lost when an overnight nitrate free dose interval is not used. Moreover the dipyridamole echocardiographic stress test, besides evaluating myocardial ischemia-induced wall motion abnormalities, is adequate to assess both the efficacy and the tolerance of transdermal nitrate therapy.

Background and Aims: 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., Methods: 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 MMSE < 24 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., Results: Prevalence of MMSE < 24 ranged from 16.7% (controls) to 21.9% (COPD). Education < 9 years (Odds Ratio = 1.56, Confidence Intervals = 1.22-1.98), a score > 6 on the 15-item Geriatric Depression Scale (OR = 1.37, CI = 1.16-1.62). a 6' walked distance < 242 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 MMSE < 24. The multivariate analysis confirmed that groups had comparable MMSE scores., Conclusions: Non-hypoxemic COPD did not increase the risk of subclinical cognitive dysfunction in an older population.

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.

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.

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 thrombolysis 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 <65, n = 166) and older (age 65, n = 78) adult patients suffering their first Q-wave AMI, all receiving thrombolysis with human-recombinant tissue-type plasmin-ogen activator (100 mg total dose within 2.5 hours of the onset of AMI., Measurements: Infarct size was estimated by isoenzyme creatine kinase-myoglobin (CK-MB) release, measuring the area under the curve as a function of time. ST elevation, the sum of ST elevation above the baseline, and the sum of R wave height in precordial leads V1-V6 were evaluated using 12-lead electrocardiograms. Myocardial reperfusion was calculated when ST-segment elevation decreased more than 60 with respect to the most abnormal peak detected., Results: CK-MB peak level was significantly smaller in younger patients than in older ones (P< .01) and was significantly correlated with increasing age (P< .0001). Area under the 36-hour CK-MB curve was lower in younger patients than in older ones (P< .0001) and was well correlated with increasing age (P< .01). Reperfusion time was significantly shorter in younger patients (P< .05), and age was significantly correlated with reperfusion time (P< .001)., Conclusions: Infarct size was greater and reperfusion time was longer in older patients than in younger ones with first Q-wave AMI treated with thrombolysis. Infarct size and reperfusion time were linearly correlated with increasing age. These findings may help explain the increase in mortality due to AMI observed with advancing age.