We prospectively studied 10 patients with stable exertional ischaemia, selected from a larger group of patients referred for suspected coronary artery disease or to detect residual ischaemia after myocardial infarction, to evaluate pharmacokinetic changes during chronic treatment with gallopamil and its correlation with clinical efficacy in patients with coronary artery disease. Our study consisted of a 1-week run-in single-blind placebo treatment and a 4-week single-blind gallopamil treatment. At the end of the run-in period patients underwent two different exercise tests, the first 2 hours and the second 7 hours after placebo administration. During active treatment all patients underwent two different exercise tests, the first 2 hours and the second 7 hours after gallopamil (50 mg) administration on the 1st and 28th days of gallopamil therapy. On the same days in eight of the patients we evaluated gallopamil pharmacokinetic changes. Our data revealed a rapid increase of unchanged gallopamil and its metabolite (norgallopamil) in the plasma, and a peak concentration of these substances about 2 hour after oral administration on both the 1st and 28th day of observation. Moreover, our results demonstrated an increase between the first and 28th day of treatment in peak concentration of unchanged gallopamil in the plasma, and of AUC 0-infinity and AUC o-c values during chronic treatment with gallopamil. Our clinical data showed an improvement in exercise results during gallopamil therapy related to increased concentration of the drug.

Aged↗

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Some peculiarities of the glucoregulatory response to glucose infusion in the rat.

The glucoregulatory response to the i.v. infusion of different doses of glucose and glucose plus insulin was studied in anesthetized rats by using the primed constant infusion of glucose-2-3H. Infusion of glucose at the rate of 10 mg/kg/min induced a rise of about 100% in blood glucose, while the hepatic release of glucose showed only a small and transient decrease. A proportional increase of glycemia and glucose utilization (Rd) was observed without any appreciable change in the metabolic clearance rate (MCR) of glucose; a two-fold increase in plasma insulin was recorded at all times. In the group of rats receiving 20 mg/kg/min of glucose, changes in the above parameters were slightly greater; MCR showed a moderate increment in spite of the six-fold rise of plasma insulin. Finally, the influsion of large doses of insulin together with 20 mg/kg/min of glucose resulted in complete cessation of glucose release by the liver and in a remarkable increase of Rd and MCR. These results suggest a poor adaptability of the glucoregulatory system of the rat in response to glucose infusion as compared to other mammalian species.

Animals↗

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Congestive heart failure and cognitive impairment in the elderly.

Congestive heart failure (CHF) represents the most frequent cause of death and disability in the elderly. The prevalence of impairment of cognitive abilities is very high in aging and several clinical studies have demonstrated high association between cardiovascular diseases (in particular CHF) and cognitive deterioration. However, little attention has been paid to the decline of cognitive functioning during congestive heart failure in elderly patients. In this paper an overview of studies investigating this association is offered, suggesting that hemodynamic alterations due to heart failure and cognitive deteriorations are very frequently associated in aging, increasing morbidity and mortality risks. Moreover, preliminary results of a prospective study on hospitalized elderly patients with heart disease are reported (CHF Italian Study). These data show that some psychosocial variables (illiteracy, depression, and particularly cognitive deterioration) determine a significant increase of the risk to develop heart failure. This paper confirms that a multidimensional approach is necessary to better characterize and treat elderly patients, in particular those with CHF. More attention should be paid to encourage mild physical activity, to provide emotional support to patients and also to assess their general cognitive abilities. Studies on large populations of patients with heart disease have to be designed to investigate psychosocial and cognitive status in these patients.

Journal Article↗

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Clinical determinants of long-term mortality in elderly patients with heart disease.

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 signs >or= 3, LVEF or= III, dyspnea, digoxin treatment, rales, number of symptoms >or= 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 LVEF <or= 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.

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Tandem action of exercise training and food restriction completely preserves ischemic preconditioning in the aging heart.

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<0.01) but not in those from SL (p=NS) vs unconditioned controls. Developed pressure recovery was partial in hearts from TL and SR (64.3 and 67.3%, respectively; p<0.05 vs controls) but it was total in those from TR (82.3%, p=NS vs A; p<0.05 vs hearts from TL and SR). Similarly, IP determined a similar increase of norepinephrine release in A (p<0.001) and in TR (p<0.001, p=NS vs adult). IP was abolished by depletion of myocardial norepinephrine stores by reserpine in all groups. Thus, IP reduces post-ischemic dysfunction in A but not in SL. Moreover, IP was preserved partially in TR and SR and totally in TR. Complete IP maybe due to full restoration of norepinephrine release in response to IP stimulus.

Aging↗

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The brain in congestive heart failure.

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.

Journal Article↗

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Congestive heart failure in the elderly.

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, aged >or=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'.

Journal Article↗

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Direct coronary vasodilator effects of intracoronary histamine administration in humans.

Histamine is widely present in human tissues and can be released by immunologic and nonimmunologic reactions. Although several direct cardiovascular effects of histamine have been demonstrated in humans, little is known about the direct effects of histamine on the human coronary circulation in vivo. Therefore, we investigated the changes in coronary hemodynamics induced by bolus intracoronary administration of 4 micrograms of histamine to 11 patients with angiographically normal coronary arteries under continuous monitoring of R-R interval from the electrocardiogram, arterial pressure (AP), and coronary sinus blood flow (CBF), measured by thermodilution. Immediately after the end of the intracoronary histamine bolus, with R-R interval and AP unchanged, CBF increased from 144 +/- 20 to 238 +/- 27 ml/min (p less than 0.01) and coronary vascular resistance decreased from 0.7 +/- 0.16 to 0.42 +/- 0.1 mm Hg/ml/min (p less than 0.01). No change in coronary hemodynamics was observed after bolus intracoronary administration of physiologic saline. The effects of histamine on systemic hemodynamics consisted of a transient fall in AP and R-R interval, starting after the onset of changes in coronary hemodynamics. These data show that histamine possesses a direct coronary vasodilator effect in humans, independent of the determinants of myocardial oxygen consumption.

Adult↗

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Increased low-density lipoprotein peroxidation in elderly men.

BACKGROUND: Oxidative modification of low-density lipoprotein (LDL) appears to play a pivotal role in atherogenesis. The specific role played by LDL peroxidation in aging is not known. Since estrogens may protect LDL from peroxidation in vitro and in vivo, we chose to investigate only men of various ages. OBJECTIVE: To determine whether LDL from healthy elderly men was differently susceptible to peroxidation than LDL of young and adult men. SUBJECTS AND METHODS: LDL was isolated from 15 normolipidemic young (aged 19-23 years), 17 adult (aged 35-55 years), and 16 elderly (aged 77-90 years) healthy men. None of the men included in the study was a smoker or a hypertensive. LDL peroxidation was achieved by exposure to 5 mumol/l copper sulfate for 18 h at 37 degrees C, and some markers of lipid peroxidation (estimating various levels of peroxidation) were evaluated. RESULTS: The levels of lipid peroxides in LDL from our elderly men were already higher under basal conditions than were those both of adult and of young men. LDL from elderly men was more susceptible to peroxidation than was that of adult and young men. Furthermore, the lag time correlated inversely to age (r = -0.68, P < 0.01), whereas lipid peroxide and malonyldialdehyde levels correlated highly to age (r = 0.79 and r = 0.77, P < 0.0002 and P < 0.0012, respectively). With aging the vitamin E content in LDL decreased whereas the arachidonic fatty acid content increased. More importantly, the relationship between the vitamin E content and the lag time made evident the parallel increase in lag time and in vitamin E level with aging. The vitamin E concentration also correlated inversely to levels of thiobarbituric acid-reactive substances in LDL from elderly patients (r = -0.61, P < 0.05). CONCLUSIONS: The present study shows that LDL peroxidation increases with age. This phenomenon may favor the progression of atherosclerosis in elderly men.

Adult↗

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Quinapril in patients with congestive heart failure: controlled trial versus captopril.

After two weeks of a wash-out run-in period with placebo, 131 patients with congestive heart failure (New York Heart Association [NYHA] class II to III) and left ventricular ejection fraction </=40% were randomly assigned to a treatment period of 4 weeks with 10 mg quinapril once daily or 12.5 mg captopril twice daily. At the end of this period, doses were titrated to 20 mg quinapril once daily or 25 mg captopril twice daily on the basis of physician judgment if there were no major adverse reactions and if blood pressure was not below 110/70 mm Hg. Clinical symptoms of heart failure were significantly relieved by both drugs at the end of a 12-week treatment period. At the beginning of the study, 23 (35%) of the 65 patients taking quinapril and 27 (41%) of the 66 patients taking captopril were in NYHA functional class III, whereas, at the end of the trial, only 4 (6%) of the patients in the quinapril group and 14 (22%; p < 0.05 versus quinapril) patients in the captopril group were classified as NYHA class III. Both drugs had a positive effect on echocardiographic parameters. There was a statistically significant increase in exercise duration in both treatment groups (quinapril, 6.2 +/- 1.8 versus 7.8 +/- 1.9 minutes, p < 0.001; captopril, 5.9 +/- 1.9 versus 7.1 +/- 2.3 minutes, p < 0.001). One patient in the quinapril group died suddenly during the study and two patients in the captopril group dropped out of the study due to persistent dry cough. No patient in the quinapril group reported side effects. Three patients in the captopril group suffered from moderate dry cough, one from taste-blindness, and another from unstable angina. The safety of the tested drugs was confirmed by laboratory tests. Quinapril was as effective as captopril in reducing signs and symptoms of heart failure and in improving the left ventricular function and the exercise capacity with few side effects.

Angiotensin-Converting Enzyme Inhibitors↗

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The effects of delapril in combination with indapamide on glomerular filtration rate in elderly hypertensive patients.

We performed a placebo-controlled trial on the effects of a combined antihypertensive treatment with delapril, a new nonsulfhydryl angiotensin-converting enzyme inhibitor, and indapamide, a sulfonamide diuretic. We studied 28 elderly patients aged 65-85 years (mean age, 69 +/- 1 years) who took 30 mg delapril in combination with 1.25 mg indapamide once daily for 24 weeks. In the present study (performed simultaneously with our trial on the effects of delapril/indapamide on left ventricular mass in elderly patients with hypertension and on the same patients), we report the effects of this drug combination on glomerular filtration rate. Sitting arterial pressure (mean +/- SE) decreased from 156 +/- 1. 5/101 +/- 1 mm Hg at baseline to 133 +/- 1/73 +/- 1 mm Hg at the end of the 24-week treatment period (p < 0.0001). No significant changes in heart rate or episodes of orthostatic hypotension were observed. Glomerular filtration rate increased from 91.8 +/- 4.42 mL/min at baseline to 106.3 +/- 4.5 mL/min (p < 0.001) at the end of treatment. Our results show that the combination of delapril and indapamide is effective in the elderly hypertensive patient, with a favorable effect on the prevention of deterioration of kidney function.

Aged↗

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Inverted response of arginine vasopressin to postural change in patients with essential hypertension.

1. This study was designed to compare the response of plasma arginine vasopressin (AVP) to head-up tilt in hypertensive patients and in normals. 2. As expected, plasma AVP showed a consistent increase (P less than 0.005) in normal subjects after tilt while plasma volume decreased significantly (P less than 0.02). On the contrary, in hypertensive patients, after tilt both plasma AVP (P less than 0.025) and plasma volume (P less than 0.05) decreased. 3. These findings, thus, indicate that essential hypertension is characterized by an inverted response of arginine vasopressin to postural change.

Adolescent↗

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Quality of life determinants and hearing function in an elderly population: Osservatorio Geriatrico Campano Study Group.

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. Copyrightz1999S.KargerAG,Basel

Aged↗