Luciana Carosella

Hypotension and cognitive impairment Selective association in patients with heart failure

Background: Arterial hypotension has been associated with increased risk of dementia in some large prospective studies; and cognitive impairment is common among elderly with left ventricular function. The authors assessed whether arterial hypotension might be associated with cognitive impairment among older subjects with heart failure. Methods: This study involved all 13,635 patients (of whom 1,583 had heart failure) without cerebrovascular disease or AD, admitted to 81 Italian academic hospitals in 1995 and 1997. The association between blood pressure and cognitive impairment (as indicated by a Hodkinson Mental Test score < 7) according to the presence of heart failure was assessed by univariate analyses, including linear discriminant analysis. This association was also verified by multivariate analyses after stratifying for diagnosis of heart failure. Results: Cognitive impairment was found in 26% of patients with heart failure and in 19% of remaining subjects (Fisher exact p < 0.0001). Blood pressure levels did not differ according to diagnosis of heart failure, but discriminant analysis indicated that systolic blood pressure levels below 130 mm Hg predicted cognitive impairment only among participants with heart failure. Among such participants, systolic blood pressure was associated with cognitive impairment in multiple logistic regression modeling (for 10 mm Hg intervals, OR = 0.78; 95% CI = 0.71 to 0.86). Again, this association was not found among participants without heart failure. Conclusions: Systolic hypotension is selectively associated with cognitive impairment in older patients with heart failure. As early treatment of cardiac low-output states can reverse cognitive dysfunction, the routine management of heart failure should include systematic assessment of cognitive performance.

Predictors of Rehabilitation Outcomes in Frail Patients Treated in a Geriatric Hospital

OBJECTIVES: To evaluate the effect of medical indicators of health status on functional gain during rehabilitation of frail older patients.

Criticality of the Biological and Physical Stimuli Array Inducing Resident Cardiac Stem Cell Determination

The replacement of injured cardiac contractile cells with stem cell‐derived functionally efficient cardiomyocytes has been envisaged as the resolutive treatment for degenerative heart diseases. Nevertheless, many technical issues concerning the optimal procedures to differentiate and engraft stem cells remain to be answered before heart cell therapy could be routinely used in clinical practice. So far, most studies have been focused on evaluating the differentiative potential of different growth factors without considering that only the synergistic cooperation of biochemical, topographic, chemical, and physical factors could induce stem cells to adopt the desired phenotype. The present study demonstrates that the differentiation of cardiac progenitor cells to cardiomyocytes does not occur when cells are challenged with soluble growth factors alone, but requires strictly controlled procedures for the isolation of a progenitor cell population and the artifactual recreation of a microenvironment critically featured by a fine‐tuned combination of specific biological and physical factors. Indeed, the scaffold geometry and stiffness are crucial in enhancing growth factor differentiative effects on progenitor cells. The exploitation of this concept could be essential in setting up suitable procedures to fabricate functionally efficient engineered tissues.

A controlled trial of verapamil in patients after acute myocardial infarction: results of the calcium antagonist reinfarction Italian study (CRIS)

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.

The impact of age on risk of adverse drug reactions to digoxin

To assess the association of age and other potential risk factors with digoxin toxicity, adverse drug reactions to digoxin (ADRDIG) were studied in all patients (n = 1338) on digoxin therapy consecutively admitted to 41 clinical wards throughout Italy during 4 months in 1988. At the time of admission, 28 patients (2.1%) had evidence of ADRDIG. In multivariate logistic regression analysis, significant associations with ADRDIG were found for age > or = 80 years compared to age 65-79 years (OR = 2.75, 95% CI = 1.17-6.45), daily digoxin dosage of > or = 0.25 mg (OR = 2.51, 95% CI = 1.16-5.47), serum creatinine > or = 120 mumol/L (OR = 3.75, 95% CI = 1.69-8.32), and for treatment with amiodarone, propafenone, quinidine or verapamil (OR = 2.60, 95% CI = 1.07-6.30). Those aged < 65 years had a similar risk of digoxin toxicity as those aged 65-79 years (OR = 1.07, 95% CI = 0.28-4.12). Adverse drug reactions to digoxin were found in 1 in 50 patients hospitalized on digoxin therapy. Patients aged 65-79 years were not at increased risk for digoxin toxicity compared to younger patients, while advanced age (> or = 80 years) was an independent risk factor for this outcome.

Exacerbated chronic obstructive pulmonary disease: a frequently unrecognized condition.

Abstract. Incalzi RA, Fuso L, Serra M, Basso S, Carosella L, Tramaglino LM, Pistelli R, Carbonin P. (Department of Geriatrics and Department of Respiratory Physiology, Catholic University, Rome, Italy). Exacerbated chronic obstructive pulmonary disease: a frequently unrecognized condition. J Intern Med 2002; 252: 48–55.

Construct Validity of the Abbreviated Mental Test in Older Medical Inpatients

Objectives: To evaluate validity and internal structure of the Abbreviated Mental Test (AMT), and to assess the dependence of the internal structure upon the characteristics of the patients examined. Design: Cross-sectional examination using data from the Italian Group of Pharmacoepidemiology in the Elderly (GIFA) database. Setting: Twenty-four acute care wards of Geriatrics or General Medicine. Participants: Two thousand eight hundred and eight patients consecutively admitted over a 4-month period. Measurements: Demographic characteristics, functional status, medical conditions and performance on AMT were collected at discharge. Sensitivity, specificity and predictive values of the AMT <7 versus a diagnosis of dementia made according to DSM-III-R criteria were computed. The internal structure of AMT was assessed by principal component analysis. The analysis was performed on the whole population and stratified for age (<65, 65–80 and >80 years), gender, education (<6 or >5 years) and presence of congestive heart failure (CHF). Results: AMT achieved high sensitivity (81%), specificity (84%) and negative predictive value (99%), but a low positive predictive value of 25%. The principal component analysis isolated two components: the former component represents the orientation to time and space and explains 45% of AMT variance; the latter is linked to memory and attention and explains 13% of variance. Comparable results were obtained after stratification by age, gender or education. In patients with CHF, only 48.3% of the cumulative variance was explained; the factor accounting for most (34.6%) of the variance explained was mainly related to the three items assessing memory. Conclusion: AMT >6 rules out dementia very reliably, whereas AMT <7 requires a second level cognitive assessment to confirm dementia. AMT is bidimensional and maintains the same internal structure across classes defined by selected social and demographic characteristics, but not in CHF patients. It is likely that its internal structure depends on the type of patients. The use of a sum-score could conceal some part of the information provided by the AMT.

Age and severe adverse drug reactions caused by nifedipine and verapamil

The association of age with risk for severe adverse drug reactions (SADRs) was studied in 2371 and 862 hospitalized patients taking nifedipine and verapamil, respectively. Nifedipine caused hypotension (n = 22), tachycardia (n = 3), and acute renal failure (n = 1) (total SADR rate, 1.1%, 26/2371). Verapamil caused hypotension (n = 3), bradycardia (n = 9), and atrioventricular blocks (n = 2) (total SADR rate, 1.6%, 14/862). The mean age of patients with and without SADRs was for nifedipine 77.1 +/- 1.7 and 71.8 +/- 0.8 years, respectively (p < 0.05), and for verapamil 73.4 +/- 2.9 and 73.1 +/- 0.4 years, respectively. Sex, length of stay, comorbidity, polypharmacy, intake of slow-release preparations, daily dosage, and new intake of calcium antagonists were examined as potential confounders of the age-SADR association. After adjusting for potential confounders, age was significantly and independently associated with SADRs caused by nifedipine, but not with SADRs caused by verapamil (OR = 1.69, 95% CI = 1.05-2.72 and OR = 1.06, 95% CI = 0.63-1.68 for 10-year increase, respectively). Although nifedipine and verapamil did not have significantly different rates of SADRs, an age-related gradient was found only for nifedipine.

Stem cell activation sustains hereditary hypertrophy in hamster cardiomyopathy.

Recent studies have documented the presence of stem cells within the myocardium and their role in the repair of ischaemic injury. Nevertheless, the pathogenic role of stem cells in non‐ischaemic myocardial diseases, as well as the factors potentially responsible for their activation, is still under debate. The present study demonstrates the presence of an increased number of c‐kit positive, MDR‐positive, and Sca‐1‐positive stem cells within the myocardium of hereditary δ‐SG null hamsters, a spontaneously occurring model of hypertrophic cardiomyopathy. When hamsters are 80 days old, ie at the ‘hypertrophic’ stage of the disease, but without haemodynamic overload, these cells associate with a multitude of cells co‐expressing c‐kit, cMet, GATA4, or MEF‐2, and proliferating myocytes co‐expressing myosin heavy chain, telomerase, ki67 and cyclin B. Furthermore, at the same animal age, the number of myocardial cells co‐expressing c‐kit and Flk‐1, and the number of capillary vessels, is also amplified. In order to identify factors potentially responsible for stem cell activation, the myocardial expression of HGF and cMet and HGF plasma levels were evaluated, demonstrating their increase in 80‐day‐old δ‐SG null hamsters. To demonstrate the possible ability of HGF to induce stem cell differentiation, bone‐marrow‐derived mesenchymal stem cells were challenged with HGF at the same plasma concentration observed in vivo. HGF induced cMet phosphorylation, and caused loss of stem cell features and overexpression of MEF‐2, TEF1, and MHC. Our results demonstrate that stem cell activation occurs within the cardiomyopathic myocardium, very likely to maintain an efficient cardiac architecture. In this context, elevated levels of HGF might play a role in induction of stem cell commitment to the cardiomyocyte lineage and in cardioprotection through its anti‐apoptotic action. Consistently, when cytokine levels declined to physiological concentrations, as in 150‐day‐old cardiomyopathic animals, myocardial apoptosis prevailed, prejudicing cardiac function. Copyright

Age-Related Incidence of Reperfusion- and Reoxygenation-induced Ventricular Tachyarrhythmias in the Isolated Rat Heart

Reperfusion- and reoxygenation-induced ventricular tachyarrhythmias were studied on 6-month-old (adult) and 24-month-old (senescent) Langendorff perfused rat hearts. The incidence of arrhythmias was significantly higher in the group of senescent hearts. Furthermore, the reperfusion- and reoxygenation-induced contracture was also more frequent in the group of senescent hearts. The interrelation between contracture and arrhythmias might represent an indirect evidence to suggest that alterations in cell calcium homeostasis have an important role in the origin of both phenomena and, possibly, in their increased incidence in the senescent heart.