Predrag Erceg

Health-related quality of life in elderly patients hospitalized with chronic heart failure

Background Chronic heart failure is a very common condition in the elderly, characterized not only by high mortality rates, but also by a strong impact on health-related quality of life (HRQOL). Previous studies of HRQOL in elderly heart failure subjects have included mostly outpatients, and little is known about determinants of HRQOL in hospitalized elderly population, especially in Serbia. In this study, we tried to identify factors that influence HRQOL in elderly patients hospitalized with chronic heart failure in Serbia. Methods The study population consisted of 136 patients aged 65 years or older hospitalized for chronic heart failure. HRQOL was assessed using the Minnesota Living with Heart Failure questionnaire. Predictors of HRQOL were identified by multiple linear regression analysis. Results Univariate analysis showed that patients with lower income, a longer history of chronic heart failure, and longer length of hospital stay, as well as those receiving aldosterone antagonists and digoxin, taking multiple medications, in a higher NYHA class, and showing signs of depression and cognitive impairment had significantly worse HRQOL. Presence of depressive symptoms (P<0.001), higher NYHA class (P=0.021), lower income (P=0.029), and longer duration of heart failure (P=0.049) were independent predictors of poor HRQOL. Conclusion Depressive symptoms, higher NYHA class, lower income, and longer duration of chronic heart failure are independent predictors of poor HRQOL in elderly patients hospitalized with chronic heart failure in Serbia. Further, there is an association between multiple medication usage and poor HRQOL, as well as a negative impact of cognitive impairment on HRQOL. Hence, measures should be implemented to identify such patients, especially those with depressive symptoms, and appropriate interventions undertaken in order to improve their HRQOL.

Ageism: Does it Exist Among Children?

Ageism is stereotyping and prejudice against individuals or groups because of their age. Robert Butler first used it in 1969, to express a systematic stereotyping and discrimination against elderly people. Available data appears to confirm that attitudes of children to the old age differ from that of adults. The study population consisted of 162 subjects (56 school children, 48 nurses and 58 elderly patients). Each subject in the survey was asked to respond to the following three questions: Question #1: “Is the old age unattractive ?”; Question #2: “How old is an old man? Question #3: “What should you do to have a long life (what is good for longevity)? The majority of polled children (33) gave positive statements about ageing in their responses to the first item, while most of the nurses gave condition answers, like: “It is not unattractive if you are healthy”. Elderly subjects made up a group with the majority of negative responses (in percentage), as only 33% of them answered that old age is not unattractive. All three groups of subjects demonstrated a good knowledge of what is considered good for longevity, and had a generally positive health attitude. Our results indicate that majority of children have positive perception and attitude about old age, which leads us to conclusion that ageism is adopted later in life.

The Privilege to Be Old

Background: Ample evidence has proven that the functional property of cells decreases over the years. Nevertheless, although it has taken decades to convince ourselves that elderly people belong to a specific age group both biologically and medicinally, and in whom special criteria have to be taken into consideration, it seems that even they themselves do not present an homogenous group. Objective: Today we often hear of authors of studies speaking of two subpopulation groups – one group that ages by all the laws of aging that we have encountered and accepted thus far, and the other group that seems to postpone aging due to ‘programmed death’, or more specifically due to low mastery/low emotional support or because of additional reasons; however, the existence of the two groups seems eminent. Methods: The identification of these two groups would allow us to find more realistic results in studies, and therefore a more efficient therapy for certain diseases. Results: This hypothesis does not contradict the theories of aging that we have accepted (at least not the majority) and also does not contradict the fact that there is a large interindividual variability. This hypothesis doubts and claims there are exceptions to the initial assumption of geriatrists and gerontologists that ‘parallel to the aging process, the functions of all organs and organ systems lessen.’ Conclusion: The identification of these two groups would allow us to find more realistic results in studies, and therefore more efficient therapy for certain diseases.

Bleeding During Enoxaparin Treatment More Common with Age Over 75 Years and Severe Renal Insufficiency

BackgroundSevere renal insufficiency, defined as a creatinine clearance <30 mL/min, increases the risk for bleeding in elderly patients receiving enoxaparin (enoxaparin sodium) treatment.MethodsThe risk/benefit ratios of enoxaparin and unfractionated heparin (UFH) in patients with acute myocardial infarction (AMI) aged >75 years were determined by investigating the parameters of efficacy (ischaemic event, lethal outcome), safety (bleeding events, renal insufficiency) or both (composite endpoint: ischaemic event or lethal outcome or bleeding event).ResultsThe study included 113 patients (59 male, 52.2%) with AMI aged >75 years; 36 of these patients received enoxaparin. In the patients who had severe renal insufficiency, bleeding events were more frequent in those receiving enoxaparin than in those patients who received UFH (3 vs 1, respectively; p = 0.024). Irrespective of the presence of renal insufficiency, bleeding events occurred more often in patients who received enoxaparin than in those who received UFH (13 vs 8, respectively; p = 0.007). The composite endpoint showed a nonsignificantly better profile in patients who received enoxaparin than in those who received UFH.ConclusionAlthough the use of enoxaparin (compared with UFH) and the presence of severe renal insufficiency significantly increased the occurrence of bleeding in patients with AMI aged >75 years, the risk/benefit difference in this population was not significant.

The Influence of Various Morphologic and Hemodynamic Carotid Plaque Characteristics on Neurological Events Onset and Deaths

A group of 72 patients with 111 asymptomatic carotid stenoses (ACS), mean age 65.42 ± 9.21, and a group of 36 patients with 58 symptomatic carotid stenoses (SCS), mean age 67.63 ± 8.79, were analyzed prospectively during a 3-year follow-up period. All patients underwent color duplex scan sonography (CDS), carotid arteriography, computed tomography (CT) scan, and neurological examination. The aim of the study was to analyze the correlation between echo plaque morphology (degree and plaque quality), local hemodynamic plaque characteristics, ischemic CT findings, and onset of new neurological events and deaths. The results analysis showed significantly more ACS in the group of 30–49% stenosis (p < 0.001), but significantly more SCS in the group of 70–89% (p < 0.0001) and ≥90% stenosis (p < 0.05). Fibrous plaque was more frequent in the ACS group (p < 0.001), while ulcerated and mixed plaques were more frequent in the SCS group (both p < 0.0001). In the SCS group, a significantly higher frequency of increased peak systolic and end diastolic velocities was noted at the beginning and end of the study (both p < 0.01), as well as for contralateral common (CCA) or internal carotid artery (ICA) occlusion (p < 0.05 and p < 0.01, respectively), but reduced carotid blood flow volume (p < 0.05) only at the end of the study. In the ACS group, the best correlation with new neurological events and deaths was shown with positive CT findings, peak systolic flow velocity over 210 cm/sec, end diastolic flow velocity over 110 cm/sec, plaque stenosis ≥70%, plaque ulceration, mixed plaque (all p < 0.0001); stenosis ≥50% (p < 0.001); and reduced carotid blood flow volume (p < 0.05).

The Timing of Infarction Pain in Patients with Acute Myocardial Infarction after Previous Revascularization

Circadian variation of onset of acute myocardial infarction (AMI) has been noted in many studies, but there are no data about subgroups of patients with previous coronary artery bypass grafting (CABG). Because of abnormalities in the circadian rhythm of autonomic tone after surgery, it was very interesting to analyze the circadian patterns in the onset of symptoms of AMI in various subgroups of 1784 patients with previous CABG. As in the other studies, a peak occurred in the morning hours with 26.3% of the patients, but there was a second nearly equal, but higher, peak (26.4%) in the evening hours. The subgroups with specific clinical characteristics exhibited different patterns that determined these peaks in all populations. In patients older than 70 years of age, in both sexes, in smokers, diabetics, in patients with hypertension, in those undergoing beta-blocker therapy, and in patients without previous angina, two nearly equal peaks were observed, with higher evening peaks, except in those patients with hypertension and without angina. Only one peak in the evening hours was observed in a subgroup of patients with previous congestive heart failure (CHF) and non-STEMI. The subgroup of patients with previous angina and previous AMI exhibited no discernible peaks. The distribution of time of onset within the four intervals was not uniform, and the difference was statistically significant only for patients undergoing beta-blocker therapy at time of onset (p = 0.0013), nonsmokers (p = 0.0283), and patients with non-STEMI (p = 0.0412). It is well known that patients with AMI have a dominant morning peak of circadian variation of onset. However, analyzing a different subgroup of patients with AMI after previous CABG, it was found that some subgroups had two peaks of onset, but a higher evening peak (patients older than 70 years of age, smokers, diabetics, and a group of patients who were taking beta-blocker therapy). This subgroup of patients, together with the subgroups of patients with a dominant evening peak (patients with CHF and those with non-STEMI) and with patients with no peak (patients with previous angina and previous AMI), probably appear to modify characteristic circadian variation of infarction onset, expressing a higher evening peak, respectively to the previous CABG, with adverse consequences for central nervous system functioning.

PREDICTION OF CARDIOVASCULAR MORTALITY IN FUNCTIONALLY DISABLED ELDERLY – A POSSIBLE NEW SCORE / KARDIOVASKULARNI MORTALITET KOD FUNKCIONALNO ZAVISNIH STARIH OSOBA - MOGUĆI PREDIKTIVNI SKOR

Summary Background: We investigated the traditional and new bio- markers as predictors of cardiovascular mortality in the func- tionally disabled elderly who are living in a community. Methods: This prospective study included 253 participants (78.3% women) aged 65 and over who were monitored for 32 months. Receiver operating curve analysis and the Cox proportional hazard model were used to identify univariate and multivariate predictors of cardiovascular mortality. The Kaplan-Meier survival curve and Log rank test were used for survival analysis. Results: During the study, 43.1% participants died from car- diovascular diseases. Cutoff points of multivariate predictors were used to build a score system. The risk score was positive in patients with three or more of the following predictors: albumin <40 g/L, body mass index <25 kg/m2, total serum bilirubin <10.5 (imol/L, blood urea nitrogen >6.5 mmol/L and high-sensitivity C-reactive protein >2.25 mg/L. The rel- ative risk for cardiovascular mortality for someone with a positive vs. negative score was 3.91 (95% Cl: 2.55-5.98; P< 0.001). There was no change in risk after adjustment for age; sex, traditional cardiovascular risk factors, comorbidities and a number of disabilities. Conclusions: Presence of lo* grade inflammation, malnulri tion and early signs of renal dy sfunction are essential for car- diovascular risk among the functional disabled elderly and may be assessed using the proposed new inflammatory m3lnuhffion-renal involved score (1MRIS). Kratak sadržaj Uvod: Istraživali smo tradicionalne faktore rizika i nove bio- markere kao prediktore za kardiovaskularni mortalitet kod funkcionalno zavisnih starih osoba koje žive u zajednici. Metode: Ova prospektivna studija obuhvatila je 253 učesni- ka starih 65 i vise godina (78,3% žena) koji su praćeni 32 meseca. ROC kriva (engl. receiver operating characteristic curve) i Coxov proporcioni hazardni model korišćeni su za identifikaciju univarijantnih i multivarijantnih prediktora kar- diovaskularnog mortaliteta. Kaplan-Meierova kriva preživlja- vanja i Log rank test korišćeni su za analizu preživljavanja. Rezultati: Tokom studije 43,1% učesnika je umrlo od kar- diovaskularnih bolesti. Na osnovu graničnih (cutoff) skoro- va multivarijantnih prediktora napravljen je prediktivni skor za kardiovaskularni mortalitet. Ovaj skor je bio pozitivan kod učesnika sa tri i vise od sledećih prediktora: albumin <40 g/L, indeks telesne mase <25 kg/m2, ukupni serum- ski bilirubin <10,5 (jmol/L, urea >6,5 mmol/L i visokosen- zitivni C-reaktivni protein >2,25 mg/L. Relativni rizikza kar- diovaskularni mortalitet ukoliko neko ima pozitivan skor bio e 3,91 (95% Cl: 2,55-5,98; P<0,001). Nije bilo promene u riziku nakon prilagođavanja za starost, pol, tradicionalne faktore rizika, komorbiditete i stepen funkcionalne zavisnosti. Zaključak: Prisustvo inflamacije niskog stepena, malnutrici- je i početni znaci bubrežne disfunkcije su esencijalni za procenu kardiovaskularnog rizika kod funkcionalno zavisnih starih osoba i mogu biti procenjeni na osnovu novog pre- diktivnog skora nazvanog IMRIS (engl. inflammatory-mal- nutrition-renal involved skor).

Remodeling of extracellular matrix of the lamina propria in the uninvolved human rectal mucosa 10 and 20 cm away from the malignant tumor

In recent years, it has been demonstrated that malignancy arises and advances through the molecular interplay between tumor cells and non-malignant elements of the tumor stroma, that is, fibroblasts and extracellular matrix. However, in contrast to the mounting evidence about the role of tumor stroma in the genesis and progression of the malignant disease, there are very few data regarding the uninvolved stromal tissue in the remote surrounding of the tumor. Using the objective morphometric approach in patients with adenocarcinoma, we demonstrate the remodeling of extracellular matrix of the lamina propria in the uninvolved rectal mucosa 10 and 20 cm away from the neoplasm. We show that the representation of basic extracellular matrix constituents (reticular and collagen fibers and ground substance) is decreased. Also, the diameter of empty spaces that appear within the extracellular matrix of the lamina propria is increased. These spaces do not represent the blood or lymphatic vessel elements. Very likely, they reflect the development of tissue edema in the remote, uninvolved lamina propria of the mucosa in patients with the malignant tumor of the rectum. We hypothesize that the remodeling of extracellular matrix in lamina propria of the rectal mucosa may increase its stiffness, modulating the mechano-signal transduction, and thus promote the progression of the malignant disease.

Morphometric study of uninvolved rectal mucosa 10 cm and 20 cm away from the malignant tumor

Recently, many details of the interplay between tumor cells and tumor-associated stromal elements leading to the progression of malignant disease were elucidated. In contrast, little is known about the role of uninvolved stromal tissue in the remote surrounding of the malignant tumor. Therefore, we performed a computer-aided morphometric study of rectal mucosa in samples taken 10 cm and 20 cm away from the malignant tumor during endoscopic examination of 23 patients older than 60 years. The samples of rectal mucosa from 10 healthy persons of corresponding age subjected to diagnostic rectoscopy during active screening for asymptomatic cancer were used as control. All structural elements of the rectal mucosa were studied and the number of nucleated cells in the lamina propria per 0.1 mm² of tissue was assessed. Our study revealed a reduced number of cells in the lamina propria of the rectal mucosa 10 cm and 20 cm away from the tumor lesion in both male and female patients. The decreased mucosal height and increased crypt number were registered in female patients 10 cm away from the tumor. The connective tissue of lamina propria showed a disorderly organization: the collagen fibers were frail, loosely arranged and signs of tissue edema were present. Small blood vessels and capillaries were much more frequently seen than in healthy tissue. Our results demonstrate the complex interactions between the cancer and remote mucosal tissue of the affected organ.

Biogerontology in Serbia

Aging is caused by gradual accumulation of cell and tissue damage. Accumulation of damage begins early and continues progressively throughout life, resulting after several decades in the overt frailty, disability and diseases associated with aging. In Serbia during the last few years, several different institutions participated in the investigation in the aging process: (1) Changes in hormone signaling with aging—the age-related increase in insulinemia and glucose metabolism deregulation was found to be attributed to changes in insulin signaling as demonstrated on murine models. (2) Changes in immunological response in aging—along with involution of thymic lymphoepithelial tissue, it has been demonstrated on a murine model that early thymocyte differentiational steps within the CD4-8-double negative developmental stage are age-sensitive. (3) Changes in cholesterol metabolism and oxidative processes in aging—the beneficial effect of long-term dietary restriction on ageing, was explained as effect on cholesterol metabolism. (4) Alzheimer’s disease—the connection between neurodegenerative processes associated to the Alzheimer’s disease and the function of the Na–K-ATPase which is known to be altered by ageing has been experimentally shown. Conclusion: The recent work of Serbian investigators suggest some new evidence that aging process influences the hormone signaling, immunological response, cholesterol metabolism and oxidative processes.