Nebojsa Despotovic

Relationship of reduced cerebral blood flow and heart failure severity in elderly males

Introduction. Brain detrimental effects are under-recognised complication of chronic heart failure (CHF). One of the major causes may be cerebral hypoperfusion. This study was designed to investigate the relationship between cerebral blood flow (CBF) and severity of CHF as well as to evaluate its determinants among different parameters of cardiac dysfunction. Methods. Seventy-one CHF males with NYHA class II and III and 20 control subjects age ≥ 55 years were recruited. CBF was evaluated by colour duplex sonography of extracranial arteries. Echocardiography, 6-min walk test, quality of life and endothelial function were also assessed. Serum NT-pro-BNP and adipokines levels (adiponectin and leptin) were measured. Results. CBF was significantly reduced in elderly patients with CHF compared to healthy controls (677 ± 170 vs 783 ± 128 ml/min, p = 0.011). Reduced CBF was associated with reduced left ventricular ejection fraction (LVEF) (r = 0.271, p = 0.022), lower 6-min walk distance (r = 0.339, p = 0.004), deteriorated quality of life (r = −0.327, p = 0.005), increased serum adiponectin (r = −0.359, p = 0.002), and NT-pro-BNP levels (r = −0.375, p = 0.001). In multivariate regression analysis, LVEF and adiponectin were independently associated with reduced CBF in CHF patients (R2 = 0.289). Conclusion. CBF was reduced in elderly males with mild-to-moderate CHF, and was associated with factors that represent the severity of CHF including high serum adiponectin and NT-pro-BNP levels, decreased LVEF, impaired physical performance, and deteriorated quality of life.

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.

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.

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.

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.

[Prospective follow-up of nebivolol in the treatment of arterial hypertension].

INTRODUCTION Nebivolol, a third-generation beta-blocker (BB) shows a highly selective beta-blockade and specific vasodilating effects due to getting free nitro-oxide from the dysfunctional endothelium. OBJECTIVE The aim of the study was to investigate the antihypertensive effect of nebivolol in patients with arterial hypertension (AH) of both sexes. METHODS Systolic and diastolic blood pressure (BP), heart rate and serum glycemia, creatinin, cholesterol and trygliceride were measured after a 6-week treatment with a single 5 mg dose of nebivolol once daily so as to assess its efficacy and metabolic effects, as well as its tolerance by using a questionnaire answered by physicians and patients. RESULTS Out of 520 patients with mild or moderate AH, 430 (82.7%) were treated with nebivolol as monotherapy. After a 6-week treatment with nebivolol, with very good tolerability and neutral metabolic effects, systolic BP was significantly decreased (in male from initial 165 +/- 19 to 129 +/- 12 mm Hg, and female from initial 169 +/- 22 to 132 +/- 15 mm Hg at the end of the study; average decrease 22.3%, p<0.001) and as well as diastolic BP (male from initial 103 +/- 12 to 79 +/- 6 mm Hg and female from initial 100 +/- 9 to 82 +/- 7 mm Hg, average decrease 22.6%; p<0.001). CONCLUSION After a 6-week treatment nebivolol significantly decreased systolic and diastolic BP in patients with mild and moderate AH, independently of the sex.