Dejana Popovic

Impact of chronic obstructive pulmonary disease on exercise ventilatory efficiency in heart failure

BACKGROUND Heart failure (HF) and chronic obstructive pulmonary disease (COPD) coexistence increases morbidity and mortality. The intercept of ventilation (VEint) on the VE vs. carbon dioxide production (VCO2) relationship during exercise has been found to vary in proportion with dead space (VD) in HF. Considering that increased VD is the key pathophysiological abnormality in COPD but a secondary finding in HF we hypothesized that a high VEint would be useful in suggesting COPD as HF co-morbidity. Our aim was to assess whether an elevated VEint suggests the presence of COPD in HF. METHODS In a multicenter retrospective study, the VE-VCO2 relationship was analyzed both as slope and intercept in HF (n = 108), HF-COPD (n = 106) and COPD (n = 95). Patients with pulmonary arterial hypertension (PAH) (n = 85) and healthy subjects (HF) (n = 56) served as positive and negative controls relative to VE-VCO2 abnormalities, respectively. RESULTS Slope and VEint varied in opposite directions in all groups (p < 0.05) being VE-VCO2 slope highest and lowest in PAH and healthy subjects, respectively. No slope differences were observed among HF, HF-COPD and COPD (32 ± 7, 31 ± 7, and 31 ± 6, respectively). VEint was higher in HF-COPD and COPD compared to HF, PAH and controls (4.8 ± 2.4 L/min, 5.9 ± 3.0 L/min, 3.0 ± 2.6L/min, 2.3 ± 3.3 L/min and 3.9 ± 2.5L/min, respectively; p < 0.01). A VEint ≥ 4.07 L/min identified patients with high probability of having COPD or HF-COPD (sensitivity of 71.6% and specificity of 72.0%). CONCLUSION These data provide novel evidence that a high VEint (≥ 4.07 L/min) should be valued to suggest coexistent COPD in HF patients.

Diagnostic value of NT-proBNP in identifying impaired coronary flow reserve in asymptomatic moderate or severe aortic stenosis

AIM NT-proBNP has been shown to be a reliable biochemical marker for left ventricular wall stress. The relationship between NT-proBNP and coronary flow reserve (CFR) was evaluated in patients with significant asymptomatic aortic stenosis (AS). METHODS A total of 74 patients with moderate or severe AS, mean age 66.68 ± 10.02 years (56.75% males), were enrolled in this prospective study. All patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis >50% in diameter). They had all undergone standard transthoracic Doppler-echo study and adenosine stress transthoracic-echo for CFR measurement and laboratory analysis for NT-proBNP measurement. RESULTS The median NT-proBNP value was significantly increased (417.0 pg/ml; interquartile range [IQR]: 176.8-962.2 pg/ml). NT-proBNP was significantly higher in the group with CFR ≤2.5 (median: 549.0 pg/ml; IQR: 311.5-1131.0 pg/ml; as opposed to median: 291.5 pg/ml; IQR: 123.0-636.2 pg/ml; W = 452; p = 0.012). NT-proBNP showed significant negative correlation with CFR (ρ = -0.377, p = 0.001). There was also significant correlation between NT-proBNP and E/E´, S´ and aortic valve resistance. The NT-proBNP value of 334.00 pg/ml was determined as the best cut-off value for the diagnosis of CFR ≤2.5 (area under the curve: 0.67; 95%CI: 0.54-0.79; p < 0.01) and the sensitivity and specificity were 74 and 64%, respectively. CONCLUSION Elevated NT-proBNP can indicate patients with impaired CFR in asymptomatic moderate or severe AS patients with preserved ejection fraction and nonobstructive coronary arteries.

The interface of hypothalamic–pituitary–adrenocortical axis and circulating brain natriuretic peptide in prediction of cardiopulmonary performance during physical stress

Brain natriuretic peptide (NT-pro-BNP) was implicated in the regulation of hypothalamic-pituitary-adrenocortical (HPA) responses to psychological stressors. However, HPA axis activation in different physical stress models and its interface with NT-pro-BNP in the prediction of cardiopulmonary performance is unclear. Cardiopulmonary test on a treadmill was used to assess cardiopulmonary parameters in 16 elite male wrestlers (W), 21 water polo player (WP) and 20 sedentary age-matched subjects (C). Plasma levels of NT-pro-BNP, cortisol and adrenocorticotropic hormone (ACTH) were measured using immunoassay sandwich technique, radioimmunoassay and radioimmunometric techniques, respectively, 10min before test (1), at beginning (2), at maximal effort (3), at 3rdmin of recovery (4). In all groups, NT-pro-BNP decreased between 1 and 2; increased from 2 to 3; and remained unchanged until 4. ACTH increased from 1 to 4, whereas cortisol increased from 1 to 3 and stayed elevated at 4. In all groups together, ΔNT-pro-BNP2/1 predicted peak oxygen consumption (B=37.40, r=0.38, p=0.007); cortisol at 3 predicted heart rate increase between 2 and 3 (r=-0.38,B=-0.06, p=0.005); cortisol at 2 predicted peak carbon-dioxide output (B=2.27, r=0.35, p<0.001); ΔACTH3/2 predicted peak ventilatory equivalent for carbon-dioxide (B=0.03, r=0.33, p=0.003). The relation of cortisol at 1 with NT-pro-BNP at 1 and 3 was demonstrated using logistic function in all the participants together (for 1/cortisol at 1 B=63.40, 58.52; r=0.41, 0.34; p=0.003, 0.013, respectively). ΔNT-pro-BNP2/1 linearly correlated with ΔACTH4/3 in WP and W (r=-0.45, -0.48; p=0.04, 0.04, respectively). These results demonstrate for the first time that HPA axis and NT-pro-BNP interface in physical stress probably contribute to integrative regulation of cardiopulmonary performance.

Magnesium Supplementation Diminishes Peripheral Blood Lymphocyte DNA Oxidative Damage in Athletes and Sedentary Young Man

Sedentary lifestyle is highly associated with increased risk of cardiovascular disease, obesity, and type 2 diabetes. It is known that regular physical activity has positive effects on health; however several studies have shown that acute and strenuous exercise can induce oxidative stress and lead to DNA damage. As magnesium is essential in maintaining DNA integrity, the aim of this study was to determine whether four-week-long magnesium supplementation in students with sedentary lifestyle and rugby players could prevent or diminish impairment of DNA. By using the comet assay, our study demonstrated that the number of peripheral blood lymphocytes (PBL) with basal endogenous DNA damage is significantly higher in rugby players compared to students with sedentary lifestyle. On the other hand, magnesium supplementation significantly decreased the number of cells with high DNA damage, in the presence of exogenous H2O2, in PBL from both students and rugby players, and markedly reduced the number of cells with medium DNA damage in rugby players compared to corresponding control nonsupplemented group. Accordingly, the results of our study suggest that four-week-long magnesium supplementation has marked effects in protecting the DNA from oxidative damage in both rugby players and in young men with sedentary lifestyle. Clinical trial is registered at ANZCTR Trial Id: ACTRN12615001237572.

Oxygen consumption and carbon-dioxide recovery kinetics in the prediction of coronary artery disease severity and outcome.

BACKGROUND Revascularization appears to be beneficial only in patients with high levels of ischemia. This study examined the utility of gas analysis during the recovery phase of cardiopulmonary exercise testing (CPET) in predicting coronary artery disease (CAD) severity and prognosis. METHODS 40 Caucasian patients (21.2% females), mean age 63.5±7.6 with significant coronary artery lesions (≥50%) were studied. Within two months of coronary angiography, CPET on a treadmill (TM) and recumbent ergometer (RE) were performed on two visits 2-4days apart; subjects were subsequently followed 32±10months. Myocardial wall motion was recorded by echocardiography at rest and peak exercise. Ischemia was quantified by the wall motion score index (WMSI). RESULTS Mean ejection fraction was 56.7±9.6%. Patients with 1-2 stenotic coronary arteries (SCA) showed a poorer CPET response during the recovery phase than patients with 3-SCA. ROC analysis revealed the change of carbon-dioxide output (∆VCO2) recovery/peak (area under ROC curve 0.77, p=0.02, Sn=87.5%, Sp=70.4%) and oxygen uptake (∆VO2) recovery/peak during TM CPET (area under ROC curve 0.76, p=0.03, Sn 75.0%, Sp 77.8%) were significant in distinguishing between 1-2-SCA and 3-SCA. The same variables predicted ΔWMSI peak/rest on univariate analysis (p<0.05). Multivariate Cox analysis revealed a high predictive value of ∆VO2 recovery/peak obtained during TM CPET for composite endpoint of cumulative cardiac events (HR=1.27, CI=1.07-1.51, p=0.008). CONCLUSIONS The current study suggests CPET parameters in recovery hold predictive value for CAD severity and prognosis. TM testing seems to be a better approach in the assessment of CAD severity and prognosis.

Pituitary-Gonadal, Pituitary-Adrenocortical Hormones and IL-6 Levels Following Long-Term Magnesium Supplementation in Male Students

Abstract Background: Sleep deprivation, malnutrition and lack of physical activity are contemporary stress-related factors present in the student population. Stress activates the HPA and often suppresses the HPG axis, but also influences cytokine synthesis and consequently regulates immune response. Since magnesium deficiency facilitates negative pathophysiological consequences, a reasonable question imposes, wheth er Mg supplementation might correct the adrenal/go - n adal hormone balance and immuno-endocrine function. Methods: Fifteen male students were given 2 × 250 mg Mg for four weeks. Serum levels of FSH, LH, testosterone (T), ACTH and cortisol (C) were measured before and after supplementation and the T/C ratio was calculated. Furthermore, IL-6, red blood cells (RBC), hemoglobin (Hb), white blood cells (WBC) and the WBC differential were measured. Results: Despite no change in the serum level of ACTH, a statistically significant (p<0.05) decrease in the serum cortisol level appeared, accompanied with an IL-6 level reduction (p<0.05) after Mg supplementation. Analysis of the pituitarygonadal axis hormones showed an increasing trend of the FSH level (p=0.087), and a significant increase (p<0.05) in the T/C ratio. An RBC count increase (p<0.001) was found, along with a decrease in the percentage of neutrophils (p< 0.05), and a trend toward a lymphocyte percentage increase. Conclusions: The results suggest that chronic oral magnesium supplementation in male students improves the balance of pituitary-gonadal and pituitary-adrenal hormones and is involved in the regulation of the basal IL-6 level. Kratak sadržaj Uvod: Nedostatak sna, fizičke aktivnosti kao i neadekvatna ishrana su savremeni faktori stresa u studentskoj populaciji. Stres aktivira hormone osovine hipotalamus-hipofiza-nad- bubreg i često suprimira aktivnost osovine hipotalamus- hipofiza-gonade, a takođe utiče i na sintezu citokina, posred- no regulišući imuni odgovor. Kako nedostatak magnezijuma (Mg) može inicirati patofiziološke posledice, postavlja se pitanje da li njegov dodatak ishrani može povoljno uticati na ravnotežu hormona nadbubrežne žlezde i gonada kao i neuro-endokrinu funkciju. Metode: U ovoj studiji petnaest studenata muškog pola dobi- jało je 2 x 250 mg Mg tokom četiri nedelje a nivoi FSH, LH, testosterona (T), ACTH i kortizola (C) mereni su u kivi pre i nakon suplementacije. Takođe, određivani su i nivoi IL-6, eri- trocita, hemoglobina, leukocita kao i leukocitarna formula. Rezultati: Uprkos tome što nije bilo promene u nivou ACTH, naši rezultati su pokazali statistički značajno smanjenje nivoa kortizola (p<0,05), koje je bilo praćeno smanjenjem nivoa IL-6 (p<0,05) nakon dodatka Mg. Analiza hipofizno-gonad- nih hormona pokazala je trend u povećanju FSH (p=0,087) i značajno povećanje T/C količnika. Uočeno je značajno povećanje broja eritrocita (p<0,001), smanjenje procenta neutrofila (p<0,05) i trend povećanja procenta limfocita. Zaključak: Rezultati studije sugerišu da dugotrajni dodatak Mg ishrani studenata doprinosi održavanju ravnoteže hipofizno-gonadnih i hipofizno-adrenokortikalnih hormona i uldjučen je u regulaciju bazalnog nivoa citokina IL-6.

Assessing the Value of Moving More-The Integral Role of Qualified Health Professionals

Being physically active or, in a broader sense, simply moving more throughout each day is one of the most important components of an individuals health plan. In conjunction with regular exercise training, taking more steps in a day and sitting less are also important components of ones movement portfolio. Given this priority, health care professionals must develop enhanced skills for prescribing and guiding individualized movement programs for all their patients. An important component of a health care professionals ability to prescribe movement as medicine is competency in assessing an individuals risk for untoward events if physical exertion was increased. The ability to appropriately assess ones risk before advising an individual to move more is integral to clinical decision-making related to subsequent testing if needed, exercise prescription, and level of supervision with exercise training. At present, there is a lack of clarity pertaining to how a health care professional should go about assessing an individuals readiness to move more on a daily basis in a safe manner. Therefore, this perspectives article clarifies key issues related to prescribing movement as medicine and presents a new process for clinical assessment before prescribing an individualized movement program.

Nonpharmacologic management of hypertension: a multidisciplinary approach

Purpose of review Nonpharmacologic lifestyle modification interventions (LMIs), such as increasing physical activity, dietary modification, weight-loss, reducing alcohol consumption and smoking cessation, are effective strategies to lower resting blood pressures (BPs) in prehypertensive or hypertensive patients. However, the limited time shared between a physician and a patient is not adequate to instill an adoption of LMI. The purpose of this review is to therefore highlight evidence-based BP lowering, LMI strategies that can feasibly be implemented in clinical practices. Recent findings Interventions focusing on modifying physical activity, diet, weight-loss, drinking and smoking habits have established greater efficacy in reducing elevated BP compared with providing guideline recommendations based on national guidelines. Alone greater reductions in BP can be achieved through programmes that provide frequent contact time with exercise, nutrition and/or wellness professionals. Programmes that educate individuals to lead peer support groups can be an efficient method of ensuring compliance to LMI. Summary Evidence of a multidisciplinary approach to LMI is an effective and attractive model in managing elevated BP. This strategy is an attractive model that provides the necessary patient attention to confer lifestyle maintenance.

Diabetes mellitus and coronary microvascular function in asymptomatic patients with severe aortic stenosis and nonobstructed coronary arteries

Background and aim: Coronary flow reserve is impaired in asymptomatic patients with aortic stenosis and has a prognostic value. We investigated whether the type II diabetes mellitus additionally impairs microvascular circulation assessed by coronary flow reserve in patients with asymptomatic severe aortic stenosis, normal left ventricular ejection fraction and nonobstructed coronary arteries. Methods: A total of 128 patients, mean age of 66.35 ± 10.51 (58.6% males), with severe aortic stenosis and normal left ventricular ejection fraction were enrolled in this study. Patients with diabetes mellitus, those who were treated for diabetes mellitus or had documentation confirming the diagnosis of diabetes mellitus, were considered. All patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis >50% in diameter), standard transthoracic Doppler-echocardiographic study and adenosine stress transthoracic echocardiography for coronary flow reserve measurement. Results: Diabetes mellitus was present in 26 patients (20.31%). There was no significant difference in aortic stenosis severity between diabetic and non-diabetic patients [aortic valve area (0.81 ± 0.18 vs 0.85 ± 0.15 cm2) and Vmax (4.20 ± 0.57 vs 4.21 ± 0.48 m/s)]. Mean coronary flow reserve in diabetic patients was 1.98 ± 0.48, while mean coronary flow reserve in non-diabetic patients was 2.64 ± 0.54 (p < 0.01). Diabetes mellitus was independent predictor of coronary flow reserve [B = −0.636, 95% confidence interval (−0.916 to −0.368), p < 0.001]. Conclusion: Diabetes mellitus additionally impairs coronary microvascular function in asymptomatic patients with severe aortic stenosis and nonobstructed coronary arteries.

Restoring tourist flows and regenerating city's image: the case of Belgrade.

The aim of this research is to examine the effects of the post-1990 transition on the relocation of tourism and changes in the structure of tourism over the last 20 years in Belgrade. Economic and social development altered spatial relations of tourist factors and elements. Apart from the old city core, new tourist zones and directions appeared. Tourist flows and economic challenges influenced the rationalisation of doing business and relocating the hotels outside the central city municipalities. Belgrade has been acknowledged as a low-cost destination of fun and nightlife and the citys new image has attracted more foreign tourists. Both the volume of foreign tourists and their countries of origin have changed significantly over the last several years. However, there have been negligible economic effects on the citys economy, despite this increase in the number of foreign tourists. In conclusion, we examine the implications of new directions in tourism development for the future position of Belgrade as a tourist destination in a competitive European market.