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Importance: Sodium glucose cotransporter 2 inhibitors reduce morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Clinicians may find estimates of the projected long-term benefits of sodium glucose cotransporter 2 inhibitors a helpful addition to clinical trial results when communicating the benefits of this class of drug to patients. Objective: To estimate the projected long-term treatment effects of dapagliflozin in patients with HFrEF over the duration of a patient’s lifetime. Design, Setting, and Participants: Exploratory analysis was performed of Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF), a phase 3 randomized, placebo-controlled clinical trial conducted at 410 sites in 20 countries. Patients with an ejection fraction less than or equal to 40% in New York Heart Association functional classification II to IV and elevated plasma levels of N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Mean (SD) duration of follow-up was 17.6 (5.2) months. Interventions: Dapagliflozin, 10 mg, once daily vs placebo in addition to standard therapy. Main Outcomes and Measures: The primary composite outcome was time to first hospitalization for heart failure, urgent heart failure visit requiring intravenous therapy, or cardiovascular death. The trial results were extrapolated to estimate the projected long-term treatment effects of dapagliflozin over the duration of a patient’s lifetime for the primary outcome and the secondary outcome of death from any cause. Results: A total of 4744 patients (1109 women [23.4%]; 3635 men [76.6%]) were randomized in DAPA-HF, with a mean (SD) age of 66.3 (10.9) years. The extrapolated mean event-free survival for an individual aged 65 years from a primary composite end point event was 6.2 years for placebo and 8.3 years for dapagliflozin, representing an event-free survival time gain of 2.1 years (95% CI, 0.8-3.3 years; P = .002). When considering death from any cause, mean extrapolated life expectancy for an individual aged 65 years was 9.1 years for placebo and 10.8 years for dapagliflozin, with a gain in survival of 1.7 years (95% CI, 0.1-3.3; P = .03) with dapagliflozin. Similar results were seen when extrapolated across the age range studied. In analyses of subgroups of patients in DAPA-HF, consistent benefits were seen with dapagliflozin on both event-free and overall survival. Conclusions and Relevance: These findings indicate that dapagliflozin provides clinically meaningful gains in extrapolated event-free and overall survival. These findings may be helpful in communicating the benefits of this treatment to patients with HFrEF. Trial registration: ClinicalTrials.gov Identifier: NCT03036124.

Koncatinovocievna arteriova ischemicka choroba (periferne arteriove ochorenie dolných koncatin - PAO DK) je doležitou manifestaciou systemovej aterosklerozy a iných arteriových chorob cievneho systemu. Cim nižsi je clenkovo-ramenový tlakový index, tým vacsie je riziko vzniku zavažných akutnych instabilných organovaskularnych prihod (napr. akutneho infarktu myokardu, nahlej cievnej mozgovej prihody). V praci sa rozobera komplexna prevencia a liecba koncatinovocievnej arteriovej choroby. Angiologia/vaskularna medicina je najrýchlejsie sa rozvijajucou specializaciou internej mediciny.

Aims: In heart failure with reduced ejection fraction (HFrEF), there is an ‘obesity paradox’, where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium–glucose co-transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). Methods and results: Body mass index was examined using standard categories, i.e. underweight (2); normal weight (18.5–24.9 kg/m2); overweight (25.0–29.9 kg/m2); obesity class I (30.0–34.9 kg/m2); obesity class II (35.0–39.9 kg/m2); and obesity class III (≥40 kg/m2). The primary outcome in DAPA-HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal-weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% confidence interval) for the primary outcome with obesity class 1, the lowest risk group, as reference was: under/normal-weight 1.41 (1.16–1.71), overweight 1.18 (0.97–1.42), obesity class II/III 1.37 (1.10–1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI, e.g. hazard ratio for primary outcome: under/normal-weight 0.74 (0.58–0.94), overweight 0.81 (0.65–1.02), obesity class I 0.68 (0.50–0.92), obesity class II/III 0.71 (0.51–1.00) (P-value for interaction = 0.79). The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7–1.1) kg (P < 0.001). Conclusion: We confirmed an ‘obesity survival paradox’ in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied. Clinical Trial Registration: ClinicalTrials.gov NCT03036124.

Aims Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). Methods and results Key inclusion criteria were: New York Heart Association Class II−IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95 mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP, Graphical Abstract

Aims: The aim of this study was to examine whether left ventricular ejection fraction (LVEF) modified efficacy and safety of dapagliflozin 10 mg compared with placebo in the 4744 patients with LVEF ≤40% randomized in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). Methods and results: We examined whether LVEF, analysed categorically or continuously, modified the effect of dapagliflozin. The primary efficacy outcome was the composite of a worsening heart failure (HF) event (unplanned HF hospitalization/an urgent HF visit requiring intravenous therapy) or cardiovascular death. Mean LVEF was 31.1% and LVEF categories analysed were: 35% (n = 1396). Each 5% decrease in LVEF was associated with a higher risk of the primary outcome [hazard ratio (HR) 1.18; 95% confidence interval (CI) 1.13–1.24]. The benefit of dapagliflozin was consistent across the spectrum of LVEF: the dapagliflozin vs. placebo HR was 0.75 (95% CI 0.59–0.95) for LVEF 35% (P for interaction = 0.762). Similarly, the effect of dapagliflozin on the components of the primary endpoint was not modified by baseline LVEF (P for interaction for cardiovascular death = 0.974, and for worsening HF = 0.161). Safety of dapagliflozin was also consistent across the range of LVEF and neither efficacy nor safety were modified by diabetes status. Conclusion: Left ventricular ejection fraction was a significant predictor of hospitalization and mortality in patients with HF with reduced ejection fraction but did not modify the beneficial effect of dapagliflozin, overall or separately, in patients with and without diabetes. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT03036124.

Aims: Elevated serum uric acid concentration (SUA) has been associated with an increased risk of cardiovascular disease, but this may be due to unmeasured confounders. We examined the association between SUA and outcomes as well as the effect of sacubitril/valsartan on SUA in patients with heart failure with reduced ejection fraction (HFrEF) in PARADIGM-HF. Methods and results: The association between SUA and the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization, its components, and all-cause mortality was examined using Cox regression analyses among 8213 patients using quintiles (Q1–Q5) of SUA adjusted for baseline prognostic variables including estimated glomerular filtration rate (eGFR), diuretic dose, and log N-terminal pro-brain natriuretic peptide. Change in SUA from baseline over 12 months was also evaluated in each treatment group. Patients in Q5 (SUA ≥8.6 mg/dL) compared with Q1 (

Background Body weight changes are associated with significant variations in blood pressure (BP). Body mass modifications may, therefore, influence hypertension control in primary care. Methods Patients with a history of essential arterial hypertension were observed for 12 months. Anthropometric data and clinical BP were evaluated at the time of the recruitment and after 12 months of follow-up. The association between (body mass index) BMI change and BP control was analyzed by logistic regression. Results Sixteen thousand five hundred and sixty-four patients were recruited, while 13,631 patients (6336 men; 7295 women) finished the 1-year follow-up. In obese patients, a BMI decrease by at least 1 kg/m2 was negatively associated with uncontrolled hypertension at the end of the follow-up (men p

Cardiovascular disease (CVD) and depressive disorders (DD) are two of the most prevalent health problems in the world. Although CVD and depression have different origin, they share some common pathophysiological characteristics and risk factors, such as the increased production of proinflammatory cytokines, endothelial dysfunction, blood flow abnormalities, decreased glucose metabolism, elevated plasma homocysteine levels, oxidative stress and disorder in vitamin D metabolism. Current findings confirm the common underlying factors for both pathologies, which are related to dramatic dietary changes in the mid-19th century. By changing dietary ratio of omega-6 to omega-3 fatty acids from 1:1 to 15-20:1 some changes in metabolism were induced, such as increased pro-inflammatory mediators and modulations of different signaling pathways following pathophysiological response related to both, cardiovascular diseases and depressive disorders.

Background: \ud In patients with type 2 diabetes, inhibitors of sodium–glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.\ud Methods: \ud In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death.\ud Results: \ud Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P

Increased concentration of uric acid (UA) is positively associated with the clinical severity but negatively associated with the prognosis of heart failure (HF). However, data related to the association between UA concentration and N-terminal pro brain natriuretic peptide (NT-proBNP) are still lacking. The aim of the study was to analyze the relationships between UA, NT-proBNP, clearance of creatinine and NYHA function class and echocardiographic variables in the Slovak population of primary care patients diagnosed with HF. The association between UA and NT-proBNP was assessed by multivariate analysis. 848 patients (402 men, 446 women) with HF were included in the study. NT-proBNP correlated with UA in both men and women after adjustment based on age, BMI and glomerular filtration rate (r=0.263, p

Impaired baroreflex function is associated with a shift in autonomic balance towards sympathetic dominance, which may play important role in the development of arterial hypertension and consequent target organ damage. To determine the effect of treatment on the cardiovascular autonomic modulation expressed by baroreflex sensitivity (BRS) in hypertensives. A total of one hundred fourteen hypertensive patients (58 male/56 female, 65 ± 13 years of age, BMI 30 ± 3.4 kg/m2) were enrolled. Control group of 20 subjects with normal blood pressure (BP) (ten male/ten female, 59 ± 8 years of age, body mass index 28.3 ± 2.5 kg/m2) without any treatment was also studied. BRS and BRSf were determined by the sequence and spectral method: a 5-min on-invasive beat-to-beat recording of blood pressure and R-R interval with use of Collin CBM-7000 monitor, controlled breathing at a frequency of 0.1 Hz. Significant negative correlation between spontaneous BRS and BP was present in hypertensives (r = −0.52, p

Background The use of antiplatelet agents is strongly recommended for the secondary prevention of ischemic events such as myocardial infarction, stroke/transient ischemic attack (TIA). Objectives The aim of our study was to analyse the use of antiplatelet medication in patients after myocardial infarction, stroke/TIA, and patients with both conditions and to identify patient-related characteristics, which determine the use of such drugs in elderly patients. Methods Study sample (n=372) was derived from 2,157 patients admitted to long-term care departments of three municipal hospitals. The study included patients aged ≥65 years after myocardial infarction, stroke/TIA or both. Results Antiplatelet medications were prescribed in 54.8 % and 68.5 % of patients at hospital admission and discharge, respectively. Hospitalisation led to a significant increase in the use of antiplatelet medication in patients after myocardial infarction and in those with the combination of both events. However, in patients after only stroke/TIA, we did not find any significant difference comparing the use of antiplatelet medication at the time of hospital admission and discharge, respectively. Conclusion Our study revealed that physicians are more aware of the benefits of antiplatelet medication in elderly patients after myocardial infarction or those after both myocardial infarction and stroke/TIA in comparison with patients after only stroke/TIA (Tab. 3, Ref. 32).

The blood concentrations of total cholesterol and low-density lipoprotein (LDL) do not predict survival in patients older than 60 years. The atherogenic index of plasma (AIP) is a logarithm of the triacylglycerol to high-density lipoprotein (HDL) ratio and a surrogate for the concentration of small dense LDL. It might be a better reflection of the risk of all-cause death in elderly patients. We conducted a prospective observational study of patients with arterial hypertension older than 60 years. The concentrations of total cholesterol, LDL, HDL and triacylglycerol were measured at the time of the recruitment and the patients were observed for 10 years. Cox regression analysis was performed to assess the effects of lipoproteins and AIP on survival. A total of 500 patients were recruited and 473 of them (226 men, 247 women) either died or successfully completed the 10-year follow-up and were included in the analysis. The AIP was positively associated, while HDL concentration was negatively associated with the risk of all-cause death adjusted for age, smoking habits, statin use, history of diabetes mellitus, myocardial infarction, stroke and peripheral artery occlusive disease (PAOD) in elderly women but not in men. The LDL, total cholesterol, triacylglycerol and non-HDL concentrations were not associated with the risk of death in both sexes. The AIP is positively associated with the risk of all-cause death in elderly women with arterial hypertension independent of age, smoking habits, statin therapy and comorbidities.

Background— The angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696) reduced cardiovascular morbidity and mortality compared with enalapril in patients with heart failure (HF) and reduced ejection fraction (EF) in the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. We evaluated the influence of EF on clinical outcomes and on the effectiveness of sacubitril/valsartan compared with enalapril. Methods and Results— Eight thousand three hundred ninety-nine patients with New York Heart Association class II to IV HF with reduced EF [left ventricular EF (LVEF) ≤40%] were randomized to sacubitril/valsartan 97/103 mg twice daily versus enalapril 10 mg twice daily and followed for a median of 27 months. The primary study end point was cardiovascular death or HF hospitalization. LVEF was assessed at the sites and recorded on case report forms. We related LVEF to study outcomes and assessed the effectiveness of sacubitril/valsartan across the LVEF spectrum. The mean LVEF in PARADIGM-HF, reported by sites, was 29.5 (interquartile range, 25–34). The risk of all outcomes increased with decreasing LVEF. Each 5-point reduction in LVEF was associated with a 9% increased risk of cardiovascular death or HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 1.05–1.13; P P interaction=0.87) or continuously ( P interaction=0.95). Conclusions— In patients with HF and reduced EF enrolled in PARADIGM-HF, LVEF was a significant and independent predictor of all outcomes. Sacubitril/valsartan was effective at reducing cardiovascular death and HF hospitalization throughout the LVEF spectrum. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01035255.

Purpose The aim of the present study was to determine which patient-related characteristics influence the selection of the antihypertensive drug class in elderly patients in Slovakia. Methods The sample for our study (n = 401) was selected from 1045 patients admitted to the Department of Internal Medicine of a general hospital during the period of 1 December 2003—31 March 2005. Patients aged 65 or more with documented arterial hypertension and treated with at least one antihypertensive drug were enrolled in our retrospective study. Specific socio-demographic and clinical characteristics as well as cardiovascular comorbid conditions were evaluated as potential factors that could have influenced the choice of antihypertensive drug class. Results The most frequently prescribed antihypertensive drugs were angiotensin-converting enzyme (ACE) inhibitors and diuretics (61.8% and 60.1% of patients, respectively). Patients aged ≥ 85 years had lower probability of ACE inhibitors prescription (OR = 0.49). Females had higher chance of calcium channel blockers use (OR = 3.84) and lower odds of diuretics administration (OR = 0.50). In patients living alone, ACE inhibitors were preferred (OR = 2.16). The use of diuretics was more frequent in polymorbid patients (OR = 1.95). Immobile patients had lower chance of being prescribed beta-blockers and calcium channel blockers (OR = 0.25 and OR = 0.39, respectively). Conclusion The present study revealed that the selection of the antihypertensive drug class in elderly patients is influenced not only by comorbid conditions present but also by socio-demographic and clinical characteristics, such as age, sex, living alone, polymorbidity and immobilization. These characteristics reflect the doctor's perception of risk from pharmacotherapy of hypertension in elderly patients. Copyright © 2009 John Wiley & Sons, Ltd.

Abstract. Background: The aim of this study was to evaluate the vasodilatation and vasomotion response to local heating in the cutaneous microcirculation of the ankle, dorsum of foot and forearm. Recently, it has been suggested that this response differs between the forearm and the leg. Probands and methods: Twenty-nine young healthy adults were recruited. They underwent measurement by laser Doppler flowmetry (LDF) in three sites of the body (ankle, dorsum of foot, forearm). Percentage change of the median flow of the skin before and after provocation and normalised perfusion flow to maximal dilation (cutaneous vascular conductance - CVC % Max) during short provocation test were monitored. Spectral analysis of laser Doppler flowmetry signals was performed using the fast Fourier transform algorithm. Results: Significant differences were found in CVC % Max between ankle/dorsum (45.18 ± 6.38% Max vs. 51.24 ± 6.87% Max, respectively; p < 0.05) and between ankle/forearm (45.18 ± 6.38% Max vs. 54.49 ± 5.37% Max, respectively; p < 0.05). Percentage change of flux after provocation has revealed significant differences between ankle/dorsum (394.1 ± 204.5% vs. 577.4 ± 273.5%, respectively; p < 0.05) and ankle/forearm (394.1 ± 204.5% vs. 637.1 ± 324.7%, respectively; p < 0.05). Total spectral activity of vasomotion has differed between ankle/dorsum and ankle/forearm: 69.59 [49.58 - 96.04] vs. 93.01 [73.15 - 121.8] (p < 0.05) and 69.59 [49.58 - 96.04] vs. 107.5 [80.55 - 155.8] (p < 0.05), respectively. Conclusions: Cutaneous microcirculation exhibits regional differences. Significant variability of function between ankle and dorsum of foot suggests that leg microcirculation is not uniform.

Introduction Cardiovascular autonomic neuropathy in diabetics is a common but often underestimated and underdiagnosed complication of diabetes mellitus. One of the most clinical apparent forms of cardiovascular autonomic neuropathy is orthostatic hypotension. Objectives To retrospectively assess the association of the orthostatic hypotension (OH) with macrovascular and microvascular complications of diabetes mellitus and to determine its effect on mortality. Design and methods We retrospectively analyzed 187 patients with diabetes mellitus (60 patients with diabetes type 1 and 127 patients with diabetes type 2). Patients were divided into groups according to presence or absence of OH and type of diabetes. Association of OH with macrovascular and microvascular complications was evaluated and the effect of OH on 10-year all-cause mortality was also assessed. Results OH was present in 31.7% of patients with diabetes type 1 (DM1) and in 32.3% of patients with diabetes type 2 (DM2). OH was positively associated with the prevalence of myocardial infarction in DM1 (OR=10.67) and with prevalence of stroke in DM2 (OR=3.33). There was also a strong association of OH and the prevalence of peripheral artery disease in both DM1 (OR=14.18) and DM2 (OR=3.26). Patients with both types of diabetes and OH had significantly higher prevalence of nephropathy (DM1 OR=8.68, DM2 OR=3.24), retinopathy (DM1 OR=8.09, DM2 OR=4.08) and peripheral neuropathy (DM1 OR=17.14, DM2 OR=7.51) Overall 10year mortality rate was higher in diabetic patients with OH. Conclusions Presence of OH in diabetics is associated with higher prevalence of macrovascular and microvascular complications of diabetes mellitus and also with higher 10-year mortality.

Background and aims. Arterial hypertension doubles the risk of coronary heart disease, heart and kidney failure, and peripheral arterial disease. Less variation in diurnal ambulatory blood pressure monitoring (ABPM) patterns may affect mortality outcome. Therefore, as hypertension occurs in over 95% of older subjects, the prognostic value of dipping status in older hypertensive patients will be assessed. Method. The retrospective study group consisted of 170 hypertensive patients, aged 75 84 years, enrolled in the years 2005 to 2007. Baseline measures included 24-h ABPM. Diurnal index and dipping status was calculated and stratified the group into dippers (40 patients, 23.5%), non-dippers (65 patients, 38.2%) and reverse-dippers (65 patients, 38.2%). Results. During a 5-year observation, after baseline we have observed 69 deaths (40.9%) from the whole group of 170 patients with 23 (35.4%) being non-dippers and 36 (55.4%) reverse-dippers. There were significant differences between the groups divided according to diurnal dipping status in survival time, number of recorded deaths and night mean blood pressure. We have identified and confirmed risk factors for the all-cause mortality: age, mean systolic and diastolic blood pressure, diurnal index and dipping status (dipping, non-dipping or reverse-dipping). Conclusion. Reverse-dippers and non-dippers revealed worse prognosis compared with dippers.

The electrophoretic separation of lipoproteins on polyacrylamide gels enables the quantification of nonatherogenic and atherogenic plasma lipoproteins including small dense low density lipoprotein (sdLDL) particles, which represent the atherogenic lipoprotein subpopulations in plasma. This methodology could help distinguish between nonatherogenic hyperlipidemia, normolipidemia with an atherogenic lipoprotein profile, non-atherogenic normolipidemia, and atherogenic hyperlipidemia. According to our pilot research of a normolipidemic population, the atherogenic lipoprotein profile might be present in about 6% of normolipidemic young healthy individuals. Therefore, if confirmed by other studies, it will be necessary to consider a different diagnostic approach and risk stratification for patients with atherogenic normolipidemia (as well as non-atherogenic hypercholesterolemia).

Background Majority of studies that focused on the influence of abdominal obesity on lipoprotein profile, were conducted in the fasting conditions. The effects of visceral fat accumulation on postprandial lipoprotein concentrations have not yet been studied in details. We therefore focused on the postprandial lipoprotein profile in otherwise healthy men and women with abdominal obesity and their comparison with the control group of volunteers with normal waist circumference. The concentration of lipoprotein classes and subclasses was measured before and 4 hours after a standard meal by linear polyacrylamide gel electrophoresis. Results A statistically significant postprandial rise in triacylglycerol concentration occurred in all subjects. VLDL increased 4 hours after meal in all subjects except the women with normal waist circumference. The concentration of large IDL particles increased in both non-obese men and women. In women with abdominal obesity, however, it decreased, while in obese men there was no statistically significant change. The concentration of small and medium-sized IDL particles decreased in all volunteers. Analyzing subclasses changes of large, medium-sized and small LDL particles we saw no significant shift in their concentrations except the subclass of large LDL particles, which decreased in men. Concentrations of medium and small HDL particles decreased postprandially in all volunteers with normal waist circumference. However, they remained unchanged in subjects with abdominal obesity. Conclusions We observed significant postprandial changes of the lipoprotein profile, but the nature and extent of these changes depended on gender and presence of abdominal obesity.

Background There is a lack of studies evaluating the factors which influence the perception of safety of over-the-counter (OTC) medications by elderly patients. Objective The aim of our questionnaire survey was to evaluate the perception of the risk of OTC medications by elderly patients and to identify patient-associated characteristics which determine elderly persons who consider OTC medications as safe. Setting 25 community pharmacies in different regions of the Slovak Republic. Methods A 54-items questionnaire was provided to patients aged ≥65 years who were purchasing at least one OTC medication during the period from May 2010 to November 2010. The questions elicited information on (a) self-assessment of health status; (b) basic characteristics of OTC medications use (e.g. frequency, duration); (c) patients’ knowledge on OTC medications; (d) participants’ perception of the risk of OTC medications; (e) the list of OTC and prescription-only medications taken; and (f) sociodemographic characteristics of respondents. Results Of the 793 questionnaires distributed, 519 were finally included in the statistical analysis (response rate of 65.4 %). Women were prevailing in the analysed group (n = 361; 69.6 %). The average age of participants was 72.2 ± 5.6 years. Majority (n = 392, 75.5 %) of the respondents considered OTC medications as safe. Multivariate analysis (binary logistic regression) revealed that elderly patients who considered OTC medications as safe were characterised by use of OTC medications every day (OR = 2.09), preferring a wide range of such drugs in pharmacies (OR = 2.86), considering such medications as effective (OR = 10.33), obtaining information on OTC drugs from pharmacists (OR = 1.91) and willingness to possibly purchase OTC medications outside pharmacies (OR = 3.35). On the other hand, allergic conditions as a reason for purchasing OTC medications (OR = 0.23), recommendation of a physician regarding the choice of OTC medications (OR = 0.51) and considering concurrent use of several medications as a factor increasing the risk of adverse drug reactions (OR = 0.62) emerged as important factors that decreased the probability of elderly patients considering OTC medications as safe. Conclusions The survey identified various factors that influenced the perceptions of the safety of OTC medications by the elderly and indicated that pharmacists represent the most trusted source of information about OTC medications.

BACKGROUND Slovakia belong to the European Union countries with the high incidence and prevalence of cardiovascular diseases in general and IHD in particular. METHOD Homocystein-Slovakia is crossectional population study realised in subjects in high risk age 35-75 years in two groups. The first consists of patients with verified stable ischemic heart disease (IHD) (M= 152; F = 167) aged 60.8±9.37 yrs (males) res. 63.1±7.56 years (females) (NS) who were randomly selected from two cardiological registrars. Second population was formed by general population who were dichotomised according their medical records into IHD patients (M= 31, F= 53) and apparently healthy controls (M= 47; F = 55), the later in significantly younger age as patients, but in same age for intergender comparison 49.6±10.3 vs 46.6±9.2 yrs (NS). RESULTS We found very high prevalence of classic as well as newer risk factors and risk markers both in IHD patients and in controls. Increased homocysteinen (Hcy >15 µmo/l for males and Hcy >13 µmo/l for females) was found even in 32.9 % of patients and 13.6 % of controls (p

2 billion people worldwide consume alcohol, and of these 76·3 million have alcohol misuse problems, with substantial morbidity, mortality, and social harm. Alcohol use is the third leading risk factor for preventable and premature disease, with a lamentable lack of any global remediable action. Despite the clear evidence of harm from excess alcohol, there is little will to prioritise the problem in the global health agenda. Therefore the challenge is to reduce this harm by strengthening policies and their implementation locally, nationally, and globally. Such strengthening requires infl uence and commitment at all levels of the health, political, and legal systems, but the health harms mandate that physicians must take a lead. Evidence-based cost-eff ective interventions reduce harm from alcohol, but advocacy for an alcohol policy is not politically attractive. The confl ict between government-driven health policy and commercial or social govern mental infl uences impedes the progress of any national or international policy. There is, therefore, an urgent need to put pressure on governments to recognise, adopt, and scale up appropriate health policies. WHO’s Global strategy to reduce harmful use of alcohol, ratifi ed at the World Health Assembly in 2010, is the fi rst step towards the introduction of an eff ective coordinated response. Physicians are in a unique position to lead and inform this initiative. An international clinical network with a coherent voice should demand action to reduce alcohol misuse across the globe. Medical professionalism includes the responsibility to speak out, to lead, and to voice advocacy. It is every clinician’s responsibility to address alcohol harm, both on a daily basis with individual patients and in the wider context of health harms and inequalities at the population level. The voice of doctors is valued and trusted within societies, and therefore we call on all doctors to show eff ective leadership by holding ministries of health accountable for their lack of action in the face of such robust evidence. We ask governments to act urgently and to champion evidence-based initiatives for the implement ation of eff ective alcohol strategies at all levels to improve the health of populations worldwide.

LCZ696 is a first-in-class inhibitor of the angiotensin II receptor and neprilysin. We aimed to establish whether the dual actions of LCZ696 lead to further lowering of blood pressure, compared with the angiotensin-receptor blocker valsartan.1328 patients aged 18-75 years with mild-to-moderate hypertension were randomly assigned (double-blind) to 8 weeks' treatment in one of eight groups: 100 mg (n=156 patients), 200 mg (n=169), or 400 mg (n=172) LCZ696; 80 mg (n=163), 160 mg (n=166), or 320 mg (n=164) valsartan; 200 mg AHU377 (n=165); or placebo (n=173). The primary endpoint was the mean difference across the three single-dose pairwise comparisons of LCZ696 versus valsartan (100 mg vs 80 mg, 200 mg vs 160 mg, and 400 mg vs 320 mg) in mean sitting diastolic blood pressure during the 8-week treatment period. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00549770.1215 patients completed the 8-week treatment period. The average reduction in mean sitting diastolic blood pressure across the doses of LCZ696 versus the appropriate comparator dose of valsartan showed significantly greater reductions with LCZ696 (mean reduction: -2.17 mm Hg, 95% CI -3.28 to -1.06; p0.0001). The reduction in mean sitting diastolic blood pressure was significantly different for 200 mg LCZ696 versus 160 mg valsartan (-2.97 mm Hg, 95% CI -4.88 to -1.07, p=0.0023) and for 400 mg LCZ696 versus 320 mg valsartan (-2.70 mm Hg, -4.61 to -0.80, p=0.0055). LCZ696 was well tolerated and no cases of angio-oedema were reported; only three serious adverse events occurred during the 8-week treatment period, of which none was judged to be related to the study drug, and no patients died.Compared with valsartan, dual-acting LCZ696 provides complementary and fully additive reduction of blood pressure, which suggests that the drug holds promise for treatment of hypertension and cardiovascular disease.Novartis.

30 Introduction Acute stroke is a severe clinical man‑ ifestation of atherothrombosis. Atherothrombo‑ sis and its complications are currently the most frequent cause of morbidity in the world. The ma‑ jor factors contributing to accelerated athero‑ thrombosis in humans are dyslipoproteinemias and hypertension, among others. The presence of atherogenic lipoproteins in plasma leads to the development of endothelial dysfunction, in‑ creases the vessel tone, and contributes to further deterioration of cerebral perfusion leading to ce‑ rebral ischemia. The aim of the present study was to evaluate atherogenic lipoproteins in patients with acute ischemic stroke admitted to the in‑ tensive care unit. Patients and methods We followed up 50 con‑ secutive patients with acute ischemic stroke (24 men and 26 women), aged from 35 to 90 years (mean age, 77.5 years ±11.8 years), and admit‑ ted to the 2nd Department of Internal Medicine of the Comenius University in Bratislava, Slo‑ vakia. The diagnosis of stroke was confirmed by a neurologist and by computed tomography. Af‑ ter admission, blood samples from the cubital vein were collected to measure routine biochem‑ ical parameters, including complete lipid profile

Ischaemic disease of the lower extremities is not a rare clinical entity as shown from epidemiological studies (5). Kinesiotherapy has been employed with these patients in recent years (1, 12). Holter ECG monitoring is a suitable noninvasive technique for evaluation of these patients during such an exercise programme (5, 7).

Background This study evaluated the short-term and long-term effects of the angiotensin II type 1 receptor antagonist candesartan cilexetil on hemodynamics, neurohormones, and clinical symptoms in patients with congestive heart failure (CHF). Methods In this multicenter, double-blind, parallel-group study, 218 patients with CHF (New York Heart Association class II or III) with impaired left ventricular function (ejection fraction ≤40%) and pulmonary capillary wedge pressure ≥13 mm Hg were randomly assigned to 12 weeks of treatment with placebo (n = 44) or candesartan cilexetil (2 mg [n = 45], 4 mg [n = 46], 8 mg [n = 39], or 16 mg [n = 44]) once daily after a 2-week placebo run-in period. Hemodynamic measurements were performed by right heart catheterization over a 24-hour period after single (day 1) and repeated (3-month) treatment with the study drug. Results On regression analysis of the time-response curves, single and multiple doses of candesartan cilexetil produced sustained, significant, and dose-dependent reductions in pulmonary capillary wedge pressure (short-term effect P = .036, long-term effect P = .035) and mean pulmonary arterial pressure (short-term effect P = .031, long-term effect P = .042). Systemic vascular resistance showed a trend toward decreasing with dose on short-term and long-term treatments. No consistent changes were seen in cardiac index. Compensatory increases in plasma renin activity and angiotensin II levels with decreases in aldosterone and atrial natriuretic peptide were dose-dependent and significant. Candesartan cilexetil improved clinical symptoms, stabilized patient New York Heart Association status compared with placebo, and was judged to be an efficacious treatment by the investigators. More patients receiving placebo stopped the trial prematurely because of an adverse event than in any candesartan cilexetil group, and there was no excess of deaths in any treatment group. Candesartan was safe and well tolerated at all dosages. Conclusions Candesartan cilexetil demonstrated significant short-term and long-term improvements in hemodynamic, neurohormonal, and symptomatic status and was well tolerated in patients with CHF. (Am Heart J 2003; 145:e14.)

Background Our goal was to investigate the effect of short term exercise on fasting and postprandial lipoprotein profile. Methods Healthy sedentary men exercised 20 min for four days. The intensity of exercise was modulated to maintain 75–80 % of a calculated HRmax. Before and after the exercise program, fasting and postprandial (4 h after standard meal) concentrations of lipoprotein subfractions were measured by an electrophoresis in polyacrylamide gel and total concentrations of TAG, LDL and HDL by enzymatic colorimetric method. After 2 days of rest, fasting and postprandial concentrations of lipoprotein fractions and subfractions were measured to determine a persistency of a changes in the lipoprotein profile. Results 4 days of physical exercise led to statistically significant decrease of concentration of triacylglycerol in fasting (76.29 ± 20.07, 53.92 ± 10.90, p

Background Assessment of cardiovascular disease (CVD) risk factors can predict clinical manifestations of atherosclerosis in adulthood. In this pilot study with hypercholesterolemic children and adolescents, we investigated the effects of a combination of plant sterols, fish oil and B vitamins on the levels of four independent risk factors for CVD; LDL-cholesterol, triacylglycerols, C-reactive protein and homocysteine. Methods Twenty five participants (mean age 16 y, BMI 23 kg/m2) received daily for a period of 16 weeks an emulsified preparation comprising plant sterols esters (1300 mg), fish oil (providing 1000 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)) and vitamins B12 (50 μg), B6 (2.5 mg), folic acid (800 μg) and coenzyme Q10 (3 mg). Atherogenic and inflammatory risk factors, plasma lipophilic vitamins, provitamins and fatty acids were measured at baseline, week 8 and 16. Results The serum total cholesterol, LDL- cholesterol, VLDL-cholesterol, subfractions LDL-2, IDL-1, IDL-2 and plasma homocysteine levels were significantly reduced at the end of the intervention period (pp Conclusions Daily intake of a combination of plant sterols, fish oil and B vitamins may modulate the lipid profile of hypercholesterolemic children and adolescents. Trial registration Current Controlled Trials ISRCTN89549017