The Effect of Early Applied Robot-Assisted Physiotherapy on Functional Independence Measure Score in Post-Myocardial Infarction Patients.

Robot-assisted training has been widely used in rehabilitation programs, but no significant clinical evidence about its use in productive working-age cardiac patients was demonstrated. Thus, we hypothesized that early applied robot-assisted physiotherapy might provide additional treatment benefits in the rehabilitation of post-myocardial infarction (MI) patients. A total of 92 (50 men, 42 women) hospitalized post-MI patients with the age of 60.9 ± 2.32 participated in the research. An early intensive physiotherapy program (7×/week, 2×/day) was applied for each patient with an average time of 45 min per session. Patients were consecutively assigned to Experimental group (EG) and Control group (CG). Then, 20 min of robot-assisted training by Motomed letto 2 or Thera-Trainer tigo was included in all EG physiotherapy sessions. The Functional Independence Measures (FIM) score at the admission and after 14 days of rehabilitation was used for an assessment. When analyzing time * group effect by repeated-measures ANOVA, we reported that EG showed a higher effect in ADL (p = 0.00), and Motor indicators (p = 0.00). There was no statistically significant effect reported in the Social indicator (p = 0.35). Early rehabilitation programs for post-MI patients might be enhanced by robotic tools, such as THERA-Trainer tigo, and Motomed letto 2. The improvement was particularly noticeable in mobility and ADLs.

Efficacy of dapagliflozin in heart failure with reduced ejection fraction according to body mass index.

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 (<18.5 kg/m2 ); 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.

Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).

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 <110 mmHg; 981 ≥ 110 < 120; 1149 ≥ 120 < 130; and 1409 ≥ 130 mmHg. The placebo-corrected reduction in SBP from baseline to 2 weeks with dapagliflozin was -2.54 (-3.33 to -1.76) mmHg (P < 0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome [20.6, 95% confidence interval (95% CI) 17.6-24.2] than those in the highest SBP category (13.8, 11.7-16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60-0.97), 0.76 (0.57-1.02), 0.81 (0.61-1.08), and 0.67 (0.51-0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined. CONCLUSION: Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.

Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.

BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

Efficacy and safety of sodium-glucose co-transporter 2 inhibition according to left ventricular ejection fraction in DAPA-HF.

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: <26% (n = 1143), 26-30% (n = 1018), 31-35% (n = 1187), and >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 <26%, 0.75 (0.57-0.98) for LVEF 26-30%, 0.67 (0.51-0.89) for LVEF 31-35%, and 0.83 (0.63-1.09) 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.

Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction.

BACKGROUND: 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. METHODS: 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. RESULTS: 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<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. (Funded by AstraZeneca; DAPA-HF ClinicalTrials.gov number, NCT03036124.).

Management of diabetic patients with lower extremity peripheral arterial disease.

Extremitovascular arterial ischemic disease (lower extremity peripheral arterial disease - PAD) is an important manifestation of systemic atherosclerosis and other arterial diseases of vascular system. The lower the ankle-brachial pressure index, the greater the risk of serious acute instable organovascular events (e. g. acute myocardial infarction, stroke). Complex prevention and treatment of extremitovascular arterial disease is discussed in this article. Angiology/vascular medicine is the fastest growing field of internal medicine.

Sacubitril/valsartan reduces serum uric acid concentration, an independent predictor of adverse outcomes in PARADIGM-HF.

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 (<5.4 mg/dL) were younger (62.8 vs. 64.2 years), more often male (88.7% vs. 63.1%), had lower systolic blood pressure (119 vs. 123 mmHg), lower eGFR (57.4 vs. 76.6 mL/min/1.73 m2 ), and greater diuretic use. Higher SUA was associated with a higher risk of the primary outcome (adjusted hazard ratios) Q5 vs. Q1 = 1.28 [95% confidence intervals (1.09-1.50), P = 0.003], cardiovascular death [1.44 (1.11-1.77), P = 0.001], HF hospitalization [1.37 (1.11-1.70), P = 0.004], and all-cause mortality [1.36 (1.13-1.64), P = 0.001]. Compared with enalapril, sacubitril/valsartan reduced SUA by 0.24 (0.17-0.32) mg/dL over 12 months (P < 0.0001). Sacubitril/valsartan improved outcomes, irrespective of SUA concentration. CONCLUSION: Serum uric acid concentration was an independent predictor of worse outcomes after multivariable adjustment in patients with HFrEF. Compared with enalapril, sacubitril/valsartan reduced SUA and improved outcomes irrespective of SUA.

The effects of body weight loss and gain on arterial hypertension control: an observational prospective study.

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 < 0.0001, OR = 0.586, 0.481-0.713, women p < 0.001, OR = 0.732, 0.611-0.876). A similar association was observed in overweight patients (men p < 0.05, OR = 0. 804, 95% CI: 0.636-0.997, women p < 0.05, OR = 0.730, 95% CI: 0.568-0.937). A BMI increase of at least 1 kg/m2 was associated with a significantly higher odd of uncontrolled hypertension in obese (men p < 0.001, OR = 1.471, 1.087-1.991, women p < 0.001, OR = 1.422, 1.104-1.833) and overweight patients (men p < 0.0001, OR = 1.901, 95% CI: 1.463-2.470, women p < 0.0001, OR = 1.647, 95% CI: 1.304-2.080). CONCLUSIONS: Weight loss is inversely associated and weight increase is positively associated with the probability of uncontrolled hypertension in obese and overweight hypertensives.

Atherogenic index of plasma is positively associated with the risk of all-cause death in elderly women : A 10-year follow-up.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Antiplatelet thromboprophylaxis of arterial vascular diseases and organovascular ischemic diseases]. / Antitrombocytová tromboprofylaxia artériových vaskulárnych chorôb a orgánovaskulárnych ischemických chorôb.

Antiplatelet therapy by acetylsalicylic acid (ASA, aspirin) provided pivotal advances in the prevention and treatment of organovascular (angiovascular, cardiovascular, cerebrovascular, extremitovascular, renovascular, genitovascular, mesenteriointestinokolonovascular, bronchopulmovascular, oculovascular, otovascular and other) arterial ischemic diseases. Currently available antiplatelet drugs have some limitations which might be overcomed by improved dosing regimens, use of combination of agents affecting different platelet functions and, in particular, by the new antiplatelet drugs (new arterial antithrombotics) with distinct pharmacodynamic properties offering new advantages, including faster onset of action, greater potency, and reversibility of effects.Key words: arteriothromboprophylaxis - arterial thrombosis - classic antiplatelet drugs - new antiplatelet agents - organovascular arterial diseases.

[Oral anticoagulants for primary and secondary prevention of venous thromboembolism]. / Perorálne antikoagulanciá v primárnej a sekundárnej prevencii vénovej tromboembólie.

Until recently, vitamin K antagonists (VKA; predominantly warfarin) were the only oral anticoagulants for primary and secondary prevention of venous thromboembolism. Prevention and therapy with novel, direct, non-VKA oral anticoagulant agents (NOACs; DOACs: dabigatran, rivaroxaban, apixaban, edoxaban), have recently become available as an alternative to VKA. NOACs have been shown to be non-inferior or superior to VKA in clinical trials. Available results suggest that real world safety of NOACs is mostly consistent with results observed in clinical trials. The most effective method is triple simultaneous prevention of venous thromboembolism (pharmaco kinezio mechano phlebothromboemboloprophylaxis).Key words: oral anticoagulants - NOAC/DOAC - thromboprophylaxis - venous thromboembolism - VKA.

Changes in vasomotion--effect of hyperbaric oxygen in patients with diabetes Type 2.

OBJECTIVES: To investigate vasomotion in diabetic patients who underwent sessions of hyperbaric oxygen (HBO2) therapy. MATERIALS AND METHODS: Seventy-one patients with diabetes Type 2 and lower-extremity neuropathy were enrolled in a prospective matched case-control study. A total of 39 patients underwent 15 sessions of HBO2 therapy consisting of 90 minutes of breathing 100% oxygen at 2.5 atmospheres; 32 were included in the control group without exposure to hyperbaric oxygen. We used laser Doppler flowmetry for measurement of flowmotion. Spectral analysis of laser Doppler flowmetry signals was performed using the Fast Fourier transform algorithm. The total spectral activity was divided into the subgroup of endothelium, adrenergic, intrinsic smooth muscle, respiratory and cardiac spectral activity. The lateral ankle and the dorsum of the foot were chosen for this study. Heating provocation test was performed on both sites. The measurement was performed 24 hours before the first HBO2 session and 24 hours after the last (15th) session of therapy. RESULTS: We observed a significant increase in respiratory, cardiac and total spectral activity of flowmotion on the ankle as well as a significant increase in cardiac and total spectral activity on the dorsum of the foot in patients without a foot ulcer. In the subgroup of patients with a diabetic ulcer, a decrease of total spectral activity of flowmotion on the dorsum of the foot was observed. CONCLUSION: Flowmotion (indirectly vasomotion) measured by laser Doppler flowmetry changed significantly after HBO2 therapy. Flowmotion dynamics may partly explain the positive effect of HBO2 on the healing process of a diabetic ulcer.

Effect of Low Dose Atorvastatin Therapy on Baroreflex Sensitivity in Hypertensives.

INTRODUCTION: 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. AIM: To determine the effect of treatment on the cardiovascular autonomic modulation expressed by baroreflex sensitivity (BRS) in hypertensives. METHODS: A total of one hundred fourteen hypertensive patients (58 male/56 female, 65 ± 13 years of age, BMI 30 ± 3.4 kg/m(2)) 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/m(2)) 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. RESULTS: Significant negative correlation between spontaneous BRS and BP was present in hypertensives (r = -0.52, p < 0.001). All cohort of hypertensive patients had significantly lower BRS than subjects with normal blood pressure (p < 0.05). The greatest decline in BRS values was in hypertensive patients with metabolic syndrome, who had BRS values <5 ms/mmHg. Hypertensives with hypercholesterolaemia on low dose statin therapy (atrovastatin 20 mg) had higher BRS/BRSf values than statin free patients (p < 0.05). Only BRSf not BRS was significantly increased in hypertensives with beta-blockers. CONCLUSION: An inverse correlation between blood pressure and BRS is present in hypertensives. BRS and BRSf is higher in low dose statin-treated patients with essential hypertension.

Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial.

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<0.001), a 9% increased risk for CV death (hazard ratio, 1.09; 95% confidence interval, 1.04-1.14), a 9% increased risk in HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 1.04-1.14) and a 7% increased risk in all-cause mortality (hazard ratio, 1.07; 95% confidence interval, 1.03-1.12) in adjusted analyses. Sacubitril/valsartan was effective across the LVEF spectrum, with no evidence of heterogeneity, when modeled either in tertiles (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.

Orthostatic hypotension in diabetic patients-10-year follow-up study.

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.

Effect of hyperbaric oxygen on lipoprotein subfractions in diabetic patients.

OBJECTIVES: Favorable metabolic changes have been observed in many in vitro and animal studies after application of hyperbaric oxygen (HBO2). Metabolic changes after hyperbaric oxygen therapy, especially focused on lipoprotein subfractions, have not been described in humans. Our aim was to investigate possible alteration in concentration of lipoprotein subfractions in diabetic patients after hyperbaric oxygen therapy. METHODS: 58 Type 2 diabetic patients were enrolled in a prospective matched case-control study. A total of 31 underwent hyperbaric oxygen therapy, and 27 were included in the control group without HBO2 exposure. Fasting concentrations of lipoprotein subfractions were measured by electrophoresis in polyacrylamide gel 24 hours before and 24 hours after hyperbaric sessions performed at 2.5 atmospheres absolute for 15 days. Homeostatic model assessment of insulin resistance, C-peptide and glycemic variability were assessed before and after therapy. RESULTS: We observed decreased subfractions of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL 3), LDL 1, LDL 2 and LDL 3-7 after hyperbaric oxygen treatment. In addition, the IDL 1 subfraction, as well as the concentration of C-peptide, increased significantly in the treatment arm. Glycemic variability improved after therapy. No differences were observed in the control group. CONCLUSION: Hyperbaric oxygen therapy is connected with antiatherogenic metabolic changes. This study demonstrates that hyperbaric oxygen therapy may hold potential for inducing metabolic changes in diabetic patients that may decrease their cardiovascular risk.

Effect of short term aerobic exercise on fasting and postprandial lipoprotein subfractions in healthy sedentary men.

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 < 0.05) and postprandial state (139.06 ± 23.72, 96.55 ± 25.21, p < 0.05) VLDL in fasting (21.88 ± 3.87, 18.00 ± 3.93, p < 0.05) and postprandial state (23.88 ± 3.52, 19.25 ± 3.62, p < 0.05), total cholesterol in fasting (162.26 ± 23.38, 148.91 ± 17.72, p < 0.05) and postprandial state (163.73 ± 23.02, 150.08 ± 18.11, p < 0.05). Atherogenic medium LDL decreased also in fasting (9.89 ± 3.27, 6.22 ± 2.55, p < 0.001) and postprandial state (8.88 ± 6.51, 6.88 ± 5.57, p < 0.001). However decrease of large IDL (25.38 ± 3.54, 23.88 ± 3.91, p < 0.05) and large LDL particles (42.89 ± 11.40, 38.67 ± 9.30) was observed only in postprandial state. Total HDL concentration remained unchanged but we observed statistically significant decrease of small HDL particles in fasting (6.11 ± 2.89, 4.22, p < 0.05) and postprandial state (6.44 ± 3.21, 4.56 ± 1.33, p < 0.05). Concentration of these particles are associated with progression of atherosclerosis. All changes of fasting and postprandial lipoprotein profile disappeared after 2 days of rest. CONCLUSION: Just 4 daily settings of 20 min of physical exercise can lead to significant positive changes of fasting and postprandial lipoprotein profile.

Regional differences of vasodilatation and vasomotion response to local heating in human cutaneous microcirculation.

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.

[Erectile dysfunction as the first sign of systemic vascular diseases and of organovascular arterial ischemic diseases. Guidelines and Challenge of the Angiology section of Slovak Medical Chamber (AS SMC, 2015)]. / Erektilná dysfunkcia ako prvý znak systémových cievnych chorôb a orgánovovaskulárnych artériových ischemických chorôb Odporúcania a výzva Angiologickej sekcie Slovenskej lekárskej komory (2015).

Erectile dysfunction is a highly prevalent and progressive condition affecting the quality of life of man and his sexual partner. Evidence is accumulating in favour of erectile dysfunction as a sign of a genitovascular disease (GVD) in the majority of patients. Erectile dysfunction may be considered as the clinical manifestation of a organovascular disease affecting penis (male genitovascular disease - MGVD) as well as angina pectoris is the typical manifestation of a vascular disease affecting coronary arteries of a heart (cardiovascular disease - CVD). Several studies confirm the assumption that erectile dysfunction symptoms were found to come prior to cardiovascular disease symptoms in 60-95 % of CVD patients with mean interval of 2-3 years and likewise of all organovascular diseases (OVD). Four potent selective PDE5Is have been approved by the EMA for the treatment of erectile dysfunction. Physicians should systematically look for erectile dysfunction in any male with vascular risk factors.