Reduced congestion and improved response to a fluid/sodium challenge in chronic heart failure patients after initiation of sacubitril/valsartan: The NATRIUM-HF study.

AIMS: The effects of initiating sacubitril/valsartan in patients with stable heart failure with reduced ejection fraction (HFrEF) on response to fluid and sodium expansion are unknown. METHODS AND RESULTS: We have explored changes in natriuresis, diuresis, and congestion in response to the administration of intravenous fluid/sodium load in patients with HFrEF before as compared to after the initiation of sacubitril/valsartan. At baseline (before sacubitril/valsartan initiation) and 2 and 3 months after the initiation, patients underwent an evaluation that consisted of three phases of 3 h: the rest phase (0-3 h), the load phase (3-6 h) in which 1 L of intravenous Ringer solution was administered, and the diuretic phase (6-9 h) at the beginning of which furosemide was administered. Overall, 216 patients completed the study. In comparison to baseline values, at 2 and 3 months after sacubitril/valsartan initiation, patients' diuresis and natriuresis in response to Ringer administration significantly increased (mean difference: 38.8 [17.38] ml, p = 0.0040, and 9.6 [2.02] mmol, p < 0.0001, respectively). Symptoms and signs of congestion after the fluid/sodium challenge were significantly decreased at months 2 and 3 compared to baseline. Compared to baseline, there was also an increment of natriuresis after furosemide administration on sacubitril/valsartan (9.8 [5.13] mmol, p = 0.0167). There was a significant decrease in body weight in subsequent visits when compared to baseline values (-0.50 [-12.7, 7.4] kg at 2 months, and -0.75 [-15.9, 7.5] kg at 3 months; both p < 0.0001). CONCLUSIONS: The initiation of sacubitril/valsartan in HFrEF patients was associated with improvements in natriuresis, diuresis, and weight loss and better clinical adaptation to potentially decongestive stressors.

N terminal pro-brain natriuretic peptide level and benefits of chronic total occlusion revascularization.

BACKGROUND: The management of revascularization of chronic total occlusions (CTOs) remains controversial. Whether specific patients gain survival benefit from CTO revascularization remains unknown. OBJECTIVES: We investigated whether (i) patients with CTO have higher N terminal pro-brain natriuretic peptide (NT pro-BNP) levels than patients without CTO, (ii) in patients with CTO, NT pro-BNP levels predict adverse events, and (iii) those with elevated levels benefit from revascularization. METHODS: In 392 patients with stable, significant coronary artery disease (CAD) and CTO undergoing coronary angiography, rates of all-cause mortality, cardiovascular death, and a composite (cardiovascular death, myocardial infarction and heart failure hospitalizations) were investigated. Unadjusted and adjusted Cox proportional and Fine and Gray sub-distribution hazard models were performed to determine the association between NT pro-BNP levels and incident event rates in patients with CTO. RESULTS: NT pro-BNP levels were higher in patients with, compared to those without CTO (median 230.0 vs. 177.7 pg/mL, p ≤0.001). Every doubling of NT pro-BNP level in patients with CTO was associated with a > 25% higher rate of adverse events. 111 (28.5%) patients underwent CTO revascularization. In patients with elevated NT pro-BNP levels (> 125 pg/mL), those who underwent CTO revascularization had substantially lower adverse event rates compared to patients without CTO revascularization (adjusted cardiovascular death hazard ratio 0.29, 95% confidence interval (0.09-0.88). However, in patients with low NT pro-BNP levels (≤ 125 pg/mL), event rates were similar in those with and without CTO revascularization. CONCLUSION: NT pro-BNP levels can help identify individuals who may benefit from CTO revascularization.

A cost-effectiveness evaluation of a high-sensitivity troponin I guided voluntary cardiovascular risk assessment program for asymptomatic women in Croatia.

Background: To estimate the effectiveness and cost-effectiveness of a high-sensitivity troponin I (hsTnI) guided cardiovascular risk assessment program in women in Croatia. Methods: An observational study of a voluntary program for cardiovascular disease (CVD) risk assessment in women aged above 45 years with no specific symptoms, no confirmed or known coronary artery disease was conducted (WHP). Participants were stratified into three categories according to their hsTnI level. Subjects in the moderate or high-risk class were referred to cardiac work-up and invasive cardiovascular investigation as appropriate. Study information were applied to a discrete-event simulation model to estimate the cost-effectiveness of WHP against current practice. The number of CVD events and deaths, costs, and quality-adjusted life years (QALY) were assessed over 10 years from a societal perspective. Results: Of 1034 women who participated in the program, 921 (89.1%), 100 (9.7%), and 13 (1.3%) subjects fall into the low, moderate, and high-risk class. Of 26 women referred for angiography, significant coronary artery disease (CAD) was diagnosed in 12 women (46.1%). WHP gained 15.8 (95%CI 12.8; 17.2) QALYs per 1000 subjects, increased costs by 490€ (95%CI 487; 500), decreased CVD-related mortality by 40%. At a willingness-to-pay threshold of 45,000 €/QALY, WHP was cost-effective with a probability of 90%. Model results were most sensitive to utility weights and cost of medical prevention. Conclusions: Assessing the cardiovascular risk in asymptomatic women with hsTnI and guiding those at higher risk to further cardiac testing, identified individuals with CAD, could reduce CVD related burden, and would be cost-effective.

NT-proBNP/cardiac troponin T ratio >7.5 on the second day of admission can differentiate Takotsubo from acute coronary syndrome with good accuracy.

BACKGROUND: Takotsubo syndrome (TTS) is not usually diagnosed until patients with suspected acute coronary syndrome (ACS) and echocardiographically detected apical aneurysm are found to have "normal" coronary angiography (CA). Our aim was to explore whether cardiac biomarkers can contribute to the early diagnosis of TTS. METHODS: Ratios of N-terminal-pro brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT) both expressed in pg/mL [admission and the 3 following days] were compared in 38 patients with TTS and 114 ACS patients of whom 58 had non-ST-elevation myocardial infarction (NSTEMI). RESULTS: NT-proBNP/cTnT ratio at admission and during the following 3 days was significantly higher in TTS compared to patients with ACS [18.4 (8.7-41.7) vs 2.9 (0.8-6.8), 29.6 (14.3-53.7) vs 1.2 (0.5-2.7), 30.0 (11.6-50.9) vs 1.7 (0.5-3.0), 27.8 (11.3-42.6) vs 1.4 (0.6-2.8), respectively, all <0.001]. Βest discrimination of TTS from ACS was possible with the ratio of NT-proBNP/cTnT on the 2nd day. A cut-off value of NT-proBNP/cTnT ratio >7.5 had a sensitivity of 97.3%, a specificity of 95.4% and an accuracy of ∼96% in detecting TTS as opposed to ACS. Furthermore, the ratio of NT-proBNP/cTnT preserved its discriminatory value in the subgroup of patients with NSTEMI. In particular, an NT-proBNP/cTnT ratio >7.5 on the 2nd day had a sensitivity of 97.3%, a specificity of 91.4%, and an accuracy of 93.7% in differentiating TTS from NSTEMI. CONCLUSIONS: An NT-proBNP/cTnT ratio >7.5 on the 2nd day of admission can be useful for the early identification of TTS among selected patients initially presenting with ACS, a ratio more clinically useful in the setting of NSTEMI.

High sensitivity troponin I as a biomarker for cardiac allograft vasculopathy: Evaluation of diagnostic potential and clinical utility.

INTRODUCTION: Cardiac allograft vasculopathy (CAV) limits long-term survival in heart transplant (HTx) recipients. The use of biomarkers in CAV surveillance has been studied, but none are used in clinical practice. The predictive value of high-sensitivity troponin I (hsTnI) has not been extensively investigated in HTx recipients. METHODS: HTx patients undergoing surveillance coronary angiograms and enrolled in the Emory Cardiovascular Biobank had plasma hsTnI measured. CAV grade was assessed using ISHLT nomenclature. Multivariable cumulative link mixed modeling was performed to determine association between hsTnI level and CAV grade. Patients were followed for adverse outcomes over a median 10-year period. Kaplan-Meier survival analysis and Cox proportional hazard modeling were performed. RESULTS: Three hundred and seventy-two angiograms were analyzed in 156 patients at a median 8.9 years after transplant. hsTnI levels were positively correlated with concurrent CAV grade after adjustment for age, age at transplant, sex, BMI, hypertension, diabetes, hyperlipidemia, estimated glomerular filtration rate, and history of acute cellular rejection (p = .016). In an adjusted Cox proportional hazard model, initial hsTnI level above the median (4.9 pg/mL) remained a predictor of re-transplantation or death (hazard ratio 1.82; 95% confidence interval 1.16-2.90; p = .01). CONCLUSION: An elevated hsTnI level reflects severity of CAV and is associated with poor long-term outcomes in patients with HTx.

Performance of the Abbott Architect Immuno-Chemiluminometric NT-proBNP Assay.

Background: We evaluated the performance of the Abbott N-terminal pro-brain natriuretic peptide (NT-proBNP) assay against the Roche NT-proBNP immunoassay across two sites. Methods: Precision, linearity, and sensitivity studies were performed. A combined method of comparison and regression analysis was performed between the Roche and Abbott assays using samples from both sites (n = 494). To verify biotin interference, lyophilised biotin powder was reconstituted and spiked into serum samples at two medical decision levels (final concentration 500/4250 ng/mL) and compared to controls. NT-proBNP was also measured in anonymised leftover sera (n = 388) in a cardio-renal healthy population and stratified into three age bands­<50 (n = 145), 50−75 (n = 183) and >75 (n = 60). Results: Between-run precision (CV%) for NT-proBNP was 4.17/4.50 (139.5/142.0 pg/mL), 3.83/2.17 (521.6/506.3), and 4.60/2.51 (5053/4973), respectively. The assay was linear from 0.7−41,501 pg/mL. The limit of blank/quantitation was 1.2/7.9 pg/mL. The assay showed no interference from biotin up to 4250 ng/mL. Passing−Bablok regression analysis showed excellent agreement between the two assays (r = 0.999, 95% CI 0.999 to 0.999, p < 0.0001). The Roche assay had a slightly persistent, negative bias across different levels of NT-proBNP. ESC age cut-offs for diagnosing acute heart failure are applicable for the Abbott assay, with the median NT-proBNP of subjects < 50 years old at 43.0 pg/mL (range 4.9−456 pg/mL), 50−75 years old at 95.1 pg/mL (range 10.5−1079 pg/mL), and >75 years old at 173.1 pg/mL (range 23.2−1948 pg/mL). Conclusions: The Abbott Architect NT-proBNP assay has good performance that agrees with the manufacturer's specifications. ESC/AHA recommended NT-proBNP age groups for acute heart failure diagnosis are applicable to this assay.

Estimating the cost-effectiveness of screening a general population for cardiovascular risk with high-sensitivity troponin-I.

AIMS: To estimate the cost-effectiveness of using the cardiac specific marker high-sensitivity troponin-I (hsTnI) for assessing cardiovascular disease (CVD) risk in a general population. METHODS AND RESULTS: A discrete-event simulation model was developed from a societal perspective of a low-risk (Germany) and a high-risk (Kazakhstan) country. The model compared a Screen&Prevent strategy guided by hsTnI against a do-nothing strategy. Risk functions were derived from published data of a prospective cohort study [Nord-Trøndelag Health (HUNT) Study]. The model assessed the number of CVD events and deaths, healthy life years, direct and indirect costs in PPP 2018 Dollar, and quality-adjusted life years (QALY) over a time horizon of 10 years. Screen&Prevent reduced the number of CVD events per 1000 subjects by 5.1 and 5.0, equal to a number-needed-to-screen of 195 and 191 in Kazakhstan and Germany. Screen&Prevent was cost saving in Kazakhstan and cost-effective in Germany with an incremental-cost-effectiveness ratio of $6755 ($2294; $24 054) per QALY gained at an opportunity-cost based willingness-to-pay threshold of $27 373. Varying input variables in univariate and probabilistic sensitivity analyses confirmed the robustness of the analysis. CONCLUSION: Assessing the cardiovascular risk with hsTnI in a general population and subsequently referring those at high risk to preventive means would very likely be cost-effective or cost-saving by avoiding CVD events and associated direct and indirect costs. This conclusion is retained even if only the direct costs or only the costs for screening and prevention are considered. Future studies should evaluate the incremental cost-effectiveness of hsTnI-guided assessment strategies against established risk algorithms.

Differential prognostic value of resistin for cardiac death in patients with coronary artery disease according to the presence of metabolic syndrome.

Resistin is associated with atherosclerosis progression by affecting inflammation and insulin resistance. There are controversial data regarding the prognostic value of resistin in stable coronary artery disease (CAD) patients. We prospectively investigated the long-term prognostic value of resistin in patients with stable CAD. A total 741 consecutive patients with stable CAD were followed for a median of 5.5 years. Serum resistin, lipids, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) levels were measured at baseline. Primary endpoints were cardiac death and secondary hospitalizations for acute coronary syndrome, arrhythmic event or ischemic stroke. Follow-up data were obtained from 703 patients of whom 79 had a cardiac death (11.2%) and 205 (29.2%) met the secondary endpoints. Resistin was positively correlated with hsCRP (r = 0.159, p < 0.001) and IL-6 (r = 0.165, p = 0.002), and negatively with high-density lipoprotein-cholesterol (r = - 0.176, p < 0.001). Resistin levels could not predict cardiac death [HR 1.044; 95% CI 0.994-1.096; p = 0.087] neither secondary endpoints [HR 1.025; 95% CI 0.983-1.068; p = 0.250). Among 298 patients (42.4%) with metabolic syndrome (MS) resistin levels were independently associated with cardiac death after adjustment for conventional risk factors [HR 1.121; 95% CI 1.045-1.204; p = 0.002). Further adjustment for ejection fraction of left ventricle (LVEF) did not change the association (HR 1.145; 95% CI 1.057-1.240; p = 0.001). Patients with resistin values ≥ 7.6 ng/mL (median level) had 2.8 times higher risk of cardiac death compared to those with resistin levels < 7.6 ng/mL after adjustment for traditional risk factors and LVEF (HR 2.882; 95% CI 1.311-6.336; p = 0.008). Resistin is independently associated with cardiac death in patients with stable CAD and MS.

Low-Dose Dobutamine Stress Echocardiography for the Early Detection of Pulmonary Arterial Hypertension in Selected Patients with Systemic Sclerosis Whose Resting Echocardiography Is Non-Diagnostic for Pulmonary Hypertension.

BACKGROUND: Dobutamine stress echocardiography (DSE) has limited application in systemic sclerosis (SSc). We examined DSE usefulness in revealing pulmonary arterial hypertension (PAH) in selected SSc patients whose resting echocardiography for pulmonary hypertension (PH) was non-diagnostic. METHODS: Forty SSc patients underwent right heart catheterization (RHC) and, simultaneously, low-dose DSE (incremental doses up to 20 µg/kg/min). Inclusion criteria were: preserved left and right ventricular (RV) function (tricuspid annulus plane systolic excursion [TAPSE] ≥ 16 mm and tissue Doppler imaging-derived systolic velocity of tricuspid annulus [RVS'] > 10 cm/s), normal pulmonary function tests, and baseline maximal tricuspid regurgitation (TR) velocity of 2.7-3.2 m/s. RESULTS: Of 36 patients who completed DSE, resting RHC diagnosed PAH in 12 patients (33.3%). At 20 µg/kg/min, patients with PAH had higher TR velocity, higher pulmonary arterial pressure measured by RHC, and lower RV inotropic response compared with patients without PAH. A cut-off value of maximal TR velocity >3.1 m/s had a sensitivity of 80%, a specificity of 84.2%, and an accuracy of 82.4% for the detection of PAH. CONCLUSIONS: Low-dose DSE has a satisfactory diagnostic accuracy for the early detection of PAH in highly selected SSc patients whose baseline echocardiographic measurements for PH lie in the gray zone.

The Role of Exercise Doppler Echocardiography to Unmask Pulmonary Arterial Hypertension in Selected Patients with Systemic Sclerosis and Equivocal Baseline Echocardiographic Values for Pulmonary Hypertension.

Recently, a lower mean pulmonary arterial pressure (PAP) cutoff of >20 mmHg for pulmonary hypertension (PH) definition has been proposed. We examined whether exercise Doppler echocardiography (EDE) can unmask PA hypertension (PAH) in systemic sclerosis (SSc) patients whose baseline echocardiography for PH is equivocal. We enrolled 49 patients with SSc who underwent treadmill EDE. Tricuspid regurgitation (TR) velocity was recorded immediately after EDE. Inotropic reserve of right ventricle (RV) was assessed by the change (post-prior to exercise) of tissue Doppler imaging-derived peak systolic velocity (S) of tricuspid annulus. Inclusion criteria comprised preserved left and RV function, and baseline TR velocity between 2.7 and 3.2 m/s. All patients had right-heart catheterization (RHC) within 48 h after EDE. From 46 patients with good quality of post-exercise TR velocity, RHC confirmed PAH in 21 (45.6%). Post-exercise TR velocity >3.4 m/s had a sensitivity of 90.5%, a specificity of 80% and an accuracy of 84.8% in detecting PAH. Inotropic reserve of RV was positively correlated with maximum achieved workload in METs (r = 0.571, p < 0.001). EDE has a good diagnostic accuracy for the identification of PAH in selected SSc patients whose baseline echocardiographic measurements for PH lie in the gray zone, and it is also potentially useful in assessing RV contractile reserve.

Metabolomics for improving pregnancy outcomes in women undergoing assisted reproductive technologies.

BACKGROUND: In order to overcome the low effectiveness of assisted reproductive technologies (ART) and the high incidence of multiple births, metabolomics is proposed as a non-invasive method to assess oocyte quality, embryo viability, and endometrial receptivity, and facilitate a targeted subfertility treatment. OBJECTIVES: To evaluate the effectiveness and safety of metabolomic assessment of oocyte quality, embryo viability, and endometrial receptivity for improving live birth or ongoing pregnancy rates in women undergoing ART, compared to conventional methods of assessment. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, CINAHL and two trial registers (Feburary 2018). We also examined the reference lists of primary studies and review articles, citation lists of relevant publications, and abstracts of major scientific meetings. SELECTION CRITERIA: Randomised controlled trials (RCTs) on metabolomic assessment of oocyte quality, embryo viability, and endometrial receptivity in women undergoing ART. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently assessed trial eligibility and risk of bias, and extracted the data. The primary outcomes were rates of live birth or ongoing pregnancy (composite outcome) and miscarriage. Secondary outcomes were clinical pregnancy, multiple and ectopic pregnancy, cycle cancellation, and foetal abnormalities. We combined data to calculate odds ratios (ORs) for dichotomous data and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. MAIN RESULTS: We included four trials with a total of 924 women, with a mean age of 33 years. All assessed the role of metabolomic investigation of embryo viability. We found no RCTs that addressed the metabolomic assessment of oocyte quality or endometrial receptivity.We found low-quality evidence of little or no difference between metabolomic and non-metabolomic assessment of embryos for rates of live birth or ongoing pregnancy (OR 1.02, 95% CI 0.77 to 1.35, I² = 0%; four RCTs; N = 924), live birth alone (OR 0.99, 95% CI 0.69 to 1.44, I² = 0%; three RCTs; N = 597), or miscarriage (OR 1.18, 95% CI 0.77 to 1.82; I² = 0%; three RCTs; N = 869). A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for live birth or ongoing pregnancy (OR 0.90, 95% CI 0.66 to 1.25, I² = 0%; two RCTs; N = 744). Our findings suggested that if the rate of live birth or ongoing pregnancy was 36% in the non-metabolomic group, it would be between 32% and 45% with the use of metabolomics.We found low-quality evidence of little or no difference between groups in rates of clinical pregnancy (OR 1.11, 95% CI 0.85 to 1.45; I²= 44%; four trials; N = 924) or multiple pregnancy (OR 1.50, 95% CI 0.70 to 3.19; I² = 0%; two RCTs, N = 180). Rates of cycle cancellation were higher in the metabolomics group (OR 1.78, 95% CI 1.18 to 2.69; I² = 51%; two RCTs; N = 744, low quality evidence). There was very low-quality evidence of little or no difference between groups in rates of ectopic pregnancy rates (OR 3.00, 95% CI 0.12 to 74.07; one RCT; N = 417), and foetal abnormality (no events; one RCT; N = 125). Data were lacking on other adverse effects. A sensitivity analysis excluding studies at high risk of bias did not change the interpretation of the results for clinical pregnancy (OR 1.03, 95% CI 0.76 to 1.38; I² = 40%; two RCTs; N = 744).The overall quality of the evidence ranged from very low to low. Limitations included serious risk of bias (associated with poor reporting of methods, attrition bias, selective reporting, and other biases), imprecision, and inconsistency across trials. AUTHORS' CONCLUSIONS: According to current trials in women undergoing ART, there is no evidence to show that metabolomic assessment of embryos before implantation has any meaningful effect on rates of live birth, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy or foetal abnormalities. The existing evidence varied from very low to low-quality. Data on other adverse events were sparse, so we could not reach conclusions on these. At the moment, there is no evidence to support or refute the use of this technique for subfertile women undergoing ART. Robust evidence is needed from further RCTs, which study the effects on live birth and miscarriage rates for the metabolomic assessment of embryo viability. Well designed and executed trials are also needed to study the effects on oocyte quality and endometrial receptivity, since none are currently available.

Effect of functional electrical stimulation on cardiovascular outcomes in patients with chronic heart failure.

Background/design Functional electrical stimulation of lower limb muscles is an alternative method of training in patients with chronic heart failure (CHF). Although it improves exercise capacity in CHF, we performed a randomised, placebo-controlled study to investigate its effects on long-term clinical outcomes. Methods We randomly assigned 120 patients, aged 71 ± 8 years, with stable CHF (New York Heart Association (NYHA) class II/III (63%/37%), mean left ventricular ejection fraction 28 ± 5%), to either a 6-week functional electrical stimulation training programme or placebo. Patients were followed for up to 19 months for death and/or hospitalisation due to CHF decompensation. Results At baseline, there were no significant differences in demographic parameters, CHF severity and medications between groups. During a median follow-up of 383 days, 14 patients died (11 cardiac, three non-cardiac deaths), while 40 patients were hospitalised for CHF decompensation. Mortality did not differ between groups (log rank test P = 0.680), while the heart failure-related hospitalisation rate was significantly lower in the functional electrical stimulation group (hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.21-0.78, P = 0.007). The latter difference remained significant after adjustment for prognostic factors: age, gender, baseline NYHA class and left ventricular ejection fraction (HR 0.22, 95% CI 0.10-0.46, P < 0.001). Compared to placebo, functional electrical stimulation training was associated with a lower occurrence of the composite endpoint (death or heart failure-related hospitalisation) after adjustment for the above-mentioned prognostic factors (HR 0.21, 95% CI 0.103-0.435, P < 0.001). However, that effect was mostly driven by the favourable change in hospitalisation rates. Conclusions In CHF patients, 6 weeks functional electrical stimulation training reduced the risk of heart failure-related hospitalisations, without affecting the mortality rate. The beneficial long-term effects of this alternative method of training require further investigation.

Prevalence of metabolic syndrome and association with burden of atherosclerotic disease in patients with stable coronary artery disease.

BACKGROUND: We aimed to estimate the prevalence of metabolic syndrome (Met.S.) and to explore the association of Met.S. with the number of diseased vessels in patients with stable coronary artery disease (C.A.D.). METHODS: This cross-sectional study enrolled stable C.A.D. patients who attended the outpatient cardiology departments of four hospitals between 2006 and 2008. Met.S. was defined according to the National Cholesterol Education Program Adult Treatment Panel III (N.C.E.P./A.T.P. III). RESULTS: In the study 742 patients (mean age: 62 ± 9 years, male: n = 631, 85.0%) with stable C.A.D. were recruited. The prevalence of Met.S. was 47.3% (95% C.I. = 43.6-50.9%). Among women, a high percentage of the patients had Met.S. (n = 68, 61.3%), whereas in male patients the prevalence of Met.S. was 44.8% (n = 283). Multivariable analysis showed that C.A.D. patients with Met.S. had 84% higher odds of double or triple vessel disease, whereas those with four or five Met.S. components had two times higher odds of double or triple vessel disease after adjustment for potential confounders (O.R. = 1.84 with 95% C.I. = 1.26-2.68, p = 0.001 and O.R. = 2.08 with 95% C.I. = 1.17-3.69, p = 0.012, respectively). Met.S. as well as the accumulation of four or five Met.S. components had a positive association with the likelihood of double or triple vessel disease and this was independent of the presence of diabetes. CONCLUSIONS: Almost one out of two patients with stable C.A.D. was found to fulfill the criteria of Met.S. Met.S. as well as four or five Met.S. components increased the odds of double or triple vessel disease in patients with stable C.A.D. The study suggests that cardiologists and health care practitioners should be aware that Met.S. is highly prevalent when established C.A.D. is present and that Met.S. and accumulation of four or five Met.S. components seem to be associated more often with double or triple vessel C.A.D.

The Effect of Reactive Oxygen Species on Embryo Quality in IVF.

UNLABELLED: BACKROUND/AIM: Reactive oxygen species (ROS) are involved in critical biological processes in human reproduction. The aim of this study was to evaluate the association of embryo quality following in vitro fertilization (IVF), with ROS levels in the serum and follicular fluid (FF). MATERIALS AND METHODS: Eighty-five participants underwent ovarian stimulation and IVF; ROS levels were measured in blood samples on the day of oocyte retrieval and in the FF from follicular aspirates using enzyme-linked immunosorbent assay. These values were associated with the quality of embryos generated. RESULTS: Univariable zero-inflated Poisson model revealed that ROS levels at both oocyte retrieval and in FF were not associated with the number of grade I, II, III and IV embryos (p>0.05). Age, body mass index, stimulation protocol and smoking status were not associated with the number of embryos of any grade (p>0.05). CONCLUSION: Neither ROS levels in serum nor in FF are associated with the quality of embryos produced following IVF.

A multicenter, epidemiological study of the treatment patterns, comorbidities and hypoglycemia events of patients with type 2 diabetes and moderate or severe chronic kidney disease - the 'LEARN' study.

Objective Management of patients with type 2 diabetes (T2DM) and stage 3 to 5 chronic kidney disease (CKD) is challenging. The aim of the 'LEARN' study was to describe treatment patterns employed in this population and to record comorbidities, glycemic control and hypoglycemia episodes in routine clinical practice in Greece. Research design and methods 'LEARN' was a non-interventional, multicenter, cross-sectional study conducted in Greece between 15 February 2013 and 4 July 2013. A total of 120 adult patients were enrolled from four hospital sites in different geographic regions of Greece. Results Participants had a mean age of 69.1 ± 10.3 years and a male:female ratio of 2:1. Nearly all patients (99.2%) suffered from at least one comorbidity, with hypertension (95.8%) and hyperlipidemia/dyslipidemia (78.3%) being the most prevalent. Of the overall study population, 57.5% was managed with insulin therapy only, 30.8% with oral antidiabetics only and 11.7% with a combination of insulin and oral antidiabetics. The overall rate of glycemic control, defined as glycated hemoglobin (HbA1c) ≤ 7.0% during the most recent assessment, was 55.0%. This rate was significantly higher among those receiving oral antidiabetics only (73.0%) compared to insulin only (47.8%) or a combination of both types of treatment (42.9%) (p = 0.03). Moreover, patients receiving oral antidiabetics only had experienced fewer hypoglycemia episodes over the last 7 days prior to the study visit (0.1 ± 0.4) compared to patients receiving insulin only (0.9 ± 1.7) (p = 0.03). Conclusions Although this is an observational study, it seems that oral antidiabetic therapy might be advantageous for heavily burdened T2DM patients with moderate or severe CKD in terms of glycemic control and hypoglycemia episodes. More data preferably from randomized trials is needed in order to validate this hypothesis.

Cardiovascular Hypertensive Crisis: Recent Evidence and Review of the Literature.

Despite the high prevalence of hypertension (HTN), only a small proportion of the hypertensive patients will ultimately develop hypertensive crisis. In fact, some patients with hypertensive crisis do not report a history of HTN or previous use of antihypertensive medication. The majority of the patients with hypertensive crisis often report non-specific symptoms, whereas heart-related symptoms (dyspnea, chest pain, arrhythmias, and syncope) are less common. Hypertensive crises can be divided into hypertensive emergencies or hypertensive urgencies according to the presence or absence of acute target organ damage, respectively. This differentiation is an extremely useful classification in clinical practice since a different management is needed, which in turn has a significant effect on the morbidity and mortality of these patients. Therefore, it is very crucial for the physician in the emergency department to identify the hypertensive emergencies and to manage them through blood pressure lowering medications in order to avoid further target organ damage or deterioration. The aim of this narrative review is to summarize the recent evidence in an effort to improve the awareness, recognition, risk stratification, and treatment of hypertensive crisis in patients referred to the emergency department.

Impact of income status on prognosis of acute coronary syndrome patients during Greek financial crisis.

BACKGROUND: The effect of income status on patient outcome merits investigation during periods of financial crisis. We evaluated the impact of income status on out-of-hospital prognosis in a cohort of acute coronary syndrome (ACS) patients, included in a countrywide study during a period of financial crisis. METHODS: The study is a secondary analysis of a prospective, multicenter, observational study-the PHAETHON study-enrolling consecutive ACS patients in 37 hospitals in Greece. Patients were classified as low or high income based on the reported net annual household income using as a cut-off point the relative poverty threshold for Greece of 12,000 Euros. The outcome measure was survival free of the primary composite endpoint (cardiovascular death, myocardial infarction, stroke/transient ischemic attack, urgent revascularization and urgent hospitalization due to cardiovascular causes). RESULTS: The study population included 794 patients. The administration rate of evidence-based medications was similar in the low- (n = 455) and high-income (n = 339) groups during hospitalization and upon discharge. In a median follow-up of 189 days (interquartile range: 180-212 days), low-income patients had 92 % higher risk of the combined endpoint as compared to high-income patients [Hazard ratio (HR):1.92, 95 % CI:1.25-2.94, p = 0.003]. The effect of low-income status on the combined outcome remained significant after adjustment for age, gender and depression (HR:1.59, 95 % CI:1.02-2.49; p = 0.043). CONCLUSIONS: In a period of financial crisis, low income is a significant and independent predictor of poor out-of-hospital outcome in ACS patients. This association has profound implications and should be taken into consideration by public health policy makers.

Frequency and risk factors of COPD exacerbations and hospitalizations: a nationwide study in Greece (Greek Obstructive Lung Disease Epidemiology and health ecoNomics: GOLDEN study).

BACKGROUND: COPD exacerbations and hospitalizations have been associated with poor prognosis for the COPD patient. OBJECTIVE: To evaluate the frequency and risk factors of COPD exacerbations, hospitalizations, and admissions to intensive care units (ICUs) in Greece by a nationwide cross-sectional study. MATERIALS AND METHODS: A nationwide observational, multicenter, cross-sectional study was conducted in the clinical practice setting of respiratory medicine physicians over a 6 month-period (October 2010 to March 2011). A total of 6,125 COPD patients were recruited by 199 respiratory physicians. RESULTS: Participants had a median age of 68.0 years, 71.3% were males, and 71.8% suffered from comorbidities. The median disease duration was 10.0 years. Of the patients, 45.3% were classified as having GOLD (Global initiative for chronic Obstructive Lung Disease) stage III or IV COPD. Patients with four or more comorbidities had 78.5% and threefold-higher than expected number of exacerbations and hospitalizations, respectively, as well as fivefold-higher risk of admission to the ICU compared to those with no comorbidities. Obese patients had 6.2% fewer expected exacerbations compared to those with a normal body mass index. Patients with GOLD stage IV had 74.5% and fivefold-higher expected number of exacerbations and hospitalizations, respectively, and nearly threefold-higher risk of admission to the ICU compared to stage I patients. An additional risk factor for exacerbations and hospitalizations was low compliance with treatment: 45% of patients reported forgetting to take their medication, and 81% reported a preference for a treatment with a lower dosing frequency. CONCLUSION: Comorbidities, disease severity, and compliance with treatment were identified as the most notable risk factors for exacerbations, hospitalizations, and ICU admissions. The results point to the need for a multifactorial approach for the COPD patient and for the development of strategies that can increase patient compliance with treatment.