natriuretic-peptide--brain and Dyslipidemias

Topics: Ankle Brachial Index; Anti-Obesity Agents; Arteriosclerosis; Biomarkers; C-Reactive Protein; Calcinosis; Coronary Disease; Diabetes Mellitus; Diagnostic Imaging; Dyslipidemias; Endarterectomy; Fibrinolytic Agents; Genetic Markers; Glycated Hemoglobin; Health Behavior; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Life Style; Lipids; Metabolic Syndrome; Natriuretic Peptide, Brain; Obesity; Risk Assessment; Risk Factors; Smoking Cessation; Stents; Stroke; Thrombosis; Troponin I

The mortality of end-stage renal disease (ESRD) patients on dialysis remains high despite great improvement of dialysis technologies in the past decades. These patients die due to infectious diseases (mainly sepsis), cardiovascular diseases such as myocardial infarction, heart failure, stroke, and, in particular, sudden cardiac death. End stage renal disease is a complex condition, where the failure of kidney function is accompanied by numerous metabolic changes affecting almost all organ systems of the human body. Many of the biomarker characteristics of the individually affected organ systems have been associated with adverse outcomes. These biomarkers are different in patients with ESRD compared to the general population in the prediction of morbidity and mortality. Biomarker research in this field should aim to identify patients at risk for the different disease entities. Traditional biomarkers such as CRP, BNP, and troponins as well as new biomarkers such as fetuin, CD154, and relaxin were analyzed in patients on dialysis. We will include observational as well as prospective clinical trials in this review. Furthermore, we will also discuss proteomics biomarker studies. The article assess the potential diagnostic value of different biomarkers in daily clinical practice as well as their usefulness for clinical drug development in end stage renal disease patients.

Topics: alpha-2-HS-Glycoprotein; Biomarkers; Blood Proteins; C-Reactive Protein; Cardiovascular Diseases; Cell Adhesion Molecules; Comorbidity; Dyslipidemias; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Homocysteine; Humans; Infections; Inflammation; Interleukin-6; Kidney Failure, Chronic; Malnutrition; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proteomics; Renal Replacement Therapy; Troponin T

Topics: Albuminuria; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Diet; Drug Therapy, Combination; Dyslipidemias; Endothelium, Vascular; Glomerular Filtration Rate; Health Behavior; Humans; Hypertension; Insulin Resistance; Kidney; Life Style; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; Risk Factors; Smoking; Smoking Cessation; Survival Analysis; Treatment Outcome; Vitamins

Visceral fat area (VFA) is a good surrogate marker of obesity-related disorders, such as hypertension, dyslipidemia and glucose intolerance. Although estimating the VFA by X-ray computed tomography (CT) is the primary index for visceral obesity, it is expensive and requires invasive radiation exposure. Dual bioelectrical impedance analysis (BIA) is a simple and reliable method to estimate VFA; however, the clinical usefulness of dual BIA remains unclear in patients with type 2 diabetes (T2D).. We estimated the VFAs by dual BIA and CT in 98 patients with T2D and assessed anthropometric parameters, blood test results, and the presence of comorbid hypertension and dyslipidemia. We compared the correlation between the VFAs examined by dual BIA and CT. Furthermore, we performed the receiver operating characteristic (ROC) analyses for the VFAs to detect the presence of comorbid hypertension and/or dyslipidemia with T2D, which are major comorbidities of visceral obesity, and estimated the area under the curve (AUC).. The measurement error between the VFAs by dual BIA and CT was significantly higher among patients with brain natriuretic peptide (BNP) ≥ 100 pg/mL than those with BNP < 100 pg/mL (39.2% ± 31.1% vs. 24.1% ± 18.6%, P < 0.05). After excluding patients with BNP ≥ 100 pg/mL, the VFA by dual BIA significantly correlated with the VFA by CT (r = 0.917; P < 0.0001). The AUC in the ROC analysis for the VFA by dual BIA to detect the presence of comorbid hypertension and/or dyslipidemia with T2D was almost equivalent to that for the VFA by CT.. In patients with T2D without elevated BNP > 100 pg/mL as indicator for fluid accumulation interfering with BIA, estimation of the VFA by dual BIA significantly correlated with that by CT and also detected comorbid hypertension and/or dyslipidemia with T2D equivalent to those detected by CT. Hence, dual BIA could be an alternative to CT as a standard method for estimating the VFA in patients with diabetes.

Topics: Adiposity; Aged; Biomarkers; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus, Type 2; Dyslipidemias; Electric Impedance; Female; Humans; Hypertension; Intra-Abdominal Fat; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Predictive Value of Tests; Prevalence; Reproducibility of Results; Risk Factors; Tomography, X-Ray Computed

Human serum albumin (HSA) is the most abundant circulating protein in the body and presents an extensive range of biological functions. As such, it is prone to undergo post-translational modifications (PTMs). The non-enzymatic early glycation of HSA, one of the several PTMs undergone by HSA, arises from the addition of reducing sugars to amine group residues, thus modifying the structure of HSA. These changes may affect HSA functions impairing its biological activity, finally leading to cell damage. The aim of this study was to quantitate glycated-HSA (GA) levels in the plasma of heart failure (HF) patients and to evaluate the biological effects of GA on HL-1 cardiomyocytes. Plasma GA content from HF patients and healthy subjects was measured by direct infusion electrospray ionization mass spectrometry (ESI-MS). Results pointed out a significant increase of GA in HF patients with respect to the control group (p < 0.05). Additionally, after stimulation with GA, proteomic analysis of HL-1 secreted proteins showed the modulation of several proteins involved, among other processes, in the response to stress. Further, stimulated cells showed a rapid increase in ROS generation, higher mRNA levels of the inflammatory cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), and higher levels of the oxidative 4-HNE-protein adducts and carbonylated proteins. Our findings show that plasma GA is increased in HF patients. Further, GA exerts pro-inflammatory and pro-oxidant effects on cardiomyocytes, which suggest a causal role in the etiopathogenesis of HF.

Topics: Aged; Case-Control Studies; Cell Death; Cell Line; Dyslipidemias; Female; Gene Expression Profiling; Gene Ontology; Glycated Serum Albumin; Glycation End Products, Advanced; Glycosylation; Heart Failure; HSP90 Heat-Shock Proteins; Humans; Hypertension; Interleukin-6; Lysine; Male; Middle Aged; Molecular Sequence Annotation; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Protein Carbonylation; Protein Processing, Post-Translational; Reactive Oxygen Species; Serum Albumin; Serum Albumin, Human; Tumor Necrosis Factor-alpha

Topics: Adult; Aged; Blood Pressure; Cardiology; Coronary Artery Disease; Drug-Eluting Stents; Dyslipidemias; Electrocardiography; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nuclear Medicine; Ventricular Dysfunction, Left

Topics: Cholesterol, HDL; Cholesterol, LDL; Chronic Disease; Creatinine; Depression; Dyslipidemias; Heart Failure; Humans; Natriuretic Peptide, Brain; Triglycerides

Emerging studies indicate that B-type natriuretic peptide (BNP), a well-known biomarker for heart failure, also plays pivotal roles in metabolic control. Circulating BNP levels progressively increase as ages grow older. However, the association between BNP levels and lipid metabolism in the elderly remains unknown.. A total of 680 eligible volunteers (male/female: 334/346) aged between 60 and 80 years old without overt heart failure (BNP <100 pg/ml) were enrolled. Random nonfasting venous samples were obtained for biochemical analysis. The subjects were stratified based on BNP quartiles: BNP Q1 (range: 2.2-9.0 pg/ml), Q2 (9.1-20.4 pg/ml), Q3 (20.5-44.4 pg/ml) and Q4 (44.6-99.7 pg/ml). Difference of metabolic parameters was compared among the subjects grouped by BNP quartiles. Univariate correlation and multiple linear regression were performed to analyze the association between BNP levels and metabolic parameters. The odds ratios (OR) and 95 % confidence intervals (CI) for dyslipidemia in subjects within BNP Q1-3 relative to subjects within BNP Q4 were calculated.. Circulating BNP levels positively correlated with age, while negatively correlated with body mass index (BMI), eGFR and non-HDL. Subjects with lower BNP quartiles had significantly elevated prevalence of dyslipidemia, including hypertriglyceridemia, hyper-LDL-emia and hypercholesterolemia. The OR of hypertriglyceridemia and hypercholesterolemia for subjects within BNP Q1-2 significantly increased relative to BNP Q4.. The elderly people with higher BNP levels have significantly reduced risks for nonfasting dyslipidemia. Verification of the cause-effect relationship between BNP and dyslipidemia may bring therapeutic implications.

Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Dyslipidemias; Fasting; Female; Humans; Linear Models; Lipids; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors

Data about the use of positive inotropic agents in patients hospitalized with acute decompensated heart failure (ADHF) is limited.. The records of 8066 patients with ADHF who were hospitalized at Hamad Medical Corporation, Qatar from 1991 to 2013 were analyzed to explore demographics and clinical characteristics of the patients according to inotropic agents use.. Eight hundred fifty eight patients [10.6%, 95% CI (10 to 11.3%)] received intravenous inotropic support. Patients receiving inotropes were more likely to be female and have preserved ejection fraction when compared to those not receiving inotropic agents. Comorbidities associated with higher likelihood of receiving inotropic treatment included acute myocardial infarction, chronic renal impairment, dyslipidemia, hypertension, obesity and hyperglycemia. Patient on inotropes were more likely to undergone percutaneous coronary intervention (PCI), intra-aortic balloon pump support and intubation. There were no differences in the mean plasma BNP and CK-MB levels between the 2 groups. Heart failure patients receiving inotropes also were more likely to have complications including ventricular tachycardia (2.0% vs. 0.9%, p = 0.003), prolonged hospital stay (8.0 vs. 5.0 days, p = 0.001), cardiac arrest (14.6% vs. 3.2%, p = 0.001) and in-hospital mortality (30.8% vs. 9.1 %, p = 0.001). Over the study period there was an increase use of inotropic agents and decreased mortality rates.. Inotropic use increased over the period whereas; female gender and conventional cardiac risk factors were predictors of inotropic agents use in the study.

Topics: Acute Disease; Administration, Intravenous; Aged; Cardiotonic Agents; Comorbidity; Creatine Kinase, MB Form; Disease Progression; Dyslipidemias; Female; Heart Arrest; Heart Failure; Hospital Mortality; Hospitalization; Humans; Hyperglycemia; Hypertension; Intra-Aortic Balloon Pumping; Intubation, Intratracheal; Length of Stay; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Obesity; Percutaneous Coronary Intervention; Population Growth; Qatar; Registries; Renal Insufficiency, Chronic; Respiration, Artificial; Retrospective Studies; Tachycardia, Ventricular

Both metabolic syndrome (MetS) and N-amino terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) confer increased risk of cardiovascular diseases (CVD). We assessed if NT-proBNP levels were greater in people with uncomplicated MetS, who had neither CVD/chronic kidney disease (CKD) nor diabetes, as compared with subjects who met none of the defining criteria of the MetS.. A case-cohort study from the non-diabetic population-based Casale Monferrato study was performed, after exclusion of all subjects with established CVD, CKD [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2)], and CRP values ≥3 mg/L. Cases (n = 161) with MetS were compared with all subjects within the cohort (n = 124) who were completely free of any component of the MetS. Serum NT-proBNP was centrally measured by immunoenzymatic assay.. NT-proBNP levels were significantly higher in cases than in control subjects [35.4 (15.5-98.2) vs 24.4 (11.7-49.6) pg/mL, p = 0.014]. In logistic regression analysis, compared with NT-proBNP values in the lower quartiles (≤49.64 pg/mL), higher values conferred odds ratio 4.17 (1.30-13.44) of having the MetS, independently of age, sex, microalbuminuria, CRP, eGFR, and central obesity. This association was evident even after the exclusion of hypertensive subjects. Further adjustment for log-HOMA and diastolic blood pressure did not modify the strength of the association, while central obesity was a negative confounder.. Compared with people without any component of the MetS, those with uncomplicated MetS, who had neither CVD/CKD nor diabetes, had increased NT-proBNP values, even if they were normotensive and although absolute values were still in the low range. The insulin resistance state did not mediate this association, while central obesity was a negative confounder.

Topics: Aged; Body Mass Index; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Dyslipidemias; Female; Humans; Hypertension; Insulin Resistance; Italy; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Obesity, Abdominal; Overweight; Peptide Fragments; Prediabetic State; Prevalence; Severity of Illness Index; Up-Regulation; Waist Circumference

The efficacy of out-patient cardiac rehabilitation (OPCR) in patients with a low prognostic risk after acute myocardial infarction (AMI) is unclear in the recent primary intervention era.. A total of 637 AMI patients who participated in in-hospital cardiac rehabilitation were divided into 2 groups; low prognostic risk group (n=219; age <65 years, successful reperfusion, Killip class I, peak serum creatine kinase <6,000U/L, and left ventricular ejection fraction ≥40%) and non-low prognostic risk group (n=418). The prevalence of coronary risk factors (CRF) was compared between the 2 groups. Then, in the low-risk group, the efficacy of OPCR was compared between active OPCR participants (n=52; ≥20 sessions/3 months) and non-active participants (n=60; <6 sessions/3 months). Compared with the non-low prognostic risk group, the low prognostic risk group had a significantly higher prevalence of current smokers (72% vs. 49%, P<0.05) and patients with multiple CRF (3 or more; 49% vs. 39%, P<0.05). Among the low- risk group, active OPCR participants showed a significantly greater improvement in exercise capacity (peak VO(2), P<0.05) and maintained a better CRF profile (total cholesterol, triglyceride and blood pressure, all P<0.05) than inactive participants at 3 months.. Low prognostic risk AMI patients have a higher prevalence of multiple CRF than non-low risk patients. Even in this low risk group, active participation in OPCR is associated with improved exercise capacity and better CRF profile.

Topics: Ambulatory Care; Biomarkers; Cardiovascular Agents; Comorbidity; Creatine Kinase; Dyslipidemias; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Obesity; Prognosis; Retrospective Studies; Risk; Smoking; Stroke Volume; Treatment Outcome

Sleep apnea syndrome increases the risk of cardiovascular morbidity and mortality. We previously reported that intermittent hypoxia increases superoxide production in a manner dependent on nicotinamide adenine dinucleotide phosphate and accelerates adverse left ventricular (LV) remodeling. Recent studies have suggested that hydrogen (H(2)) may have an antioxidant effect by reducing hydroxyl radicals. In this study, we investigated the effects of H(2) gas inhalation on lipid metabolism and LV remodeling induced by intermittent hypoxia in mice. Male C57BL/6J mice (n = 62) were exposed to intermittent hypoxia (repetitive cycle of 1-min periods of 5 and 21% oxygen for 8 h during daytime) for 7 days. H(2) gas (1.3 vol/100 vol) was given either at the time of reoxygenation, during hypoxic conditions, or throughout the experimental period. Mice kept under normoxic conditions served as controls (n = 13). Intermittent hypoxia significantly increased plasma levels of low- and very low-density cholesterol and the amount of 4-hydroxy-2-nonenal-modified protein adducts in the LV myocardium. It also upregulated mRNA expression of tissue necrosis factor-α, interleukin-6, and brain natriuretic peptide, increased production of superoxide, and induced cardiomyocyte hypertrophy, nuclear deformity, mitochondrial degeneration, and interstitial fibrosis. H(2) gas inhalation significantly suppressed these changes induced by intermittent hypoxia. In particular, H(2) gas inhaled at the timing of reoxygenation or throughout the experiment was effective in preventing dyslipidemia and suppressing superoxide production in the LV myocardium. These results suggest that inhalation of H(2) gas was effective for reducing oxidative stress and preventing LV remodeling induced by intermittent hypoxia relevant to sleep apnea.

Topics: Administration, Inhalation; Aldehydes; Analysis of Variance; Animals; Cholesterol, LDL; Cholesterol, VLDL; Disease Models, Animal; Dyslipidemias; Fibrosis; Free Radical Scavengers; Gases; Gene Expression Regulation; Heart Diseases; Heart Ventricles; Hemodynamics; Hydrogen; Hypoxia; Interleukin-6; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; RNA, Messenger; Superoxides; Time Factors; Tumor Necrosis Factor-alpha; Ventricular Remodeling

The plasma B-type natriuretic peptide (BNP) level is elevated in cardiac ischemia and may be useful in assessing prognosis in acute coronary syndromes (ACS). This study aimed to: (1) establish BNP levels and its determinants in a healthy Gulf Arab population and in a group of patients with acute myocardial infarction and (2) investigate associations between BNP levels and markers of myocardial damage (ejection fractions, cardiac troponin I [cTnI] levels) and inflammation (serum C-reactive protein [CRP]).. We studied 2 groups of Arab subjects: (1) Healthy control (HC), 142 healthy control subjects; (2) Coronary heart disease (CHD), 257 patients with proven acute myocardial infarction within 1 day of admission. Each subject was assessed clinically, and ejection fractions (left ventricular ejection fraction [LVEF]) were determined by echocardiography in those with CHD. Fasting blood samples were processed for full blood counts and serum glucose, urea, creatinine, uric acid, and lipids (total cholesterol [TC], triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein [LDL], and apolipoprotein B [apoB]), cTnI, BNP, and high-sensitivity (hs) CRP levels. The results were compared between groups, and the associations of BNP with other parameters were explored.. In comparison to HC, the CHD group had a greater waist-hip ratio (WHR) (P < 0.01), worse atherogenic profile, worse renal function, and higher values for CRP and BNP (all P < 0.001). There were no significant differences in values for BNP related to age, diabetes, hypertension, WHR, and hematocrit, although there was a consistent trend in both HC and CHD groups toward a negative relationship of BNP with body mass, TG, and apoB levels, and a positive relationship with HDL, independent only for HDL and apoB on multiple logistic regression. No correlations could be established with cTnI, CRP, and LVEF. The patterns of cross-correlations did not differ significantly with diabetic status.. In an Arab population with CHD, blood levels of BNP are higher than in a healthy control population and appear correlated to body mass and atherogenic lipids but not CRP, troponin, or ejection fraction. BNP levels did not appear to be influenced by the classical CHD risk factors of diabetes, hypertension, cigarette smoking, hematocrit, or WHR. The independent link with atherogenic dyslipidemia suggests that BNP is important in atherogenesis and may not be just an index of cardiac contractile dysfunction.

Topics: Acute Coronary Syndrome; Adult; Aged; Arabs; Atherosclerosis; Body Mass Index; Case-Control Studies; Dyslipidemias; Female; Humans; Kuwait; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Risk Factors

Adiponectin, an adipocyte-derived hormone, appears to be a modulator of lipid metabolism and systemic inflammation and is present in particularly low concentrations in patients with coronary heart disease (CHD). However, the clinical importance of adiponectin in individuals at markedly high risk for future cardiovascular morbidity and mortality has not been fully elucidated. We examined the associations between serum adiponectin and several biomarkers related to cardiovascular disease and heart failure in a large high-risk population comprising patients with prevalent CHD.. We measured fasting adiponectin, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and markers of lipoprotein metabolism in 1174 patients with CHD.. After adjustment for age and sex, adiponectin was associated with HDL-cholesterol (HDL-C; r = 0.25; P <0.0001), NT-proBNP (r = 0.17; P <0.0001), and plasma triglyceride (r = -0.21; P <0.0001) concentrations. There was, however, no statistically significant association between adiponectin and markers of systemic inflammation. In partial correlation analyses further adjusted for body mass index, alcohol intake, smoking status, presence of diabetes and/or hypertension, lipid-lowering drug therapy, and fasting plasma glucose, adiponectin remained significantly associated with HDL-C (r = 0.21; P <0.0001), NT-proBNP (r = 0.15; P <0.0001), and plasma triglycerides (r = -0.16; P <0.0001).. Serum adiponectin is associated with the presence of atherogenic dyslipidemia and with NT-proBNP concentration but not with markers of systemic inflammation in patients with manifest CHD. Thus, atherogenic dyslipidemia may link adiponectin with the progression of atherosclerosis. Moreover, serum adiponectin may be related to BNP in patients with CHD.

Topics: Adiponectin; Adult; Aged; Atherosclerosis; Biomarkers; Coronary Disease; Cross-Sectional Studies; Dyslipidemias; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Risk Factors; Socioeconomic Factors; Ventricular Function, Left

Topics: Adiponectin; Atherosclerosis; Biomarkers; Coronary Disease; Dyslipidemias; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

We wanted to investigate the relationship of N-terminal pro brain natriuretic peptide (Nt-proBNP) to metabolic and hemodynamic cardiovascular (CV) risk factors in the general population. From a population-based sample of 2656 people 41, 51, 61, or 71 years of age, we selected 2070 patients without previous stroke or myocardial infarction who did not receive any CV, antidiabetic, or lipid-lowering treatment in 1993 to 1994. Traditional CV risk factors, 24-hour blood pressures, left ventricular (LV) mass, and ejection fraction by echocardiography, pulse wave velocity, urine albumin/creatinine ratio (UACR), and serum Nt-proBNP were measured in 1993 to 1994. The metabolic syndrome was defined in accordance with the definition of the European Group for the Study of Insulin Resistance (EGIR). Higher log(Nt-proBNP) was in multiple regression analysis related to female gender (beta=-0.37), older age (beta=0.32), higher clinic pulse pressure (beta=0.20), lower serum total cholesterol (beta=-0.15), lower LVEF (beta=-0.08, all P<0.001), lower log(serum insulin) (beta=-0.07), lower log(plasma glucose) (beta=-0.06, both P<0.01, lower log(serum triglyceride) (beta=-0.06), lower body mass index (beta=-0.05); lower heart rate (beta=-0.05), higher logUACR (beta=0.04, all P<0.05) and higher log(LV mass index) (beta=0.04, P=0.07), adjusted R2=0.35, P<0.001). The metabolic syndrome was associated with lower Nt-proBNP (35 pg/mL versus 48 pg/mL; P<0.001) and shifted the positive relationship between pulse pressure and Nt-proBNP to the right (ie, higher blood pressure for a given level of Nt-proBNP). The metabolic syndrome was associated with lower Nt-proBNP levels and shifted the positive relationship between Nt-proBNP and pulse pressure to the right, creating a possible link between the metabolic syndrome and hypertension.

Topics: Adult; Aging; Blood Pressure; Cardiovascular Diseases; Dyslipidemias; Echocardiography; Female; Humans; Hyperinsulinism; Hypertension; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Risk Factors; Sex Factors; Stroke Volume