Stress In Heart Failure Patients Research Articles

Association between antioxidant metabolites and N-terminal fragment brain natriuretic peptides in insulin-resistant individuals.

Oxidative stress plays a pivotal role in the development of metabolic syndrome, including heart failure and insulin resistance. The N-terminal fragment of brain natriuretic peptide (NT-proBNP) has been associated with heightened oxidative stress in heart failure patients. Yet, its correlation with insulin resistance remains poorly understood. Our objective is to investigate the association between oxidative stress markers and NT-proBNP levels in insulin-resistant individuals. In this cross-sectional study involving 393 participants from the Qatar Biobank, clinical and metabolic data were collected, and the association between NT-proBNP and 72 oxidative stress metabolites was compared between insulin-sensitive and insulin-resistant individuals. Our results showed significantly lower NT-proBNP levels in insulin-resistant individuals (median = 17 pg/ml; interquartile range = 10.3-29) when compared to their insulin-sensitive counterparts (median = 31 pg/ml; interquartile range = 19-57). Moreover, we revealed notable associations between NT-proBNP levels and antioxidant metabolic pathways, particularly those related to glutathione metabolism, in insulin-resistant, but not insulin-sensitive individuals. The significant decrease in NT-proBNP observed in individuals with insulin resistance may be attributed to a direct or indirect enhancement in glutathione production, which is regarded as a compensatory mechanism against oxidative stress. This study could advance our understanding of the interplay between oxidative stress during insulin resistance and cardiovascular risk, which could lead to novel therapeutic approaches for managing cardiovascular diseases. Further investigations are needed to assess the practical utility of these potential metabolites and understand the causal nature of their association with NT-proBNP in the etiology of insulin resistance.

Hyperuricemia and Its Association With the Severity and Complications of Congestive Heart Failure: A Systematic Review.

Several studies have shown that an association exists between hyperuricemia and heart failure. Despite several innovative management strategies, heart failure is a significant cause of mortality worldwide. Hyperuricemia in heart failure patients leads to poorer outcomes. Additionally, hyperuricemia can be a strong surrogate marker for increased oxidative stress in heart failure patients. This oxidative stress leads to vascular endothelial damage and is linked to worsening heart failure and subsequent mortality. Hence, the measurement of serum uric acid levels in these patients can predict the present and future risk of complications of heart failure. Despite this knowledge, serum uric acid levels are not usually followed up in heart failure patients. This systematic review aims to give additional clarity to this association. We used research from the last twenty years (2002 to 2022) obtained from databases such as PubMed, PubMed Central (PMC), Google Scholar, and Science Direct. We used the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 guidelines. We removed duplicates, screened articles on the basis of title and abstract, applied eligibility criteria, and performed quality appraisal. Eventually, 15 articles were selected for review. There were 12 observational studies, two randomized controlled trials, and one meta-analysis. Our review showed that serum uric acid elevation is associated with the severity and complications of congestive heart failure. Serum uric acid can serve as a useful surrogate marker of oxidative stress in congestive heart failure (CHF) patients. The role of xanthine oxidase inhibitors needs to be evaluated further in CHF patients.

PO104 Comparison Between High-Intensity Interval Training and Moderate-Intensity Continuous Training for Evaluated Erectile Function and Oxidative Stress In Heart Failure Patients

PO104 Comparison Between High-Intensity Interval Training and Moderate-Intensity Continuous Training for Evaluated Erectile Function and Oxidative Stress In Heart Failure Patients

Evaluation of oxidant status in both systolic and diastolic heart failure

Objective: Oxidative stress status in subgroup of heart failure (HF) syndrome still remains unknown. We aimed to study Total Antioxidant Status (TAS), Total Oxidant Status (TOS) and Oxidative Stress Index (OSI) in both systolic and diastolic HF, and also in both ischemic and non-ischemic HF. Materials and Methods: Consecutive 123 chronic HF patients were included in this cross-sectional study. Group 1 consisted of 73 systolic HF patients (50 ischemic patients and 23 non-ischemic patients) and group 2 consisted of 50 diastolic HF patients. As a control group (group 3), 37 healthy subjects were included. Echocardiographic evaluation was performed and TAS, TOS and OSI were studied in all patients. Results: The highest TAS value (1.10±0.24) was found in Group 1, but the lowest in Group 2 (0.90±0.14). Diastolic HF group had the highest TOS value (37.2±10.41) while systolic HF group (32.9±7.26) and control group (26.19±8.00) followed it. OSI was found the highest in diastolic HF group (4.37±1.24) and the lowest in systolic HF group (2.24±0.80). TOS and OSI were similar between ischemic and non-ischemic subgroups of systolic HF but TAS was statistically higher in non-ischemic (p:0.0005). Conclusions: We found higher oxidative stress in HF patients, predominantly in diastolic HF patients. The difference between diastolic and systolic HF with regard to oxidative and antioxidative status seems to come from distinct drugs usage between the groups, which have potential effects on oxidative and antioxidative parameters. To reduce, at least, oxidative stress in diastolic HF patients, medical therapy is needed.

α-1 Protein evaluation to stratify heart failure patients

Heart failure is a pathological condition characterized by cardiac dysfunction and neuroendocrine system activation. The aim of this study was to evaluate serum α-1 proteins in the characterization of heart failure patients. The study included 69 patients with documented heart failure disease and 44 healthy individuals. We included 12 out of 69 patients with preserved (>50%) left ventricular ejection fraction. α-1 protein levels were evaluated using routine capillary electrophoresis. Markers of inflammation, such as interleukin-6 (IL-6) and tumor necrosis factor-α, were measured with UltraSensitive ELISA Kits. C-reactive protein and brain natriuretic peptide were determined by automated assays. No difference in α-1 protein levels between patients with reduced versus preserved left ventricular ejection fraction was observed. IL-6, tumor necrosis factor-α, and C-reactive protein concentrations were significantly increased in patients with respect to the control group (P <0.001, P <0.01, and P <0.05, respectively). A progressive increase in α-1 protein levels across NYHA classes (P = 0.0077) was observed. Brain natriuretic peptide median value of the patient group was 287 ng/l (92–602 ng/l) and was significantly associated with α-1 proteins and IL-6 levels (P <0.05 and P <0.01, respectively). Considering recent findings and our preliminary data, we hypothesized that the overexpression of α-1 antitrypsin (AAT) protein (and probably elevated AAT levels) is a compensatory mechanism as a consequence of the loss of the antiprotease activity, induced by the increase of oxidative stress in heart failure patients. In conclusion, we assume that α-1 proteins and AAT could contribute to the prognostic stratification of heart failure patients.

(1087) - Oxydative Stress in Heart Failure Patients after Implantation of Continuous Flow Left Ventricular Assist Devices

Prior studies have demonstrated an increase in the levels of reactive oxygen species (ROS) in patients with heart failure (HF) compared to the general population. Increased oxidative stress is implicated in most types of heart failure, including that resulting from ischemic and non-ischemic cardiomyopathy. The adverse effects of oxidative stress in HF patients are vascular endothelial dysfunction, cardiac hypertrophy, interstitial fibrosis, myocyte contractile dysfunction, and adverse left ventricular remodeling. Little is known about the role of continuous flow LVADs on oxidative stress among HF patients. We measured free radical levels at the time of LVAD implant and at the time of heart transplantation to determine if ventricular assist devices reduce ROS levels At the time of LVAD implantation and at the time of heart transplantation a sample of peripheral blood and cardiac tissue were obtained. Methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine (CMH) and an electron paramagnetic resonance (EPR) spectroscopy buffer were added to the samples, incubated for 1 hour and then frozen in liquid nitrogen. Using EPR, the CMH radical signal was recorded and EPR spectrum amplitude was measured. We collected blood and tissue from 33 patients at the time of LVAD surgery and from 7 patients at the time of transplant. Data was analyzed by unpaired t test. The free radical level in peripheral blood at the time of LVAD implantation was 3.23×106 ± 1.44×106 EPR AU/mL compared to 3.13×106 ± 1.38×106 EPR AU/mL at the time of heart transplant (p = 0.87) suggesting no difference between these groups. The free radical level in cardiac tissue was 5.25×105 ± 1.3×105 EPR AU/mg at the time of LVAD implantation and 5.49×105 ± 3.31×105 EPR AU/mg at time of transplant (p=0.79) also suggesting no difference between these groups. This study shows that LVAD implanted HF patients have elevated oxidative stress. Also, there was no difference in measured levels of free radicals in peripheral blood or cardiac tissue at the time of LVAD implantation compared to the level at the time of transplantation. Elevated oxidative stress may be directly or indirectly related to several consequences like inflammation, bacterial infections, GI bleeding, thromboembolism that are common complications found during LVAD support.

Quantifying passive myocardial stiffness and wall stress in heart failure patients using personalized ventricular mechanics

Quantifying passive myocardial stiffness and wall stress in heart failure patients using personalized ventricular mechanics

Increase in the Oxidized Low-density Lipoprotein Level by Sleep-Disordered Breathing and Correlation with Obesity in Patients with Heart Failure

Sleep disordered breathing (SDB) is associated with increased mortality in heart failure (HF), but the underlying mechanism is not fully elucidated. Oxidative stress plays an essential role in the pathogenesis of HF. We investigated the association of SDB with oxidative stress in HF patients. Overnight polygraphy was performed in 71 patients with HF (ischemic cardiomyopathy n=17, dilated cardiomyopathy n=41, others n=13). Based on the presence of severe SDB, these patients were divided into two groups: Group A (apnea hypopnea index [AHI]≧ 30/h, n=17) and Group B (AHI<30/h, n=54). We measured plasma levels of malondialdehyde-modified low-density lipoprotein (MDA-LDL), one of the representative oxidized LDL. MDA-LDL levels were higher in Group A than Group B (136±56vs.102±34 U/L; p>0.05). Plasma levels of BNP, troponin T and CRP, and FABP were not different between two groups. Plasma MDA-LDL level were higher in patients with obese (BMI>25) than those without (141±51vs.101±36 U/L; p>0.005), but not associated with other cardiovascular risk factors, etiology of HF, cardiovascular medications, and other biomarkers. Multiple regression analysis showed that the most important determinants of log MDA-LDL level was obesity (β=0.39, p<0.005). SDB is associated with enhanced oxidative status, but obesity is the most important determinants of oxidative stress in HF. Weight reduction might be an important strategy to control oxidative stress in HF with SDB.

Type D personality is associated with low cardiovascular reactivity to acute mental stress in heart failure patients

BackgroundThe distressed (Type D) personality is associated with adverse coronary heart disease outcomes, but the mechanisms accounting for this association remain to be elucidated. We examined whether myocardial and hemodynamic responses to mental stress are disrupted in Type D patients with chronic heart failure (HF). MethodsNinety-nine HF patients (mean age 65±12years; 75% men) underwent a public speech task, during which heart rate (HR) and blood pressure (BP) were recorded. Type D personality and its components negative affectivity (NA) and social inhibition (SI) were assessed with the DS14. General linear models with repeated measures and logistic regression were used to assess differences in stress response and recovery. ResultsType D personality was associated with a reduced HR response (F1,93=4.31, p<.05) independent of the use of beta adrenergic blocking agents and the presence of atrial fibrillation. There were no differences between HF patients with and without a Type D personality with respect to the BP response. Examining continuous NA and SI scores and their interaction (NA∗SI), revealed a significant association of NA∗SI with the SBP response (F1,93=4.11, p<.05), independent of BP covariates. Results with respect to HR and DBP responses were comparable to the findings using the dichotomous Type D measure. No significant associations between Type D and recovery patterns were found. ConclusionHF patients with Type D personality may show an inadequate response to acute social stress, characterized by a blunted HR response.

Statin therapy lowers muscle sympathetic nerve activity and oxidative stress in patients with heart failure

Despite standard drug therapy, sympathetic nerve activity (SNA) remains high in heart failure (HF) patients making the sympathetic nervous system a primary drug target in the treatment of HF. Studies in rabbits with pacing-induced HF have demonstrated that statins reduce resting SNA, in part, due to reductions in reactive oxygen species (ROS). Whether these findings can be extended to the clinical setting of human HF remains unclear. We first performed a study in seven statin-naïve HF patients (56 ± 2 yr; ejection fraction: 31 ± 4%) to determine if 1 mo of simvastatin (40 mg/day) reduces muscle SNA (MSNA). Next, to control for possible placebo effects and determine the effect of simvastatin on ROS, a double-blinded, placebo-controlled crossover design study was performed in six additional HF patients (51 ± 3 yr; ejection fraction: 22 ± 4%), and MSNA, ROS, and superoxide were measured. We tested the hypothesis that statin therapy decreases resting MSNA in HF patients and this would be associated with reductions in ROS. In study 1, simvastatin reduced resting MSNA (75 ± 5 baseline vs. 65 ± 5 statin bursts/100 heartbeats; P < 0.05). Likewise, in study 2, simvastatin also decreased resting MSNA (59 ± 5 placebo vs. 45 ± 6 statin bursts/100 heartbeats; P < 0.05). In addition, statin therapy significantly reduced total ROS and superoxide. As expected, cholesterol was reduced after simvastatin. Collectively, these findings indicate that short-term statin therapy concomitantly reduces resting MSNA and total ROS and superoxide in HF patients. Thus, in addition to lowering cholesterol, statins may also be beneficial in reducing sympathetic overactivity and oxidative stress in HF patients.

Predictors of oxidative stress in heart failure patients with Cheyne–Stokes respiration

Cheyne-Stokes respiration during sleep is associated with increased mortality in heart failure. The magnitude of oxidative stress is a marker of disease severity and a valuable predictor of mortality in heart failure. Increased oxidative stress associated with periodic breathing during Cheyne-Stokes respiration may mediate increased mortality in these patients. We hypothesized that the presence of Cheyne-Stokes respiration is associated with oxidative stress by increasing the formation of reactive oxygen species in patients with heart failure. Twenty-three patients with heart failure [left ventricular ejection fraction 30.2 ± 9% (mean ± standard deviation)] and 11 healthy controls underwent nocturnal polysomnography. Subjects with obstructive sleep apnea were excluded. The majority (88%) of patients with heart failure had Cheyne-Stokes respiration during sleep. The intensity of oxidative stress in neutrophils was greater in patients with heart failure (4,218 ± 1,706 mean fluorescence intensity/cell vs. 1,003 ± 348 for controls, p < 0.001) and correlated with the duration of Cheyne-Stokes respiration. Oxidative stress was negatively correlated with SaO(2) nadir during sleep (r = -0.43, p = 0.039). The duration of Cheyne-Stokes respiration predicted severity of oxidative stress in patients with heart failure (beta = 483 mean fluorescence intensity/cell, p < 0.02). Levels of oxidative stress are increased in patients with heart failure and Cheyne-Stokes respiration during sleep compared with healthy controls. The duration of Cheyne-Stokes respiration predicts the magnitude of oxidative stress in heart failure. Increased oxidative stress may mediate increased mortality associated with Cheyne-Stokes respiration in patients with heart failure.

Increases in B-Type Natriuretic Peptide After Acute Mental Stress in Heart Failure Patients Are Associated With Alcohol Consumption

The aim of this study was to investigate in heart failure (HF) patients whether acute mental stress induces increases in the HF-severity biomarker B-type natriuretic peptide (BNP) and if alcohol consumption is associated with such stress-induced increases. Twenty-one male HF patients and 19 male non-HF controls (M = 56 years, SEM = 2) underwent a 15-minute acute mental stress test combining public speaking and mental arithmetic. Plasma levels of BNP were determined immediately before as well as 2 hours after the stress test. Alcohol consumption was assessed by self-reported number of drinks per month and history of use. HF patients had higher BNP levels before and after stress, F(1, 38) = 23.42, p < .001, and showed greater stress-induced increases in BNP levels, F(1, 38) = 4.52, p = .04, compared with controls. HF status (beta = .32, p = .015, deltaR(2) = .10) and higher alcohol consumption ((beta = .61, p< .001, deltaR(2) = .37) were independently associated with higher BNP stress increases. Moreover, higher alcohol consumption moderated the greater BNP stress increases in HF patients but not in controls (p = .49, p < .001, delta(2) = .20), although alcohol consumption did not differ between groups. For individuals with HF, particularly those who drink moderate to more substantial amounts of alcohol, exposure to acute psychological stress leads to increases in circulating levels of BNP, a biomarker which is associated with increased morbidity and mortality in HF.

Treating Central Sleep Apnea in Heart Failure

A recent enhanced appreciation of sleep–cardiovascular interactions, particularly in patients with congestive heart failure (CHF), has prompted careful consideration of the relevance of sleep-disordered breathing to CHF pathophysiology, progression, and treatment.1 Sleep-disordered breathing may be broadly classified as either obstructive sleep apnea (OSA) or central sleep apnea (CSA).1 The former is characterized by repetitive collapse of the upper airway, whereas in patients with CHF, the latter is most often due to periodic alternation of diminished ventilatory drive and compensatory hyperventilation typical of Cheyne-Stokes respiration (Figure 1). CSA is likely a consequence rather than a cause of CHF. Although the mechanisms that underlie CSA/Cheyne-Stokes respiration in patients with CHF are not well understood, pulmonary congestion with increased lung J-receptor stimulation and greater chemosensitivity may play a role in the genesis of the periodic breathing that characterizes this disorder.1,2 Figure 1. Ventilation during sleep from a patient with CHF and CSA. The ventilatory pattern is characteristic of Cheyne-Stokes respiration: apnea followed by crescendo-decrescendo breathing followed by apnea. The cycle may be repeated throughout sleep. Article p 3173 Of 5 million North Americans with CHF, an estimated 50% may have coexistent sleep apnea. Although the prevalence of OSA is much higher than CSA in the general population,3 it appears that this relationship may be reversed among patients with systolic heart failure. Case series have reported frequencies of CSA exceeding 40% for stable, ambulatory patients with CHF in a ratio >2:1 relative to the frequency of OSA. Indeed, the frequency of OSA in these same series was similar to that observed in the general population, whereas the frequency of CSA was strikingly higher.4,5 Furthermore, in patients with CHF, CSA has been associated with increased morbidity and mortality,5–7 increased neurohormonal activation,1 increased ventricular arrhythmia,8 decreased exercise capacity, …

230 N-terminal pro brain natriuretic peptide plasma levels show better relationship with end-diastolic than with end-systolic wall stress in heart failure patients irrespective of the etiology

230 N-terminal pro brain natriuretic peptide plasma levels show better relationship with end-diastolic than with end-systolic wall stress in heart failure patients irrespective of the etiology

Sympathetic activation restrains endothelium-mediated muscle vasodilatation in heart failure patients

Although the vasodilatory response during mental stress is blunted in heart failure (HF), the mechanisms underlying this phenomenon are not fully understood. We tested the hypothesis that sympathetic activity limits the endothelium-dependent vasodilatation during mental stress in chronic HF patients. Twenty-one HF patients (age 45 +/- 2 yr, functional classes III and IV, New York Heart Association) and 22 age-matched normal controls (NC; age 42 +/- 2 yr, P = 0.13) were studied at rest and during 4 min of Stroop color-word test with brachial intra-arterial saline, acetylcholine (endothelium dependent), phentolamine (alpha-blocker), and phentolamine plus acetylcholine infusion. Forearm blood flow was measured by venous occlusion plethysmography. Baseline forearm vascular conductance (FVC) was significantly lower in HF patients (2.18 +/- 0.12 vs. 3.66 +/- 0.22 units, P = 0.001). During mental stress with saline, the changes in FVC were significantly blunted in HF patients compared with NC (0.92 +/- 0.20 vs. 2.13 +/- 0.39 units, P = 0.001). In HF, the vasodilatation with acetylcholine was similar to saline control and significantly lower than in NC. In HF patients, phentolamine significantly increased FVC responses (1.16 +/- 0.20 vs. 2.09 +/- 0.29 units, P = 0.001), and the difference between HF patients and NC tended to decrease (2.09 +/- 0.29 vs. 3.61 +/- 0.74 units, P = 0.052). The vasodilatation with phentolamine plus acetylcholine was similar between HF and NC (4.23 +/- 0.73 vs. 4.76 +/- 1.03 units, P = 0.84). In conclusion, sympathetic activation mediates the blunted muscle endothelium-mediated vasodilatation during mental stress in HF patients.

Oxidative Stress Status in the Transition of Hypertrophy to Heart Failure

In response to a variety of stressful conditions such as pressure overload, volume overload, myocardial infarction and different types of cardiomyopathies, the heart undergoes an adaptation process during which it grows in size, a phenomenon referred to as hypertrophy. During this compensatory phase, the heart is better able to meet the increased work demand. However, if left untreated for a prolonged period, it can advance into the decompensated hypertrophic or the failing stage. It is now clear that transition of heart hypertrophy to the failure stage involves a number of abnormalities which include ionic imbalances, impairment in energy production and utilization, altered calcium metabolism and defects in the contractile proteins. More recently, alterations in free radicals and “antioxidant reserve” have been identified in the hypertrophy as well as failing stages. Discussion in this review is focussed on the role of oxidative stress in both compensated and decompensated stages, in various animal models of heart failure. Some clinical data on oxidative stress in heart failure patients is also reviewed. It is suggested that an increase in oxidative stress may play a role in the pathogenesis of heart failure.