The importance of oxidative stress in patients with chronic renal failure whose hypertension is treated with peritoneal dialysis

Increased oxidative stress is a well-known phenomenon in dialysis patients. However, the contribution of hypertension to the oxidative stress in peritoneal dialysis patients has not yet been assessed. The present study aimed to investigate if hypertension had an additional effect on oxidative stress in peritoneal dialysis patients. A total of 50 patients treated with peritoneal dialysis were divided into two groups: The patients with mean of last three blood pressure results as 135/90 mmHg and above were considered hypertensive, the patients with lower blood pressure were considered normotensive. The control group included 25 healthy individuals. Serum malondialdehyde (MDA), advanced oxidation protein product (AOPP), myeloperoxidase (MPO), catalase (CAT) and glutathione peroxidase (GSH-Px) levels were measured in all groups. MDA level, an indicator of lipid peroxidation, was significantly higher in the hypertensive group compared to the control group, while the increase in the normotensive group was not significant. However, the difference between the hypertensive and normotensive groups was significant. The levels of AOPP, an indicator of protein oxidation level, and MPO, an indicator of neutrophil activation, were not different between the groups, while the activities of antioxidant CAT and GSH-Px decreased in both normotensive and hypertensive groups compared to the control group, and there was no significant difference between the patient groups. This study shows that both normotensive and hypertensive peritoneal dialysis patients have increased-oxidative stress and decreased antioxidant levels and hypertension might have an additional effect on oxidative stress by increasing MDA level in peritoneal dialysis patients.     

Catestatin is useful in detecting patients with stage B heart failure

Screening patients with stage B heart failure(HF) may be one strategy for reducing human morbidity. To describe catestatin levels in different stages of HF and evaluate the diagnostic utility of catestatin for detecting stage B HF, we included 300 patients. Catestatin, BNP testing and echocardiogram were performed. Our studies showed catestatin decreased gradually from stage A to C. There was significant difference between stage A and B. Cutoff value for detecting stage B HF was 19.73?ng/ml for catestatin with 90% sensitivity and 50.9% specificity. These results may have implications in the new method to detect patients with stage B HF.     

Catestatin is useful in detecting patients with stage B heart failure

Screening patients with stage B heart failure(HF) may be one strategy for reducing human morbidity. To describe catestatin levels in different stages of HF and evaluate the diagnostic utility of catestatin for detecting stage B HF, we included 300 patients. Catestatin, BNP testing and echocardiogram were performed. Our studies showed catestatin decreased gradually from stage A to C. There was significant difference between stage A and B. Cutoff value for detecting stage B HF was 19.73?ng/ml for catestatin with 90% sensitivity and 50.9% specificity. These results may have implications in the new method to detect patients with stage B HF.     

Sildenafil is more selective pulmonary vasodilator than prostaglandin E1 in patients with pulmonary hypertension due to heart failure

In some patients, heart failure (HF) is associated with increased pulmonary vascular resistance (PVR). The magnitude and the reversibility of PVR elevation affect the HF management. Sildenafil has been recently recognized as potent PVR-lowering drug in HF. The aim of the study was to compare hemodynamic effects and pulmonary selectivity of sildenafil to prostaglandin E(1) (PGE(1)). Right-heart catheterization was performed in 13 euvolemic advanced HF patients with elevated PVR (6.3+/-2 Wood's units). Hemodynamic parameters were measured at the baseline, during i.v. infusion of PGE1 (alprostadil 200 ng · kg(-1) · min(-1)) and after 40 mg oral dose of sildenafil. Both drugs similarly reduced systemic vascular resistance (SVR), but sildenafil had higher effect on PVR (-28 % vs. -49 %, p = 0.05) and transpulmonary pressure gradient than PGE(1). The PVR/SVR ratio--an index of pulmonary selectivity, did not change after PGE(1) (p = 0.7) but it decreased by -32 % (p = 0.004) after sildenafil. Both drugs similarly reduced pulmonary artery mean and wedge pressures and increased cardiac index (+27 % and +28 %). Sildenafil led more often to transplant-acceptable PVR while causing smaller drop of mean systemic pressure than PGE(1). In conclusion, vasodilatatory effects of sildenafil in patients with heart failure are more pronounced in pulmonary than in systemic circulation.     

Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension

Pulmonary hypertension provokes right heart failure and arrhythmias. Better understanding of the mechanisms underlying these arrhythmias is needed to facilitate new therapeutic approaches for the hypertensive, failing right ventricle (RV). The aim of our study was to identify the mechanisms generating arrhythmias in a model of RV failure induced by pulmonary hypertension. Rats were injected with monocrotaline to induce either RV hypertrophy or failure or with saline (control). ECGs were measured in conscious, unrestrained animals by telemetry. In isolated hearts, electrical activity was measured by optical mapping and myofiber orientation by diffusion tensor-MRI. Sarcoplasmic reticular Ca(2+) handling was studied in single myocytes. Compared with control animals, the T-wave of the ECG was prolonged and in three of seven heart failure animals, prominent T-wave alternans occurred. Discordant action potential (AP) alternans occurred in isolated failing hearts and Ca(2+) transient alternans in failing myocytes. In failing hearts, AP duration and dispersion were increased; conduction velocity and AP restitution were steeper. The latter was intrinsic to failing single myocytes. Failing hearts had greater fiber angle disarray; this correlated with AP duration. Failing myocytes had reduced sarco(endo)plasmic reticular Ca(2+)-ATPase activity, increased sarcoplasmic reticular Ca(2+)-release fraction, and increased Ca(2+) spark leak. In hypertrophied hearts and myocytes, dysfunctional adaptation had begun, but alternans did not develop. We conclude that increased electrical and structural heterogeneity and dysfunctional sarcoplasmic reticular Ca(2+) handling increased the probability of alternans, a proarrhythmic predictor of sudden cardiac death. These mechanisms are potential therapeutic targets for the correction of arrhythmias in hypertensive, failing RVs.     

Circulating multimarker profile of patients with symptomatic heart failure supports enhanced fibrotic degradation and decreased angiogenesis

Background: Heart failure (HF) involves myocardial fibrosis and dysregulated angiogenesis.

Objective: We explored whether biomarkers of fibrosis and angiogenesis correlate with HF severity.

Methods: Biomarkers of fibrosis [procollagen types I and III (PIP and P3NP), carboxyterminal-telopeptide of type I collagen (ICTP), matrix metalloproteases (MMP2 and MMP9), tissue inhibitor of MMP1 (TIMP1)]; and angiogenesis [placental growth factor (PGF), vascular endothelial growth factor (VEGF), soluble Fms-like tyrosine kinase-1 (sFlt1)] were measured in 52 HF patients and 19 controls.

Results: P3NP, ICTP, MMP2, TIMP1, PGF, and sFlt1 levels were elevated in HF, while PIP/ICTP, PGF/sFlt1, and VEGF/sFlt1 ratios were reduced. PIP/ICTP, MMP-9/TIMP1, and VEGF/sFlt1 ratios were lowest among patients with severe HF.

Conclusions: Severe HF is associated with collagen breakdown and reduced angiogenesis. A multimarker approach may guide therapeutic targeting of fibrosis and angiogenesis in HF.     

Circulating LIPCAR is a potential biomarker of heart failure in patients post-acute myocardial infarction

In heart failure (HF) patients with reduced ejection fraction, LIPCAR, a long noncoding RNA is elevated and is associated with left ventricular remodeling and poor prognosis. We studied the role of LIPCAR in patients with HF post-acute myocardial infarction (AMI) to find biomarkers for early detection of HF. We conducted a study of 127 patients with AMI, of which 59 were patients with HF post-AMI. LIPCAR levels were higher in HF patients post-AMI than patients without HF, and LIPCAR had a high predictive value for diagnosis of HF, which was estimated by receiver operating characteristic curves (AUC: 0.985). The results indicate that LIPCAR may be a marker of early HF after AMI.     

Suppression of cerebral hemodynamics is associated with reduced functional capacity in patients with heart failure

This investigation elucidated the underlying mechanisms of functional impairments in patients with heart failure (HF) by simultaneously comparing cardiac-cerebral-muscle hemodynamic and ventilatory responses to exercise among HF patients with various functional capacities. One hundred one patients with HF [New York Heart Association HF functional class II (HF-II, n = 53) and functional class III (HF-III, n = 48) patients] and 71 normal subjects [older control (O-C, n = 39) and younger control (Y-C, n = 32) adults] performed an incremental exercise test using a bicycle ergometer. A recently developed noninvasive bioreactance device was adopted to measure cardiac hemodynamics, and near-infrared spectroscopy was employed to assess perfusions in the frontal cerebral lobe (Δ[THb](FC)) and vastus lateralis muscle (Δ[THb](VL)). The results demonstrated that the Y-C group had higher levels of cardiac output, Δ[THb](FC), and Δ[THb](VL) during exercise than the O-C group. Moreover, these cardiac/peripheral hemodynamic responses to exercise in HF-III group were smaller than those in both HF-II and O-C groups. Although the change of cardiac output caused by exercise was normalized, the amounts of blood distributed to frontal cerebral lobe and vastus lateralis muscle in the HF-III group significantly declined during exercise. The HF-III patients had lower oxygen-uptake efficiency slopes (OUES) and greater Ve-Vo(2) slopes than the HF-II patients and age-matched controls. However, neither hemodynamic nor ventilatory response to exercise differed significantly between the HF-II and O-C groups. Cardiac output, Δ[THb](FC), and Δ[THb](VL) during exercise were directly related to the OUES and Vo(2peak) and inversely related to the Ve-Vco(2) slope. Moreover, cardiac output or Δ[THb](FC) was an effect modifier, which modulated the correlation status between Δ[THb](VL) and Ve-Vco(2) slope. We concluded that the suppression of cerebral/muscle hemodynamics during exercise is associated with ventilatory abnormality, which reduces functional capacity in patients with HF.     

Magnitude and time course of hemodynamic responses to Mueller maneuvers in patients with congestive heart failure

To simulate theimmediate hemodynamic effect of negative intrathoracic pressure duringobstructive apneas in congestive heart failure (CHF), without inducingconfounding factors such as hypoxia and arousals from sleep, eightawake patients performed, at random, 15-s Mueller maneuvers (MM) attarget intrathoracic pressures of 20 (MM 20) and40 cmH₂O (MM 40),confirmed by esophageal pressure, and 15-s breath holds, as apneic timecontrols. Compared with quiet breathing, at baseline, before theseinterventions, the immediate effects [first 5 cardiac cycles(SD), P values refer to MM 40compared with breath holds] of apnea, MM 20, and MM 40 were, for left ventricular (LV) systolic transmural pressure (Ptm), 1.0 ± 1.9, 7.2 ± 3.5, and 11.3 ± 6.8 mmHg(P < 0.01); for systolic bloodpressure (SBP), 2.9 ± 2.6, 5.5 ± 3.4, and 12.1 ± 6.8 mmHg (P < 0.01); and forstroke volume (SV) index, 0.4 ± 2.8, 4.1 ± 2.8, and6.9 ± 2.3 ml/m²(P < 0.001), respectively.Corresponding values over the last five cardiac cycles were for LVPtm6.4 ± 4.4, 5.4 ± 6.6, and 4.5 ± 9.1 mmHg (P < 0.01); for SBP6.9 ± 4.2, 8.2 ± 7.7, and 24.2 ± 6.9 mmHg (P < 0.01); and for SVindex 0.4 ± 2.1, 5.2 ± 2.8, and 9.2 ± 4.8 ml/m²(P < 0.001), respectively.Thus, in CHF patients, the initial hemodynamic response to thegeneration of negative intrathoracic pressure includes an immediateincrease in LV afterload and an abrupt fall in SV. The magnitude ofresponse is proportional to the intensity of the MM stimulus. By theend of a 15-s MM 40, LVPtm falls below baseline values, yet SVand SBP do not recover. Thus, when 40cmH₂O intrathoracic pressure issustained, additional mechanisms, such as a drop in LV preload due toventricular interaction, are engaged, further reducing SV. The neteffect of MM 40 was a 33% reduction in SV index (from 27 to 18 ml/min²), and a 21% reductionin SBP (from 121 to 96 mmHg). Obstructive apneas can have adverseeffects on systemic and, possibly, coronary perfusion in CHF throughdynamic mechanisms that are both stimulus and timedependent.

     

Uncovering heart failure with preserved ejection fraction in patients with type 2 diabetes in primary care: time for a change

Undetected heart failure appears to be an important health problem in patients with type 2 diabetes and aged ≥ 60 years. The prevalence of previously unknown heart failure in these patients is high, steeply rises with age, and is overall higher in women than in men. The majority of the patients with newly detected heart failure have a preserved ejection fraction. A diagnostic algorithm to detect or exclude heart failure in these patients with variables from the medical files combined with items from history taking and physical examination provides a good to excellent accuracy. Annual screening appears to be cost-effective. Both unrecognised heart failure with reduced and with preserved ejection fraction were associated with a clinically relevant lower health status in patients with type 2 diabetes. Also the prognosis of these patients was worse than of those without heart failure. Existing disease-management programs for type 2 diabetes pay insufficient attention to early detection of cardiovascular diseases, including heart failure. We conclude that more attention is needed for detection of heart failure in older patients with type 2 diabetes.     

年龄与老年高血压并发心力衰竭患者发生多器官功能衰竭的关系

目的:分析年龄对老年高血压患者伴发心力衰竭(CHF)后诱发多器官功能衰竭(MODSE)的关系,探讨年龄和CHF对老年高血压患者发生MODSE的预测值。方法:回顾性分析≥60岁高血压患者的19996例病历资料(男性13229例,女性6767例,平均年龄74.21±7.52),以10岁为界60~69岁、70~79岁、80~89岁和≥90岁划分年龄段,以69、79和89岁为分界点,分别分析各年龄段及各分界年龄上下老年高血压患者中因CHF并发MODSE的发生率。结果:①所有CHF患者中MODSE的发生率较非CHF患者升高(7.43%vs3.05%,χ2195.15,说明CHF是影响老年高血压患者出现MODSE的重要影响因素;②60~69岁、70~79,80~89岁和≥90岁发生CHF的比例分别10.60%vs18.88%vs30.11%vs60.57%,P<0.05,差异有统计学意义。4个年龄段发生MODSE分别为1.68%vs7.06%vs17.08%vs25.47%,P<0.05,有统计学差异。高血压患者中CHF的发生率与CHF中MODSE的发生率呈正相关r=0.696(P<0.01);年龄与老年高血压患者并发CHF的发生率以及年龄与CHF中MODSE发生率亦呈正相关r=0.987(P<0.01)。排除年龄因素的影响对CHF与MODSE的发生率进行偏相关分析表明r=-0.776(P>0.05),说明年龄是老年高血压患者并发CHF后出现MODSE的重要影响因素,且69岁以上各分界年龄上下之间差异最明显,具有统计学意义(P<0.05)。结论:年龄与CHF诱发老年高血压患者发生MODSE具有一定的早期预测值,69岁以上的高血压患者如合并CHF是发生MODSE的高危人群。     

Prevalence and characteristics of sleep apnoea in patients with stable heart failure: Results from a heart failure clinic

Background

There is much interest in the possibility that perinatal factors may influence the risk of disease in later life. We investigated the influence of maternal and perinatal factors on subsequent hospital admission for asthma in children.

Methods

Analysis of data from the Oxford record linkage study (ORLS) to generate a retrospective cohort of 248 612 records of births between 1970 and 1989, with follow-up to records of subsequent hospital admission for 4 017 children with asthma up to 1999.

Results

Univariate analysis showed significant associations between an increased risk of admission for asthma and later years of birth (reflecting the increase in asthma in the 1970s and 1980s), low social class, asthma in the mother, unmarried mothers, maternal smoking in pregnancy, subsequent births compared with first-born, male sex, low birth weight, short gestational age, caesarean delivery, forceps delivery and not being breastfed. Multivariate analysis, identifying each risk factor that had a significant effect independently of other risk factors, confirmed associations with maternal asthma (odds ratio (OR) 3.1, 95% confidence interval 2.7-3.6), male sex (versus female, 1.8, 1.7-2.0), low birth weight (1000-2999 g versus 3000-3999 g, 1.2, 1.1-1.3), maternal smoking (1.1, 1.0-1.3) and delivery by caesarean section (1.2; 1.0-1.3). In those first admitted with asthma under two years old, there were associations with having siblings (e.g. second child compared with first-born, OR 1.3, 1.0-1.7) and short gestational age (24-37 weeks versus 38-41 weeks, 1.6, 1.2-2.2). Multivariate analysis confined to those admitted with asthma aged six years or more, showed associations with maternal asthma (OR 3.8, 3.1-4.7), age of mother (under 25 versus 25-34 at birth, OR 1.16, 1.03-1.31; over 35 versus 25-34, OR 1.4, 1.1-1.7); high social class was protective (1 and 2, compared with 3, 0.72; 0.63-0.82). Hospital admission for asthma in people aged over six was more common in males than females (1.4; 1.2-1.5); but, by the teenage years, the sex ratio reversed and admission was more common in females than males.

Conclusion

Several maternal characteristics and perinatal factors are associated with an elevated risk of hospital admission for asthma in the child in later life.     

Redox modulation of the inotropic response to dobutamine is impaired in patients with heart failure

It has been suggested that oxidative stress contributes to impaired left ventricular (LV) contractility in the setting of heart failure (HF). To test this hypothesis, we studied the effect of an antioxidant on contractility at rest and in response to dobutamine in 10 HF patients. We hypothesized that vitamin C would augment contractility in HF and that this effect would be of a greater magnitude in HF patients compared with patients with normal LV (NLV) function. Data from 10 patients with NLV function who participated in this study are included in this report and have been published elsewhere. A micromanometer-tipped catheter was introduced into the LV. In the experimental protocol, an infusion catheter was positioned in the left main coronary artery. The peak positive rate of change of LV pressure (LV +dP/dt) was measured in response to the intravenous infusion of dobutamine before and during the intracoronary infusion of vitamin C (96 mg/min). Vitamin C had no effect on basal LV +dP/dt in either HF or NLV groups. The infusion of vitamin C augmented the LV +dP/dt response to dobutamine by 22 +/- 4% in the NLV function group. In contrast, vitamin C had no effect on the inotropic response to dobutamine in the HF group. In the control protocol, without vitamin C, no differences were observed between responses to two sequential dobutamine infusions in either group (HF, n = 11; NLV, n = 9). Therefore, a positive effect of vitamin C on contractility was limited to patients with NLV function. The absence of this effect in HF patients may suggest that normal redox responsiveness is lost in this disease state.     

Alpha-human atrial natriuretic polypeptide (alpha-hANP) in normal volunteers and patients with heart failure or hypertension

The presence of alpha-hANP immunoreactive material in human heart and plasma was investigated with a specific and sensitive radioimmunoassay and immunohistochemical method. It was found that alpha-hANP immunoreactive staining of specific atrial granules was located around the nucleus of atrial cardiocytes. No immunoreactive staining was found in the ventricle. The content of immunoreactive hANP was 0.5 pmol/mg protein in the atria and 0.11 +/- 0.01 pmol/ml in the plasma of 26 normal volunteers. In 16 patients with congestive heart failure and 26 patients with essential hypertension, the plasma level of immunoreactive alpha-hANP was significantly lower than that in normal humans. The above evidence indicate that alpha-hANP is a putative hormone secreted by human atrium. A relative shortage of alpha-hANP in the circulatory system may be involved in the mechanism of heart failure and hypertension.     

Prevalence,concentration, and prognostic importance of proteinuria in patients with malignancies

Protein was found significantly more frequently in single urine samples from 504 patients with malignancy (290; 58%) than in 529 controls (119; 22%) (p<0·001). Median protein concentration was greater (p<0·001) in patients with neoplasia (0·14 g/l) than in controls (0·07 g/l). Actuarial analysis showed a median survival of 4·5 months in patients with proteinuria compared with 10 months in those without (p<0·001). The association between proteinuria and shorter survival was statistically significant for patients with gut tumours, lung tumours, and tumours at other sites analysed as a group. Patients with myeloma or urinary tract tumours were not studied.In many patients with malignancy the presence of proteinuria may be associated with a substantially reduced survival time.     

The deceleration of the heart frequency in the waterfleaDaphnia magna by adrenoceptor agonists and antagonists

Beat-to-beat measurements with 30 micro-seconds accuracy were carried out in order to determine the chronotropic effects on the heart ofDaphnia magna induced by adrenoceptor agonists and antagonists dissolved in water. Agonists and antagonists were either ineffective or lowered the heart frequency (P < 0.05). In addition, the negative chronotropic effect of the agonist epinephrine could not be blocked by the antagonist propranolol. It may, therefore, well be that the drug actions were not mediated through adrenoceptors.