Frailty, hospitalization, and progression of disability in a cohort of disabled older women

Purpose

To determine the association between a previously validated frailty phenotype and the development of new-onset dependence in activities of daily living, independent of hospitalizations and other established predictors of disability.

Subjects

Seven hundred and forty-nine women enrolled in the Women’s Health and Aging Study-I who were independent in all activities in daily living when enrolled in the cohort.

Methods

Assessments and interviews were conducted through home visits at 6-month intervals for 3 years. Frailty was classified using a validated phenotype (≥3 of the following: weight loss, exhaustion, slow walking, sedentariness, and weak grip), and hospitalizations were identified by self-report. Grouped-time proportional hazard models assessed associations among frailty, hospitalization, and the development of dependence in activities in daily living, adjusting for other factors.

Results

Twenty-five percent of the cohort (186/749) were frail at baseline; 56% (104/186) of frail versus 20% (23/117) of nonfrail women developed dependence in activities in daily living (P <.001). In multivariate analysis, frailty was independently associated with the development of dependence in activities in daily living (hazard ratio [HR] = 2.2; 95% confidence interval [CI]: 1.4 to 3.6), adjusting for hospitalization status, age, race, education, baseline functional status, cognition, depressive symptoms, number of chronic diseases, and self-reported health status. Additionally, a dose-response relationship existed between the number of frailty criteria that a woman had and the hazard of subsequent dependence in activities in daily living.

Conclusion

Frailty, conceptualized as an underlying vulnerability, and hospitalization, which marks an acute deterioration in health, were strongly and independently associated with new-onset dependence in activities in daily living. Additional research is needed to determine if dependence can be minimized by targeting resources and programs to frail older persons.     

Age,severe comorbidity and functional impairment independently contribute to poor survival in cancer patients

Purpose With the increasing number of elderly patients suffering from cancer, comorbidity and functional impairment become common problems in patients with cancer. Both comorbidity and functional impairment are associated with a shorter survival time in cancer patients, but their independent role has rarely been addressed before. Methods Within a prospective trial we recruited 427 cancer patients, irrespective of age and type of cancer, admitted as inpatients prior to the start of chemotherapy. Comorbidity was assessed with the cumulative illness rating scale (CIRS-G), functional impairment with WHO performance status (WHO-PS), basal (ADL) and instrumental (IADL) activities of daily living. Results Median follow-up was 34.2 months. A total, 61.4%. of patients died. Median survival time was 21.0 months. Age, kind of tumour (solid vs. haematological), treatment approach (non-curative vs. curative), WHO-PS (2–4 vs. 0–1), IADL (<8 vs. 8), and severe comorbidity (CIRS-level 3–4 vs. none) were significantly associated with shorter survival time in univariate analysis. In a multivariate Cox-regression-analysis, age (HR 1.019; 95%-CI 1.007–1.032; P = 0.003), kind of tumour (HR 1.832; 95%-CI 1.314–2.554; P < 0.001), WHO-PS (HR 1.455; 95%-CI 1.059–2.000; P = 0.021), and comorbidity level 3–4 (HR 1.424; 95%-CI 1.012–2.003; P = 0.043) maintained their significant association. Conclusions Age, severe comorbidity, functional impairment, and kind of tumour are independently related to shorter survival time in cancer patients.     

Multiple inflammatory markers and 15-year incident ADL disability in admixed older adults: The Bambui-Epigen Study

BackgroundThe ability of inflammatory markers to predict disability in later life has received growing attention. However, the current evidence came predominantly from Caucasians and the role of genomic ancestry has not been investigated.ObjectiveWe investigated the prognostic value of multiple citokynes and chemokines for incident disability in admixed older Brazilians and whether genomic African and Native American ancestry affects the association.DesignPopulation-based longitudinal study.SettingThe Bambui-Epigen (Brazil) Cohort Study of Aging.Subjects1171 males and females aged ≥60 years over 15-year of follow-up.MethodsOutcome examined was incident activity of daily living (ADL) disability assessed annually (10,039 measures were performed). Serum levels of citokynes (IL6, IL12, TNF, IL10, and IL1β) and chemokines (CCL2, CCL5, CXCL8, CXCL9 and CXCL10) were measured at baseline. We used 370,539 Single Nucleotide Polymorphisms (SNPs) to estimate each individual genomic ancestry proportions. Potential confounding variables included a wide range of socio-demographic variables and health indicators. Statistical analyses were based on competing risk framework.ResultsThe incidence rate of disability was 57.9 per 1000 person-years. IL6 level at the highest quartile showed an independent association with ADL disability (SRH = 1.32; 95% CI: 1.03, 1.70). Other inflammatory markers showed no statistically significant associations with the outcome. Neither genomic African nor Native American ancestry had an effect modifier on the associations (P for interaction >0.05 for all).ConclusionAmong multi-inflammatory markers, only IL6 had the potential to identify people at increased risk of ADL disability, independently of ethno-racial background.     

绝经后妇女体力活动与桡骨骨密度、皮质厚度和相关骨代谢指标关系的研究

目的　探讨绝经后女性日常体力活动与桡骨骨密度 (BMD)、皮质厚度和相关骨代谢指标的关系。　方法　以单纯随机抽样的方法 ,抽取江门市 12家工厂和企事业单位自然绝经的女性职工 137名作为研究对象 ,采用标准化的体力活动问卷MOSPA评价其体力活动水平 ,并测量有关桡骨皮质骨结构指标和相关骨代谢指标。　结果　在校正年龄、体质指数 (BMI)、血清雌二醇、膳食钙和维生素D摄入水平等因素后 ,高体力活动组女性的桡骨BMD〔分别为 (0 5 88± 0 0 0 7)、(0 6 34±0 0 0 4 )g/cm2 〕和骨皮质指数均高于低体力活动组 ,而其骨髓腔宽度则低于低体力活动组 (P <0 0 5 ) ,但两组间的血清钙、磷、碱性磷酸酶 (AKP)、抗酒石酸盐酸性磷酸酶 (TRAP)以及空腹尿钙和肌酐比较 ,差异均无显著性 (P >0 0 5 )。与低体力活动组相比较 ,高体力活动组的TRAP有下降趋势。　结论　绝经后妇女体力活动与桡骨BMD、骨皮质厚度呈正相关关系     

Self-rated health status as a predictor of death, functional and cognitive impairment: a longitudinal cohort study

Understanding the prognostic capacity of a simple measure of self-rated health (SRH) by older people becomes increasingly important as the population ages. SRH has been shown to predict survival, functional status and service use. The relationship with cognitive impairment has not been widely investigated. This paper investigates SRH as a predictor of death, functional impairment (inability to perform activities of daily living) and cognitive impairment (MMSE < 18) over a 10-year follow-up of participants in the MRC Cognitive Function and Ageing Study. A stratified random sample of 13,004 people aged 65 or over resident in five areas in England and Wales were interviewed. Analysis used data from interviews at baseline, 2, 6 and 10 year follow-up. Hazard ratios for risk of death, functional and cognitive impairment were estimated, unadjusted and adjusted for potential confounding baseline factors. Of the 13,004 participants recruited, 6,882 had died by 10 years and 1,252 and 481 new cases of functional and cognitive impairment respectively were recorded. SRH was associated with a higher risk of death, functional and cognitive impairment. The associations remained after adjustment for age, gender, functional ability and MMSE at baseline: comparing those who rated their health as excellent and good, hazard ratios for risk of death, functional and cognitive impairment were 0.8 (95% CI 0.8–0.9), 0.6 (95% CI 0.5–0.7) and 0.7(95% CI 0.5–0.9), respectively. In-depth qualitative study designs are needed to investigate why the meaning older people give to their health status predicts long-term outcomes.     

Flexibility, functional autonomy and quality of life (QoL) in elderly yoga practitioners

The aim of this study was to assess the levels of flexibility, functional autonomy and QoL in elderly yoga practitioners. The subjects were divided into a yoga group (YG; n = 52; age = 66.79 ± 3.30 years; BMI = 24.77 ± 3.18) and control group (CG; n = 31; age = 69.33 ± 4.84 years; BMI = 24.32 ± 3.71) and submitted to flexibility tests through goniometry, the LADEG autonomy protocol and QoL, using the WHOQOL-Old questionnaire. Repeated measures ANOVA showed increases in articular range of motion in shoulder abduction (Δ%SA = 14.11%; p = 0.0001), horizontal shoulder extension (Δ%HSE = 33.90%; p = 0.0001), lumbar spine flexion (Δ%LSF = 50.74%; p = 0.0001), hip flexion (Δ%HF = 35.75%; p = 0.0001), hip extension (Δ%HE = 10.93%; p = 0.021) and knee flexion (Δ%KF = 3.90%; p = 0.001) and in the GDLAM autonomy index (Δ%AI = −13.67%; p = 0.0001) in the YG compared to the CG. The Mann-Whitney test revealed increases in QoL scores in Facet 1 (Δ%Fac1 = 9.04%; p = 0.043), Facet 5 (Δ%Fac5 = 51.06%; p = 0.0001) and in overall QoL (Δ%OqoL = 8.13%; p = 0.046) in the YG compared to the CG. The remaining variables showed no significant intergroup modifications. Thus, the study suggests that the regular practice of yoga may lead to improved range of motion in the performance of activities of daily living in elderly women.     

老年原发性高血压内皮功能与高敏C反应蛋白、内皮素1关系的研究

目的研究老年原发性高血压（EH）患者大动脉粥样斑块、内皮功能与血清内皮索1（ET-1）和高敏C反应蛋白（h-CRP）的关系。方法选择69例EH患者，其中男性36例，女性33例，平均年龄（66．8±6．2）岁。应用B超对所有病例的颈动脉、肱动脉进行筛查，检测颈动脉内膜中层厚度（IMT）及粥样斑块，在静息、反应性充血时对肱动脉内径进行检测。用免疫学方法测定血液中ET-1、h-CRP的浓度。结果ET-1、h-CRP与IMT呈正相关，IMT增厚组ET-1[（75．49±6．10）pg／L]、h-CRP[（9．96±1．69）pg／L]分别高于IMT非增厚组ET-1[（52．44±6．52）pg／L]、h-CRP[（4．53±1．52）mg／L]，P〈0．05。加压充血后，肱动脉管径平均扩增率（Flow—MD）与ET-1、h-CRP呈负相关，相关系数分别是-0．607、-0．661，P〈0．01。结论老年原发性高血压患者血液中ET-1—1、h-CRP浓度增高与动脉内皮细胞功能受损、粥样硬化关系密切。     

慢性阻塞性肺疾病患者血浆血浆内皮素-1与炎性标记物的相关性研究

目的 通过观察慢性阻塞性肺疾病（COPD）急性加重期患者治疗前后血浆内皮素-1（ET-1）等炎性因子的变化,探讨其临床意义及其相互关系.方法 用ELISA法测定30例COPD急性加重期患者治疗前后血浆ET-1、降钙素基因相关肽（CGRP）的水平,半定量免疫色谱法检测血清降钙素原（PCT）水平,免疫散射比浊法检测血浆C反应蛋白（CRP）水平,同时进行血气分析,并与我院同期30例健康体检者组成的对照组进行比较.结果 COPD急性加重期组和缓解期组ET-1、PCT、CRP水平均较对照组明显升高（P＜0.01）,血浆CGRP水平较对照组明显下降（P＜0.01）;COPD缓解期组ET-1、PCT、CRP水平较急性加重期组明显下降（P＜0.01）,CGRP水平较急性加重期组明显升高（P＜0.01）.直线相关分析显示,COPD急性加重期组ET-1、PCT、CRP三者之间呈显著正相关,且均与CGRP呈显著负相关;CGRP与PaO2呈显著正相关,ET-1、CRP、PCT均与PaO2呈显著负相关.结论 联合检测ET-1、CGRP、PCT、CRP有助于COPD患者病情监测和指导治疗.     

Association of three polymorphisms in the gene coding for endothelin-1 with essential hypertension,overweight and smoking

OBJECTIVE:

To evaluate the association of three endothelin-1 (ET-1) gene polymorphisms with essential hypertension, as well as with two cardiovascular risk factors: body mass index (BMI) and smoking.

DESIGN:

Three gene polymorphisms and the genotype and allelic distributions were compared between normotensive healthy volunteers and patients with essential hypertension. The genetic association of the three genotypes with BMI and smoking status was calculated.

PATIENTS AND METHODS:

CA/CT dinucleotide repeat polymorphism, G(8002)A polymorphism and −3A/−4A polymorphism (−138 insertion/deletion) were examined in the gene coding for ET-1 (6p21.3) in 398 subjects: 192 normotensives (healthy volunteers) and 206 patients with essential hypertension. Normotension was verified by 24 h ambulatory blood pressure monitoring.

RESULTS:

Significant inner associations were observed between all three polymorphisms, which suggests possible complex interactions inside the gene. The only significant difference in a single gene case control study was in the lengths of allelic variants of CA/CT dinucleotide repeat polymorphism. In hypertensive patients, the alleles of G(8002)A and −3A/−4A ET-1 polymorphisms were found to be significantly associated (G with −3A and A with −4A). None of the ET-1 gene polymorphisms was associated with BMI. A highly significant increase of the −3A allele of the −3A/−4A ET-1 polymorphism was found in hypertensive men who were current smokers or had smoked at least seven cigarettes a week for at least one year at any time in their life compared with hypertensive men who had never smoked (odds ratio 1.54, 95% CI 1.03 to 2.32, P=0.009).

CONCLUSIONS:

Smoking seems to be an independent cardiovascular risk factor genetically codetermined by the ET-1 gene variant.     

Functional Decline and Recovery of Activities of Daily Living in Hospitalized, Disabled Older Women: The Women's Health and Aging Study I

OBJECTIVES: To determine, in disabled, older, community-dwelling women who were hospitalized, the rates and predictors of functional decline, the probability and time course of subsequent functional recovery, and predictors of functional recovery.
DESIGN: Population-based observational cohort.
SETTING: Woman's Health and Aging Study.
PARTICIPANTS: A subset of the 1,002 moderately to severely disabled community-dwelling older women who were hospitalized over 3 years (N=457).
MEASUREMENTS: Functional decline and complete and partial recovery were defined using a 0 to 6 scale of dependencies in activities of daily living (ADLs) evaluated every 6 months over 3 years. Complete recovery was defined as returning to baseline function (function at visit immediately preceding hospitalization) after functional decline; partial recovery was defined as any improvement in the ADL scale after functional decline. Multiple logistic regression analysis was used to determine predictors of functional decline. Kaplan-Meier curves estimate the proportions recovering as a function of time since hospitalization. Discrete-time proportional hazards models regress the time-to-recovery hazards on the predictor variables.
RESULTS: Thirty-three percent of hospitalized women experienced functional decline at the first visit after hospitalization. Frailty, longer length of stay, and higher education were associated with functional decline. Fifty percent fully recovered over the subsequent 30 months, with 33% recovering within 6 months and an additional 14% over the following 6 months. Younger women were more likely to recover (aged 80 to 70, hazard ratio=0.39, 95% confidence interval=0.24–0.64).
CONCLUSION: Although most recovery of function occurs by 6 months after the first visit after a hospitalization, a substantial proportion of disabled community-dwelling women recover over the following 2 years.     

Characteristic Profiles of Activities of Daily Living and Relationship with Cognitive Performance in Thai Elderly with Different Stages from Normal Cognitive Function,Mild Cognitive Impairment to Dementia

ABSTRACT

Objective: The objectives were twofold—first, to evaluate the functional difference among normal cognitive elderly, mild cognitive impairment (MCI), and people with dementia; and second, to investigate the relationship between cognitive performance and functional abilities. Method: The Disability Assessment for Dementia (DAD) was administered to 90 participants: 20 normal controls (NC), 20 with MCI, 25 with mild dementia, 15 with moderate dementia and 10 with severe dementia patients. Results: The mean (SD) scores on instrumental activities of daily living (IADL) were 94.8 (6.4) for NC, 89.1 (9.9) for MCI, 33.6 (21.7) for mild dementia, 13 (12.2) for moderate dementia and 1.7 (4.2) for severe dementia. MCI participants presented slightly noticeable deficit in one IADL domain: ‘finance and correspondence’, whereas mild dementia presented deficit in all six IADL domains. Scores of basic activities of daily living (BADL) of the NC and MCI groups were equal at a perfect 100. The scores were slightly reduced in mild dementia patients (92.7 [12.3]) and were decreased in moderate (68.6 [26.4]) and severe dementia participants (10 [14.4]). Conclusions: Our studies demonstrated that IADL can be subtly impaired in people with MCI, but markedly impaired in those with mild dementia. BADL begin to decline in moderate dementia and then reach a level of severe impairment in severe dementia.     

Relationship between vitamin D and IL-23,IL-17 and macrophage chemoattractant protein-1 as markers of fibrosis in hepatitis C virus Egyptians

AIM:To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS:The study was conducted on 50 Egyptian hepatitis C virus (HCV) genotype number IV-infected patients and 25 ageand gender-matched healthy subjects. Venous blood samples were obtained. Samples were allowed to clot and sera were separated by centrifugation and stored at -20 ℃. A 25 hydroxy vitamin D assay was carried out using solid phase RIA. A 1,25 dihydroxy vitamin D assay was carried out using a commercial kit purchased from Incstar Corporation. IL-17 and -23 and MCP-1 were assayed by an enzyme immunoassay. Quantitative and qualitative polymerase chain reaction for HCV virus were done by TaqMan technology. Only HCV genotype IV-infected subjectswere included in the study. The mean ± SD were determined, a t-test for comparison of means of different parameters was used. Correlation analysis was done using Pearson’s correlation. Differences among different groups were determined using the Kruskal-Wallis test. RESULTS:The mean vitamin D level in HCV patients (groupⅠ) was 15 ± 5.2 ng/mL while in control (group Ⅱ) was 39.7 ± 10.8. For active vitamin D in groupⅠas 16.6 ± 4.8 ng/mL while in group Ⅱ was 41.9 ± 7.9. IL-23 was 154 ± 97.8 in group Ⅰ and 6.7 ± 2.17 in group Ⅱ. IL-17 was 70.7 ± 72.5 in cases and 1.2 ± 0.4 in control. MCP-1 was 1582 ± 794.4 in group Ⅰand 216.1 ± 5.38 in group Ⅱ. Vitamin D deficiency affected 72% of HCV-infected patients and 0% of the control group. Vitamin D insufficiency existed in 28% of HCV-in-fected patients and 12% of the control group. One hundred percent of the cirrhotic patients and 40% of non cirrhotic HCV-infected patients had vitamin D deficiency. IL-23, IL-17, and MCP-1 were markedly increased in HCV-infected patients in comparison to controls.A significant negative correlation between vitamin D and IL-17 and-23 and MCP-1 was detected. HCV-infected males and females showed no differences with respect to viral load, vitamin D levels, IL-17, IL-23 and MCP-1. The viral load was negatively correlated with vitamin D and active vitamin D (P = 0.0001 and P = 0.001, respectively), while positively correlated with IL-23, IL-17, and MCP-1. We classified the patients according to sonar findings into four groups. Group Ⅰa with bright hepatomegaly and included 14 patients. Group Ⅰb with perihepatic fibrosis and included 11 patients. Group Ⅰc with liver cirrhosis and included 11 patients. Group Ⅰd with he patocellular carcinoma (HCC) and included 14 patients. Vitamin D and active vitamin D were shown to be lower in cirrhotic patients and much lower in patients with HCC, and this difference was highly significant (P = 0.0001). IL-17 and-23 and MCP-1 were higher in advanced liver disease) and the differences were highly significant (P = 0.0001).CONCLUSION:Whether the deficiency of vitamin D is related to HCV-induced chronic liver disease or predisposing factor for higher viral load is a matter of debate.     

2型糖尿病大鼠肺组织内皮素-1、降钙素基因相关肽及P物质水平变化及其对肺动脉高压的影响

目的 探讨2型糖尿病大鼠肺组织内皮素-1(ET-1)、降钙素基因相关肽(CGRP)、P物质(SP)的变化.方法 3个月龄健康雄性Wistar大鼠10只,采用高脂饲料喂养联合30μg/g链脲佐菌素尾静脉注射制备2型糖尿病大鼠模型.另设正常对照组(n=8),给予普通饮食.造模成功后12周末股动脉放血处死大鼠,取右下肺组织行Weigert来复红弹力纤维染色,计算与呼吸性细支气管、肺泡管伴行的肺小动脉管壁厚度占血管外径百分比(WT%)以及管壁面积占血管总面积百分比(WA%).应用免疫组织化学方法观察肺组织ET-1、CGRP、SP表达水平.数据统计采用独立样本t检验.结果 与正常对照组比较,糖尿病组大鼠肺泡隔面积与视场总面积比(0.42±0.10 vs 0.29±0.06,t=5.842,P＜0.05)、肺动脉WT%(26%±8%vs 19%±9%,t=3.023,P＜0.05)和WA%(42%±8% vs 36%±9%,t=2.526,P＜0.05)均显著增加,ET-1、SP平均吸光度(ET-1:86±5 vs 83±4,t=2.402,P＜0.05;SP:101±4 vs 100±3,t=2.530,P＜0.05)和阳性面积/视场总面积比(ET-1:0.016±0.017 vs0.010±0.008,t=2.501,P＜0.05;SP:0.014±0.014 vs 0.009±0.009,t=2.127,P＜0.05)显著增加,CGRP平均吸光度和阳性面积/视场总面积比差异无统计学意义.结论 糖尿病大鼠存在肺动脉高压的病理结构改变,可能与其肺组织ET-1表达增加有关.     

阻塞性睡眠呼吸暂停低通气综合征合并高血压患者血浆内皮素1、血管性假血友病因子及血栓调节蛋白的水平研究

目的 研究阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)及OSAHS合并高血压血浆内皮素1(endothelin-1,ET-1)、血栓调节蛋白(thrombomodulin,TM)、血管性假血友病因子(yon Willebrand factor,vWF)的变化.方法 检测OSAHS、OSAHS合并高血压患者血浆ET-1、TM、vWF含量并与睡眠呼吸监测指标进行相关性分析.结果 单纯OSAHS、OSAHS合并高血压患者与对照组比较,ET-1、TM及vWF水平升高,并与两者病情严重程度有相关性;ET-1、TM、vWF水平的升高在OSAHS合并高血压患者组更明显.结论 OSAHS及OSAHS合并高血压患者均存在血管内皮损伤,内皮功能损伤在OSAHS合并高血压患者中更为明显.血管内皮损伤在OSAHS合并高血压的发病中有重要的作用.     

Effects of endothelin-1 on epicardial coronary tone,coronary blood flow,ECG-ST change and regional wall motion in anesthetized dogs

Summary The effects of intracoronaryadministrated endothelin-1 on coronary hemodynamics and regional myocardial function were studied in anesthetized open-chest dogs. Epicardial coronary diameter (CoD) and coronary blood flow (CBF) were measured by a sonomicrometer of 10 MHz piezoelectric crystals and an electromagnetic flow probe on the left circumflex coronary artery (LCX). Regional wall motion was sonomicrometrically measured at regions supplied by the LCX and left anterior descending artery (LAD) and electrocardiograms were recorded. Endothelin-1, administered as a bolus injections into the LCX via an intracoronary cannula, in a dose-dependent manner reduced COD and CBF. The extent of the reduction of COD and CBF at a dose of 300 pmol was 12.3±1.5% (P<0.01) and 86±5% (p<0.01), respectively, of the control. The extent of CBF reduction and deterioration of systolic wall motion were linearly related with the dosage of endothelin-1. ST-elevation (lead II) and fatal ECG abnormalities, including complete atrioventricular block or ventricular fibrillation, were observed with doses above 60 and 100 pmol, respectively. Coronary angiography revealed that filling defects of dye were propagated from the third or distal branches to those of more proximal arteries when the doses of endothelin-1 were cumulatively infused into the LCX. Accordingly, lethal myocardial ischemia induced by endothelin-1 is produced by critical obstruction of rather small coronary vessels.Part of the study was supported by Grants-in-Aid for Scientific Research (Nos. 02454259, 02404045) from the Ministry of Education, Science, and Culture, Japan, and a Research Grant for Cardiovascular Disease (1S-1) from the Ministry of Health and Welfare, Japan.     

Direct comparison between endothelin-1, N-terminal proatrial natriuretic factor, and brain natriuretic peptide as prognostic markers of survival in congestive heart failure

BACKGROUND: Endothelin-1 (ET-1) and cardiac natriuretic peptide plasma concentrations have prognostic significance in congestive heart failure (CHF). However, their respective prognostic values in this setting have never been directly compared. METHODS AND RESULTS: We studied the prognostic performances of ET-1, N-terminal proatrial natriuretic factor (N-proANF), and brain natriuretic peptide (BNP) to predict the long-term cardiac mortality in fully treated patients with CHF. Peripheral plasma concentrations of the 3 peptides were measured in 109 patients (left ventricular ejection fraction [LVEF] < 35%) in New York Heart Association (NYHA) functional classes II (n = 65) or III to IV (n = 44). The outcome of the patients was evaluated 3 years after the beginning of the study, and a Cox regression model was used to identify predictors of death. Plasma concentrations of the 3 peptides increased with the severity of heart failure. By univariate analysis, 6 parameters were significantly associated with death during follow-up: ET-1 level, NYHA classes III to IV, N-proANF level, BNP level, LVEF, and age (all P < .01). By multivariate analysis, only ET-1 level and, to a lesser extent, N-proANF level contributed significantly and independently to risk stratification (chi2 = 53.4 and 12.8; P < .0001 and P < .001, respectively). CONCLUSION: In a group of patients in whom the vast majority were administered angiotensin-converting enzyme inhibitor therapy, plasma ET-1 and N-proANF concentrations identify better than several clinical markers a very high-risk group, fairly amenable to heart transplantation or new therapies.     

兔肺动脉栓塞再灌注中内皮素1、一氧化氮、血管假血友病因子、热休克蛋白的变化

目的 探讨兔肺动脉栓塞缺血再灌注模型中肺损伤发生的可能机制.方法 健康新西兰白兔30只,雌雄不拘.运用5F Berman球囊堵塞左下肺动脉,然后球囊放气,复制肺动脉栓塞缺血再灌注模型.随机分为5组:假手术组、肺动脉栓塞1 h组、肺动脉栓塞2 h组、肺动脉栓寒2 h再灌注1 h组和肺动脉栓塞2 h再灌注2 h组.各组动物分别在实验结束放血处死,即刻抽取静脉血,分别采用放射免疫法测定血浆内皮素1(ET-1)的含量,硝酸还原酶显色法测定一氧化氮(NO)的含量,酶联免疫法测定血管假血友病因子(vWF)的含量.实验结束取肺组织分别用4%多聚甲醛及4%戊二醛固定,采用免疫组织化学方法测定热休克蛋白70(HSP70)的表达,并进行组织病理分析观察组织超微结构变化.结果 与假手术组相比,肺栓塞1 h、2 h血浆中ET-1、NO、vWF的含量明显增多;再灌注后进一步增高,再灌注2 h升高最为明显.血浆中NO/ET-1在肺栓塞1 h,肺栓塞2 h、再灌注1 h、再灌注2 h明显降低.兔肺动脉栓塞时肺组织细胞HSP70的表达明显增加,再灌注后1 h、2 h蛋白表达继续增加,并随着再灌注时间延长而增加(P＜0.01).肺栓塞再灌注后透射电镜显示超微结构毛细血管内皮细胞肿胀、空泡化、部分胞浆溶解,核染色质浓缩,线粒体部分或大部分嵴和膜融合消失.结论 肺动脉柃塞再灌注过程中血浆的ET-1、NO、vWF含量增加及肺组织超微结构变化提示,内皮细胞损伤及功能障碍可能参与肺缺血再灌注损伤.HSP70在肺栓塞缺血再灌注过程中表达增加,推测HSP70参与了肺缺血再灌注损伤的保护.