CARDIAC RISK STRATIFICATION IN PATIENTS WITH CONGESTIVE HEART FAILURE: A CATECHOLAMINES-β- ADRENOCEPTOR-cAMP PATHWAY

Objective To investigate the stratification risk of catecholamines-β-adrenoceptor (β-AR)-cAMP pathway for cardiogenic death events in patients with congestive heart failure (CHF).Methods A total of 83 identified CHF patients with a baseline and follow-up plasma levels of norepinephrine (NE)and epinephrine (E), lymphocytes β-AR density (Bmax), and intralymphocyte cAMP content in peripheral blood were followed up. Major cardiogenic death events were registered.Results The period between the initial entry and the last follow-up measurement were 51± 16 months, the total duration of clinical follow-up after the last measurement were 14±8 months. During follow-up, 39 patients died of cardiogenic (sudden death 17 patients, worsening heart failure 22 patients). Persistence of high NE, E, and cAMP from baseline to follow-up were confirmed as risk predicting factors of cardiovascular events. Persistence NE above 4.0 nmol/L, E above adverse prognostic predictors. The major cardiogenic death events rates per 100 patients-years were 1.33 and 4.82 in patients with NE below and above 4.0 nmol/L (HR: 2.91; 95% CI: 1.08-7.33; P = 0.015); were 1.42 and 4.36 in the patients with E levels below and above 3.5 nmol/L (HR: 2.64; 95% CI: 1.02-6.41; P = 0.019); were 1.81 and 4.67 in the 0.017), but difference was not significant between the β-AR density below and above median.Conclusions Persistent increase in circulating catecholamines and intralymphocyte cAMP content may increase the long-term mortality in CHF patients.     

Effects of thyroxine on cardiac function and lymphocyte β-adrenoceptors in patients with chronic congestive heart failure

Objective To explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte β-adrenoceptors (β-ARs) of patients with chronic congestive heart failure (CHF). Methods Twenty-eight patients with class Ⅲ or Ⅳ advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM) were randomly divided into groups A and B. L-thyroxine (L-T50) was administered to group B. Exercise tolerance, chest X-rays, and echocardiographic parameters were obtained before and after one month of treatment, Ficoll-hypaque solution was used to separate peripheral lymphocytes, and 125I-pindolol radioligand binding was used to measure β-AR levels in peripheral lymphocytes. Results L-T50 therapy improved cardiac output ［CO, （2.98±0.31）L/min vs （3.24±0.28） L/min, P<0.01］, left ventricular ejection fraction (LVEF, 26.21%±3.21% vs 37.93%±9.01%, P<0.01), and decreased isovolumetric relaxation time (IVRT, 0.12±0.04 vs 0.10±0.02, P<0.01). Serum TH levels and the maximal number of β-AR binding sites (βmax ) in peripheral lymphocytes were lower in patients with CHF than in normal healthy people, but L-T50 administration induced a β-AR up-regulation on peripheral lymphocyte surfaces. L-T50 was well tolerated without episodes of ischemia or arrhythmia. There was no significant change in heart rate or metabolic rate. Conclusion TH administration improves cardiac function and β-AR expression in peripheral lymphocytes of patients with CHF.     

Clinical significance of changes in β-adrenoreceptors in peripheral lymphocytes in patients with essential hypertension

Objective To explore the relationship of β-adrenoreceptor density and function with the condition of patients with essential hypertension.Methods In the present study, 69 male patients with essential hypertension at different stages were compared with a group of age-matched normotensive controls. β-ad renoreceptor maximum bound volume (B(max)) in peripheral lymphocytes was mea sured by (3)H-dihydroalprenolol ((3)H-DHA) radio ligand binding. β- adrenoreceptor responsiveness was determined by Salbutamol (injection). Results In patients with essential hypertension at stages Ⅰ and Ⅱ, B(max) was si gnificantly higher (P<0.01 and P<0.001, respectively) and the chronot ropic doses of Salbutamol required to increase the heart rate by 30 beats/min (CD(30)) were significantly lower (P<0.01 and P<0.001, respect ively) than in age-matched normotensive control subjects. In patients with ess ential hypertension at stage Ⅲ, B(max) was significantly lower and CD(30)was significantly higher (both P<0.01) than those in the age-matched n ormotensive control subjects. B(max) was significantly higher and CD(30) was significantly lower (both P<0.001) in patients with essential hyper tensi on and with left ventricular hypertrophy (LVH) than that in patients with essent ial hypertension but without LVH. In patients with essential hypertension and heart failure, B(max) was significantly lower and CD(30) was significant ly higher (both P<0.001) than those in patients with essential hypertension without heart failure.Conclusions The changes of β-adrenoreceptor density and function were related to hypertens ion, hypertension complicated with ventricular hypertrophy, and heart failure. They may be viewed as indexes of the condition in the patients with essential hy pertension.     

Chronic blocking of β3-adrenoceptor ameliorates cardiac function in rat model of heart failure

Background Stimulation of the heart β(3)-adrenoceptor (AR) may result in a negative inotropic effect. Being up-regulated, β(3)-AR plays a more important role in the regulation of cardiac function during heart failure. However, the effect of chronic blocking of β(3)-AR on heart failure has not been fully elucidated. In this study, we used a selective β(3)-AR antagonist SR59230A to treat a well defined heart failure rat model chronically, then evaluated its effect on cardiac function and investigated the mechanism.Methods Male Wistar rats were chosen randomly as controls (n=8). Isoproterenol induced heart failure rats were randomly divided into ISO group (n=10) and SR group (n=10). The ISO group received intraperitoneal injection of 1 ml saline twice a day; the SR group received intraperitoneal injection of SR59230A 85 nmol in 1 ml saline twice a day; and the control group received no treatment. The treatment was started 24 hours after the last isoproterenol injection and continued for 7 weeks. Then we measured the following indexes: the ratio of heart weight to body weight (HW/BW) and the ratio of left ventricular weight to body weight (LVW/BW), collagen volume fraction (CVF), left ventricular end diastolic dimension (LVEDd), left ventricular end systolic dimension (LVESd), ejection fraction (EF), fractional shortening (FS) and the ratio of E wave to A wave (E/A),the mRNA and protein expression of β(3)-AR and eNOS, and cGMP level in the heart.Results The ratios HW/BW and LVW/BW were significantly increased in the ISO group compared with the control group (P<0.01), but they were limited in the SR group (P<0.05 compared with the ISO group). CVF increased in the ISO group and the SR group (P<0.01), but it was significantly attenuated in the SR group (P<0.01). LVEDd, LVESd and E/A ratio were significantly increased in the ISO group compared with the control group (P<0.01), while EF and FS were significantly decreased (P<0.01). Compared with the ISO group, the SR group showed that LVEDd, LVESd and E/A ratio were significantly decreased (P<0.01), whereas EF and FS were significantly increased (P<0.01). β(3)-AR and eNOS mRNA and protein in the ISO group were significantly increased when compared with the control group (P<0.01). These increases were all attenuated in the SR group compared with the ISO group (P<0.01). The level of cGMP in myocardial tissue was significantly increased in the ISO group compared with the control group (P<0.01), whereas SR59230A treatment normalized this increment (P<0.01).Conclusions Chronic blocking of β(3)-AR could ameliorate cardiac function in heart failure rats and its mechanism involves inhibition of the negative inotropic effect and attenuation of cardiac remodeling.     

Clinical significance of serum cardiac troponin T in patients with congestive heart failure

Objective To determine whether the level of serum cardiac troponin T (cTnT) was increased in patients with congestive heart failure (CHF). Methods This study consisted of 265 patients with CHF and 75 healthy people. Serum cTnT was measured by electrochemiluminescence immunoassay using an Elecsys 1010 automatic analyzer. Results cTnT concentration was 0. 181±0. 536 ng/mL in CHF patients and 0. 003±0. 001 ng/mL in controls (P<0. 001). Patients were categorized according to the levels of heart function and left ventricular ejection fraction (LVEF). In the first group consisting of 105 patients with LVEF≤35%, cTnT was 0. 311±0. 221 ng/mL. In the second group of 106 patients with LVEF>35%, cTnT was 0. 07±0. 0 5ng/mL (P<0. 01). In patients with NYHA class Ⅰ, Ⅱ, Ⅲ and Ⅳ, cTnT values were 0. 062±0. 022 ng/mL, 0. 113±0. 121 mg/mL, 0. 191±0. 231 mg/ml and 0. 384±0. 211 mg/mL, respectively (class Ⅰ vs class Ⅱ P>0.05, class Ⅱ vs clas s Ⅲ P<0. 01, class Ⅲ vs class Ⅳ P<0. 01). A negative correlation was observed between serum cTnT concentration and LVEF in 265 patients with CHF ( r=-0. 493, P<0. 001). Conclusions This study shows that the level of serum cTnT is increased in patients with CHF and that the increased level indicates the severity of CHF.     

Effectiveness and safety of noninvasive positive-pressure ventilation for severe hypercapnic encephalopathy due to acute exacerbation of chronic obstructive pulmonary disease: a prospective case-control study

Background Although severe encephalopathy has been proposed as a possible contraindication to the use of noninvasive positive-pressure ventilation (NPPV), increasing clinical reports showed it was effective in patients with impaired consciousness and even coma secondary to acute respiratory failure, especially hypercapnic acute respiratory failure (HARF). To further evaluate the effectiveness and safety of NPPV for severe hypercapnic encephalopathy, a prospective case-control study was conducted at a university respiratory intensive care unit (RICU) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) during the past 3 years.Methods Forty-three of 68 consecutive AECOPD patients requiring ventilatory support for HARF were divided into 2 groups, which were carefully matched for age, sex, COPD course, tobacco use and previous hospitalization history, according to the severity of encephalopathy, 22 patients with Glasgow coma scale (GCS) <10 served as group A and 21 with GCS ≥10 as group B. Results Compared with group B, group A had a higher level of baseline arterial partial CO2 pressure ((102±27) mmHg vs (74±17) mmHg, P<0.01), lower levels of GCS (7.5±1.9 vs 12.2±1.8, P<0.01), arterial pH value (7.18±0.06 vs 7.28±0.07, P<0.01) and partial O(2) pressure/fraction of inspired O(2) ratio (168±39 vs 189±33, P<0.05). The NPPV success rate and hospital mortality were 73% (16/22) and 14% (3/22) respectively in group A,which were comparable to those in group B (68% (15/21) and 14% (3/21) respectively, all P>0.05), but group A needed an average of 7 cmH(2)O higher of maximal pressure support during NPPV, and 4, 4 and 7 days longer of NPPV time, RICU stay and hospital stay respectively than group B (P<0.05 or P<0.01). NPPV therapy failed in 12 patients (6 in each group) because of excessive airway secretions (7 patients), hemodynamic instability (2), worsening of dyspnea and deterioration of gas exchange (2), and gastric content aspiration (1).Conclusions Selected patients with severe hypercapnic encephalopathy secondary to HARF can be treated as effectively and safely with NPPV as awake patients with HARF due to AECOPD; a trial of NPPV should be instituted to reduce the need of endotracheal intubation in patients with severe hypercapnic encephalopathy who are otherwise good candidates for NPPV due to AECOPD.     

The effect of theophylline on sleep-disordered breathing in patients with stable chronic congestive heart failure

Objective To determine the prevalence of sleep-disordered breathing in patients with stable, optimally treated chronic congestive heart failure and the effect of short-term oral theophylline therapy on periodic breathing in these patients.Methods Patients with stable, optimally treated chronic congestive heart failure were monitored by polysomnography during nocturnal sleep. The effects of theophylline therapy on periodic breathing associated with stable heart failure were observed before and after treatment.Results Patients were divided into two groups. GroupⅠ(n=21) consisted of individuals with 15 episodes of apnea and hypopnea ［as determined by the apnea-hypopnea index (AHI)］ per hour or less; Group Ⅱ (n=15, 41.7%) individuals had an index of more than 15 episodes per hour. In group Ⅱ, the AHI varied from 16.8 to 78.8 (42.6±15.5) in which the obstructive AHI was 11.1±8.4 and the central AHI was 31.5±9.6. Group Ⅱ had significantly more arousals (36.8±21.3 compared with 19.4±11.2 in group Ⅰ) that were directly attributable to episodes of apnea and hypopnea, lower arterial oxyhemoglobin saturation (76.7%±4.6% compared with 86.5%±2.8%) and lower left ventricular ejection fraction (24.2%±8.8% compared with 31.5%±10.6%). Thirteen patients with compensated heart failure and periodic breathing received theophylline orally (at an average dose of 4.3 mg/kg) for five to seven days. After treatment, the mean plasma theophylline concentration was (11.3±2.5) μg/ml. Theophylline therapy resulted in significant decreases in the number of AHI (20.8±13.2 vs. 42.6±15.5; P<0.001) and the number of episodes of central apnea-hypopnea per hour (10.1±7.6 vs. 31.5±9.6; P<0.001). Furthermore, the percentage of total sleep time during which arterial oxyhemoglobin saturation (SaO2) was less than 90 percent (8.8%±8.6% vs. 23.4%±24.1%; P<0.05) and the arousals per hour (18.7±21.2 vs. 36.8±21.3; P<0.05) were also lower. There were no significant differences in the characteristics of sleep or obstructive AHI before and after theophylline treatment.Conclusions The prevalence of sleep-disordered breathing (mainly periodic respiration or cheyne-stokes respiration with central sleep apnea) is high in patients with stable chronic congestive heart failure. The sleep-disordered breathing episodes are associated with severe nocturnal arterial blood oxyhemoglobin desaturation and excessive arousals. In these patients, oral theophylline therapy may reduce the number of episodes of central apnea and hypopnea and the duration of arterial oxyhemoglobin desaturation during nocturnal sleep.     

Differential acetylcholine and choline concentrations in the cerebrospinal fluid of patients with Alzheimer’s disease and vascular dementia

Background An important aspect of Alzheimer’s disease (AD) is loss or impairment of cholinergic neurons. It is controversial whether there is a similar cholinergic impairment and cerebral deficit of acetylcholine (ACh) in the case of vascular dementia (VD). The purpose of this study was to explore the levels of ACh and choline (Ch) in the cerebrospinal fluid (CSF) of patients with AD and VD, and their possible relationship with cognitive impairment.Methods Twenty-two AD patients, twenty-two VD patients, and twenty normal controls were recruited and scored with a Mini-Mental State Examination (MMSE). CSF concentrations of ACh and Ch were measured using high-performance liquid chromatography with an electrochemical detector (HPLC-ECD) and the results were then compared to cognitive status.Results ACh concentrations in CSF of AD patients ［(10.7±5.1） nmol/L］ and VD patients ［(16.8±7.4） nmol/L］ were both significantly lower than in controls ［(34.5±9.0） nmol/L, t=10.67, P<0.001; t=6.91, P<0.001］. Both results correlated positively with MMSE scores (rs=0.88 and rs=0.85, respectively, P<0.01). The CSF concentration of Ch was significantly higher in VD patients ［(887.4±187.4） nmol/L］ compared to AD patients ［(627.6±145.1） nmol/L, t=6.4, P<0.001］ and controls ［(716.0±159.4） nmol/L, t=4.2, P=0.002］. CSF Ch concentration showed no difference between AD patients and normal controls, nor did it correlate with MMSE score in any of the three groups. Conclusions The positive correlation between ACh deficit and cognitive impairment suggests that ACh is an important neurotransmitter for memory. The similar decrease in ACh concentration in AD and VD patients may imply a similar pathogenesis for the process of cognitive impairment involved in these two disorders. The elevated CSF levels of Ch in VD patients compared to AD patients may be useful diagnostically. Cholinesterase inhibitors may be helpful not only for AD patients, but also for VD patients.     

Clinical, brain electric earth map, endothelin and transcranial ultrasonic Doppler findings after hyperbaric oxygen treatment for severe brain injury

Objective　To analyze the effect and mechanism of hyperbaric oxygen (HBO) treatment for severe brain injury (SBI). Methods　Fifty-five patients were divided into a treatment group of 35 patients and a control group of 20 patients. We observed the alterations of clinical, brain electric earth map (BEAM), endothelin (ET) and transcranial ultrasonic Doppler (TCD) findings before and after HBO treatment as well as outcome. Results　In the treatment group, Glasgow coma scale, BEAM and outcome improved after HBO treatment; compared with that of the control group, it showed a significant difference. After one course of treatment, treatment group ET was reduced from 91.24±12.18?ng/L to 68.88±14.37?ng/L (P<0.01); in control group, ET was reduced from 90.78±15.71?ng/L to 83.12±12.22?ng/L, with a statistically significant difference (P<0.05). TCD records of MCA mean velocity (Vm) was reduced from 64.2±4.8?cm/s to 51.6±4.2?cm/s (P<0.01), and a decrease in MCA systolic velocity (Vs) and pulse index (PI) values was statistically significant (P<0.01). Conclusion　HBO treatment can improve the clinical, BEAM and outcome of severely brain injured patients, by decreasing acute stage ET and improving the blood velocity of MCA and decreasing cerebral vascular resistance. HBO treatment can reduce cerebral vascular spasms, cerebral ischemia and hypoxia. One of the important mechanisms of HBO treatment for severe brain injury is the lowering of intracranial pressure.     

CARDIAC RISK STRATIFICATION IN PATIENTS WITH CONGESTIVE HEART FAILURE： A CATECHOLAMINES-β- ADRENOCEPTOR-cAMP PATHWAY

GREATEST attentiohnas been giventotheconc-eptthattheprogressionof heartfailureisdue toneurohorm onalabnorm alities.1 A sustaining ad-renergic stim ulation has been view ed as notonly a conse-quence of myocardialpathologicremodeling but also animportantdeterminantof congestiveheartfailure(CHF )progressionand inductionof malignantarrhythmi.a2,3 β-ad-renergicpathways imperativelmyediatebiologicaelffectosfcatecholamineon myocardialcell.4,5 Studiesaccumulatedevidenceof pathologicβ-adrenergicp…     

血管紧张素转换酶抑制剂对慢性心力衰竭患者脑钠肽和去甲肾上腺素的作用

目的探讨不同剂量血管紧张素转换酶抑制剂(ACEI)对慢性心力衰竭患者脑钠肽和去甲肾上腺素(NE)的作用,以及较大剂量ACEI治疗的可行性与安全性。方法将66例慢性心力衰竭患者随机分为培哚普利较小剂量组(33例,2～4mg/d)和较大剂量组(33例,8～10mg/d)治疗12周,治疗前后测定各项指标[NE、脑钠肽浓度,左室舒张末内径(LVED),左室射血分数(LVEF)等]。并且选择30名年龄相仿的健康对照者,分别测定基础NE、脑钠肽浓度。结果慢性心力衰竭患者血浆中脑钠肽浓度随着纽约心脏病协会心功能分级增加而升高,与LVEF呈显著负相关(r=-0.327,P=0.012);脑钠肽与LVED和NE呈显著正相关(r=0.42,P=0.015;r=0.402,P=0.002)。治疗12周后7例患者因出现不能耐受的咳嗽反应而退出(其中较小剂量组3例,较大剂量组4例),其余59例完成研究。较小剂量组治疗后脑钠肽浓度为8μg/L±4μg/L,NE浓度为387ng/L±211ng/L,较大剂量组治疗后脑钠肽浓度为6μg/L±4μg/L,NE浓度为250ng/L±63ng/L,较大剂量组治疗后的脑钠肽、NE浓度明显低于较小剂量组治疗后(均P<0.05)。结论心力衰竭时血浆脑钠肽浓度与心力衰竭严重程度密切相关,且与NE浓度呈正相关。在慢性心力衰竭患者中采用小剂量逐渐递增剂量方式给予培哚普利可明显降低脑钠肽、NE,且耐受性良好。     

Stimulatory activity of anti-peptide antibodies against the second extracellular loop of human M2 muscarinic receptors

Objective To study the activity of anti-peptide antibodies against the second extracellular loop of human M(2) muscarinic receptors on cAMP production and inward calcium currents (I(Ca)) in guinea pig ventricular myocytes.A comparison was also made with those of a muscarinic receptor agonist.Methods cAMP content was determined by radioimmunoassay and the I(Ca) in guinea pig single ventricular cells were recorded by the whole-cell patch clamp technique.Results Both the muscarinic receptor agonist, carbachol (Carb 10 μmol/L), and anti-peptide antibodies (Abs 100 nmol/L) could decrease basal cAMP levels (by 46.9%±4.2% and 60.2%±4.6%, respectively) and basal I(Ca).Both Carb (10 μmol/L) and Abs (100 nmol/L) could also inhibit the isoprenaline-induced (Iso 0.8 μmol/L) increases in cAMP production (from 108.2±7.0 to 88.4±7.2 pmol/mg·protein/min for Carb and 88.6±5.1 pmol/mg·protein/min for Abs, respectively) and the increases in I(Ca).The muscarinic receptor antagonist atropine (Atr) was able to prevent these effects of Carb and Abs.Conclusions Anti-peptide antibodies against an epitope located in the second extracellular loop of human M(2) muscarinic receptors, similar to muscarinic receptor agonist, could decrease the basal I(Ca) and β-receptor agonist stimulated increase of I(Ca) by decreasing the basal and β-receptor agonist stimulated increase of cAMP production, and therefore could have an effect on their target receptor.These results further suggest that autoimmunity may participate in the pathogenesis of human cardiomyopathy and the second extracellular loop of human M(2)muscarinic receptor could be the main immunodominant region.     

Effect of advanced glycosylation end products on activity of protein kinase C in human peripheral blood mononuclear cells

Objectives To investigate the effect of advanced glycosylation end products (AGEs) on the a ctivity of protein kinase C (PKC) in human peripheral blood mononuclear cells (P BMC) and to observe whether aminoguanidine (AG) can influence the effect of AGEs .Methods After PBMC were isolated from human peripheral blood and incubated with differen t concentrations of AGEs-BSA for various periods, total PKC activity in PBMC wa s determined by measuring the incorporation of (32)P from ［γ-(32) P］ ATP into a special substrate using Promega PKC assay kit.Results AGEs-BSA increased the total PKC activity in PBMC from 83.43±6.57 pmol/min/ mg protein to 116.8±13.82 pmol/min/mg protein with a peak at 15 min. AGEs -BSA also increased the total PKC activity in a concentration-dependent manner fro m 83.1±6.4 pmol/min/mg protein (control) to 119.1±13.3 pmol/min/mg prote in (control vs AGEs-BSA 400 mg/L, P&lt;0.01).Furthermore, AGEs-BSA induc ed an elevation of PKC activity in a glycosylating time-related manner, from 80 .9±8.2 (control) to 118.3±11.5 pmol/min/mg protein (glycosylation for 12 wk, P&lt;0.01).The total PKC activity stimulated by AGEs-BSA pretreated wi th AG (100, 200 mg/L) was markedly lower than that of AGEs-BSA group not pretr eated with AG (P&lt;0.05, P&lt;0.01).Conclusions AGEs-BSA increased the total PKC activity in PBMC in a concentration and incuba tion time dependent manner. The ability of AGEs-BSA to stimulate PKC activity was markedly decreased by pretreatment of AGEs-BSA with AG.     

护骨素和骨钙素与骨密度的关系

目的　探讨血清护骨素 (sOPG)、血清骨钙素 (sBGP)、尿脱氧吡啶啉 (uDPD)与女性年龄和骨密度 (BMD)之间的关系。方法　用ELISA测定 6 72名 2 0 80岁女性志愿者的sOPG、sBGP和uDPD/Cr,用双能X线吸收法 (DXA)测定腰椎正位总体和股骨颈的BMD。根据年龄段、是否绝经分组。结果　 ( 1)sOPG、sBGP和uDPD/Cr在 30 39岁年龄段最低 ( 2 8pmol/L± 1 4pmol/L、5 μg/L± 3μg/L、4 9nmol/mmol± 2 5nmol/mmol) ,与 4 0 6 9岁的各组比较差异有显著意义 (P均 <0 0 5 )。 ( 2 ) 4 0～ 5 9岁人群中 ,绝经后组的sOPG、sBGP和uDPD/Cr( 5 7pmol/L± 3 1pmol/L、11μg/L±5 μg/L、6 9nmol/mmol± 3 3nmol/mmol)高于绝经前组 ( 3 4pmol/L± 2 0pmol/L、6 μg/L± 3μg/L、5 2nmol/mmol± 3 9nmol/mmol) (P均 <0 0 0 1)。 ( 3)年龄与sOPG、sBGP、uDPD/Cr和腰椎及股骨颈的BMD相关 (r值分别为0 130、0 35 5、0 10 6、- 0 6 0 0、- 0 5 4 5 ,P均 <0 0 1) ;sOPG、sBGP与腰椎和股骨颈的BMD呈负相关 (r =- 0 183和 - 0 10 8,P <0 0 1;r=- 0 5 4 1和 - 0 4 4 1,P <0 0 0 1)。sOPG与sBGP、uDPD/Cr也存在正相关关系 (r值分别为 0 2 16、0 0 83,P均 <0 0 5 )。结论　sOPG、sBGP和uDPD/Cr能敏感地反映妇女随年     

正常甲状腺病态综合征对慢性心力衰竭患者远期预后的影响研究

背景　甲状腺激素的代谢异常参与了慢性心力衰竭（CHF）的病理过程,而目前国内对伴正常甲状腺病态综合征（ESS）的CHF患者的远期预后研究甚少。目的　探讨ESS对CHF患者远期预后的影响。方法　选取2017年1月-2019年6月于复旦大学附属中山医院吴淞医院心内科住院的CHF患者304例。将三碘甲状腺原氨酸（T3）<1.01 nmol/L和/或游离三碘甲状腺原氨酸（FT3）<3.28 nmol/L的患者纳入ESS组,T3为1.01~2.48 nmol/L及FT3为3.28~6.47 nmol/L的患者纳入甲功正常组。比较两组患者一般资料及实验室检查指标。出院后对所有患者进行随访,随访截至2020年6月,观察主要终点是全因死亡（包括因心力衰竭死亡和非心源性死亡）,次要终点是因心力衰竭再入院。依据患者存活情况将患者分为存活组与全因死亡组,再将全因死亡组分为心力衰竭死亡亚组和非心源性死亡亚组。比较存活组与全因死亡组、存活组与心力衰竭死亡亚组和非心源性死亡亚组甲状腺激素〔T3、FT3、甲状腺素（T4）、游离甲状腺素（FT4）、促甲状腺激素（TSH）〕、B型脑钠肽（BNP）、左心室射血分数（LVEF）。比较ESS组和甲功正常组患者心力衰竭再入院率、心力衰竭死亡率、全因死亡率,并绘制生存分析曲线;采用Cox回归分析探究CHF患者发生心力衰竭死亡、全因死亡的影响因素。结果　CHF患者中ESS组164例,甲功正常组140例。两组患者美国纽约心脏病协会（NYHA）分级比较,差异有统计学意义（P<0.05）;ESS组患者T3、FT3、FT4、TSH、ALB、Hb水平及LVEF低于甲功正常组,BNP、C反应蛋白（CRP）、肌酐水平高于甲功正常组（P<0.05）。中位随访时间25.7（14.2）月,发现全因死亡46例（因心力衰竭死亡32例、非心源性死亡14例）,存活258例（出现至少1次因心力衰竭再入院115例）。全因死亡组及心力衰竭死亡亚组患者T3、FT3水平及LVEF低于存活组,BNP水平高于存活组（P<0.05）。ESS组患者心力衰竭再入院率、心力衰竭死亡率、全因死亡率高于甲功正常组（P<0.05）。经Kaplan-Meier法分析结果显示：ESS组心力衰竭死亡率、全因死亡率均高于甲功正常组（P<0.016）。Cox回归分析结果显示,年龄〔HR=1.056,95%CI（1.009,1.105）〕、FT3〔HR=0.564,95%CI（0.325,0.976）〕、Hb〔HR=0.955,95%CI（0.932,0.980）〕、LVEF〔HR=0.980,95%CI（0.961,1.000）〕是CHF患者发生心力衰竭死亡的影响因素（P<0.05）;年龄〔HR=1.055,95%CI（1.019,1.093）〕、Hb〔HR=0.964,95%CI（0.944,0.984）〕、LVEF〔HR=0.979,95%CI（0.963,0.994）〕是CHF患者发生全因死亡的影响因素（P<0.05）。结论　CHF伴ESS患者肾功能、肝功能情况较差,且心力衰竭死亡率、全因死亡率高于单纯CHF患者,远期预后较差,而T3、FT3可以反映CHF患者病情严重程度及预后情况。     

Impact of potentially lethal ventricular arrhythmias on long-term outcome in patients with chronic heart failure

Background  Potentially lethal ventricular arrhythmias (PLVAs) occur frequently in survivors after acute myocardial infarction and are increasingly recognized in other forms of structural heart diseases. This study investigated the prevalence and prognostic significance of PLVAs in patients with chronic heart failure (CHF).

Methods  Data concerning demographics, etiology of heart failure, NYHA functional class, biochemical variables, electrocardiographic and echocardiographic findings, and medical treatments were collected by reviewing hospital medical records from 1080 patients with NYHA II–IV and a left ventricular (LV) ejection fraction ≤45%. PLVAs were defined as multi-focal ventricular ectopy (>30 beats/h on Holter monitoring), bursts of ventricular premature beats, and nonsustained ventricular tachycardia. All-cause mortality, sudden death, and rehospitalization due to worsening heart failure, or cardiac transplantation during 5-year follow-up after discharge were recorded.

Results  The occurrence rate of PLVAs in CHF was 30.2%, and increased with age; 23.4% in patients <45 years old, 27.8% in those between 45–65 years old, and 33.5% in patients >65 years old (P=0.033). Patients with PLVAs had larger LV size and lower ejection fraction (both P <0.01) and higher all-cause mortality (P=0.014) during 5-year follow-up than those without PLVAs. Age (OR 1.041, 95% CI 1.004–1.079, P=0.03) and LV end-diastolic dimension (OR 1.068, 95% CI 1.013–1.126, P=0.015) independently predicted the occurrence of PLVAs. And PLVA was an independent factor for all-cause mortality (RR 1.702, 95% CI 1.017–2.848, P=0.031) and sudden death (RR 1.937, 95% CI 1.068–3.516, P=0.030) in patients with CHF.

Conclusion  PLVAs are common and exert a negative impact on long-term clinical outcome in patients with CHF.