Arrhythmia/Electrophysiology
1.Mechanism Underlying Initiation of Paroxysmal Atrial Flutter/Atrial Fibrillation by Ectopic Foci
A Simulation Study
Yunfan Gong, PhD; Fagen Xie, PhD; Kenneth M. Stein, MD; Alan Garfinkel, PhD; Calin A. Culianu, MS; Bruce B. Lerman, MD; David J. Christini, PhD
Received February 9, 2006; accepted February 16, 2007.
Background— The mechanisms underlying paroxysmal atrial flutter/atrial fibrillation initiation by ectopic foci from various locations are unclear.
Methods and Results— We used parallel computational techniques to study an anatomically accurate 3-dimensional atrial structure incorporating a detailed ionic-current model of an atrial myocyte. At the single-cell level, upregulation of the L-type Ca2+ current ICa,L steepened restitution curves of action potential duration and conduction velocity compared with the control. Spontaneous firings of ectopic foci, coupled with sinus activity, produced dynamic spatial dispersions of repolarization, including discordant alternans, which caused conduction block and reentry only for the elevated ICa,L case. For each foci location, a vulnerable window for atrial flutter/atrial fibrillation induction was identified as a function of the coupling interval and focus cycle length. For ectopic foci in the pulmonary veins and left atrium, the site of conduction block and reentry gradually shifted, as a function of coupling interval, from the right atrium to the interatrial area and finally to the left atrium. The size of the vulnerable window was largest for pulmonary vein foci, becoming markedly smaller for right atrial foci, especially those near the sinoatrial node.
Conclusions— These findings suggest that a mechanism of dynamically induced repolarization dispersion, especially discordant alternans, underlies the induction of atrial flutter/atrial fibrillation by atrial ectopic foci. The sites and likelihood of reentry induction varied according to ectopic focus location and timing, with the largest vulnerable window corresponding to the pulmonary vein region.
Abstract 2 of 14 (Circulation. 2007;115:2103-2110.)
2007 American Heart Association, Inc.
Coronary Heart Disease
2.C-Terminal Provasopressin (Copeptin) as a Novel and Prognostic Marker in Acute Myocardial Infarction
Leicester Acute Myocardial Infarction Peptide (LAMP) Study
Sohail Q. Khan, MB; Onkar S. Dhillon, MB; Russell J. O’Brien, MB; Joachim Struck, PhD; Paulene A. Quinn, MPhil; Nils G. Morgenthaler, PhD; Iain B. Squire, MD; Joan E. Davies, PhD; Andreas Bergmann, PhD; Leong L. Ng, MD
Received July 28, 2006; accepted February 16, 2007.
Background— The role of the vasopressin system after acute myocardial infarction is unclear. Copeptin, the C-terminal part of the vasopressin prohormone, is secreted stoichiometrically with vasopressin. We compared the prognostic value of copeptin and an established marker, N-terminal pro-B-type natriuretic peptide (NTproBNP), after acute myocardial infarction.
Methods and Results— In this prospective single-hospital study, we recruited 980 consecutive post–acute myocardial infarction patients (718 men, median [range] age 66 [24 to 95] years), with follow-up over 342 (range 0 to 764) days. Plasma copeptin was highest on admission (n=132, P<0.001, day 1 versus days 2 to 5) and reached a plateau at days 3 to 5. In the 980 patients, copeptin (measured at days 3 to 5) was elevated in patients who died (n=101) or were readmitted with heart failure (n=49) compared with survivors (median [range] 18.5 [0.6 to 441.0] versus 6.5 [0.3 to 267.0] pmol/L, P<0.0005). With logistic regression analysis, copeptin (odds ratio, 4.14, P<0.0005) and NTproBNP (odds ratio, 2.26, P<0.003) were significant independent predictors of death or heart failure at 60 days. The area under the receiver operating characteristic curves for copeptin (0.75) and NTproBNP (0.76) were similar. The logistic model with both markers yielded a larger area under the curve (0.84) than for NTproBNP (P<0.013) or copeptin (P<0.003) alone, respectively. Cox modeling predicted death or heart failure with both biomarkers (log copeptin [hazard ratio, 2.33], log NTproBNP [hazard ratio, 2.70]). In patients stratified by NTproBNP (above the median of 900 pmol/L), copeptin above the median ( 7 pmol/L) was associated with poorer outcome (P<0.0005). Findings were similar for death and heart failure as individual end points.
Conclusions— The vasopressin system is activated after acute myocardial infarction. Copeptin may predict adverse outcome, especially in those with an elevated NTproBNP (more than 900 pmol/L).
Abstract 3 of 14 (Circulation. 2007;115:2111-2118.)
2007 American Heart Association, Inc.
Epidemiology
3.Defining Obesity Cut Points in a Multiethnic Population
Fahad Razak, BASc, MSc; Sonia S. Anand, MD, PhD, FRCP; Harry Shannon, PhD; Vladimir Vuksan, PhD; Bonnie Davis, RN; Ruby Jacobs, RN; Koon K. Teo, M***h, PhD; Matthew McQueen, FRCP; Salim Yusuf, MBBS, DPhil, FRCP, for the SHARE Investigators
Received June 19, 2006; accepted February 9, 2007.
Background— Body mass index (BMI) is widely used to assess risk for cardiovascular disease and type 2 diabetes. Cut points for the classification of obesity (BMI >30 kg/m2) have been developed and validated among people of European descent. It is unknown whether these cut points are appropriate for non-European populations. We assessed the metabolic risk associated with BMI among South Asians, Chinese, Aboriginals, and Europeans.
Methods and Results— We randomly sampled 1078 subjects from 4 ethnic groups (289 South Asians, 281 Chinese, 207 Aboriginals, and 301 Europeans) from 4 regions in Canada. Principal components factor analysis was used to derive underlying latent or "hidden" factors associated with 14 clinical and biochemical cardiometabolic markers. Ethnic-specific BMI cut points were derived for 3 cardiometabolic factors. Three primary latent factors emerged that accounted for 56% of the variation in markers of glucose metabolism, lipid metabolism, and blood pressure. For a given BMI, elevated levels of glucose- and lipid-related factors were more likely to be present in South Asians, Chinese, and Aboriginals compared with Europeans, and elevated levels of the blood pressure–related factor were more likely to be present among Chinese compared with Europeans. The cut point to define obesity, as defined by distribution of glucose and lipid factors, is lower by 6 kg/m2 among non-European groups compared with Europeans.
Conclusions— Revisions may be warranted for BMI cut points to define obesity among South Asians, Chinese, and Aboriginals. Using these revised cut points would greatly increase the estimated burden of obesity-related metabolic disorders among non-European populations.
Abstract 4 of 14 (Circulation. 2007;115:2119-2127.)
2007 American Heart Association, Inc.
Epidemiology
4.Relative Value of Inflammatory, Hemostatic, and Rheological Factors for Incident Myocardial Infarction and Stroke
The Edinburgh Artery Study
Ioanna Tzoulaki, PhD; Gordon D. Murray, PhD; Amanda J. Lee, PhD; Ann Rumley, PhD; Gordon D.O. Lowe, DSc; F. Gerald R. Fowkes, MBChB, PhD
Received January 12, 2006; accepted January 31, 2007.
Background— The aim of our present study was to compare the association of a wide range of 17 biomarkers of inflammation, hemostasis, and blood rheology with incident heart disease and stroke after accounting for an indicator of subclinical atherosclerotic disease and traditional risk factors and also to determine their incremental predictive ability.
Methods and Results— We used data from the Edinburgh Artery Study, a population cohort study started in 1987 that comprised 1592 men and women aged 55 to 74 years. Subjects were followed for a mean of 17 years, and 416 of them suffered at least 1 cardiovascular event. In analyses adjusted for cardiovascular risk factors and history of cardiovascular disease (CVD): C-reactive protein, interleukin-6, fibrinogen, fibrin D-dimer, tissue plasminogen activator (t-PA), leukocyte elastase, and lipoprotein (all P<0.01), as well as von Willebrand factor and plasma viscosity (both P<0.05), had significant hazard ratios for incident CVD. Further adjustment for a measure of subclinical atherosclerosis (ankle brachial index) had little impact on these associations. The hazard ratios (95% CI) for incident CVD between top and bottom tertiles in the latter analysis were 1.78 (1.30 to 2.45) for C-reactive protein, 1.85 (1.33 to 2.58) for interleukin-6, and 1.76 (1.35 to 2.31) for fibrinogen. Single biomarkers provided little additional discrimination of incident CVD to that obtained from cardiovascular risk factors and the ankle brachial index. An incremental score of multiple markers [interleukin-6, t-PA, intercellular adhesion molecule 1, and lipoprotein] provided some added discrimination.
Conclusions— Several "novel" risk factors predicted CVD after adjustments for conventional risk factors and also for a measure of asymptomatic disease. However, their incremental predictive ability was modest and their clinical utility remains uncertain.
Abstract 5 of 14 (Circulation. 2007;115:2128-2135.)
2007 American Heart Association, Inc.
Health Services and Outcomes Research
5.Adherence to Statin Therapy Under Drug Cost Sharing in Patients With and Without Acute Myocardial Infarction
A Population-Based Natural Experiment
Sebastian Schneeweiss, MD, ScD; Amanda R. Patrick, MS; Malcolm Maclure, ScD; Colin R. Dormuth, ScD; Robert J. Glynn, PhD, ScD
Received September 20, 2006; accepted February 1, 2007.
Background— As medication spending grows, Medicare Part D will need to adapt its coverage policies according to emerging evidence from a variety of insurance policies. We sought to evaluate the consequences of copayment and coinsurance policies on the initiation of statin therapy after acute myocardial infarction and adherence to therapy in statin initiators using a natural experiment of all British Columbia residents aged 66 years and older.
Methods and Results— Three consecutive cohorts that included all patients who began statin therapy during full drug coverage (2001), coverage with a $10 or $25 copay (2002), and coverage with a 25% coinsurance benefit (2003–2004) were followed up with linked healthcare utilization data (n=51 561). Follow-up of cohorts was 9 months after each policy change. Adherence to statin therapy was defined as 80% of days covered. Relative to full-coverage policies, adherence to new statin therapy was significantly reduced, from 55.8% to 50.5%, under a fixed copayment policy (–5.4% points; 95% CI, –6.4% to –4.4%) and the subsequent coinsurance policy (–5.4% points; 95% CI, –6.3% to –4.4%). An uninterrupted increase in the proportion of patients initiating statin therapy after an acute myocardial infarction (1.7% points per quarter) was observed over the study period, similar to a Pennsylvania control population with full coverage. Sudden changes to full out-of-pocket spending, similar to Medicare’s Part D "doughnut hole," almost doubled the risk of stopping statins (adjusted odds ratio, 1.94, 95% CI, 1.82 to 2.08).
Conclusions— Fixed patient copayment and coinsurance policies have negative effects on adherence to statin lipid-lowering drug therapy but not on their initiation after myocardial infarction.
Abstract 6 of 14 (Circulation. 2007;115:2136-2144.)
2007 American Heart Association, Inc.
Heart Failure
6.Reduced Ventricular Volumes and Improved Systolic Function With Cardiac Resynchronization Therapy
A Randomized Trial Comparing Simultaneous Biventricular Pacing, Sequential Biventricular Pacing, and Left Ventricular Pacing
Rajni K. Rao, MD; Uday N. Kumar, MD; Jill Schafer, MS; Esperanza Viloria, RN, MS; David De Lurgio, MD; Elyse Foster, MD
Received April 19, 2006; accepted February 21, 2007.
Background— Cardiac resynchronization therapy has emerged as an important therapy for advanced systolic heart failure. Among available cardiac resynchronization therapy pacing modes that restore ventricular synchrony, it is uncertain whether simultaneous biventricular (BiV), sequential BiV, or left ventricular (LV) pacing is superior. The Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure (DECREASE-HF) trial is the first randomized trial comparing these 3 cardiac resynchronization therapy modalities.
Methods and Results— The DECREASE-HF Trial is a multicenter trial in which 306 patients with New York Heart Association class III or IV heart failure, an LV ejection fraction 35%, and a QRS duration 150 ms were randomized to simultaneous BiV, sequential BiV, or LV pacing. LV volumes and systolic and diastolic function were assessed with echocardiography at baseline, 3 months, and 6 months. All groups had a significant reduction in LV end-systolic and end-diastolic dimensions (P<0.001). The simultaneous BiV pacing group had the greatest reduction in LV end-systolic dimension (P=0.007). Stroke volume (P<0.001) and LV ejection fraction (P<0.001) improved in all groups with no difference across groups.
Conclusions— Compared with LV pacing, simultaneous BiV pacing was associated with a trend toward greater improvement in LV size. There is little difference between simultaneous BiV pacing and sequential BiV pacing as programmed in this trial.
Abstract 7 of 14 (Circulation. 2007;115:2145-2152.)
2007 American Heart Association, Inc.
Hypertension
7.Diagnostic Thresholds for Ambulatory Blood Pressure Monitoring Based on 10-Year Cardiovascular Risk
Masahiro Kikuya, MD, PhD; Tine W. Hansen, MD, PhD; Lutgarde Thijs, MSc; Kristina Björklund-Bodegård, MD, PhD; Tatiana Kuznetsova, MD, PhD; Takayoshi Ohkubo, MD, PhD; Tom Richart, MD, MBE; Christian Torp-Pedersen, MD, PhD; Lars Lind, MD, PhD; Hans Ibsen, MD, PhD; Yutaka Imai, MD, PhD; Jan A. Staessen, MD, PhD, on behalf of the International Database on Ambulatory blood pressure monitoring in relation to Cardiovascular Outcomes (IDACO) Investigators
Received August 31, 2006; accepted February 16, 2007.
Background— Current diagnostic thresholds for ambulatory blood pressure (ABP) mainly rely on statistical parameters derived from reference populations. We determined an outcome-driven reference frame for ABP measurement.
Methods and Results— We performed 24-hour ABP monitoring in 5682 participants (mean age 59.0 years; 43.3% women) enrolled in prospective population studies in Copenhagen, Denmark; Noorderkempen, Belgium; Ohasama, Japan; and Uppsala, Sweden. In multivariate analyses, we determined ABP thresholds, which yielded 10-year cardiovascular risks similar to those associated with optimal (120/80 mm Hg), normal (130/85 mm Hg), and high (140/90 mm Hg) blood pressure on office measurement. Over 9.7 years (median), 814 cardiovascular end points occurred, including 377 strokes and 435 cardiac events. Systolic/diastolic thresholds for optimal ABP were 116.8/74.2 mm Hg for 24 hours, 121.6/78.9 mm Hg for daytime, and 100.9/65.3 mm Hg for nighttime. Corresponding thresholds for normal ABP were 123.9/76.8, 129.9/82.6, and 110.2/68.1 mm Hg, respectively, and those for ambulatory hypertension were 131.0/79.4, 138.2/86.4, and 119.5/70.8 mm Hg. After rounding, approximate thresholds for optimal ABP amounted to 115/75 mm Hg for 24 hours, 120/80 mm Hg for daytime, and 100/65 mm Hg for nighttime. Rounded thresholds for normal ABP were 125/75, 130/85, and 110/70 mm Hg, respectively, and those for ambulatory hypertension were 130/80, 140/85, and 120/70 mm Hg.
Conclusions— Population-based outcome-driven thresholds for optimal and normal ABP are lower than those currently proposed by hypertension guidelines.
Abstract 8 of 14 (Circulation. 2007;115:2153-2158.)
2007 American Heart Association, Inc.
Hypertension
8.Predictors of Outcome in Chronic Thromboembolic Pulmonary Hypertension
Diana Bonderman, MD; Nika Skoro-Sajer, MD; Johannes Jakowitsch, PhD; Christopher Adlbrecht, MD; Daniela Dunkler, MSc; Sharokh Taghavi, MD; Walter Klepetko, MD; Meinhard Kneussl, MD; Irene M. Lang, MD
Received August 28, 2006; accepted March 2, 2007.
Background— Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by intraluminal thrombus organization and fibrous obliteration of pulmonary arteries. Recently, associated medical conditions such as splenectomy, ventriculoatrial shunt for the treatment of hydrocephalus, permanent central intravenous lines, inflammatory bowel disease, and osteomyelitis were found to be associated with the development of CTEPH. The study aim was to define the impact of these novel risk factors on survival.
Methods and Results— Between January 1992 and December 2006, 181 patients diagnosed with CTEPH were tracked with the use of our center’s customized computer database. A Cox regression model was used to examine relations between survival and associated medical conditions, age, sex, hemodynamic parameters, modified New York Heart Association functional class at diagnosis, CTEPH type, pulmonary endarterectomy, and anti-cardiolipin antibodies/lupus anticoagulant. During a median observation time of 22.1 (range, 0.03 to 152) months, the clinical end point of cardiovascular death or lung transplantation occurred in 48 cases (27%). Pulmonary endarterectomy (hazard ratio, 0.14; 95% CI, 0.05 to 0.41; P=0.0003), associated medical conditions (hazard ratio, 3.17; 95% CI, 1.70 to 5.92; P=0.0003), and pulmonary vascular resistance (hazard ratio, 1.02; 95% CI, 1.00 to 1.04; P=0.04) were predictors of survival. Thirty-day postoperative mortality (24% versus 9%) and the incidence of postoperative pulmonary hypertension (92% versus 20%) were substantially higher in patients with associated medical conditions.
Conclusions— CTEPH-predisposing medical conditions, such as splenectomy, permanent central intravenous lines, and certain inflammatory disorders, predict poor survival in CTEPH.
Abstract 9 of 14 (Circulation. 2007;115:2159-2167.)
2007 American Heart Association, Inc.
Molecular Cardiology
9.Compartmentalization of Cardiac ß-Adrenergic Inotropy Modulation by Phosphodiesterase Type 5
Eiki Takimoto, MD, PhD; Diego Belardi, MD*; Carlo G. Tocchetti, MD, PhD*; Susan Vahebi, PhD*; Gianfrancesco Cormaci, MD; Elizabeth A. Ketner, BS; An L. Moens, MD, PhD; Hunter C. Champion, MD, PhD; David A. Kass, MD
Received June 2, 2006; accepted February 16, 2007.
Background— Recent cell-based studies have found that cGMP synthesis and hydrolysis by phosphodiesterase (PDE) appear compartmentalized, with nitric oxide synthase–derived and/or PDE type 5 (PDE-5)–hydrolyzable cGMP undetected at the sarcolemmal membrane in contrast to cGMP stimulated by natriuretic peptide. In the present study, we determine the functional significance of such compartments with a comparison of ß-adrenergic modulation by PDE-5 inhibition to that of natriuretic peptide stimulation in both cardiomyocytes and intact hearts. The potential role of differential cGMP and protein kinase G stimulation by these 2 modulators was also studied.
Methods and Results— Intact C57/BL6 mouse hearts were studied with pressure-volume analysis, and adult isolated myocytes were studied with fluorescence microscopy. PDE-5 inhibition with 0.1 to 1 µmol/L sildenafil (SIL) suppressed isoproterenol (ISO)-stimulated contractility, whereas 10 µmol/L atrial natriuretic peptide (ANP) had no effect. ISO suppression by SIL was prevented in cells pretreated with a protein kinase G inhibitor. Surprisingly, myocardial cGMP changed little with SIL+ISO yet rose nearly 5-fold with ANP, whereas protein kinase G activation (vasodilator-stimulated protein phosphorylation; ELISA assay) displayed the opposite: increased with SIL+ISO but unaltered by ANP+ISO. PDE-5 and ANP compartments were functionally separated, as inhibition of nitric oxide synthase by Nw-nitro-L-arginine methyl ester eliminated antiadrenergic effects of SIL, yet this was not restorable by co-stimulation with ANP.
Conclusions— Regulation of cardiac ß-adrenergic response by cGMP is specifically linked to a nitric oxide–synthesis/PDE-5–hydrolyzed pool signaling via protein kinase G. Natriuretic peptide stimulation achieves greater detectable increases in cGMP but not protein kinase G activity and does not modulate ß-adrenergic response. Such disparities likely contribute to differential cardiac regulation by drugs that modulate cGMP synthesis and hydrolysis.
Abstract 10 of 14 (Circulation. 2007;115:2168-2177.)
2007 American Heart Association, Inc.
Molecular Cardiology
10.Lactadherin Deficiency Leads to Apoptotic Cell Accumulation and Accelerated Atherosclerosis in Mice
Hafid Ait-Oufella, MD; Kiyoka Kinugawa, MD; Joffrey Zoll, PhD; Tabassome Simon, MD, PhD; Jacques Boddaert, MD, PhD; Silvia Heeneman, PhD; Olivier Blanc-Brude, PhD; Véronique Barateau; Stéphane Potteaux, PhD; Régine Merval; Bruno Esposito; Elisabeth Teissier, PhD; Mat J. Daemen, MD, PhD; Guy Lesèche, MD, PhD; Chantal Boulanger, PhD; Alain Tedgui, PhD; Ziad Mallat, MD, PhD
Received August 30, 2006; accepted February 16, 2007.
Background— Atherosclerosis is an immunoinflammatory disease; however, the key factors responsible for the maintenance of immune regulation in a proinflammatory milieu are poorly understood.
Methods and Results— Here, we show that milk fat globule-EGF factor 8 (Mfge8, also known as lactadherin) is expressed in normal and atherosclerotic human arteries and is involved in phagocytic clearance of apoptotic cells by peritoneal macrophages. Disruption of bone marrow–derived Mfge8 in a murine model of atherosclerosis leads to substantial accumulation of apoptotic debris both systemically and within the developing lipid lesions. The accumulation of apoptotic material is associated with a reduction in interleukin-10 in the spleen but an increase in interferon- production in both the spleen and the atherosclerotic arteries. In addition, we report a dendritic cell-dependent alteration of natural regulatory T-cell function in the absence of Mfge8. These events are associated with a marked acceleration of atherosclerosis.
Conclusions— Lack of Mfge8 in bone marrow–derived cells enhances the accumulation of apoptotic cell corpses in atherosclerosis and alters the protective immune response, which leads to an acceleration of plaque development.
Abstract 11 of 14 (Circulation. 2007;115:2178-2187.)
2007 American Heart Association, Inc.
Molecular Cardiology
11.Lack of the Antioxidant Enzyme Glutathione Peroxidase-1 Accelerates Atherosclerosis in Diabetic Apolipoprotein E–Deficient Mice
Paul Lewis, BSc, LLB (Hons); Nada Stefanovic, BSc; Josefa Pete, BSc (Hons); Anna C. Calkin, PhD; Sara Giunti, MD, PhD; Vicki Thallas-Bonke, BAppSci; Karin A. Jandeleit-Dahm, MD, PhD; Terri J. Allen, PhD; Ismail Kola, PhD; Mark E. Cooper, MBBS, FRACP, PhD; Judy B. de Haan, MSc, PhD
Received September 11, 2006; accepted February 21, 2007.
Background— Recent clinical studies have suggested a major protective role for the antioxidant enzyme glutathione peroxidase-1 (GPx1) in diabetes-associated atherosclerosis. We induced diabetes in mice deficient for both GPx1 and apolipoprotein E (ApoE) to determine whether this is merely an association or whether GPx1 has a direct effect on diabetes-associated atherosclerosis.
Methods and Results— ApoE-deficient (ApoE–/–) and ApoE/GPx1 double-knockout (ApoE–/–GPx1–/–) mice were made diabetic with streptozotocin and aortic lesion formation, and atherogenic pathways were assessed after 10 and 20 weeks of diabetes. Aortic proinflammatory and profibrotic markers were determined by both quantitative reverse-transcription polymerase chain reaction analysis after 10 weeks of diabetes and immunohistochemical analysis after 10 and 20 weeks of diabetes. Sham-injected nondiabetic counterparts served as controls. Atherosclerotic lesions within the aortic sinus region, as well as arch, thoracic, and abdominal lesions, were significantly increased in diabetic ApoE–/–GPx1–/– aortas compared with diabetic ApoE–/– aortas. This increase was accompanied by increased macrophages, -smooth muscle actin, receptors for advanced glycation end products, and various proinflammatory (vascular cell adhesion molecule-1) and profibrotic (vascular endothelial growth factor and connective tissue growth factor) markers. Quantitative reverse-transcription polymerase chain reaction analysis showed increased expression of receptors for advanced glycation end products (RAGE), vascular cell adhesion molecule-1, vascular endothelial growth factor, and connective tissue growth factor. Nitrotyrosine levels were significantly increased in diabetic ApoE–/–GPx1–/– mouse aortas. These findings were observed despite upregulation of other antioxidants.
Conclusions— Lack of functional GPx1 accelerates diabetes-associated atherosclerosis via upregulation of proinflammatory and profibrotic pathways in ApoE–/– mice. Our study provides evidence of a protective role for GPx1 and establishes GPx1 as an important antiatherogenic therapeutic target in patients with or at risk of diabetic macrovascular disease.
Abstract 12 of 14 (Circulation. 2007;115:2188-2195.)
2007 American Heart Association, Inc.
Vascular Medicine
12.Mutation of the Circadian Clock Gene Per2 Alters Vascular Endothelial Function
Hema Viswambharan, PhD*; João M. Carvas, MSc*; Vladan Antic, MD, PhD; Ana Marecic, MSc; Corinne Jud, MSc; Christian E. Zaugg, PhD; Xiu-Fen Ming, MD, PhD; Jean-Pierre Montani, MD; Urs Albrecht, PhD; Zhihong Yang, MD
Received July 20, 2006; accepted February 23, 2007.
Background— The circadian clock regulates biological processes including cardiovascular function and metabolism. In the present study, we investigated the role of the circadian clock gene Period2 (Per2) in endothelial function in a mouse model.
Methods and Results— Compared with the wild-type littermates, mice with Per2 mutation exhibited impaired endothelium-dependent relaxations to acetylcholine in aortic rings suspended in organ chambers. During transition from the inactive to active phase, this response was further increased in the wild-type mice but further decreased in the Per2 mutants. The endothelial dysfunction in the Per2 mutants was also observed with ionomycin, which was improved by the cyclooxygenase inhibitor indomethacin. No changes in the expression of endothelial acetylcholine-M3 receptor or endothelial nitric oxide synthase protein but increased cyclooxygenase-1 (not cyclooxygenase-2) protein levels were observed in the aortas of the Per2 mutants. Compared with Per2 mutants, a greater endothelium-dependent relaxation to ATP was observed in the wild-type mice, which was reduced by indomethacin. In quiescent aortic rings, ATP caused greater endothelium-dependent contractions in the Per2 mutants than in the wild-type mice, contractions that were abolished by indomethacin. The endothelial dysfunction in the Per2 mutant mice is not associated with hypertension or dyslipidemia.
Conclusions— Mutation in the Per2 gene in mice is associated with aortic endothelial dysfunction involving decreased production of NO and vasodilatory prostaglandin and increased release of cyclooxygenase-1–derived vasoconstrictor. The results suggest an important role of the Per2 gene in maintenance of normal cardiovascular functions.
Abstract 13 of 14 (Circulation. 2007;115:2208-2220.)
2007 American Heart Association, Inc.
Interventional Cardiac Electrophysiology
13.Interventional Electrophysiology and Cardiac Resynchronization Therapy
Delivering Electrical Therapies for Heart Failure
J. David Burkhardt, MD; Bruce L. Wilkoff, MD
Implantable devices have become a readily available option for patients with heart failure. Not only do these patients develop bradycardia and ventricular tachycardia, but their ventricular dysfunction can often improve with cardiac resynchronization therapy. However, this is a complex and rapidly developing clinical science for which the physician chooses techniques and selects patients on the basis of the results of clinical trials, clinical experience, and rapidly evolving tools. The results depend on the interplay of these complex variables. Placement of the left ventricular lead has forced the device physician to develop new skills and/or interdisciplinary relationships with physicians with vascular intervention, imaging, and surgical skills. Familiarity with the cardiac venous anatomy, occlusive venography, venoplasty, guide wire tools, guiding catheters, stenting, and new intracardiac visualization and magnetic intracardiac lead positioning tools are examples of just a few of the novel skills that are useful in the delivery of cardiac resynchronization therapy. Beyond implantation, these patients and devices require specialized follow-up with continued medical therapy and echo-guided adjustments of device programming. Finally, there are ongoing controversies and many as yet unanswered questions that are the subject of ongoing and planned clinical trials.
Key Words: electrical stimulation • heart failure • pacemakers • defibrillators, implantable
Abstract 14 of 14 (Circulation. 2007;115:2231-2246.)
2007 American Heart Association, Inc.
AHA Conference Proceedings
14.Understanding the Complexity of Trans Fatty Acid Reduction in the American Diet
American Heart Association Trans Fat Conference 2006: Report of the Trans Fat Conference Planning Group*
Robert H. Eckel, MD, FAHA, Immediate Past President of the AHA; Susan Borra, RD, Co-Chair; Alice H. Lichtenstein, DSc, FAHA, Co-Chair; Shirley Y. Yin-Piazza, MS, MBA
A 2-day forum was convened to discuss the current status and future implications of reducing trans fatty acids without increasing saturated fats in the food supply while maintaining functionality and consumer acceptance of packaged, processed, and prepared foods. Attendees represented the agriculture and oilseed industry and oil processing, food manufacturing, food service, government, food technology, and health and nutrition disciplines. Presentations included food science behind fatty acid technology, the health science of dietary fatty acids, alternatives to trans fatty acids, and the use of alternatives in food manufacturing and food service. The reduction of trans fatty acids in the food supply is a complex issue involving interdependent and interrelated stakeholders. Actions to reduce trans fatty acids need to carefully consider both intended and unintended consequences related to nutrition and public health. The unintended consequence of greatest concern is that fats and oils high in saturated fats, instead of the healthier unsaturated fats, might be used to replace fats and oils with trans fatty acids. Many different options of alternative oils and fats to replace trans fatty acids are available or in development. Decisions on the use of these alternatives need to consider availability, health effects, research and development investments, reformulated food quality and taste, supply-chain management, operational modifications, consumer acceptance, and cost. The conference demonstrated the value of collaboration between the food industry and health and nutrition professionals, and this conference model should be used to address other food development, processing, and/or technology issues.
Key Words: AHA Conference Proceedings • diet • fatty acids • nutrition • trans fat • trans fatty acids
认领第14篇
13篇
13.Interventional Electrophysiology and Cardiac Resynchronization Therapy
Delivering Electrical Therapies for Heart Failure
J. David Burkhardt, MD; Bruce L. Wilkoff, MD
Implantable devices have become a readily available option for patients with heart failure. Not only do these patients develop bradycardia and ventricular tachycardia, but their ventricular dysfunction can often improve with cardiac resynchronization therapy. However, this is a complex and rapidly developing clinical science for which the physician chooses techniques and selects patients on the basis of the results of clinical trials, clinical experience, and rapidly evolving tools. The results depend on the interplay of these complex variables. Placement of the left ventricular lead has forced the device physician to develop new skills and/or interdisciplinary relationships with physicians with vascular intervention, imaging, and surgical skills. Familiarity with the cardiac venous anatomy, occlusive venography, venoplasty, guide wire tools, guiding catheters, stenting, and new intracardiac visualization and magnetic intracardiac lead positioning tools are examples of just a few of the novel skills that are useful in the delivery of cardiac resynchronization therapy. Beyond implantation, these patients and devices require specialized follow-up with continued medical therapy and echo-guided adjustments of device programming. Finally, there are ongoing controversies and many as yet unanswered questions that are the subject of ongoing and planned clinical trials.
Key Words: electrical stimulation • heart failure • pacemakers • defibrillators, implantable
介入电生理及心脏同步化治疗
心衰患者的电治疗安置术
植入装置已经成为心衰患者的一种快速有效的治疗手段。心脏同步化治疗不但对这些将发展为心动过缓和室性心动过速的患者有效，同样也能改善心室功能不全患者的心功能。然而，这是一个复杂和发展迅速的临床科学，内科医生选择的技术以及挑选的患者都是建立在临床试验、临床经验以及快速发展的工具的基础之上的。这些结果依赖于这么复杂因素的相互作用。左室电极的安置要求医生学习新的技能和/或者是跨学科的，包括血管介入、影象以及手术技能。熟悉心脏静脉解剖、静脉造影、血管成形术、指引导丝工具、引导管、支架术以及新的心内显象技术和磁导航心腔内电极安置工具仅仅是心脏同步化治疗安置术中应用的新技术的一部分。除了植入术，这些患者及装置还需要持续的药物治疗以及超声介导的参数的调整等专业的随访。最后, 目前正在争论和许多尚未解答的问题正在进行和计划进行临床试验.
关键词：电刺激、心衰、起搏器、植入式除颤器
第7篇
7.Diagnostic Thresholds for Ambulatory Blood Pressure Monitoring Based on 10-Year Cardiovascular Risk
Masahiro Kikuya, MD, PhD; Tine W. Hansen, MD, PhD; Lutgarde Thijs, MSc; Kristina Björklund-Bodegård, MD, PhD; Tatiana Kuznetsova, MD, PhD; Takayoshi Ohkubo, MD, PhD; Tom Richart, MD, MBE; Christian Torp-Pedersen, MD, PhD; Lars Lind, MD, PhD; Hans Ibsen, MD, PhD; Yutaka Imai, MD, PhD; Jan A. Staessen, MD, PhD, on behalf of the International Database on Ambulatory blood pressure monitoring in relation to Cardiovascular Outcomes (IDACO) Investigators
Received August 31, 2006; accepted February 16, 2007.
Background— Current diagnostic thresholds for ambulatory blood pressure (ABP) mainly rely on statistical parameters derived from reference populations. We determined an outcome-driven reference frame for ABP measurement.
Methods and Results— We performed 24-hour ABP monitoring in 5682 participants (mean age 59.0 years; 43.3% women) enrolled in prospective population studies in Copenhagen, Denmark; Noorderkempen, Belgium; Ohasama, Japan; and Uppsala, Sweden. In multivariate analyses, we determined ABP thresholds, which yielded 10-year cardiovascular risks similar to those associated with optimal (120/80 mm Hg), normal (130/85 mm Hg), and high (140/90 mm Hg) blood pressure on office measurement. Over 9.7 years (median), 814 cardiovascular end points occurred, including 377 strokes and 435 cardiac events. Systolic/diastolic thresholds for optimal ABP were 116.8/74.2 mm Hg for 24 hours, 121.6/78.9 mm Hg for daytime, and 100.9/65.3 mm Hg for nighttime. Corresponding thresholds for normal ABP were 123.9/76.8, 129.9/82.6, and 110.2/68.1 mm Hg, respectively, and those for ambulatory hypertension were 131.0/79.4, 138.2/86.4, and 119.5/70.8 mm Hg. After rounding, approximate thresholds for optimal ABP amounted to 115/75 mm Hg for 24 hours, 120/80 mm Hg for daytime, and 100/65 mm Hg for nighttime. Rounded thresholds for normal ABP were 125/75, 130/85, and 110/70 mm Hg, respectively, and those for ambulatory hypertension were 130/80, 140/85, and 120/70 mm Hg.
Conclusions— Population-based outcome-driven thresholds for optimal and normal ABP are lower than those currently proposed by hypertension guidelines.
10年心血管病危险性基础上建立的动态血压诊断阈值
背景：当前动态血压的诊断阈值的确定主要是建立在人群资料的统计参数分析上的。我们确定一个结果为向导的参照系测量动态血压。
方法和结果：我们对在丹麦的哥本哈根、比利时的Noorderkempen、日本的Ohasama以及瑞典的乌普萨拉等中心注册的前瞻性人群研究中的5682名参与者进行24小时动态血压测量。在多因素分析中，通过与在诊所测量的最佳血压120/80 mm Hg、 正常血压130/85 mm Hg以及高血压140/90 mm Hg具有相当的10年患心血管疾病的危险性确定动态血压的阈值。在平均9.7年的观察中，包括377例中风和435例心脏事件共814心血管终点事件发生。动态血压中24小时最佳收缩压/舒张压的阈值是116.8/74.2 mm Hg，白天最佳的是121.6/78.9 mm Hg 以及晚上最佳血压是100.9/65.3 mm Hg。相应的，正常动态血压阈值分别是123.9/76.8, 129.9/82.6,和110.2/68.1 mm Hg，以及高血压阈值分别是131.0/79.4, 138.2/86.4, 和119.5/70.8 mm Hg。取整数以后，最佳动态血压24小时阈值是115/75 mm Hg，白天的是120/80 mm Hg以及晚上的是100/65 mm Hg，正常动态血压相应阈值分别是125/75, 130/85, 和110/70 mm Hg，以及高血压相应阈值分别是130/80, 140/85, and 120/70 mm Hg。
结论：人群为基础的结果为导向的最佳及正常动态血压阈值均低于当前高血压指南推荐的数值。
关键词：动态血压、血压、高血压、心血管疾病、流行病学
AHA Conference Proceedings
美国心脏病协会会议记录
14.Understanding the Complexity of Trans Fatty Acid Reduction in the American Diet
American Heart Association Trans Fat Conference 2006: Report of the Trans Fat Conference Planning Group*
题目：了解减少美式饮食中反式脂肪酸（含量）的复杂性
美国心脏病协会反式脂肪酸会议2006：反式脂肪酸讨论计划组报告
A 2-day forum was convened to discuss the current status and future implications of reducing trans fatty acids without increasing saturated fats in the food supply while maintaining functionality and consumer acceptance of packaged, processed, and prepared foods. Attendees represented the agriculture and oilseed industry and oil processig, food manufacturing, food service, government, food technology, and health and nutrition disciplines. Presentations included food science behind fatty acid technology, the health science of dietary fatty acids, alternatives to trans fatty acids, and the use of alternatives in food manufacturing and food service. The reduction of trans fatty acids in the food supply is a complex issue involving interdependent and interrelated stakeholders. Actions to reduce trans fatty acids need to carefully consider both intended and unintended consequences related to nutrition and public health. The unintended consequence of greatest concern is that fats and oils high in saturated fats, instead of the healthier unsaturated fats, might be used to replace fats and oils with trans fatty acids. Many different options of alternative oils and fats to replace trans fatty acids are available or in development. Decisions on the use of these alternatives need to consider availability, health effects, research and development investments, reformulated food quality and taste, supply-chain management, operational modifications, consumer acceptance, and cost. The conference demonstrated the value of collaboration between the food industry and health and nutrition professionals, and this conference model should be used to address other food development, processing, and/or technology issues.
两天的会议集中讨论了在减少官能上和消费者接受的包装食品，加工食品和速食食品中反式脂肪酸而不增加饱和脂肪（酸）上目前的状况和将来的趋势。出席者包括农业，油料种子工业，食油加工业，食品加工工业，食品服务业，政府，食品工艺业以及健康和营养监督方面的代表。议题包括食品科学方面的脂肪酸加工学，脂肪酸饮食中的保健学，反式脂肪酸的替代品以及如何在食品加工业和食品服务业应用替代品。减少食物中反式脂肪酸是一个复杂的问题涉及到相互独立和相互联系的利益者。减少反式脂肪酸的的行动需要仔细考虑与营养和公共健康有关的预期的和非预期后果。与最主要的非预期后果有关的是在饱和脂肪中富含脂肪和油酸，替代脂肪和油酸为健康一些的非饱和脂肪可能会应用反式脂肪酸来代替脂肪和油酸。许多可以代替反式脂肪酸的脂肪和油酸的替代品是可用的或正在研制中。决定应用这些替代品需要考虑到其可行性，健康影响，调查和研制费用，重新评估食品质量和口味，（食物）供应链的管理，操作的可变通性，消费者的认可以及成本。此次会议体现了食品工业与营养和健康专家合作的价值，并且此种会议模式应该会用于解决其他食品制造，食品加工和食品工艺方面的问题。
Key Words: AHA Conference Proceedings ? diet ? fatty acids ? nutrition ? trans fat ? trans fatty acids
关键词；美国心脏病协会会议记录，饮食，脂肪酸，营养学，反式脂肪，反式脂肪酸
6.Reduced Ventricular Volumes and Improved Systolic Function With Cardiac Resynchronization Therapy
A Randomized Trial Comparing Simultaneous Biventricular Pacing, Sequential Biventricular Pacing, and Left Ventricular Pacing
Rajni K. Rao, MD; Uday N. Kumar, MD; Jill Schafer, MS; Esperanza Viloria, RN, MS; David De Lurgio, MD; Elyse Foster, MD
Received April 19, 2006; accepted February 21, 2007.
Background— Cardiac resynchronization therapy has emerged as an important therapy for advanced systolic heart failure. Among available cardiac resynchronization therapy pacing modes that restore ventricular synchrony, it is uncertain whether simultaneous biventricular (BiV), sequential BiV, or left ventricular (LV) pacing is superior. The Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure (DECREASE-HF) trial is the first randomized trial comparing these 3 cardiac resynchronization therapy modalities.
Methods and Results— The DECREASE-HF Trial is a multicenter trial in which 306 patients with New York Heart Association class III or IV heart failure, an LV ejection fraction 35%, and a QRS duration 150 ms were randomized to simultaneous BiV, sequential BiV, or LV pacing. LV volumes and systolic and diastolic function were assessed with echocardiography at baseline, 3 months, and 6 months. All groups had a significant reduction in LV end-systolic and end-diastolic dimensions (P<0.001). The simultaneous BiV pacing group had the greatest reduction in LV end-systolic dimension (P=0.007). Stroke volume (P<0.001) and LV ejection fraction (P<0.001) improved in all groups with no difference across groups.
Conclusions— Compared with LV pacing, simultaneous BiV pacing was associated with a trend toward greater improvement in LV size. There is little difference between simultaneous BiV pacing and sequential BiV pacing as programmed in this trial.
6.心脏再同步治疗可减少心室容积并改善收缩功能—比较双室同时起搏、双室顺序起搏和左室起搏的随机临床试验
背景：心脏再同步治疗已成为晚期收缩性心力衰竭的一种重要的治疗方法。目前采用的恢复心室收缩同步性的心脏再同步治疗主要有三种模式：双室同时起搏、双室顺序起搏和左室起搏，但现在尚不清楚哪种模式更好。DECREASE-HF是第一个比较这三种心脏再同步治疗模式的随机实验。
方法与结果— DECREASE-HF是一个多中心的研究，共入选306例NYHA分级为III 或IV级的心衰患者，左室射血分数均低于35%，且QRS间期大于150 ms。随机分入双室同时起搏、双室顺序起搏或左室起搏组。 通过心脏超声分别测定基线、3个月和6个月时的左室容积及收缩舒张功能。三组均能明显降低左左室收缩末及舒张末容积 (P<0.001). 双室同时起搏组降低左室收缩末容积 (P=0.007)、增加每搏输出量 (P<0.001) 和左室射血分数 (P<0.001) 的作用最强，但三组之间无区别。
结论— 与左室起搏相比，双室同时起搏能更好地改善左室体积。在本研究未发现双室同时与双室顺序起搏有明显差异。
认领第8篇
认领第3篇
Abstract 3 of 14 (Circulation. 2007;115:2111-2118.)
2007 American Heart Association, Inc.
Epidemiology
3.Defining Obesity Cut Points in a Multiethnic Population
Fahad Razak, BASc, MSc; Sonia S. Anand, MD, PhD, FRCP; Harry Shannon, PhD; Vladimir Vuksan, PhD; Bonnie Davis, RN; Ruby Jacobs, RN; Koon K. Teo, M***h, PhD; Matthew McQueen, FRCP; Salim Yusuf, MBBS, DPhil, FRCP, for the SHARE Investigators
Received June 19, 2006; accepted February 9, 2007.
Background— Body mass index (BMI) is widely used to assess risk for cardiovascular disease and type 2 diabetes. Cut points for the classification of obesity (BMI >30 kg/m2) have been developed and validated among people of European descent. It is unknown whether these cut points are appropriate for non-European populations. We assessed the metabolic risk associated with BMI among South Asians, Chinese, Aboriginals, and Europeans.
Methods and Results— We randomly sampled 1078 subjects from 4 ethnic groups (289 South Asians, 281 Chinese, 207 Aboriginals, and 301 Europeans) from 4 regions in Canada. Principal components factor analysis was used to derive underlying latent or "hidden" factors associated with 14 clinical and biochemical cardiometabolic markers. Ethnic-specific BMI cut points were derived for 3 cardiometabolic factors. Three primary latent factors emerged that accounted for 56% of the variation in markers of glucose metabolism, lipid metabolism, and blood pressure. For a given BMI, elevated levels of glucose- and lipid-related factors were more likely to be present in South Asians, Chinese, and Aboriginals compared with Europeans, and elevated levels of the blood pressure–related factor were more likely to be present among Chinese compared with Europeans. The cut point to define obesity, as defined by distribution of glucose and lipid factors, is lower by 6 kg/m2 among non-European groups compared with Europeans.
Conclusions— Revisions may be warranted for BMI cut points to define obesity among South Asians, Chinese, and Aboriginals. Using these revised cut points would greatly increase the estimated burden of obesity-related metabolic disorders among non-European populations.
对各种族人群肥胖的界定点
背景－体质指数已被广泛用于评估心血管疾病和2型糖尿病的危险性。在欧洲人群中，肥胖分级的界定点已经建立并得到了认可。而这个界定点是否适合欧洲以外的人群仍是未知数。我们假定在南亚、中国、土著及欧洲的人群中代谢的危险因素与体质指数有关。
方法和结果－我们从加拿大4个不同地区的4个不同种族中随机选择了1078个人（289个南亚人，281个中国人，207个土著人，及301个欧洲人）。主要因素的分析被用于取得潜在的或隐藏的与14个临床及生化的心脏代谢标志物有关的因素。特定种族体质指数的界定点是得自3种心脏代谢因素。这三种主要潜在因素显示糖代谢，脂代谢和血压指标的变异占56％。对于一个特定的体质指数，糖和脂质相关因子在南亚、中国及土著人群中的升高较欧洲人群明显，而血压相关因子在中国人群中的升高较欧洲人群明显。根据糖和脂质因子的分布，非欧洲人群肥胖的界定点应比欧洲人群低6 kg/m2。
结论－对南亚、中国和土著人群用于界定肥胖分级的体质指数应予以修正。通过这些修正的界定点可以极大地提高非欧洲人群中肥胖相关性代谢障碍地评估能力。
Abstract 8 of 14 (Circulation. 2007;115:2153-2158.)
2007 American Heart Association, Inc.
Hypertension
8.Predictors of Outcome in Chronic Thromboembolic Pulmonary Hypertension
慢性血栓栓塞性肺动脉高压预后因素
Diana Bonderman, MD; Nika Skoro-Sajer, MD; Johannes Jakowitsch, PhD; Christopher Adlbrecht, MD; Daniela Dunkler, MSc; Sharokh Taghavi, MD; Walter Klepetko, MD; Meinhard Kneussl, MD; Irene M. Lang, MD
Received August 28, 2006; accepted March 2, 2007.
Background— Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by intraluminal thrombus organization and fibrous obliteration of pulmonary arteries. Recently, associated medical conditions such as splenectomy, ventriculoatrial shunt for the treatment of hydrocephalus, permanent central intravenous lines, inflammatory bowel disease, and osteomyelitis were found to be associated with the development of CTEPH. The study aim was to define the impact of these novel risk factors on survival.
背景：慢性血栓栓塞性肺动脉高压（CTEPH）是以管腔内血栓机化和肺动脉纤维性闭塞为特点的疾病。最近医学进展发现，某些医疗措施或伴随的疾病，如脾切除，脑积水房室分流治疗，永久性中央静脉嵴，炎症性肠病及骨髓炎与CTEPH的恶化有关。此研究目的是确定这些新的CTEPH的危险因素对患者生存的影响。
Methods and Results— Between January 1992 and December 2006, 181 patients diagnosed with CTEPH were tracked with the use of our center’s customized computer database. A Cox regression model was used to examine relations between survival and associated medical conditions, age, sex, hemodynamic parameters, modified New York Heart Association functional class at diagnosis, CTEPH type, pulmonary endarterectomy, and anti-cardiolipin antibodies/lupus anticoagulant. During a median observation time of 22.1 (range, 0.03 to 152) months, the clinical end point of cardiovascular death or lung transplantation occurred in 48 cases (27%). Pulmonary endarterectomy (hazard ratio, 0.14; 95% CI, 0.05 to 0.41; P=0.0003), associated medical conditions (hazard ratio, 3.17; 95% CI, 1.70 to 5.92; P=0.0003), and pulmonary vascular resistance (hazard ratio, 1.02; 95% CI, 1.00 to 1.04; P=0.04) were predictors of survival. Thirty-day postoperative mortality (24% versus 9%) and the incidence of postoperative pulmonary hypertension (92% versus 20%) were substantially higher in patients with associated medical conditions.
方法和结果：1992到2006年间我们为181位诊为CTEPH的患者建立了个人的电脑数据库并进行了随访。我们采用COX回归模型检验患者生存与采取上述的医疗措施或伴随的疾病（包括年龄、性别、血流动力学情况、NYHA分级改变、CTEPH类型、肺动脉内膜切除术及抗心磷脂抗体/狼疮抗凝血治疗）的关系。中位观察时间为22.1个月（最小0.03个月，最长152个月），以患者死亡或接受肺移植作为临床终点事件，随访中临床终点事件发生率为27%（48例）。对患者的生存预测危险比具体为：肺动脉内膜切除术（HR=0.14;95%可信区间，0.05到0.41;P=0.0003）,采取上述医疗措施或伴随疾病（HR=3.17,95%可信区间,1.70到5.92,P=0.0003）, 肺循环血管阻力(HR=1.02;95%可信区间,1.00到1.04，P=0.04)。在采取上述医疗措施或伴随疾病的患者中，术后30天死亡率（24% VS 9%）及术后肺动脉高压发生率（92% VS 20%）均明显高于无上述伴随疾病者。
Conclusions— CTEPH-predisposing medical conditions, such as splenectomy, permanent central intravenous lines, and certain inflammatory disorders, predict poor survival in CTEPH.
结论：CTEPH患者中采取医疗措施或伴随有其他疾病，如脾切除，永久性中央静脉嵴和炎症机能紊乱提示预后不良。
第二次做翻译，有些词用得不太好，望指正！
刚才技术错误，多发了一次，现在删除，对不起！
第二次做翻译，有些词用得不太好，望指正！
认领第11篇
认领第四篇
4.Relative Value of Inflammatory, Hemostatic, and Rheological Factors for Incident Myocardial Infarction and Stroke
The Edinburgh Artery Study
炎症因子、止血及流变学因子在心肌梗死和中风事件中相关价值
爱丁堡动脉研究
Ioanna Tzoulaki, PhD; Gordon D. Murray, PhD; Amanda J. Lee, PhD; Ann Rumley, PhD; Gordon D.O. Lowe, DSc; F. Gerald R. Fowkes, MBChB, PhD
Received January 12, 2006; accepted January 31, 2007.
Background— The aim of our present study was to compare the association of a wide range of 17 biomarkers of inflammation, hemostasis, and blood rheology with incident heart disease and stroke after accounting for an indicator of subclinical atherosclerotic disease and traditional risk factors and also to determine their incremental predictive ability.
背景－本研究比较经亚临床动脉粥样硬化指示因子和传统危险因素校正后一系列炎症、止血、血液流变学方面17种因子在心脏事件及中风事件的相关性并确定他们的增值预测能力。
Methods and Results— We used data from the Edinburgh Artery Study, a population cohort study started in 1987 that comprised 1592 men and women aged 55 to 74 years. Subjects were followed for a mean of 17 years, and 416 of them suffered at least 1 cardiovascular event. In analyses adjusted for cardiovascular risk factors and history of cardiovascular disease (CVD): C-reactive protein, interleukin-6, fibrinogen, fibrin D-dimer, tissue plasminogen activator (t-PA), leukocyte elastase, and lipoprotein (all P<0.01), as well as von Willebrand factor and plasma viscosity (both P<0.05), had significant hazard ratios for incident CVD. Further adjustment for a measure of subclinical atherosclerosis (ankle brachial index) had little impact on these associations. The hazard ratios (95% CI) for incident CVD between top and bottom tertiles in the latter analysis were 1.78 (1.30 to 2.45) for C-reactive protein, 1.85 (1.33 to 2.58) for interleukin-6, and 1.76 (1.35 to 2.31) for fibrinogen. Single biomarkers provided little additional discrimination of incident CVD to that obtained from cardiovascular risk factors and the ankle brachial index. An incremental score of multiple markers [interleukin-6, t-PA, intercellular adhesion molecule 1, and lipoprotein ] provided some added discrimination.
方法和结果－我们采用爱丁堡动脉研究数据。此研究开始于1987年，人群包括年龄55－74岁1592 例。对象平均随访17年，416人发生至少一例心血管事件。通过校正心血管危险因素和心血管病史之后结果发现：C反映蛋白、IL－6、纤维蛋白原、D二聚体、组织酶原激活物、白细胞弹性蛋白酶、脂蛋白a（p<0.01）及vWF 因子和血粘度（p<0.05）有显著心血管病(CVD)危险比。进一步校对亚临床动脉粥样硬化（踝臂指数）指标后相关性结果不变。C反映蛋白、IL－6、纤维蛋白原心血管事件危险比（95％可信区间）及首、末三分位数分别是：1.78 (1.30 to 2.45)、 1.85 (1.33 to 2.58) 、1.76 (1.35 to 2.31)。非校正心血管危险因子和踝臂指数的单纯生物标记物不具有鉴别CVD价值。多种标记物增量分表（IL－6、t-PA、ICAM-1、脂蛋白a）提供额外鉴别价值。
Conclusions— Several "novel" risk factors predicted CVD after adjustments for conventional risk factors and also for a measure of asymptomatic disease. However, their incremental predictive ability was modest and their clinical utility remains uncertain.
结论－一些新型经传统因子和无症状的疾病检测指标校对后的危险因子可预测CVD。但是他们增量预测能力一般且他们的临床应用依然不确定。
领第5篇
Abstract 10 of 14 (Circulation. 2007;115:2168-2177.)
2007 American Heart Association, Inc.
Molecular Cardiology
10.Lactadherin Deficiency Leads to Apoptotic Cell Accumulation and Accelerated Atherosclerosis in Mice
Hafid Ait-Oufella, MD; Kiyoka Kinugawa, MD; Joffrey Zoll, PhD; Tabassome Simon, MD, PhD; Jacques Boddaert, MD, PhD; Silvia Heeneman, PhD; Olivier Blanc-Brude, PhD; Véronique Barateau; Stéphane Potteaux, PhD; Régine Merval; Bruno Esposito; Elisabeth Teissier, PhD; Mat J. Daemen, MD, PhD; Guy Lesèche, MD, PhD; Chantal Boulanger, PhD; Alain Tedgui, PhD; Ziad Mallat, MD, PhD
Received August 30, 2006; accepted February 16, 2007.
Background— Atherosclerosis is an immunoinflammatory disease; however, the key factors responsible for the maintenance of immune regulation in a proinflammatory milieu are poorly understood.
Methods and Results— Here, we show that milk fat globule-EGF factor 8 (Mfge8, also known as lactadherin) is expressed in normal and atherosclerotic human arteries and is involved in phagocytic clearance of apoptotic cells by peritoneal macrophages. Disruption of bone marrow–derived Mfge8 in a murine model of atherosclerosis leads to substantial accumulation of apoptotic debris both systemically and within the developing lipid lesions. The accumulation of apoptotic material is associated with a reduction in interleukin-10 in the spleen but an increase in interferon- production in both the spleen and the atherosclerotic arteries. In addition, we report a dendritic cell-dependent alteration of natural regulatory T-cell function in the absence of Mfge8. These events are associated with a marked acceleration of atherosclerosis.
Conclusions— Lack of Mfge8 in bone marrow–derived cells enhances the accumulation of apoptotic cell corpses in atherosclerosis and alters the protective immune response, which leads to an acceleration of plaque development.
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Abstract 10 of 14 (Circulation. 2007;115:2168-2177.)
2007 American Heart Association, Inc.
Molecular Cardiology
10.Lactadherin Deficiency Leads to Apoptotic Cell Accumulation and Accelerated Atherosclerosis in Mice
乳凝集素缺乏导致凋亡细胞积聚,加速了小鼠动脉粥样硬化
Hafid Ait-Oufella, MD; Kiyoka Kinugawa, MD; Joffrey Zoll, PhD; Tabassome Simon, MD, PhD; Jacques Boddaert, MD, PhD; Silvia Heeneman, PhD; Olivier Blanc-Brude, PhD; Véronique Barateau; Stéphane Potteaux, PhD; Régine Merval; Bruno Esposito; Elisabeth Teissier, PhD; Mat J. Daemen, MD, PhD; Guy Lesèche, MD, PhD; Chantal Boulanger, PhD; Alain Tedgui, PhD; Ziad Mallat, MD, PhD
Received August 30, 2006; accepted February 16, 2007.
Background— Atherosclerosis is an immunoinflammatory disease; however, the key factors responsible for the maintenance of immune regulation in a proinflammatory milieu are poorly understood.
背景——动脉粥样硬化是一种免疫炎性疾病；但是‘我们对在促炎症反应环境中维持免疫调节的关键因子却知之甚少。
Methods and Results— Here, we show that milk fat globule-EGF factor 8 (Mfge8, also known as lactadherin) is expressed in normal and atherosclerotic human arteries and is involved in phagocytic clearance of apoptotic cells by peritoneal macrophages. Disruption of bone marrow–derived Mfge8 in a murine model of atherosclerosis leads to substantial accumulation of apoptotic debris both systemically and within the developing lipid lesions. The accumulation of apoptotic material is associated with a reduction in interleukin-10 in the spleen but an increase in interferon- production in both the spleen and the atherosclerotic arteries. In addition, we report a dendritic cell-dependent alteration of natural regulatory T-cell function in the absence of Mfge8. These events are associated with a marked acceleration of atherosclerosis.
方法和结果——在此，我们显示牛乳脂肪球表皮生长因子8（Mfge8,也称为乳凝集素）在正常人和动脉粥样硬化患者动脉中的表达及其与凋亡细胞被腹膜巨噬细胞吞噬清除的关系。在老鼠动脉粥样硬化模型中，骨髓源的Mfge8的分裂导致了本质的全身性和脂质损害发展中的细胞凋亡残骇的积聚。细胞凋亡的物质的堆积与脾脏白细胞介素10的减少 、脾和动脉粥样硬化的动脉中的干扰素增加有关。此外，我们报告一个树突状细胞－在Mfge8缺失时依赖自然调控T细胞功能变更。这些情况都显著加快了动脉粥样硬化。Conclusions— Lack of Mfge8 in bone marrow–derived cells enhances the accumulation of apoptotic cell corpses in atherosclerosis and alters the protective immune response, which leads to an acceleration of plaque development.
结论——骨髓源细胞中的Mfge8 的缺失促进了动脉粥样硬化中已凋亡细胞的积聚，改变了保护性的免疫反应，加快了斑块的形成。
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11.Lack of the Antioxidant Enzyme Glutathione Peroxidase-1 Accelerates Atherosclerosis in Diabetic Apolipoprotein E–Deficient Mice
抗氧化酶－谷光苷肽过氧化酶1（GPx-1）缺乏加速载脂蛋白E缺失（ApoE–／–）的糖尿病小鼠动脉粥样硬化进展
Paul Lewis, BSc, LLB (Hons); Nada Stefanovic, BSc; Josefa Pete, BSc (Hons); Anna C. Calkin, PhD; Sara Giunti, MD, PhD; Vicki Thallas-Bonke, BAppSci; Karin A. Jandeleit-Dahm, MD, PhD; Terri J. Allen, PhD; Ismail Kola, PhD; Mark E. Cooper, MBBS, FRACP, PhD; Judy B. de Haan, MSc, PhD
Received September 11, 2006; accepted February 21, 2007.
Background— Recent clinical studies have suggested a major protective role for the antioxidant enzyme glutathione peroxidase-1 (GPx1) in diabetes-associated atherosclerosis. We induced diabetes in mice deficient for both GPx1 and apolipoprotein E (ApoE) to determine whether this is merely an association or whether GPx1 has a direct effect on diabetes-associated atherosclerosis.
背景：最近的临床研究提示，抗氧化酶－谷光苷肽过氧化酶1（GPx-1）在糖尿病动脉粥样硬化中起着较大的保护作用。我们将APoE和 GPx-1缺乏小鼠造模产生糖尿病，分析GPx-1对于糖尿病相关动脉粥样硬化的发展是否具有直接效应，还是仅仅为一种相关现象。
Methods and Results— ApoE-deficient (ApoE–/–) and ApoE/GPx1 double-knockout (ApoE–/–GPx1–/–) mice were made diabetic with streptozotocin and aortic lesion formation, and atherogenic pathways were assessed after 10 and 20 weeks of diabetes. Aortic proinflammatory and profibrotic markers were determined by both quantitative reverse-transcription polymerase chain reaction analysis after 10 weeks of diabetes and immunohistochemical analysis after 10 and 20 weeks of diabetes. Sham-injected nondiabetic counterparts served as controls.
结果与方法：采用注射STZ使ApoE(-/-)及双缺失（GPx-1(-/-)ApoE(-/-)）的小鼠生成糖尿病，糖尿病10周和20周后分别评价动脉损伤形成及致动脉硬化途径。糖尿病后10周和20周采用免疫组化测定动脉促炎症和促纤维化标志物，第10周同时行定量PCR分析。假注射组作为非糖尿病阴性对照。
Atherosclerotic lesions within the aortic sinus region, as well as arch, thoracic, and abdominal lesions, were significantly increased in diabetic ApoE–/–GPx1–/– aortas compared with diabetic ApoE–/– aortas.
结果发现，与ApoE(-/-)的糖尿病小鼠的动脉相比，双缺失（GPx-1(-/-)ApoE(-/-)）的小鼠在主动脉窦、主动脉弓、胸主动脉、腹主动脉等区域的动脉粥样硬化损伤都显著增加。
This increase was accompanied by increased macrophages, -smooth muscle actin, receptors for advanced glycation end products, and various proinflammatory (vascular cell adhesion molecule-1) and profibrotic (vascular endothelial growth factor and connective tissue growth factor) markers.
此增加伴随着巨噬细胞、平滑肌肌动蛋白、晚期糖基化终末端产物受体（RAGE）、各种促炎症因子（血管细胞粘附分子VCAM）标志物及各种促纤维化因子（血管内皮生长因子VEGF及结缔组织生长因子CTGF）标志物的增加。
Quantitative reverse-transcription polymerase chain reaction analysis showed increased expression of receptors for advanced glycation end products (RAGE), vascular cell adhesion molecule-1, vascular endothelial growth factor, and connective tissue growth factor. Nitrotyrosine levels were significantly increased in diabetic ApoE–/–GPx1–/– mouse aortas. These findings were observed despite upregulation of other antioxidants.
定量PCR分析显示，RAGE、VCAM－1、VEGF、CTGF的表达均增高，硝基酪氨酸水平在双缺失的小鼠动脉中亦显著上升。尽管有其他抗氧化因子的上调，但是我们仍观察到上述变化。
Conclusions— Lack of functional GPx1 accelerates diabetes-associated atherosclerosis via upregulation of proinflammatory and profibrotic pathways in ApoE–/– mice. Our study provides evidence of a protective role for GPx1 and establishes GPx1 as an important antiatherogenic therapeutic target in patients with or at risk of diabetic macrovascular disease.
结论：在载脂蛋白E缺乏的小鼠身上缺乏GPx-1，会通过上调促炎症和促纤维化途径来加速糖尿病动脉粥样硬化的进程。我们的研究为GPx-1的保护作用以及确立GPx-1作为糖尿病大血管疾病的患者或高危人群一个重要的抗动脉粥样硬化治疗靶点提供了依据。
抗氧化酶－谷光苷肽过氧化酶1（GPx-1）缺乏加速载脂蛋白E缺失（ApoE–／–）的糖尿病小鼠动脉粥样硬化进展
背景：最近的临床研究提示，抗氧化酶－谷光苷肽过氧化酶1（GPx-1）在糖尿病动脉粥样硬化中起着较大的保护作用。我们将APoE和 GPx-1缺乏小鼠造模产生糖尿病，分析GPx-1对于糖尿病相关动脉粥样硬化的发展是否具有直接效应，还是仅仅为一种相关现象。
结果与方法：采用注射STZ使ApoE(-/-)及双缺失（GPx-1(-/-)ApoE(-/-)）的小鼠生成糖尿病，糖尿病10周和20周后分别评价动脉损伤形成及致动脉硬化途径。糖尿病后10周和20周采用免疫组化测定动脉促炎症和促纤维化标志物，第10周同时行定量PCR分析。假注射组作为非糖尿病阴性对照。定量PCR分析显示，RAGE、VCAM－1、VEGF、CTGF的表达均增高，硝基酪氨酸水平在双缺失的小鼠动脉中亦显著上升。尽管有其他抗氧化因子的上调，但是我们仍观察到上述变化。
结论：在载脂蛋白E缺乏的小鼠身上缺乏GPx-1，会通过上调促炎症和促纤维化途径来加速糖尿病动脉粥样硬化的进程。我们的研究为GPx-1的保护作用以及确立GPx-1作为糖尿病大血管疾病的患者或高危人群一个重要的抗动脉粥样硬化治疗靶点提供了依据。
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Abstract 1 of 14 (Circulation. 2007;115:2094-2102.)
Arrhythmia/Electrophysiology
1.Mechanism Underlying Initiation of Paroxysmal Atrial Flutter/Atrial Fibrillation by Ectopic Foci
异位兴奋灶产生阵发性房颤/房扑的潜在机制
A Simulation Study
Yunfan Gong, PhD; Fagen Xie, PhD; Kenneth M. Stein, MD; Alan Garfinkel, PhD; Calin A. Culianu, MS; Bruce B. Lerman, MD; David J. Christini, PhD
Received February 9, 2006; accepted February 16, 2007.
Background— The mechanisms underlying paroxysmal atrial flutter/atrial fibrillation initiation by ectopic foci from various locations are unclear.
背景：不同位置的异位兴奋灶产生阵发性房颤/房扑的潜在机制仍不清楚。
Methods and Results— We used parallel computational techniques to study an anatomically accurate 3-dimensional atrial structure incorporating a detailed ionic-current model of an atrial myocyte.
我们采用平行计算技术来研究精确的、三维的心房解剖结构，同时整合了具体的心房细胞的离子电流模型。
At the single-cell level, upregulation of the L-type Ca2+ current ICa,L steepened restitution curves of action potential duration and conduction velocity compared with the control.
和对照组相比，在单个细胞水平，上调L-型钙通道的离子流可以导致动作电位持续时间和传导速率的重建曲线变的陡峭。
Spontaneous firings of ectopic foci, coupled with sinus activity, produced dynamic spatial dispersions of repolarization, including discordant alternans, which caused conduction block and reentry only for the elevated ICa,L case.
和窦房结电活动配对产生的异位病灶的自发冲动，可以导致复极时空间上的动态分散，包括不协调的电交替、这些现象仅仅在L-型钙通道活性增高组可以进一步导致传导阻滞和折返。
For each foci location, a vulnerable window for atrial flutter/atrial fibrillation induction was identified as a function of the coupling interval and focus cycle length.
对于每一个异位灶来说，产生房颤/房扑的易损窗口取决于它们的配对间期和异位循环的长度。
For ectopic foci in the pulmonary veins and left atrium, the site of conduction block and reentry gradually shifted, as a function of coupling interval, from the right atrium to the interatrial area and finally to the left atrium.
对于位于肺静脉和左房的异位灶，由于配对间期的不同，其发生传导阻滞和折返的位置逐渐推移，从右房到房间隔区域，最后到达左房。
The size of the vulnerable window was largest for pulmonary vein foci, becoming markedly smaller for right atrial foci, especially those near the sinoatrial node.
肺静脉异位灶的易损窗口最宽，右房异位灶的易损窗口明显变窄，在窦房结附近的异位灶，易损窗口尤其窄。
Conclusions— These findings suggest that a mechanism of dynamically induced repolarization dispersion, especially discordant alternans, underlies the induction of atrial flutter/atrial fibrillation by atrial ectopic foci. The sites and likelihood of reentry induction varied according to ectopic focus location and timing, with the largest vulnerable window corresponding to the pulmonary vein region.
结论：本研究发现产生复极离散度的动力学机制，尤其不协调的电交替是心房异位灶产生房颤/房扑的潜在因素。折返产生的位置及可能性根据异位灶的位置和异位冲动的时间而有所变化，肺静脉区域为易损窗口最宽的区域。
异位兴奋灶产生阵发性房颤/房扑的潜在机制
背景：不同位置的异位兴奋灶产生阵发性房颤/房扑的潜在机制仍不清楚。
方法和结果：我们采用平行计算技术来研究精确的、三维的心房解剖结构，同时整合了具体的心房细胞的离子电流模型。和对照组相比，在单个细胞水平，上调L-型钙通道的离子流可以导致动作电位持续时间和传导速率的重建曲线变的陡峭。和窦房结电活动配对产生的异位病灶的自发冲动，可以导致复极时空间上的动态分散，包括不协调的电交替、这些现象仅仅在L-型钙通道活性增高组可以进一步导致传导阻滞和折返。对于每一个异位灶来说，产生房颤/房扑的易损窗口取决于它们的配对间期和异位循环的长度。传导阻滞和折返的位置逐渐推移，从右房到房间隔区域，最后到达左房。肺静脉异位灶的易损窗口最宽，右房异位灶的易损窗口明显变窄，在窦房结附近的异位灶，易损窗口尤其窄。
结论：本研究发现产生复极离散度的动力学机制，尤其不协调的电交替是心房异位灶产生房颤/房扑的潜在因素。折返产生的位置及可能性根据异位灶的位置和异位冲动的时间而有所变化，肺静脉区域为易损窗口最宽的区域。
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C-Terminal Provasopressin (Copeptin) as a Novel and Prognostic Marker in Acute Myocardial Infarction
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第2篇Coronary Heart Disease 冠心病
C-Terminal Provasopressin (Copeptin) as a Novel and Prognostic Marker in Acute Myocardial Infarction
羧基端血管加压素原（Copeptin）是AMI的一个新的预后指标。
Leicester Acute Myocardial Infarction Peptide (LAMP) Study
莱彻斯特AMI肽(LAMP)研究（莱彻斯特皇家医院）
Background— The role of the vasopressin system after acute myocardial infarction is unclear. Copeptin, the C-terminal part of the vasopressin prohormone, is secreted stoichiometrically with vasopressin. We compared the prognostic value of copeptin and an established marker, N-terminal pro-B-type natriuretic peptide (NTproBNP), after acute myocardial infarction.
Methods and Results— In this prospective single-hospital study, we recruited 980 consecutive post–acute myocardial infarction patients (718 men, median [range] age 66 [24 to 95] years), with follow-up over 342 (range 0 to 764) days. Plasma copeptin was highest on admission (n=132, P<0.001, day 1 versus days 2 to 5) and reached a plateau at days 3 to 5. In the 980 patients, copeptin (measured at days 3 to 5) was elevated in patients who died (n=101) or were readmitted with heart failure (n=49) compared with survivors (median [range] 18.5 [0.6 to 441.0] versus 6.5 [0.3 to 267.0] pmol/L, P<0.0005). With logistic regression analysis, copeptin (odds ratio, 4.14, P<0.0005) and NTproBNP (odds ratio, 2.26, P<0.003) were significant independent predictors of death or heart failure at 60 days. The area under the receiver operating characteristic curves for copeptin (0.75) and NTproBNP (0.76) were similar. The logistic model with both markers yielded a larger area under the curve (0.84) than for NTproBNP (P<0.013) or copeptin (P<0.003) alone, respectively. Cox modeling predicted death or heart failure with both biomarkers (log copeptin [hazard ratio, 2.33], log NTproBNP [hazard ratio, 2.70]). In patients stratified by NTproBNP (above the median of 900 pmol/L), copeptin above the median ( 7 pmol/L) was associated with poorer outcome (P<0.0005). Findings were similar for death and heart failure as individual end points.
Conclusions— The vasopressin system is activated after acute myocardial infarction. Copeptin may predict adverse outcome, especially in those with an elevated NTproBNP (more than 900 pmol/L).
背景：AMI后血管加压素系统的作用还不清楚。Copeptin，血管加压素原羧基端部分，与血管加压素一起按化学配比分泌。我们比较AMI后，Copeptin与已有确定价值指标N末端B型钠尿肽原(NTproBNP)的预后价值。
方法与结果：在这个前瞩性的、单医院的研究中，我们连续纳入980名AMI后患者(男718 人, 年龄中位数 [范围] 66[24 to 95] 岁)，随访342 (范围 0 to 764)天。血浆copeptin入院时最高(n=132, P<0.001, 第1天 vs 第 2 - 5天)，在第3 – 5天达到一个平台。在980名患者中，死亡的患者(n=101)或因心衰再入院的患者(n=49)与幸存者相比，copeptin（在第3-5天检测）升高(中位数 [范围] 18.5 [0.6 to 441.0] vs 6.5 [0.3 to 267.0] pmol/L, P<0.0005)。logistic回归分析，在60天时copeptin (优势比, 4.14, P<0.0005) 与 NTproBNP (优势比, 2.26, P<0.003)明显独立于死亡或心衰的预测因子。Copeptin (0.75)与NTproBNP (0.76)工作特性(曲线)下面积相似。与NTproBNP (P<0.013) 或copeptin (P<0.003)单独分析相比，综合两个指标的Logistic模型有一个更大的曲线下面积(0.84)。Cox模型用此二指标预测死亡或心衰(log copeptin [危害比, 2.33], log NTproBNP [危害比, 2.70])。患者按NTproBNP分层（>中位数 900 pmol/L）的，copeptin 在中位数( 7 pmol/L)以上的预后差(P<0.0005)。死亡与心衰作为单独的终点，研究发现结果是相似的。
结论：AMI后血管加压素系统被激活。Copeptin的水平可以预示不良后果，特别是在那些NTproBNP (more than 900 pmol/L)水平升高的患者。
Abstract 12 of 14 (Circulation. 2007;115:2188-2195.)
2007 American Heart Association, Inc.
Vascular Medicine
12.Mutation of the Circadian Clock Gene Per2 Alters Vascular Endothelial Function
昼夜节律钟基因－Per2的突变可改变血管内皮功能
Hema Viswambharan, PhD*; João M. Carvas, MSc*; Vladan Antic, MD, PhD; Ana Marecic, MSc; Corinne Jud, MSc; Christian E. Zaugg, PhD; Xiu-Fen Ming, MD, PhD; Jean-Pierre Montani, MD; Urs Albrecht, PhD; Zhihong Yang, MD
Received July 20, 2006; accepted February 23, 2007.
Background— The circadian clock regulates biological processes including cardiovascular function and metabolism. In the present study, we investigated the role of the circadian clock gene Period2 (Per2) in endothelial function in a mouse model.
背景：昼夜节律钟调节包括心血管功能与代谢的生物学行为。在本研究中，我们研究小鼠昼夜节律钟基因－Per2在调节血管内皮功能的作用。
Methods and Results— Compared with the wild-type littermates, mice with Per2 mutation exhibited impaired endothelium-dependent relaxations to acetylcholine in aortic rings suspended in organ chambers. During transition from the inactive to active phase, this response was further increased in the wild-type mice but further decreased in the Per2 mutants. The endothelial dysfunction in the Per2 mutants was also observed with ionomycin, which was improved by the cyclooxygenase inhibitor indomethacin. No changes in the expression of endothelial acetylcholine-M3 receptor or endothelial nitric oxide synthase protein but increased cyclooxygenase-1 (not cyclooxygenase-2) protein levels were observed in the aortas of the Per2 mutants. Compared with Per2 mutants, a greater endothelium-dependent relaxation to ATP was observed in the wild-type mice, which was reduced by indomethacin. In quiescent aortic rings, ATP caused greater endothelium-dependent contractions in the Per2 mutants than in the wild-type mice, contractions that were abolished by indomethacin. The endothelial dysfunction in the Per2 mutant mice is not associated with hypertension or dyslipidemia.
方法和结果：与同窝出生Per2野生型小鼠比较，Per2突变小鼠的主动脉环显示受损的针对乙酰胆碱内皮依赖性舒张。在非活动期至活动期的过渡期，Per2野生型小鼠舒张作用更明显， Per2突变小鼠与此相反。Per2突变小鼠针对伊屋诺霉素也可观察到内皮功能失调，加入环氧合酶抑制剂吲哚美辛可改善此种情况。与野生型小鼠比较，在Per2突变小鼠的主动脉血管内皮乙酰胆碱M3受体和一氧化氮合酶表达无变化，环氧合酶－1蛋白表达升高。Per2野生型小鼠显示ATP作用下较大的内皮依赖性舒张，吲哚美辛可减小舒张作用。在主动脉环活动静止期，Per2突变型小鼠显示ATP作用下较大的内皮依赖性收缩，吲哚美辛可废除收缩作用。内皮舒缩功能失调与高血压和血脂障碍不相关。
Conclusions— Mutation in the Per2 gene in mice is associated with aortic endothelial dysfunction involving decreased production of NO and vasodilatory prostaglandin and increased release of cyclooxygenase-1–derived vasoconstrictor . The results suggest an important role of the Per2 gene in maintenance of normal cardiovascular functions.
结论：小鼠Per2基因突变与主动脉舒缩功能失调相关，减少一氧化氮和致血管舒张的前列腺素的生成，增加环氧合酶－1 衍生的血管收缩素的释放。以上结果说明Per2在维持心血管正常功能有重要作用。
昼夜节律钟基因－Per2的突变可改变血管内皮功能
背景：昼夜节律钟调节包括心血管功能与代谢的生物学行为。在本研究中，我们研究小鼠昼夜节律钟基因－Per2在调节血管内皮功能的作用。
方法和结果：与同窝出生Per2野生型小鼠比较，Per2突变小鼠的主动脉环显示受损的针对乙酰胆碱内皮依赖性舒张。在非活动期至活动期的过渡期，Per2野生型小鼠舒张作用更明显， Per2突变小鼠与此相反。Per2突变小鼠针对伊屋诺霉素也可观察到内皮功能失调，加入环氧合酶抑制剂吲哚美辛可改善此种情况。与野生型小鼠比较，在Per2突变小鼠的主动脉血管内皮乙酰胆碱M3受体和一氧化氮合酶表达无变化，环氧合酶－1蛋白表达升高。Per2野生型小鼠显示ATP作用下较大的内皮依赖性舒张，吲哚美辛可减小舒张作用。在主动脉环活动静止期，Per2突变型小鼠显示ATP作用下较大的内皮依赖性收缩，吲哚美辛可废除收缩作用。内皮舒缩功能失调与高血压和血脂障碍不相关。
结论：小鼠Per2基因突变与主动脉舒缩功能失调相关，减少一氧化氮和致血管舒张的前列腺素的生成，增加环氧合酶－1 衍生的血管收缩素的释放。以上结果说明Per2在维持心血管正常功能有重要作用。
认领第2篇
认领第九篇
Abstract 2 of 14 (Circulation. 2007;115:2103-2110.)
2007 American Heart Association, Inc.
Coronary Heart Disease
2.C-Terminal Provasopressin (Copeptin) as a Novel and Prognostic Marker in Acute Myocardial Infarction
急性心肌梗塞新的预后标志物－抗利尿激素C末端激素原Copeptin
Leicester Acute Myocardial Infarction Peptide (LAMP) Study
Sohail Q. Khan, MB; Onkar S. Dhillon, MB; Russell J. O’Brien, MB; Joachim Struck, PhD; Paulene A. Quinn, MPhil; Nils G. Morgenthaler, PhD; Iain B. Squire, MD; Joan E. Davies, PhD; Andreas Bergmann, PhD; Leong L. Ng, MD
Received July 28, 2006; accepted February 16, 2007.
Background— The role of the vasopressin system after acute myocardial infarction is unclear. Copeptin, the C-terminal part of the vasopressin prohormone, is secreted stoichiometrically with vasopressin. We compared the prognostic value of copeptin and an established marker, N-terminal pro-B-type natriuretic peptide (NTproBNP), after acute myocardial infarction.
背景：急性心肌梗塞后抗利尿激素系统的作用还不清楚。Copeptin作为抗利尿激素原的C末端部分，是抗利尿激素系统定量分泌的。抗利尿激素原的N末端NTproBNP为已确定的标志物，我们比较这两个标志物在急性心肌梗塞的预后价值。
Methods and Results— In this prospective single-hospital study, we recruited 980 consecutive post–acute myocardial infarction patients (718 men, median [range] age 66 [24 to 95] years), with follow-up over 342 (range 0 to 764) days. Plasma copeptin was highest on admission (n=132, P<0.001, day 1 versus days 2 to 5) and reached a plateau at days 3 to 5. In the 980 patients, copeptin (measured at days 3 to 5) was elevated in patients who died (n=101) or were readmitted with heart failure (n=49) compared with survivors (median [range] 18.5 [0.6 to 441.0] versus 6.5 [0.3 to 267.0] pmol/L, P<0.0005). With logistic regression analysis, copeptin (odds ratio, 4.14, P<0.0005) and NTproBNP (odds ratio, 2.26, P<0.003) were significant independent predictors of death or heart failure at 60 days. The area under the receiver operating characteristic curves for copeptin (0.75) and NTproBNP (0.76) were similar. The logistic model with both markers yielded a larger area under the curve (0.84) than for NTproBNP (P<0.013) or copeptin (P<0.003) alone, respectively. Cox modeling predicted death or heart failure with both biomarkers (log copeptin [hazard ratio, 2.33], log NTproBNP [hazard ratio, 2.70]). In patients stratified by NTproBNP (above the median of 900 pmol/L), copeptin above the median ( 7 pmol/L) was associated with poorer outcome (P<0.0005). Findings were similar for death and heart failure as individual end points.
方法和结果：前瞻性对单个医院入院患者进行研究 ，患急性心肌梗塞连续入院980例患者纳入，（718名男性，平均年龄66岁（年龄范围24-95岁）。平均随访342天（随访时间范围0-764天）132例患者入院时血浆copeptin最高(P<0.001,入院第1天 VS入院第2－5天)，入院后3-5天达到一个平高线。在980例患者中，101例患者住院数日后死亡，49例患者因心衰再次入院，与存活者比较，第一次入院后第3-5天检测血浆copeptin值明显增高[中位值18.5（范围0.6-441.0）VS中位值6.5（范围0.3-267.0）, P<0.0005]。logistic回归分析显示copeptin(OR=4.14, P<0.0005)和NTproBNP (OR= 2.26, P<0.003)是60天内死亡和心衰的重要独立的预后因子。接收机操作曲线下面积两者类似，（copeptin 0.75， NTproBNP 0.76）。两个标志物联合检测其回归模型曲线下面积为0.84，与两者单独比较差异显著（NTproBNP P<0.013 ； copeptin P<0.003)
两标志物预测死亡和心衰风险的COX模型[log copeptin (风险比＝2.33), log NTproBNP（风险比＝2.70] 分层分析显示血浆NTproBNP浓度在中位值900 pmol/L copeptin在中位值7 pmol/L以上预后较差(P<0.0005)。死亡和心衰作为个体随访终点，两者结果相似。
Conclusions— The vasopressin system is activated after acute myocardial infarction. Copeptin may predict adverse outcome, especially in those with an elevated NTproBNP (more than 900 pmol/L).
结论：急性心肌梗塞可激活抗利尿激素系统。血浆Copeptin浓度高，预后较差，尤其在血浆NTproBNP浓度高（＞900 pmol/L）的患者表现更为明显。
急性心肌梗塞新的预后标志物－抗利尿激素C末端激素原Copeptin
背景:急性心肌梗塞后抗利尿激素系统的作用还不清楚。Copeptin作为抗利尿激素原的C末端部分，是抗利尿激素系统定量分泌的。抗利尿激素原的N末端NTproBNP为已确定的标志物，我们比较这两个标志物在急性心肌梗塞的预后价值。
方法和结果：前瞻性对单个医院入院患者进行研究 ，患急性心肌梗塞连续入院980例患者纳入，（718名男性，平均年龄66岁（年龄范围24-95岁）。平均随访342天（随访时间范围0-764天）132例患者入院时血浆copeptin最高(P<0.001,入院第1天 VS入院第2－5天)，入院后3-5天达到一个平高线。在980例患者中，101例患者住院数日后死亡，49例患者因心衰再次入院，与存活者比较，第一次入院后第3-5天检测血浆copeptin值明显增高[中位值18.5（范围0.6-441.0）VS中位值6.5（范围0.3-267.0）, P<0.0005]。logistic回归分析显示copeptin(OR=4.14, P<0.0005)和NTproBNP (OR= 2.26, P<0.003)是60天内死亡和心衰的重要独立的预后因子。接收机操作曲线下面积两者类似，（copeptin 0.75， NTproBNP 0.76）。两个标志物联合检测其回归模型曲线下面积为0.84，与两者单独比较差异显著（NTproBNP P<0.013 ； copeptin P<0.003)
两标志物预测死亡和心衰风险的COX模型[log copeptin (风险比＝2.33), log NTproBNP（风险比＝2.70] 分层分析显示血浆NTproBNP浓度在中位值900 pmol/L copeptin在中位值7 pmol/L以上预后较差(P<0.0005)。死亡和心衰作为个体随访终点，两者结果相似。
结论：急性心肌梗塞可激活抗利尿激素系统。血浆Copeptin浓度高，预后较差，尤其在血浆NTproBNP浓度高（＞900 pmol/L）的患者表现更为明显。
认领第5篇