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11. |
Parallel Analysis of Tissue‐Type Plasminogen Activator and Type 1 Plasminogen Activator Inhibitor in Plasma and Endothelial Cells Derived From Patients With Chronic Pulmonary Thromboemboli |
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Circulation,
Volume 90,
Issue 2,
1994,
Page 706-712
Irene Lang,
James Marsh,
Mitchell Olman,
Kenneth Moser,
Raymond Schleef,
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摘要:
BackgroundChronic thromboembolic pulmonary hyper-tension is the result of nonresolving pulmonary emboli that lead to chronic obstruction of the central pulmonary arteries.Methods and ResultsTo determine if the failure to lyse pulmonary thromboemboli is caused by an abnormality in the endothelial cell (EC)-associated fibrinolytic system, conditions were established to culture ECs from patient main pulmonary arteries during surgical pulmonary thromboendarterectomies and to analyze the conditioned media for levels of tissue-type plasminogen activator (TPA) and type 1 plasminogen activator inhibitor (PAI-1). Our data indicate that the levels of TPA antigen and PAI-1 activity in media conditioned by primary ECs harvested from areas free of thrombus were not significantly different between patients with chronic thromboemboli and organ donors. In 13 consecutive patients, no correlation was obtained in either the TPA antigen or PAI-1 activity level in a patient's plasma and the respective levels in media conditioned by the patient's pulmonary ECs. Moreover, patient pulmonary arterial ECs were observed to increase the secretion of TPA and PAI-1 in response to thrombin in a fashion similar to donor pulmonary artery ECs.ConclusionsThe data suggest that an inherent EC-mediated fibrinolytic imbalance is not a generalized phenomenon observed in pulmonary arteries of patients with chronic pulmonary thromboemboli.
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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12. |
Spatiotemporal Relation Between Gap Junctions and Fascia Adherens Junctions During Postnatal Development of Human Ventricular Myocardium |
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Circulation,
Volume 90,
Issue 2,
1994,
Page 713-725
Nicholas Peters,
Nicholas Severs,
Stephen Rothery,
Christopher Lincoln,
Magdi Yacoub,
Colin Green,
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摘要:
BackgroundThe growing postnatal human heart maintains electromechanical function while undergoing substantial changes of cellular topology and myocardial architecture. The capacity for growth and remodeling of ventricular myocardium in adaptation to the hemodynamic changes of early infancy later declines. This decline is associated with changes in electromechanical properties of the myocardium, which suggest that the electrical and mechanical interactions between the myocytes may change in an age-dependent manner. Thus, reduction in the capacity for myocardial growth and adaptability may relate to age-dependent alterations in the patterns of the intercellular junctions that mediate electrical and mechanical coupling. We therefore examined the hypotheses that (1) age-dependent changes in the distribution patterns of gap junctions and fasciae adherentes, the intercellular junctions responsible, respectively, for electrical and mechanical coupling, accompany postnatal development in the human heart and that (2) such changes continue into the first few years of childhood. Further, the spatial relation between the two types of junction, for which a close association has been hypothe-sized as necessary, was explored.Methods and ResultsVentricular myocardial gap-junction distribution was investigated in 23 pediatric surgical patients (4 weeks to 15 years old) by quantitative immunohistochemical localization of the principal cardiac gap-junctional protein, connexin43, using confocal microscopy. Immunolocalization of fascia adherens junctions by labeling N-cadherin, and correlative immunogold and standard electron microscopy, were performed in parallel. In the neonate, connexin43 gap junctions have a punctate distribution over the entire surface of the ventricular myocytes. With advancing age, gap junctions become progressively confined to the transverse terminals of the cell, ie, toward the distribution within the intercalated disk characteristic of the adult ventricle. The transversely arrayed proportion of gap-junctional label showed a linear increase with age (R=.88,P<.001), reaching the adult pattern at about 6 years, and the fascia adherens junctions showed a similar progression. Electron microscopy confirmed the changing pattern of junctional contacts and demonstrated that initially gap junctions and adhering junctions are frequently not closely adjacent but become increasingly so with maturation of the intercalated disk.ConclusionsChanges in the spatiotemporal patterns of the intercellular junctions responsible for electrical and mechanical coupling are closely coordinated in postnatal human ventricular myocardium and continue to about 6 years of age. Over this period there is a close and increasing association between the gap junctions and fascia adherens junctions. These changes in the distribution of intercellular electrical and adhering junctions may parallel the changing functional requirements of the ventricle, from a distribution that facilitates the remodeling necessitated by rapid growth and changing hemodynamics to that of the relatively stable and rapidly conducting adult myocardium. These age-related changes may also diminish the ability for appropriate myocardial remodeling in response to physiological, pathological, or surgical hemodynamic alterations.
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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13. |
Double‐Blind Efficacy and Safet Study of a Novel Anti‐Ischemic Agent, Ranolazine, Versus Placebo in Patients With Chronic Stable Angina Pectoris |
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Circulation,
Volume 90,
Issue 2,
1994,
Page 726-734
Udho Thadani,
Michael Ezekowitz,
Linda Fenney,
Yu-Kun Chiang,
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摘要:
BackgroundRanolazine modulates the metabolism of ischemic myocardial cells and improves the efficiency of oxygen use. This study was conducted to evaluate the antianginal and anti-ischemic effects and safety of different doses of ranolazine administered three times daily (tid) compared with placebo in patients with stable angina pectoris.Methods and ResultsPatients with stable angina pectoris took part in the study. Previous antianginal drugs were discontinued under medical supervision. Three hundred nineteen patients received single-blind placebo for up to 18 days, and 318 stopped exercise because of angina of moderate severity, had evidence of myocardial ischemia (≥1-mm ST segment depression), and were randomized to one of four study groups in a double-blind manner: ranolazine 30 mg tid (n=81), ranolazine 60 mg tid (n=81), ranolazine 120 mg tid (n=78), and placebo tid (n=79). After the 4-week double-blind phase, symptom-limited exercise tests were repeated at 1 hour (peak test) and 8 hours (trough test) after the study medication was administered. In addition, patients kept an angina diary throughout the study and wore a Holter monitor for 48 hours. Total exercise duration at baseline (±SEM) was 5.9±0.2 minutes for the placebo group and 6.4+0.3, 5.9±0.3, and 6.6±0.2 minutes for the ranolazine 30-, 60-, and 120-mg groups, respectively (P=NS). After 4 weeks of double-blind therapy, compared with baseline values, at 1 hour after the study medication was administered (peak effect), total exercise duration (±SEM) increased by 0.45±0.2 minutes in the placebo group and by 0.3±0.2, 0.6±0.2, and 0.5±0.2 minutes in the ranolazine 30-, 60-, and 120-mg groups, respectively (placebo versus ranolazine,P=NS). Times to 1-mm ST seg-ment depression at baseline were similar in the four groups and, after 4 weeks of therapy in each group, increased significantly by similar magnitudes at 1 hour after the administration of the medications. Similar changes were seen for the time to onset of angina. Eight hours after administration (trough effect), no differences in total exercise time or any other exercise variables were observed between the placebo and the ranolazine groups. Compared with the baseline values, the number of anginal attacks per week and the number and duration of ischemic episodes per 48 hours during Holter monitoring decreased significantly by similar magnitudes in the placebo and ranolazine groups.ConclusionsTherapy with ranolazine 30, 60, and 120 mg tid was not superior to placebo. Our study does not support the published beneficial effects of similar doses of ranolazine on either myocardial ischemia or exercise performance or on anginal attacks during daily life in patients with angina pectoris.
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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14. |
Histological Alterations in Chronically Hypoperfused MyocardiumCorrelation With PET Findings |
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Circulation,
Volume 90,
Issue 2,
1994,
Page 735-745
Alex Maes,
Willem Flameng,
Johan Nuyts,
Marcel Borgers,
Bharati Shivalkar,
Jannie Ausma,
Guy Bormans,
Christiaan Schiepers,
Michel De Roo,
Luc Mortelmans,
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摘要:
BackgroundIn patients with chronic coronary artery disease (CAD) and left ventricular dysfunction, flow/metabolic studies of the myocardium with positron emission tomography (PET) are able to distinguish viable but dysfunctional myocardium from irreversible ischemic injury and scar tissue. In this study, PET findings of blood flow and metabolism in chronically hypoperfused myocardium were correlated with histology.Methods and ResultsWe studied 33 patients suffering from CAD. In each patient, myocardial blood flow and metabolism were measured with PET 1 or 2 days before revascularization. During surgery, transmural biopsies were taken from the left ventricular anterior wall and planimetrically scored for the degree of myolysis (sarcomere loss). The amount of connective tissue was calculated using morphometric techniques. Contrast ventriculography demonstrated abnormal wall motion in 23 patients. Fourteen patients with a mismatch pattern (decreased flow with preserved metabolism) in the biopsy region after quantitative analysis of the PET data showed 11±6 vol% fibrosis and 25±13% cells with sarcomere loss. The space formerly occupied by sarcomeres was mainly replaced by glycogen and mitochondria. A significant wall motion improvement was noted 3 months after surgery. Nine patients showed a match pattern (concordant flow/metabolism defects). The biopsies revealed 35±25% fibrosis and 24±15% glycogen-storing cells. The biopsies of the 10 patients with normal anterior wall motion showed 8±4% fibrosis and 12±8% glycogen-accumulating cells.ConclusionsIt can be concluded that areas with impaired wall motion and a PET match pattern show extensive fibrosis. Regions with reduced flow and preserved FDG metabolism, however, contain predominantly viable cells. In these regions, significant recovery of wall motion is found after revascularization. Regions with normal wall motion contain predominantly viable cells. Cells with reduced contractile material and increased glycogen content are mainly found in areas with wall motion impairment but are also present in areas with normal wall motion and a severe stenosis of the coronary vessel.
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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15. |
Effects of Thrombolytic Therapy Administered 6 to 24 Hours After Myocardial Infarction on the Signal‐Averaged ECGResults of a Multicenter Randomized Trial |
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Circulation,
Volume 90,
Issue 2,
1994,
Page 746-752
Jonathan Steinberg,
Judith Hochman,
Christopher Morgan,
Paul Dorian,
C. Naylor,
Pierre Theroux,
Eric Topol,
Paul Armstrong,
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摘要:
BackgroundThrombolytic therapy reduces mortality after acute myocardial infarction, even when treatment is initiated relatively late after onset of symptoms. The mechanism underlying this survival benefit is incompletely understood.Methods and ResultsIn a prospectively designed ancillary study of a randomized, placebo-controlled trial of late thrombolytic therapy (LATE), the signal-averaged (SA) ECG was recorded before hospital discharge in an effort to assess the effect of thrombolytic therapy on arrhythmia substrate. Three hundred ten patients were enrolled at 23 participating sites; 160 patients received placebo, and 150 patients received recombinant tissue-type plasminogen activator (rTPA) therapy 6 to 24 hours after onset of symptoms. Compared with placebo, rTPA tended to reduce the frequency of SAECG abnormality (filtered QRS duration >120 milliseconds) by 37% (95% CI, −64%, +6%;P=.087) and the filtered QRS duration (105.7±13.8 versus 108.8±14.6 milliseconds,P=.05). In the prespecified subgroup of 185 patients with ST elevation on the qualifying ECG, rTPA resulted in a 52% reduction (95% CI, 4% to 77%,P=.011) of SAECG abnormality and a shorter filtered QRS duration (105.7±10.9 versus 110.7±15.9 milliseconds,P=.01). No benefit was seen in patients without ST elevation on ECG.ConclusionsLate thrombolytic therapy produced a more stable electrical substrate, which probably represents an important mechanism of mortality benefit.
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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16. |
Limitation of Infarct Size and Preservation of Left Ventricular Function After Primary Coronary Angioplast Compared With Intravenous Streptokinase in Acute Myocardial Infarction |
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Circulation,
Volume 90,
Issue 2,
1994,
Page 753-761
Menko De boer,
Harry Suryapranata,
Jan Hoorntje,
Stoffer Reiffers,
Ay Liem,
Kor Miedema,
Wim Hermens,
Marcel Van den brand,
Felix Zijlstra,
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摘要:
BackgroundEarly and effective flow through the infarct-related vessel is probably of paramount importance for limitation of infarct size and preservation of left ventricular function in patients with acute myocardial infarction. Primary coronary angioplasty may offer advantages in these respects compared with thrombolytic therapy. The purpose of the present study was to assess the effects on estimated enzymatic infarct size and left ventricular function in patients with acute myocardial infarction randomly assigned to undergo primary angioplasty or to receive intravenous streptokinase.Methods and ResultsWe evaluated 301 patients with signs of acute myocardial infarction and without contraindications for thrombolysis who presented within 6 hours after onset of symptoms or between 6 and 24 hours if there was evidence of ongoing ischemia. One hundred fifty-two patients were randomly assigned to undergo primary angioplasty, and 149 patients were assigned to receive treatment with streptokinase (1.5 million U IV). Infarct size was estimated from enzyme release. Global left ventricular ejection fraction and regional wall motion, if possible in combination with exercise testing, were evaluated by radionuclide ventriculography before discharge. Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 through the infarct-related vessel within 120 minutes after admission was achieved in 92% of all patients assigned to receive primary angioplasty therapy. Myocardial infarct size was 23% smaller in the angioplasty group compared with patients assigned to receive streptokinase (1003±784 versus 1310±1198 U/L,P=.012). Global left ventricular ejection fraction (50±9% versus 45±11%,P<.001) and regional wall motion in the infarct-related zones (42±14% versus 34±13%,P<.001) were better in the angioplasty group, which could mainly be contributed to myocardial salvage in the infarct-related areas. The observed differences were more pronounced in patients with an anterior wall myocardial infarction, although patients with a nonanterior infarct location also showed a beneficial effect of primary coronary angioplasty on left ventricular function compared with streptokinase therapy. Furthermore, the observed differences appeared to be more pronounced in patients presenting relatively early (within 2 hours) after onset of symptoms.ConclusionsIn patients with acute myocardial infarction, primary angioplasty results in a smaller infarct size and a better preserved myocardial function compared with patients randomized to receive treatment with intravenous streptoki-nase. This is probably due to early and optimal blood flow through the infarct-related vessel, as can be accomplished in a very high percentage of patients undergoing primary coronary angioplasty.
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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17. |
Effects of Treatment on Outcome in Mildly Symptomatic Patients With Ischemia During Daily LifeThe Atenolol Silent Ischemia Study (ASIST) |
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Circulation,
Volume 90,
Issue 2,
1994,
Page 762-768
Carl Pepine,
Peter Cohn,
Prakash Deedwania,
Robert Gibson,
Eileen Handberg,
James Hill,
Elinor Miller,
Ronald Marks,
Udho Thadani,
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摘要:
BackgroundDetection of asymptomatic ischemia in patients with coronary artery disease has been associated with increased risk for adverse outcome, but treatment of patients with asymptomatic ischemia remains controversial. Accordingly, the purpose of this study was to determine if treatment reduces adverse outcome in patients with daily life ischemia.Methods and ResultsA multicenter, randomized, double-blind, placebo- controlled study of asymptomatic or minimally symptomatic outpatients with daily life silent ischemia due to coronary artery disease was conducted. The primary outcome measure was event- free survival at 1 year by Kaplan-Meier analysis. Events were death, resuscitated ventricular tachycardia/ fibrillation, myocardial infarction, hospitalization for unstable angina, aggravation of angina, or revascularization. The secondary outcome was ischemia during ambulatory ECG monitoring at 4 weeks. Three hundred six outpatients with mild or no angina (Canadian Cardiovascular Society class I or II), abnormal exercise tests, and ischemia on ambulatory monitoring were randomized to receive either atenolol (100 mg/d) or placebo. After 4 weeks of treatment, the number (mean±SD, 3.6±4.2 versus 1.7±4.6 episodes,P<.001) and average duration (30±3.3 versus 16.4+6.7 minutes,P<.001) of ischemic episodes per 48 hours of ambulatory monitoring decreased in atenolol- compared with placebo-assigned patients (4.4±4.6 to 3.1±6.0 episodes and 36.6±4.1 to 30±5.5 minutes). Event-free survival improved in atenolol-treated patients (P<.0066), who had an increased time to onset of first adverse event (120 versus 79 days) and fewer total first events compared with placebo (relative risk, 0.44; 95% confidence intervals, 0.26 to 0.75;P=.001). There was a nonsignificant trend for fewer serious events (death, resuscitation from ventricular tachycardia/fibrillation, nonfatal myocardial infarction, or hospitalization for unstable angina) in atenolol-treated patients (relative risk, 0.55; 95% confidence intervals, 0.22 to 1.33;P=.175). The most powerful univariate and multivariate correlate of event-free survival was absence of ischemia on ambulatory monitoring at 4 weeks. Side effects were mild and generally similar comparing atenolol- and placebo-treated patients, although bradycardia was more frequent with atenolol.ConclusionsAtenolol treatment reduced daily life ischemia and was associated with reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients compared with placebo.
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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18. |
Associations of the HDL2and HDL3Cholesterol Subfractions With the Development of Ischemic Heart Disease in British MenThe Caerphilly and Speedwell Collaborative Heart Disease Studies |
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Circulation,
Volume 90,
Issue 2,
1994,
Page 769-774
Peter Sweetnam,
Colin Bolton,
John Yarnell,
David Bainton,
Ian Baker,
Peter Elwood,
Norman Miller,
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摘要:
BackgroundThe relative importance of HDL2 and HDL3 cholesterol as risk factors for ischemic heart disease (IHD) is still uncertain. Their associations with the incidence of IHD in the Caerphilly and Speedwell prospective studies are described.Methods and ResultsThe two studies have a common core protocol and are based on a total of 4860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell: 251 major IHD events had occurred. Lipid levels were measured on fasting samples. Different laboratories were used by the two studies. Each laboratory used ultracentrifugation to separate HDL2and HDL3. Both subfractions were inversely associated with risk of IHD. Standardized relative odds of developing major IHD were 0.95 (95% confidence interval [CI], 0.80 to 1.14) for HDL2 cholesterol and 0.83 (95% CI, 0.68 to 1.00) for HDL3 cholesterol in Caerphilly and 0.76 (95% CI, 0.57 to 1.01) for HDL2 and 0.64 (95% CI, 0.49 to 0.83) for HDL3 in Speedwell. The association with incident IHD appeared to be stronger for HDL3in both areas. No linear combination of the two subfractions was a better predictor of IHD than total HDL cholesterol alone.ConclusionsIn British men, both HDL2and HDL3cholesterol are inversely associated with the incidence of IHD. However, the prediction of the risk of IHD from total HDL cholesterol alone could not be improved upon by measurement of the two HDL subfractions. The relative value of the two HDL subfractions as predictors of risk is still unresolved. The uncertainty may be due, at least in part, to problems associated with their measurement.
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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19. |
Macrophage Infiltration in Acute Coronary SyndromesImplications for Plaque Rupture |
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Circulation,
Volume 90,
Issue 2,
1994,
Page 775-778
Pedro Moreno,
Erling Falk,
Igor Palacios,
John Newell,
Valentín fuster,
John Fallon,
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摘要:
BackgroundRupture of atherosclerotic plaques is probably the most important mechanism underlying the sudden onset of acute coronary syndromes. Macrophages may release lytic enzymes that degrade the fibrous cap and therefore produce rupture of the atherosclerotic plaque. This study was designed to quantify macrophage content in coronary plaque tissue from patients with stable and unstable coronary syndromes.Methods and ResultsHematoxylin and eosin and immuno-staining with anti-human macrophage monoclonal antibody (PG-M1) were performed. Computerized planimetry was used to analyze26 atherectomy specimens comprising 524 pieces of tissue from 8 patients with chronic stable angina, 8 patients with unstable angina, and 10 patients with non-Q-wave myo-cardial infarction. Total plaque area was 417±87 mm2× 10−2in patients with stable angina, 601±157 mm2×10−2in patients with unstable angina, and 499±87 mm2× 10−2in patients with non-Q-wave myocardial infarction (P=NS). The macrophage-rich area was larger in plaques from patients with unstable angina (61±18 mm2x 102) and non-Q-wave myocardial infarction (87±32mm2× 10−2) than in plaques from patients with stable angina (14±5 mm2×10−2) (P=.024). The percentage of the total plaque area occupied by macrophages was also larger in patients with unstable angina (13.3 ±5.6%) and non-Q-wave myocardial infarction (14.6±4.6%) than in patients with stable angina (3.14±1%) (P=.018). Macrophagerich sclerotic tissue was largest in patients with non-Q-wave myocardial infarction (67±30 mm2× 1010−2) and unstable angina (55±19 mm2× 10−2) than in patients with stable angina (11.5±4.1 mm2× 10−2) (P=.046). Macrophage-rich atheromatous gruel was also larg-est in patients with non-Q-wave myocardial infarction (15±4 mm2×10−2) than in patients with unstable angina (3.3±1.7 mm2×10−2) or stable angina (2.4±1.2 mm2× 10−2) (P=.026).ConclusionsMacrophage-rich areas are more frequently found in patients with unstable angina and non-Q-wave myocardial infarction. This suggests that macrophages are a marker of unstable atherosclerotic plaques and may play a significant role in the pathophysiology of acute coronary syndromes.
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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20. |
Association Between QT Interval and Coronary Heart Disease in Middle‐aged and Elderly MenThe Zutphen Study |
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Circulation,
Volume 90,
Issue 2,
1994,
Page 779-785
Jacqueline Dekker,
Evert Schouten,
Peter Klootwijk,
Jan Pool,
Daan Kromhout,
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摘要:
BackgroundHeart-rate-adjusted QT-interval (QTc) is prognostic of sudden death in myocardial infarction patients. So far, population studies have yielded conflicting results on the predictive value of QTcfor coronary heart disease morbidity and mortality. Therefore, we investigated this in a longitudinal study of middle-aged and elderly men.Methods and ResultsFrom 1960 to 1985, 877 middle-aged men were followed and repeatedly examined in the Zutphen Study. In 1985 the remaining cohort was extended to 835 elderly men from the same birth cohort and followed until 1990. Men with prolonged QTc(420 ms1/2or more) had a higher risk of myocardial infarction and coronary heart disease death relative to men with QTcless than 385 ms1/2. Ageadjusted coronary heart disease mortality rate ratios were 4.3 (95% confidence interval, 1.3 to 13.8) in middle-aged men and 3.3 (95% confidence interval, 1.0 to 11.6) in elderly men. These associations could not be attributed to prevalent heart disease and were independent of other cardiovascular risk factors.ConclusionsThese results indicate that within the normal range of QTcin the general population, men with long QTcare at higher risk for coronary heart disease. Because QTcis easily determined, it may provide a valuable contribution to risk stratification.
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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