Showing papers in "Circulation in 1997"
TL;DR: Evidence is provided that an increased common carotid IMT is associated with future cerebrovascular and cardiovascular events and Stroke risk increased gradually with increasing IMT.
Abstract: Background Noninvasive assessment of intima-media thickness (IMT) is widely used in observational studies and trials as an intermediate or proxy end point for cardiovascular disease. However, data showing that IMT predicts cardiovascular disease are limited. We studied whether common carotid IMT is related to future stroke and myocardial infarction. Methods and Results We used a nested case-control approach among 7983 subjects aged ≥55 years participating in the Rotterdam Study. At baseline (March 1990 through July 1993), ultrasound images of the common carotid artery were stored on videotape. Determination of incident myocardial infarction and stroke was predominantly based on hospital discharge records. Analysis (logistic regression) was based on 98 myocardial infarctions and 95 strokes that were registered before December 31, 1994. IMT was measured from videotape for all case subjects and a sample of 1373 subjects who remained free from myocardial infarction and stroke during follow-up. The mean durati...
2,355 citations
TL;DR: The late fall in DBP after age 60 years, associated with a continual rise in SBP, cannot be explained by "burned out" diastolic hypertension or by "selective survivorship" but is consistent with increased large artery stiffness.
Abstract: Background We attempted to characterize age-related changes in blood pressure in both normotensive and untreated hypertensive subjects in a population-based cohort from the original Framingham Heart Study and to infer underlying hemodynamic mechanisms. Methods and Results A total of 2036 participants were divided into four groups according to their systolic blood pressure (SBP) at biennial examination 10, 11, or 12. After excluding subjects receiving antihypertensive drug therapy, up to 30 years of data on normotensive and untreated hypertensive subjects from biennial examinations 2 through 16 were used. Regressions of blood pressure versus age within individual subjects produced slope and curvature estimates that were compared with the use of ANOVA among the four SBP groups. There was a linear rise in SBP from age 30 through 84 years and concurrent increases in diastolic blood pressure (DBP) and mean arterial pressure (MAP); after age 50 to 60 years, DBP declined, pulse pressure (PP) rose steeply, and MA...
2,176 citations
TL;DR: The incidence of AF in older adults may be higher than estimated by previous population studies and left atrial size appears to be an important risk factor, and the control of blood pressure and glucose may be important in preventing the development of AF.
Abstract: Background This study aimed to describe the incidence of atrial fibrillation (AF) among older adults during 3 years of follow-up. Methods and Results In this cohort study, 5201 adults ≥65 years old were examined annually on four occasions between June 1989 and May 1993. At baseline, participants answered questionnaires and underwent a detailed examination that included carotid ultrasound, pulmonary function tests, ECG, and echocardiography. Subjects with a pacemaker or AF at baseline (n=357) were excluded. New cases of AF were identified from three sources: (1) annual self-reports, (2) annual ECGs, and (3) hospital discharge diagnoses. Cox proportional-hazards models were used to assess baseline risk factors as predictors of incident AF. Among 4844 participants, 304 developed a first episode of AF during an average follow-up of 3.28 years, for an incidence of 19.2 per 1000 person-years. The onset was strongly associated with age, male sex, and the presence of clinical cardiovascular disease. For men 65 to...
1,418 citations
TL;DR: Abnormal atrial histology was uniformly found in multiple biopsy specimens in all patients with LAF and was compatible with a diagnosis of myocarditis in 66% of patients and of noninflammatory localized cardiomyopathy in 17% and was represented by patchy fibrosis in 17%.
Abstract: Background Lone atrial fibrillation (LAF) is a common clinical syndrome, but its origin remains unknown. Methods and Results We performed endomyocardial biopsies of the right atrial septum (2 to 3 per patient; mean, 2.8) and of the two ventricles (6 per patient) in 12 patients (10 men, 2 women; mean age, 32 years) with paroxysmal LAF refractory to conventional antiarrhythmic treatment. As controls, we used endomyocardial biopsies (3 to 5 per patient; mean, 4.4) from the right atrial septum of 11 patients with Wolff-Parkinson-White syndrome (WPW) undergoing resection of the abnormal AV pathway. The weight of the biopsies ranged from 2.8 to 4.5 mg. Biopsy samples were processed for histology and electron microscopy and were read by a pathologist blinded to clinical data. All patients underwent two-dimensional Doppler echocardiography; cardiac catheterization; coronary angiography; and hormonal, virologic, and electrophysiological studies. All tests and WPW biopsies were normal, but all LAF atrial biopsy spe...
1,366 citations
TL;DR: Results of logistic regression analyses indicated that the relationship of ICAM-1 and E-selectin with CHD and CAA was independent of other known CHD risk factors and was most pronounced in the highest quartile.
Abstract: Background Recruitment of circulating leukocytes at sites of atherosclerosis is mediated through a family of adhesion molecules. The function of circulating forms of these adhesion molecules remains unknown, but their levels may serve as molecular markers of subclinical coronary heart disease (CHD). Methods and Results To determine the ability of circulating vascular cell adhesion molecule-1 (VCAM-1), endothelial-leukocyte adhesion molecule-1 (E-selectin), and intercellular adhesion molecule-1 (ICAM-1) to serve as molecular markers of atherosclerosis and predictors of incident CHD, we studied 204 patients with incident CHD, 272 patients with carotid artery atherosclerosis (CAA), and 316 control subjects from the large, biracial Atherosclerosis Risk In Communities (ARIC) study. Levels of VCAM-1 were not significantly different among the patients with incident CHD, those with CAA, and control subjects. Higher levels of E-selectin and ICAM-1 were observed for the patients with CHD (means [ng/mL]: E-selectin,...
1,362 citations
TL;DR: Central aortic pressures can be accurately estimated from radial tonometry with the use of a generalized TF, and the reconstructed waveform can provide arterial compliance estimates but may underestimate the augmentation index because the latter requires greater fidelity reproduction of the wave contour.
Abstract: Background Central aortic pressures and waveform convey important information about cardiovascular status, but direct measurements are invasive. Peripheral pressures can be measured noninvasively, and although they often differ substantially from central pressures, they may be mathematically transformed to approximate the latter. We tested this approach, examining intersubject and intrasubject variability and the validity of using a single averaged transformation, which would enhance its applicability. Methods and Results Invasive central aortic pressure by micromanometer and radial pressure by automated tonometry were measured in 20 patients at steady state and during hemodynamic transients (Valsalva maneuver, abdominal compression, nitroglycerin, or vena caval obstruction). For each patient, transfer functions (TFs) between aortic and radial pressures were calculated by parametric model and results averaged to yield individual TFs. A generalized TF was the average of individual functions. TFs varied among patients, with coefficients of variation for peak amplitude and frequency at peak amplitude of 24.9% and 16.9%, respectively. Intrapatient TF variance with altered loading (>20% variation in peak amplitude) was observed in 28.5% of patients. Despite this, the generalized TF estimated central arterial pressures to ≤0.2±3.8 mm Hg error, arterial compliance to 6±7% accuracy, and augmentation index to within −7% points (30±45% accuracy). Individual TFs were only marginally superior to the generalized TF for reconstructing central pressures. Conclusions Central aortic pressures can be accurately estimated from radial tonometry with the use of a generalized TF. The reconstructed waveform can provide arterial compliance estimates but may underestimate the augmentation index because the latter requires greater fidelity reproduction of the wave contour.
1,211 citations
TL;DR: In some patients, the surface ECG pattern of atrial fibrillation is due to a focal rapidly firing source of activity that can be eliminated by discrete radiofrequency energy applications.
Abstract: Background Atrial fibrillation is usually thought to be due to multiple circulating reentrant wavelets. From previous studies, a focal mechanism is considered to be very unlikely. In this report, focal atrial fibrillation is defined on an ECG pattern of atrial fibrillation and later demonstrated to be due to a focal source. Methods and Results Nine patients (five men and four women; age, 38±7 years) with paroxysmal focal atrial fibrillation are reported here. All were free of structural heart disease and had frequent episodes of atrial fibrillation despite the use of a mean of 4±2 antiarrhythmic drugs. Atrial fibrillation was associated with runs of irregular atrial tachycardia or monomorphic extrasystoles. The electrophysiological study demonstrated that all the atrial arrhythmias were due to the same focus firing irregularly and exhibiting a consistent and centrifugal pattern of activation. Three foci were found to be located in the right atrium, two near the sinus node and one in the ostium of the coro...
1,178 citations
TL;DR: These results represent the first prospective evidence suggesting that the presence of small, dense LDL particles may be associated with an increased risk of subsequently developing IHD in men and suggest that the risk attributed to small LDL particle may be partly independent of the concomitant variation in plasma lipoprotein-lipid concentrations.
Abstract: Background Case-control studies have reported that patients with ischemic heart disease (IHD) have a higher proportion of small, dense LDL particles than do healthy control subjects. The extent to ...
1,122 citations
TL;DR: Although exercise testing is generally a safe procedure, both myocardial infarction and death have been reported and can be expected to occur at a rate of up to 1 per 2500 tests, good clinical judgment should be used in deciding which patients should undergo exercise testing.
Abstract: The American College of Cardiology/American Heart Association Task Force on Practice Guidelines was formed to make recommendations regarding the appropriate use of testing in the diagnosis and treatment of patients with known or suspected cardiovascular disease. Exercise testing is widely available and relatively low in cost. For the purposes of these guidelines, exercise testing is a cardiovascular stress test using treadmill or bicycle exercise and electrocardiographic and blood pressure monitoring. Pharmacological stress testing and imaging modalities (radionuclide imaging, echocardiography) are beyond the scope of these guidelines.
These guidelines have been endorsed by the American College of Sports Medicine, the American Society of Echocardiography, and the American Society of Nuclear Cardiology.
This executive summary appears in the July 1, 1997, issue of Circulation. The guidelines in their entirety are published in the July 1997 issue of the Journal of the American College of Cardiology. Reprints of both the executive summary and the full text are available from both organizations.
Exercise testing is a well-established procedure that has been in widespread clinical use for many decades. It is described in detail in previous publications of the AHA, to which interested readers are referred.
Although exercise testing is generally a safe procedure, both myocardial infarction and death have been reported and can be expected to occur at a rate of up to 1 per 2500 tests. Good clinical judgment should therefore be used in deciding which patients should undergo exercise testing. Absolute and relative contraindications to exercise testing are summarized in Table 1⇓.
View this table:
Table 1.
Contraindications to Exercise Testing
The vast majority of treadmill exercise testing is performed in adults with symptoms of known or suspected ischemic heart disease. Special groups who are exceptions to this norm are discussed in detail in sections VI and VII. Sections II through IV illustrate the variety …
1,076 citations
TL;DR: This review examines the physiological foundations of sympathovagal balance, a model whose order (the number of parameters) is selected automatically to minimize Akaike’s information criterion statistic.
Abstract: Given the importance of the autonomic nervous system to cardiovascular health, it is not surprising that there is and has been great interest in measurements of human sympathetic and vagus nerve traffic as tools that might inform physiological and pathophysiological mechanisms. Pagani and coworkers1 advanced the provocative notion that the instantaneous balance between sympathetic and vagal nerve activities can be captured by a single number, obtained by dividing RR-interval spectral power centered at ≈0.1 Hz by spectral power centered at higher, primarily respiratory frequencies. This ratio, or sympathovagal balance, has been embraced with great enthusiasm2 because it offers new possibilities for understanding dynamic, critically important autonomic interrelations in humans by the use of totally noninvasive, unobtrusive means.3
The broad bases for this mathematical treatment are as follows: (1) 0.1-Hz RR intervals are importantly mediated by fluctuations of sympathetic nerve activity; (2) higher-frequency RR-interval rhythms are mediated almost exclusively by fluctuations of vagal-cardiac nerve activity; and (3) physiological interventions tend to provoke reciprocal changes of sympathetic and vagal neural outflows. Sympathovagal balance, the ratio of these periodicities, is taken to reflect the balance between the opposing neural mechanisms. This review examines the physiological foundations of sympathovagal balance.
The ECG is recorded with the subject in a steady state (when rhythms are stationary) for a period sufficiently long to define events occurring over frequencies of interest. RR-interval spectral power is calculated from this series of intervals with an autoregressive algorithm, which yields center frequencies and absolute power of component fluctuations, based on a model whose order (the number of parameters) is selected automatically to minimize Akaike’s information criterion statistic.4 (The statistical uncertainty and consequences of the automatic selection of the autoregressive model have not been defined fully; however, it is clear that the model order importantly determines both …
1,057 citations
TL;DR: In adults with asymptomatic AS, the rate of hemodynamic progression and clinical outcome are predicted by jet velocity, the rates of change inJet velocity, and functional status.
Abstract: Background Only limited data on the rate of hemodynamic progression and predictors of outcome in asymptomatic patients with valvular aortic stenosis (AS) are available. Methods and Results In 123 adults (mean age, 63±16 years) with asymptomatic AS, annual clinical, echocardiographic, and exercise data were obtained prospectively (mean follow-up of 2.5±1.4 years). Aortic jet velocity increased by 0.32±0.34 m/s per year and mean gradient by 7±7 mm Hg per year; valve area decreased by 0.12±0.19 cm2 per year. Kaplan-Meier event-free survival, with end points defined as death (n=8) or aortic valve surgery (n=48), was 93±5% at 1 year, 62±8% at 3 years, and 26±10% at 5 years. Univariate predictors of outcome included baseline jet velocity, mean gradient, valve area, and the rate of increase in jet velocity (all P≤.001) but not age, sex, or cause of AS. Those with an end point had a smaller exercise increase in valve area, blood pressure, and cardiac output and a greater exercise decrease in stroke volume. Multiv...
TL;DR: It is indicated that plasma BNP is more useful than ANP for assessing the mortality in patients with chronic CHF and that the plasma levels of BNP provide prognostic information independent of other variables previously associated with a poor prognosis.
Abstract: Background Patients with congestive heart failure (CHF) have high plasma levels of atrial natriuretic peptide (ANP), mainly from the atrium, and brain natriuretic peptide (BNP), mainly from the ventricle. We examined the prognostic role of plasma BNP in chronic CHF patients in comparison with plasma ANP and other variables previously known to be associated with high mortality. We also evaluated the relationship between mortality and plasma cGMP, a biological marker of ANP and BNP. Methods and Results The study subjects were 85 patients with chronic CHF (left ventricular ejection fraction <0.45) who were followed for 2 years. The plasma levels of ANP, BNP, cGMP, and norepinephrine increased with the severity of CHF. Among plasma levels of ANP, BNP, cGMP, and norepinephrine and clinical and hemodynamic parameters, only high levels of plasma BNP (P<.0001) and pulmonary capillary wedge pressure (P=.003) were significant independent predictors of the mortality in patients with CHF by Cox proportional hazard an...
TL;DR: Observations indicate that within 1 month of treatment with simvastatin, both the stimulated and basal nitric oxide dilator functions of the endothelium are augmented, and the benefits of this HMG-coenzyme A reductase inhibitor persist with continued therapy.
Abstract: Background Cholesterol-lowering therapy can improve cardiovascular morbidity and mortality in patients with atherosclerosis. Although the mechanisms responsible are unclear, these benefits precede macroscopic changes in the vasculature. Emerging evidence that improvement in endothelial function may occur requires substantiation; in particular, it is unclear how early any such improvement would be detectable after initiation of therapy. Methods and Results This randomized, double-blind, placebo-controlled crossover study evaluated the effect of simvastatin (20 mg daily for 4 weeks) on endothelium-dependent and endothelium-independent vasodilation and on the response to the inhibitor of nitric oxide synthesis, NG-monomethyl-l-arginine (L-NMMA), in the forearm vasculature of subjects with moderate elevation of total serum cholesterol (6.0 to 10.0 mmol/L) by use of strain-gauge plethysmography. Studies were repeated after 3 more months of open therapy. When the results are expressed as percentage changes in f...
TL;DR: In patients undergoing coronary angioplasty for acute coronary syndromes, tirofiban protects against early adverse cardiac events related to thrombotic closure.
Abstract: BACKGROUND
Adverse cardiovascular events associated with thrombotic occlusion occur in 4% to 12.8% of patients after coronary angioplasty. Recently, potent antiplatelet agents have been used to reduce those thrombotic complications. Tirofiban is a highly selective, short-acting inhibitor of fibrinogen binding to platelet glycoprotein (GP) IIb/IIIa that inhibits ex vivo platelet aggregation in response to a variety of agonists.
METHODS AND RESULTS
The RESTORE trial (Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis) was a randomized, double-blind, placebo-controlled trial of tirofiban in patients undergoing coronary interventions (balloon angioplasty or directional atherectomy) within 72 hours of presentation with an acute coronary syndrome (unstable angina pcctoris or acute myocardial infarction). The end points of the study were death from any cause, myocardial infarction, coronary bypass surgery due to angioplasty failure or recurrent ischemia, repeat target-vessel angioplasty for recurrent ischemia, and insertion of a stent due to actual or threatened abrupt closure of the dilated artery, and the primary end point was a composite representing the occurrence of any of these events. The prespecified primary hypothesis of the study was that tirofiban, administered as a bolus of 10 microg/kg over a 3-minute period and followed by a 36-hour infusion of 0.15 microg x kg(-1) x min(-1), would result in a reduction in the 30-day composite end point compared with placebo. Patients (n=2139) who were already receiving treatment with aspirin and heparin were randomized to receive tirofiban or placebo. The primary composite end point at 30 days was reduced from 12.2% in the placebo group to 10.3% in the tirofiban group, a 16% relative reduction (P=.160). However, 2 days after angioplasty, the tirofiban group had a 38% relative reduction in the composite end point (P< or =.005), and at 7 days there was a 27% relative reduction (P=.022), largely because of a reduction in nonfatal myocardial infarction and the need for repeat angioplasty. When repeat angioplasty or coronary artery bypass surgery procedures were included in the composite only if performed on an urgent or emergency basis, the composite 30-day event rates were 10.5% for the placebo group and 8.0% for the tirofiban group, a relative reduction of 24% (P=.052). Major bleeding, including transfusion, was not significantly different between the two groups (3.7% in the placebo group and 5.3% in the tirofiban group; P=.096). When the Thrombolysis In Myocardial Infarction (TIMI) criteria for major bleeding were used, the incidence was 2.1% in the placebo group compared with 2.4% in the tirofiban group (P=.662). Thrombocytopenia was similar in the placebo and tirofiban groups (0.9% for the placebo group versus 1.1% for the tirofiban group; P=.709).
CONCLUSIONS
In patients undergoing coronary angioplasty for acute coronary syndromes, tirofiban protects against early adverse cardiac events related to thrombotic closure. At 30 days, however, the reduction in adverse cardiac events was no longer statistically significant. The bleeding observed with tirofiban was not statistically different from that observed with placebo.
TL;DR: There is a predominance in the LF oscillation of blood pressure, RR interval, and sympathetic nerve activity during sympathetic activation in normal humans and during sympathetic inhibition, the HF component of cardiovascular variability predominates.
Abstract: Background Spectral analysis of RR interval and systolic arterial pressure variabilities may provide indirect markers of the balance between sympathetic and vagal cardiovascular control. Methods and Results We examined the relationship between power spectral measurements of variabilities in RR interval, systolic arterial pressure, and muscle sympathetic nerve activity (MSNA) obtained by microneurography over a range of blood pressures. In eight healthy human volunteers, MSNA, RR interval, intra-arterial pressure, and respiration were measured during blood pressure reductions induced by nitroprusside and during blood pressure increases induced by phenylephrine. Both low-frequency (LF; 0.10±0.01 Hz) and high-frequency (HF; 0.23±0.01 Hz) components were detected in MSNA variability. Increasing levels of MSNA were associated with a shift of the spectral power toward its LF component. Decreasing levels of MSNA were associated with a shift of MSNA spectral power toward the HF component. Over the range of pressu...
TL;DR: The main shortcomings of conventional mapping-namely, prolonged x-ray exposure, low spatial resolution, and the inability to accurately navigate to a predefined site-can all be overcome with this new method.
Abstract: Background Cardiac mapping is essential for understanding the mechanisms of arrhythmias and for directing curative procedures. A major limitation of the current methods is the inability to accurately relate local electrograms to their spatial orientation. The objective of this study was to present and test the accuracy of a new method for nonfluoroscopic, catheter-based, endocardial mapping. Methods and Results The method is based on using a new locatable catheter connected to an endocardial mapping and navigating system. The system uses magnetic technology to accurately determine the location and orientation of the catheter and simultaneously records the local electrogram from its tip. By sampling a plurality of endocardial sites, the system reconstructs the three-dimensional geometry of the chamber, with the electrophysiological information color-coded and superimposed on the anatomy. The accuracy of the system was tested in both in vitro and in vivo studies and was found to be highly reproducible (SD, ...
TL;DR: Hypertension caused by chronically elevated angiotensin II is mediated in part by .O2-, likely via degradation of endothelium-derived NO, and may contribute to vascular disease in high renin/angiotens in II states.
Abstract: Background The major source of superoxide (·O2−) in vascular tissues is an NADH/NADPH-dependent, membrane-bound oxidase. We have previously shown that this oxidase is activated in angiotensin II– but not norepinephrine-induced hypertension. We hypothesized that hypertension associated with chronically elevated angiotensin II might be caused in part by vascular ·O2− production. Methods and Results We produced hypertension in rats by a 5-day infusion of angiotensin II or norepinephrine. Rats were also treated with liposome-encapsulated superoxide dismutase (SOD) or empty liposomes. Arterial pressure was measured in conscious rats under baseline conditions and during bolus injections of either acetylcholine or nitroprusside. Vascular ·O2− production was assessed by lucigenin chemiluminescence. In vitro vascular relaxations were examined in organ chambers. Norepinephrine infusion increased blood pressure to a similar extent as angiotensin II infusion (179±5 and 189±4 mm Hg, respectively). In contrast, angiote...
TL;DR: Vasopressin plasma levels are inappropriately low in vasodilatory shock, most likely because of impaired baroreflex-mediated secretion.
Abstract: Background The hypotension of septic shock is due to systemic vasodilation. On the basis of a clinical observation, we investigated the possibility that a deficiency in vasopressin contributes to the vasodilation of septic shock. Methods and Results In 19 patients with vasodilatory septic shock (systolic arterial pressure [SAP] of 92±2 mm Hg [mean±SE], cardiac output [CO] of 6.8±0.7 L/min) who were receiving catecholamines, plasma vasopressin averaged 3.1±1.0 pg/mL. In 12 patients with cardiogenic shock (SAP, 99±7 mm Hg; CO, 3.5±0.9 L/min) who were also receiving catecholamines, it averaged 22.7±2.2 pg/mL (P<.001). A constant infusion of exogenous vasopressin to 2 patients with septic shock resulted in the expected plasma concentration, indicating that catabolism of vasopressin is not increased in this condition. Although vasopressin is a weak pressor in normal subjects, its administration at 0.04 U/min to 10 patients with septic shock who were receiving catecholamines increased arterial pressure (systoli...
TL;DR: A simple, generalizable predictive model for survival after out-of-hospital cardiac arrest due to ventricular fibrillation is developed and can be generalized to other US populations and used to project the local effectiveness of interventions to improve cardiac arrest survival.
Abstract: Background The study objective was to develop a simple, generalizable predictive model for survival after out-of-hospital cardiac arrest due to ventricular fibrillation. Methods and Results Logistic regression analysis of two retrospective series (n=205 and n=1667, respectively) of out-of-hospital cardiac arrests was performed on data sets from a Southwestern city (population, 415 000; area, 406 km2) and a Northwestern county (population, 1 038 000; area, 1399 km2). Both are served by similar two-tiered emergency response systems. All arrests were witnessed and occurred before the arrival of emergency responders, and the initial cardiac rhythm observed was ventricular fibrillation. The main outcome measure was survival to hospital discharge. Patient age, initiation of CPR by bystanders, interval from collapse to CPR, interval from collapse to defibrillation, bystander CPR/collapse-to-CPR interval interaction, and collapse-to-CPR/collapse-to-defibrillation interval interaction were significantly associated...
TL;DR: This study provides evidence that in addition to overt necrosis, a subset of myocytes undergo apoptosis during ischemia-reperfusion injury and may provide a new target for cardioprotection during evolving AMI in humans.
Abstract: Background After reopening of the infarct-related coronary artery, cardiomyocytes continue to die during reperfusion. The mechanisms of cell death have been subject to debate. We studied whether an apoptotic type of cell death occurs in human acute myocardial infarction (AMI). Methods and Results We studied myocardial samples of eight patients who died of AMI and had patent infarct-related arteries at autopsy. Six of the patients had received initially successful thrombolysis. Extensive formation of DNA strand breaks, the typical biochemical feature of apoptosis, was detected with the use of the in situ DNA end-labeling method. Apoptotic cardiomyocytes were observed particularly in the border zones of histologically infarcted myocardium, whereas very few apoptotic cells were present in the remote noninfarcted myocardium. Internucleosomal fragmentation was confirmed by agarose gel electrophoresis of DNA isolated from the representative myocardial areas. Conclusions This study provides evidence that in addi...
TL;DR: It is suggested that the syndrome of heart failure progresses to cardiac cachexia if the normal metabolic balance between catabolism and anabolism is altered.
Abstract: Background The role of hormonal and cytokine abnormalities in the development of cardiac cachexia remains obscure. Methods and Results Healthy control subjects (n=16) and patients with chronic heart failure (CHF), classified clinically as cachectic (8% to 35% weight loss over ≥6 months before study, n=16) or noncachectic (n=37), were assessed for markers of disease severity (maximal oxygen consumption, left ventricular ejection fraction, NYHA functional class). These markers were compared with plasma concentrations of potentially important anabolic and catabolic factors. The degree of neurohormonal activation and catabolic/anabolic imbalance was closely related to wasting but not to conventional measures of the severity of heart failure. Compared with control subjects and noncachectic patients, cachectic patients had reduced plasma sodium and increased norepinephrine, epinephrine (all P<.0001), cortisol, tumor necrosis factor (TNF)-α (both P<.002), and human growth hormone (P<.05). Insulin-like growth fac...
TL;DR: This goat model of AF offers a new approach to study the cascade of events leading to sustained AF and its maintenance, and leads to predominantly structural changes in the atrial myocytes similar to those seen in ventricular myocytes from chronic hibernating myocardium.
Abstract: Background After cardioversion of sustained atrial fibrillation (AF), the electrical and contractile functions of the atria are impaired, and recurrences of AF frequently occur. Whether remodeling of the structure of atrial myocardium is the basis for this problem is not known. Methods and Results Sustained AF was induced by electrical pacing in 13 goats instrumented long-term. The goats were killed after 9 to 23 weeks, and the atrial myocardium was examined by light and electron microscopy. The changes were quantified in left and right atrial free walls, appendages, trabeculae, the interatrial septum, and the bundle of Bachmann. A substantial proportion of the atrial myocytes (up to 92%) revealed marked changes in their cellular substructures, such as loss of myofibrils, accumulation of glycogen, changes in mitochondrial shape and size, fragmentation of sarcoplasmic reticulum, and dispersion of nuclear chromatin. These changes were accompanied by an increase in size of the myocytes (up to 195%). There we...
TL;DR: The present study demonstrates that prolonged exposure to high glucose increases eNOS gene expression, protein expression, and NO release, however, upregulation of eNos andNO release is associated with a marked concomitant increase of O2- production.
Abstract: Background Hyperglycemia is a primary cause of premature vascular disease. Endothelial cell dysfunction characterized by diminished endothelium-dependent relaxations is likely to be involved. Little is known about the molecular mechanisms of hyperglycemia-induced endothelial dysfunction. Methods and Results This study was designed to determine the effect of hyperglycemia on the l-arginine/nitric oxide (NO) pathway. Expression of endothelial nitric oxide synthase (eNOS) mRNA and production of NO were studied in human aortic endothelial cells exposed to control levels (5.5 mmol/L) and high levels (22.2 mmol/L) of glucose for 5 days. We examined the effect of glucose on NO release by measuring changes in nitrite (NO2−) levels by Griess reaction. Superoxide anion (O2−) production was also examined by the ferrocytochrome c assay. NOS mRNA and protein expression, which were evaluated by reverse transcription–polymerase chain reaction and Western blotting, were approximately twofold greater in endothelial cells ...
TL;DR: The assumption that the authors can all agree that hypercholesterolemia−particularly hyperbetalipoproteinemia−is an important causative factor in atherogenesis and that correction of it can strikingly reduce the risk of coronary heart disease (CHD) is the assumption.
Abstract: I want to express my thanks to Dr Sidney Smith, President of the American Heart Association, for selecting me to present the 1995 Conner Memorial Lecture. I want also to express my admiration for and gratitude to this remarkable organization, the American Heart Association, and its wonderful staff, with whom I have worked for more than 30 years. I have missed very few AHA meetings since 1959 when the American Society for Study of Arteriosclerosis became the American Heart Association Council on Arteriosclerosis. I−indeed all of us−owe a great debt to the AHA for its tireless efforts over the years to support medical research and improve medical care.
I start with the assumption that we can all agree that hypercholesterolemia−particularly hyperbetalipoproteinemia−is an important causative factor in atherogenesis and that correction of it can strikingly reduce the risk of coronary heart disease (CHD). Yet it was not so long ago that this argument had to be vigorously defended. It was only in 1983 that the National Institutes of Health (NIH) officially endorsed the position that hypercholesterolemia must be treated. That decision followed closely on the completion of the landmark Lipid Research Clinic Intervention Trial, initiated by Dr Donald S. Fredrickson and Dr Robert I. Levy and shepherded to completion by Dr Basil Rifkind.1 The following year I had the privilege of chairing the NIH Consensus Conference on Lowering Blood Cholesterol,2 which concluded unanimously that there was an unarguable cause-and-effect relationship and that lowering blood cholesterol should be an important national goal. The following year the National Heart, Lung, and Blood Institute (NHLBI) organized and spearheaded the National Cholesterol Education Program (NCEP). Actually this year marks the 10th anniversary of the NCEP, and I think we can again all agree that it has accomplished a great deal under the able …
TL;DR: The risk of ARF after cardiac surgery can be accurately quantified on the basis of readily available preoperative data and may be used by physicians and surgeons to provide patients with improved risk estimates and to target high-risk subgroups for interventions aimed at reducing the risk and ameliorating the consequences of this serious complication.
Abstract: Background After cardiac surgery, acute renal failure (ARF) requiring dialysis develops in 1% to 5% of patients and is strongly associated with perioperative morbidity and mortality. Prior studies have attempted to identify predictors of ARF but have had insufficient power to perform multivariable analyses or to develop risk stratification algorithms. Methods and Results We conducted a prospective cohort study of 43 642 patients who underwent coronary artery bypass or valvular heart surgery in 43 Department of Veterans Affairs medical centers between April 1987 and March 1994. Logistic regression analysis was used to identify independent predictors of ARF requiring dialysis. A risk stratification algorithm derived from recursive partitioning was constructed and was validated on an independent sample of 3795 patients operated on between April and December 1994. The overall risk of ARF requiring dialysis was 1.1%. Thirty-day mortality in patients with ARF was 63.7%, compared with 4.3% in patients without AR...
TL;DR: Elevated levels of fibrinogen, white blood cell count, factor VIII, and von Willebrand factor are risk factors and may play causative roles in coronary heart disease, however, their measurement in healthy adults appears to add little to prediction of coronary events beyond that of more established risk factors.
Abstract: Background Although hemostatic factors contribute to acute coronary syndromes and atherogenesis, few studies have prospectively evaluated the association between multiple hemostatic factors and coronary heart disease incidence. Methods and Results The Atherosclerosis Risk in Communities Study recruited 14 477 adults from 45 to 64 years of age who were initially free of coronary heart disease. Coronary disease risk factors and several plasma hemostatic factors were measured, and incidence of coronary heart disease was ascertained during an average follow-up of 5.2 years. Age-, race-, and field center–adjusted relative risks of coronary heart disease were significantly elevated (P≤.05) per higher value of fibrinogen (relative risk: men, 1.76; women, 1.54), white blood cell count (men, 1.68; women, 2.23), factor VIII coagulant activity (women, 1.25), and von Willebrand factor antigen (men, 1.20; women, 1.18). Adjustment for other risk factors attenuated these associations for fibrinogen (adjusted relative ri...
TL;DR: Paclitaxel inhibits haSMC proliferation and migration in a dose-dependent manner in monocultures and cocultures even in the presence of mitogens, and prevents neointima formation in rabbits after balloon angioplasty.
Abstract: Background The antineoplastic compound paclitaxel (Taxol) causes an increased assembly of extraordinarily stable microtubules. The present study was designed to characterize the effects of paclitax...
TL;DR: The myocardial phosphocreatine-to-ATP ratio, measured noninvasively with 31P-MR spectroscopy, is a predictor of both total and cardiovascular mortality in patients with dilated cardiomyopathy.
Abstract: Background In patients with heart failure due to dilated cardiomyopathy, cardiac energy metabolism is impaired, as indicated by a reduction of the myocardial phosphocreatine-to-ATP ratio, measured noninvasively by 31P-MR spectroscopy. The purpose of this study was to test whether the phosphocreatine-to-ATP ratio also offers prognostic information in terms of mortality prediction as well as how this index compares with well-known mortality predictors such as left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) class. Methods and Results Thirty-nine patients with dilated cardiomyopathy were followed up for 928±85 days (2.5 years). At study entry, LVEF and NYHA class were determined, and the cardiac phosphocreatine-to-ATP ratio was measured by localized 31P-MR spectroscopy of the anterior myocardium. During the study period, total mortality was 26%. Patients were divided into two groups, one with a normal phosphocreatine-to-ATP ratio (>1.60; mean±SE, 1.98±0.07; n=19; healthy volunte...
TL;DR: Despite an overall reduction in the death rate due to cardiovascular disease (CVD) in the United States over the last several decades, the rate of decline is less for women than men and less for African-American women than white women as discussed by the authors.
Abstract: Despite an overall reduction in the death rate due to cardiovascular disease (CVD) in the United States over the last several decades, the rate of decline is less for women than men and less for African-American women than white women.1 Due to an aging population, the absolute number of deaths due to CVD in women is actually increasing (Fig 1⇓).2 In the year 2000 nearly 50 million American women will be older than 50 years. Because the risk of CVD increases with age, there is a need for an increased awareness of the importance of CVD as a major public health issue for older women. The estimated direct and indirect costs of CVD and stroke in men and women combined will exceed $250 billion in 1997.2 CVD ranks first among all disease categories in hospital discharges for women. The sheer magnitude of the epidemic in women necessitates a strong emphasis on prevention to reduce the burden of CVD in our society.
Figure 1.
CVD, particularly coronary heart disease (CHD) and stroke, remains the leading killer of women in America and most developed countries. In 1994, the last year for which statistics are available, CVD claimed the lives of more than one half million women and accounted for 45.2% of all deaths in women, more than all forms of cancer combined.2 CVD is a particularly important problem among minority women. The death rate due to CVD is 69% higher in black women than white women. Misperceptions still exist that CVD is not a real problem for women, although it is estimated that 1 in 2 women will eventually die of heart disease or stroke, compared with 1 in 25 who will eventually die of breast cancer.2 This report discusses recent advances in knowledge of the occurrence, …
TL;DR: An increased anti-Cp antibody titre may be a predictor for further adverse cardiovascular events in post-MI patients and taking a short course of azithromycin may lower this risk, possibly by acting against Cp.
Abstract: Background The clinical significance of the association between elevated anti– Chlamydia pneumoniae (Cp) antibody titres and coronary heart disease (CHD) is unclear. We explored the relationship between antibodies against Cp and future cardiovascular events in male survivors of myocardial infarction (MI). The effect of azithromycin antibiotic therapy was assessed in a subgroup of post-MI patients. Methods and Results We screened 220 consecutive male survivors of MI for anti-Cp antibodies. Of these, 213 patients were stratified into three groups: group Cp-ve (n=59), no detectable Cp antibodies; group Cp-I (n=74), intermediate titres of 1/8 to 1/32 dilution; and group Cp+ve (n=80), seropositive at ≥1/64 dilution. Patients with persisting seropositivity of ≥1/64 were randomized to either oral azithromycin (Cp+ve-A, 500 mg/d for 3 days [n=28] or 500 mg/d for 6 days [n=12]) or placebo (Cp+ve-P, n=20). Cp+ve-NR (n=20) represented patients not recruited into the antibiotic trial. The incidence of adverse cardiovascular events (over a mean follow-up period of 18±4 months) was recorded and shown to increase with increasing anti-Cp titre: Cp-ve, n=4 (7%); Cp-I, n=11 (15%); Cp+ve-NR, n=6 (30%); and Cp+ve-P, n=5 (25%). Cp+ve-NR and Cp+ve-P groups had a fourfold-increased risk for adverse cardiovascular events compared with the Cp-ve group (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.2 to 15.5; P =.03). In contrast, the OR for cardiovascular events in patients receiving azithromycin (Cp+ve-A, single or double course) was the same as in the Cp-ve group (OR, 0.9; 95% CI, 0.2 to 4.6, P =NS). Patients receiving azithromycin were more likely to experience a decrease in IgG anti-Cp titres than were those in the placebo group ( P =.02). Conclusions An increased anti-Cp antibody titre may be a predictor for further adverse cardiovascular events in post-MI patients. Taking a short course of azithromycin may lower this risk, possibly by acting against Cp.