Showing papers in "Circulation in 1998"
TL;DR: A simple coronary disease prediction algorithm was developed using categorical variables, which allows physicians to predict multivariate CHD risk in patients without overt CHD.
Abstract: Background—The objective of this study was to examine the association of Joint National Committee (JNC-V) blood pressure and National Cholesterol Education Program (NCEP) cholesterol categories with coronary heart disease (CHD) risk, to incorporate them into coronary prediction algorithms, and to compare the discrimination properties of this approach with other noncategorical prediction functions. Methods and Results—This work was designed as a prospective, single-center study in the setting of a community-based cohort. The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up. During the 12 years of follow-up, a total of 383 men and 227 women developed CHD, which was significantly associated with categories of blood pressure, total cholesterol, LDL cholesterol, and HDL cholesterol (all P,.001). Sex-specific prediction equations were formulated to predict CHD risk according to age, diabetes, smoking, JNC-V blood pressure categories, and NCEP total cholesterol and LDL cholesterol categories. The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used. After adjustment for other factors, ’28% of CHD events in men and 29% in women were attributable to blood pressure levels that exceeded high normal ($130/85). The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ($200 mg/dL) was 27% in men and 34% in women. Conclusions—Recommended guidelines of blood pressure, total cholesterol, and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample. A simple coronary disease prediction algorithm was developed using categorical variables, which allows physicians to predict multivariate CHD risk in patients without overt CHD. (Circulation. 1998;97:1837-1847.)
9,227 citations
TL;DR: There was a significant AF-sex interaction: AF diminished the female advantage in survival and AF remained significantly associated with excess mortality, with about a doubling of mortality in both sexes in subjects free of valvular heart disease and preexisting cardiovascular disease.
Abstract: Background—Atrial fibrillation (AF) causes substantial morbidity. It is uncertain whether AF is associated with excess mortality independent of associated cardiac conditions and risk factors. Methods and Results—We examined the mortality of subjects 55 to 94 years of age who developed AF during 40 years of follow-up of the original Framingham Heart Study cohort. Of the original 5209 subjects, 296 men and 325 women (mean ages, 74 and 76 years, respectively) developed AF and met eligibility criteria. By pooled logistic regression, after adjustment for age, hypertension, smoking, diabetes, left ventricular hypertrophy, myocardial infarction, congestive heart failure, valvular heart disease, and stroke or transient ischemic attack, AF was associated with an OR for death of 1.5 (95% CI, 1.2 to 1.8) in men and 1.9 (95% CI, 1.5 to 2.2) in women. The risk of mortality conferred by AF did not significantly vary by age. However, there was a significant AF-sex interaction: AF diminished the female advantage in survi...
4,390 citations
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TL;DR: Total mortality, rather than classifications of cardiac and arrhythmic mortality, should be used as primary objectives for many outcome studies.
Abstract: Sudden cardiac death describes the unexpected natural death from a cardiac cause within a short time period, generally ≤ 1 h from the onset of symptoms, in a person without any prior condition that would appear fatal [1, 2]. Such a rapid death is often attributed to a cardiac arrhythmia, but with the advent of monitoring capabilities from implantable cardioverter-defibrillators (ICDs), it is now well recognized that classifications based on clinical circumstances can be misleading and often impossible, because 40% of sudden deaths can be unwitnessed [3]. Only an ECG or a ventricular electrogram recorded from an implanted device at the time of death can provide definitive information about an arrhythmia. Prodromal symptoms are often nonspecific, and even those taken to indicate ischemia (chest pain), a tachyarrhythmia (palpitations), or congestive heart failure symptoms (dyspnea) can only be considered suggestive. For these reasons, total mortality, rather than classifications of cardiac and arrhythmic mortality, should be used as primary objectives for many outcome studies.
2,590 citations
TL;DR: Findings suggest that HMG CoA reductase inhibitors may have beneficial effects in atherosclerosis beyond that attributed to the lowering of serum cholesterol by increasing ecNOS activity.
Abstract: Background—Oxidized low-density lipoprotein (ox-LDL) causes endothelial dysfunction in part by decreasing the availability of endothelial nitric oxide (NO). Although HMG CoA reductase inhibitors restore endothelial function by reducing serum cholesterol levels, it is not known whether they can also directly upregulate endothelial NO synthase (ecNOS) activity. Methods and Results—Human saphenous vein endothelial cells were treated with ox-LDL (50 μg/mL thiobarbituric acid reactive substances 12 to 16 nmol/mg) in the presence of HMG CoA reductase inhibitors simvastatin and lovastatin. In a time-dependent manner, ox-LDL decreased ecNOS mRNA and protein levels (91±4% and 67±8% reduction after 72 hours, respectively). Both simvastatin (1 μmol/L) and lovastatin (10 μmol/L) upregulated ecNOS expression by 3.8-fold and 3.6-fold, respectively, and completely prevented its downregulation by ox-LDL. These effects of simvastatin on ecNOS expression correlated with changes in ecNOS activity. Although l-mevalonate alon...
1,890 citations
TL;DR: CRP is a strong independent risk factor for cardiovascular disease that adds to the predictive value of risk models based on usual factors alone and was a predictor among subgroups of women with low as well as high risk as defined by other cardiovascular risk factors.
Abstract: Background—C-reactive protein (CRP) predicts risk of myocardial infarction (MI) and stroke among apparently healthy men, but in women, virtually no data are available Methods and Results—CRP was measured in baseline blood samples from 122 apparently healthy participants in the Women’s Health Study who subsequently suffered a first cardiovascular event and from 244 age- and smoking-matched control subjects who remained free of cardiovascular disease during a 3-year follow-up period Women who developed cardiovascular events had higher baseline CRP levels than control subjects (P=00001), such that those with the highest levels at baseline had a 5-fold increase in risk of any vascular event (RR=48; 95% CI, 23 to 101; P=00001) and a 7-fold increase in risk of MI or stroke (RR=73; 95% CI, 27 to 199; P=00001) Risk estimates were independent of other risk factors, and prediction models that included CRP provided a better method to predict risk than models that excluded CRP (all P values <001) In str
1,695 citations
TL;DR: MBF can be quantified with myocardial contrast echocardiography during a venous infusion of microbubbles and has potential for measuring tissue perfusion in any organ accessible to ultrasound.
Abstract: Background—Ultrasound can cause microbubble destruction. If microbubbles are administered as a continuous infusion, then their destruction within the myocardium and measurement of their myocardial ...
1,631 citations
TL;DR: Both enhanced catabolism of triglyceride-rich particles and reduced secretion of VLDL underlie the hypotriglyceridemic effect of fibrates, whereas their effect on HDL metabolism is associated with changes in HDL apolipoprotein expression.
Abstract: Treatment with fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations. Recent investigations indicate that the effects of fibrates are mediated, at least in part, through alterations in transcription of genes encoding for proteins that control lipoprotein metabolism. Fibrates activate specific transcription factors belonging to the nuclear hormone receptor superfamily, termed peroxisome proliferator-activated receptors (PPARs). The PPAR-alpha form mediates fibrate action on HDL cholesterol levels via transcriptional induction of synthesis of the major HDL apolipoproteins, apoA-I and apoA-II. Fibrates lower hepatic apoC-III production and increase lipoprotein lipase--mediated lipolysis via PPAR. Fibrates stimulate cellular fatty acid uptake, conversion to acyl-CoA derivatives, and catabolism by the beta-oxidation pathways, which, combined with a reduction in fatty acid and triglyceride synthesis, results in a decrease in VLDL production. In summary, both enhanced catabolism of triglyceride-rich particles and reduced secretion of VLDL underlie the hypotriglyceridemic effect of fibrates, whereas their effect on HDL metabolism is associated with changes in HDL apolipoprotein expression.
1,604 citations
TL;DR: Evidence of inflammation after MI is associated with increased risk of recurrent coronary events, and therapy with pravastatin may decrease this risk, an observation consistent with a nonlipid effect of this agent.
Abstract: Background —We studied whether inflammation after myocardial infarction (MI) is a risk factor for recurrent coronary events and whether randomized treatment with pravastatin reduces that risk. Methods and Results —A nested case-control design was used to compare C-reactive protein (CRP) and serum amyloid A (SAA) levels in prerandomization blood samples from 391 participants in the Cholesterol and Recurrent Events (CARE) trial who subsequently developed recurrent nonfatal MI or a fatal coronary event (cases) and from an equal number of age- and sex-matched participants who remained free of these events during follow-up (control subjects). Overall, CRP and SAA were higher among cases than control subjects (for CRP P =0.05; for SAA P =0.006) such that those with levels in the highest quintile had a relative risk (RR) of recurrent events 75% higher than those with levels in the lowest quintile (for CRP RR=1.77, P =0.02; for SAA RR=1.74, P =0.02). The study group with the highest risk was that with consistent evidence of inflammation (elevation of both CRP and SAA) who were randomly assigned to placebo (RR=2.81, P =0.007); this risk estimate was greater than the product of the individual risks associated with inflammation or placebo assignment alone. In stratified analyses, the association between inflammation and risk was significant among those randomized to placebo (RR=2.11, P =0.048) but was attenuated and nonsignificant among those randomized to pravastatin (RR=1.29, P =0.5). Conclusions —Evidence of inflammation after MI is associated with increased risk of recurrent coronary events. Therapy with pravastatin may decrease this risk, an observation consistent with a nonlipid effect of this agent.
1,450 citations
TL;DR: After infarction, MRI-determined microvascular obstruction predicts more frequent cardiovascular complications, and infarct size determined by MRI also relates directly to long-term prognosis in patients with acute myocardial infarctions.
Abstract: Background—The extent of microvascular obstruction during acute coronary occlusion may determine the eventual magnitude of myocardial damage and thus, patient prognosis after infarction. By contras...
1,353 citations
TL;DR: Elevation of ADMA is associated with impaired endothelium-dependent vasodilation and reduced urinary nitrate excretion and this abnormality is reversed by administration of L-arginine.
Abstract: Background—Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase. Because endothelial NO elaboration is impaired in hypercholesterolemia, we investigated whether plasma concentrations of ADMA are elevated in young, clinically asymptomatic hypercholesterolemic adults. We further studied whether such elevation of ADMA levels was correlated with impaired endothelium-dependent, NO-mediated vasodilation and urinary nitrate excretion. In a randomized, double-blind, placebo-controlled study, we investigated whether these changes could be reversed with exogenous l-arginine. Methods and Results—We measured plasma levels of l-arginine, ADMA, and symmetrical dimethylarginine (SDMA) by high-performance liquid chromatography in 49 hypercholesterolemic (HC) and 31 normocholesterolemic (NC) humans. In 8 HC subjects, endothelium-dependent forearm vasodilation was assessed before and after an intravenous infusion of l-arginine or placebo and compared with 8 NC control subj...
1,216 citations
TL;DR: Patients with mildly abnormal scans after exercise stress are at low risk for cardiac death but intermediate risk for nonfatal myocardial infarction and thus may benefit from a noninvasive strategy and may not require invasive management.
Abstract: Background—The incremental prognostic value of stress single photon emission computed tomography (SPECT) for the prediction of cardiac death as an individual end point and the implications for risk stratification are undefined. Methods and Results—We identified 5183 consecutive patients who underwent stress/rest SPECT and were followed up for the occurrence of cardiac death or myocardial infarction. Over a mean follow up of 642±226 days, 119 cardiac deaths and 158 myocardial infarctions occurred (3.0% cardiac death rate, 2.3% myocardial infarction rate). Patients with normal scans were at low risk (≤0.5%/y), and rates of both outcomes increased significantly with worsening scan abnormalities. Patients who underwent exercise stress and had mildly abnormal scans had low rates of cardiac death but higher rates of myocardial infarction (0.7%/y versus 2.6%/y; P<.05). After adjustment for prescan information, scan results provided incremental prognostic value toward the prediction of cardiac death. The identifi...
TL;DR: Sleep disruption and arterial oxyhemoglobin desaturation were significantly more severe and the prevalence of atrial fibrillation and ventricular arrhythmias were greater in group 2 than in group 1.
Abstract: Background—Heart failure is a highly prevalent disorder that continues to be associated with repeated hospitalizations, high morbidity, and high mortality. Sleep-related breathing disorders with repetitive episodes of asphyxia may adversely affect heart function. The main aims of this study were to determine the prevalence, consequences, and differences in various sleep-related breathing disorders in ambulatory male patients with stable heart failure. Methods and Results—This article reports the results of a prospective study of 81 of 92 eligible patients with heart failure and a left ventricular ejection fraction <45%. There were 40 patients without (hourly rate of apnea/hypopnea, 4±4; group 1) and 41 patients with (51% of all patients; hourly rate of apnea/hypopnea, 44±19; group 2) sleep apnea. Sleep disruption and arterial oxyhemoglobin desaturation were significantly more severe and the prevalence of atrial fibrillation (22% versus 5%) and ventricular arrhythmias were greater in group 2 than in group ...
TL;DR: In this article, the authors investigated the value of angiographic evidence of myocardial reperfusion (myocardial blush grade) in relation to the extent of ST-segment elevation resolution, enzymatic infarct size, left ventricular function, and long-term mortality.
Abstract: Background—The primary objective of reperfusion therapies for acute myocardial infarction is not only restoration of blood flow in the epicardial coronary artery but also complete and sustained reperfusion of the infarcted part of the myocardium. Methods and Results—We studied 777 patients who underwent primary coronary angioplasty during a 6-year period and investigated the value of angiographic evidence of myocardial reperfusion (myocardial blush grade) in relation to the extent of ST-segment elevation resolution, enzymatic infarct size, left ventricular function, and long-term mortality. The myocardial blush immediately after the angioplasty procedure was graded by two experienced investigators, who were otherwise blinded to all clinical data: 0, no myocardial blush; 1, minimal myocardial blush; 2, moderate myocardial blush; and 3, normal myocardial blush. The myocardial blush was related to the extent of the early ST-segment elevation resolution on the 12-lead ECG. Patients with blush grades 3, 2, and...
TL;DR: CHF is associated with autonomic dysfunction, which can be quantified by measuring HRV, and a reduction in SDNN identifies patients at high risk of death and is a better predictor of death due to progressive heart failure than other conventional clinical measurements.
Abstract: Background—Patients with chronic heart failure (CHF) have a continuing high mortality. Autonomic dysfunction may play an important role in the pathophysiology of cardiac death in CHF. UK-HEART exam...
TL;DR: Findings may be cautiously interpreted to indicate that intramuscular injection of naked plasmid DNA achieves constitutive overexpression of VEGF sufficient to induce therapeutic angiogenesis in selected patients with critical limb ischemia.
Abstract: Background—Preclinical studies have indicated that angiogenic growth factors can stimulate the development of collateral arteries, a concept called “therapeutic angiogenesis.” The objectives of this phase 1 clinical trial were (1) to document the safety and feasibility of intramuscular gene transfer by use of naked plasmid DNA encoding an endothelial cell mitogen and (2) to analyze potential therapeutic benefits in patients with critical limb ischemia. Methods and Results—Gene transfer was performed in 10 limbs of 9 patients with nonhealing ischemic ulcers (n=7/10) and/or rest pain (n=10/10) due to peripheral arterial disease. A total dose of 4000 μg of naked plasmid DNA encoding the 165-amino-acid isoform of human vascular endothelial growth factor (phVEGF165) was injected directly into the muscles of the ischemic limb. Gene expression was documented by a transient increase in serum levels of VEGF monitored by ELISA. The ankle-brachial index improved significantly (0.33±0.05 to 0.48±0.03, P=.02); newly v...
TL;DR: A multifaceted strategy aimed at prevention of vein graft disease is emerging, elements of which include: continued improvements in surgical technique; more effective antiplatelet drugs; increasingly intensive risk factor modification; and a number of evolving therapies, such as gene transfer and nitric oxide donor administration, which target vein graft Disease at an early and fundamental level.
Abstract: Aortocoronary saphenous vein graft disease, with its increasing clinical sequelae, presents an important and unresolved dilemma in cardiological practice. During the 1st month after bypass surgery, vein graft attrition results from thrombotic occlusion, while later the dominant process is atherosclerotic obstruction occurring on a foundation of neointimal hyperplasia. Although the risk factors predisposing to vein graft atherosclerosis are broadly similar to those recognized for native coronary disease, the pathogenic effects of these risk factors are amplified by inherent deficiencies of the vein as a conduit when transposed into the coronary arterial circulation. A multifaceted strategy aimed at prevention of vein graft disease is emerging, elements of which include: continued improvements in surgical technique; more effective antiplatelet drugs; increasingly intensive risk factor modification, in particular early and aggressive lipid-lowering drug therapy; and a number of evolving therapies, such as gene transfer and nitric oxide donor administration, which target vein graft disease at an early and fundamental level. At present, a key measure is to circumvent the problem of vein graft disease by preferential selection of arterial conduits, in particular the internal mammary arteries, for coronary bypass surgery whenever possible.
TL;DR: The discordant trend of rising CVD mortality rates in Eastern Europe, however, is in sharp contrast to the decline in Western Europe.
Abstract: As the twentieth century draws to a close, it is clear that cardiovascular disease (CVD) has become a ubiquitous cause of morbidity and a leading contributor to mortality in most countries.1 2 The rise and recent decline of the CVD epidemic in the developed countries have been well documented.3 4 The identification of major risk factors through population-based studies and effective control strategies combining community education and targeted management of high risk individuals have contributed to the fall in CVD mortality rates (inclusive of coronary and stroke deaths) that has been observed in almost all industrialized countries. It has been estimated that during the period 1965 to 1990, CVD related mortality fell by ≈50% in Australia, Canada, France, and the United States and by 60% in Japan.1 Other parts of Western Europe reported more modest declines (20% to 25%). The decline in stroke mortality has been more marked compared with the decline in coronary mortality. In the United States, the decline in stroke mortality commenced nearly two decades earlier than the decline in coronary mortality and maintained a sharper rate of decline. During the period 1979 to 1989, the age-adjusted mortality from stroke declined, in that country, by about one third, whereas the corresponding decline in coronary mortality was 22%.4 5 In Japan, where stroke mortality outweighs coronary mortality, the impressive overall decline in CVD mortality is principally contributed by the former. The discordant trend of rising CVD mortality rates in Eastern Europe, however, is in sharp contrast to the decline in Western Europe.1
The emergence of the CVD epidemic in the developing countries during the past two to three decades has attracted less comment and little public health response, even within these countries. It is not widely realized that at present, the developing countries …
TL;DR: In prospective data from a large cohort of apparently healthy men, baseline CRP level added to the predictive value of lipid parameters in determining risk of first MI.
Abstract: Background—C-reactive protein (CRP) is a sensitive marker of inflammation, and elevated levels have been associated with future risk of myocardial infarction (MI). However, whether measurement of CRP adds to the predictive value of total cholesterol (TC) and HDL cholesterol (HDL-C) in determining risk is uncertain. Methods and Results—Among 14 916 apparently healthy men participating in the Physicians’ Health Study, baseline levels of CRP, TC, and HDL-C were measured among 245 study subjects who subsequently developed a first MI (cases) and among 372 subjects who remained free of cardiovascular disease during an average follow-up period of 9 years (controls). In univariate analyses, high baseline levels of CRP, TC, and TC:HDL-C ratio were each associated with significantly increased risks of future MI (all P values <0.001). In multivariate analyses, models incorporating CRP and lipid parameters provided a significantly better method to predict risk than did models using lipids alone (all likelihood ratio ...
TL;DR: This initial experience with naked gene transfer as sole therapy for myocardial ischemia suggests that directMyocardial injection of naked plasmid DNA, via a minimally invasive chest wall incision, is safe and may lead to reduced symptoms and improved myocardian perfusion in selected patients with chronic myocardia.
Abstract: Background—We initiated a phase 1 clinical study to determine the safety and bioactivity of direct myocardial gene transfer of vascular endothelial growth factor (VEGF) as sole therapy for patients with symptomatic myocardial ischemia. Methods and Results—VEGF gene transfer (GTx) was performed in 5 patients (all male, ages 53 to 71) who had failed conventional therapy; these men had angina (determined by angiographically documented coronary artery disease). Naked plasmid DNA encoding VEGF (phVEGF165) was injected directly into the ischemic myocardium via a mini left anterior thoracotomy. Injections caused no changes in heart rate (pre-GTx=75±15/min versus post-GTx=80±16/min, P=NS), systolic BP (114±7 versus 118±7 mm Hg, P=NS), or diastolic BP (57±2 versus 59±2 mm Hg, P=NS). Ventricular arrhythmias were limited to single unifocal premature beats at the moment of injection. Serial ECGs showed no evidence of new myocardial infarction in any patient. Intraoperative blood loss was 0 to 50 cm3, and total chest ...
TL;DR: In this paper, the authors evaluated all patients receiving a first diagnosis of congestive heart failure in Olmsted County, Minnesota, in 1991 (n=216) and found that the prognosis of patients with a new diagnosis of CHF was poor; survival was 86±2% at 3 months, 76±3% at 1 year, and 35±3%.
Abstract: Background—Data are limited regarding the classification and prognosis of patients with congestive heart failure (CHF) in the community. Methods and Results—Using the resources of the Rochester Epidemiology Project, we evaluated all patients receiving a first diagnosis of CHF in Olmsted County, Minnesota, in 1991 (n=216). Among these patients, 88% were ≥65 years and 49% were ≥80 years of age. The prognosis of patients with a new diagnosis of CHF was poor; survival was 86±2% at 3 months, 76±3% at 1 year, and 35±3% at 5 years. Of the 216 patients, 137 (63%) had an assessment of ejection fraction. In these patients, systolic function was preserved (ejection fraction ≥50%) in 59 (43%) and reduced (ejection fraction <50%) in 78 (57%). Survival adjusted for age, sex, NYHA class, and coronary artery disease was not significantly different between patients with preserved and those with reduced systolic function (relative risk, 0.80; P=0.369). ACE inhibitors were used in only 44% of the total population with CHF. ...
TL;DR: These guidelines follow the format established in previous American College of Cardiology/American Heart Association (ACC/AHA) guidelines for classifying indications for diagnostic and therapeutic procedures, and make recommendations for diagnostic testing, treatment, and physical activity.
Abstract: This executive summary and recommendations appears in the November 3, 1998, issue of Circulation . The guidelines in their entirety, including the ACC/AHA Class I, II, and III recommendations, are published in the November 1, 1998, issue of the Journal of the American College of Cardiology . Reprints of both the full text and the executive summary and recommendations are available from both organizations.
During the past 2 decades, major advances have occurred in diagnostic techniques, the understanding of natural history, and interventional cardiological and surgical procedures for patients with valvular heart disease. The information base from which to make clinical management decisions has greatly expanded in recent years, yet in many situations, management issues remain controversial or uncertain. Unlike many other forms of cardiovascular disease, there is a scarcity of large-scale multicenter trials addressing the diagnosis and treatment of valvular disease from which to derive definitive conclusions, and the literature represents primarily the experiences reported by single institutions in relatively small numbers of patients.
The Committee on Management of Patients With Valvular Disease was given the task of reviewing and compiling this information base and making recommendations for diagnostic testing, treatment, and physical activity. These guidelines follow the format established in previous American College of Cardiology/American Heart Association (ACC/AHA) guidelines for classifying indications for diagnostic and therapeutic procedures:
Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective
Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment
IIa. Weight of evidence/opinion is in favor of usefulness/efficacy
IIb. Usefulness/efficacy is less well established by evidence/opinion.
Class III: Conditions for which there is evidence and/or general agreement that the procedure/treatment is not useful and in some cases …
TL;DR: It is indicated that among apparently healthy men, baseline levels of CRP predict future risk of developing symptomatic PAD and thus provide further support for the hypothesis that chronic inflammation is important in the pathogenesis of atherothrombosis.
Abstract: Background—Among apparently healthy men, elevated levels of C-reactive protein (CRP), a marker for systemic inflammation, predict risk of myocardial infarction and thromboembolic stroke. Whether increased levels of CRP are also associated with the development of symptomatic peripheral arterial disease (PAD) is unknown. Methods and Results—Using a prospective, nested, case-control design, we measured baseline levels of CRP in 144 apparently healthy men participating in the Physicians’ Health Study who subsequently developed symptomatic PAD (intermittent claudication or need for revascularization) and in an equal number of control subjects matched on the basis of age and smoking habit who remained free of vascular disease during a follow-up period of 60 months. Median CRP levels at baseline were significantly higher among those who subsequently developed PAD (1.34 versus 0.99 mg/L; P=.04). Furthermore, the risks of developing PAD increased significantly with each increasing quartile of baseline CRP concentr...
TL;DR: Diabetic patients and nondiabetic patients with impaired fasting glucose are at high risk of recurrent coronary events that can be substantially reduced by pravastatin treatment.
Abstract: Background—Although diabetes is a major risk factor for coronary heart disease (CHD), little information is available on the effects of lipid lowering in diabetic patients. We determined whether li...
TL;DR: The authors' data suggest that the "pathophysiological U" wave observed in acquired or congenital LQTS is more likely to be a second component of an interrupted T wave, and argue for use of the term T2 in place of U to describe this event.
Abstract: Background—This study probes the cellular basis for the T wave under baseline and long-QT (LQT) conditions using an arterially perfused canine left ventricular (LV) wedge preparation, which permits direct temporal correlation of cellular transmembrane and ECG events. Methods and Results—Floating microelectrodes were used to record transmembrane action potentials (APs) simultaneously from epicardial, M-region, and endocardial sites or subendocardial Purkinje fibers. A transmural ECG was recorded concurrently. Under baseline and LQT conditions, repolarization of the epicardial action potential, the earliest to repolarize, coincided with the peak of the T wave; repolarization of the M cells, the last to repolarize, coincided with the end of the T wave. Thus, the action potential duration (APD) of the longest M cells determine the QT interval and the Tpeak–Tend interval serves as an index of transmural dispersion of repolarization. Repolarization of Purkinje fibers outlasted that of the M cell but failed to r...
TL;DR: Ongoing studies will elucidate the effect of ACE inhibitor on cardiovascular mortality in essential hypertension, the role of ACE inhibitors in patients without ventricular dysfunction after myocardial infarction, and the roleof ACE inhibitors compared with newly available angiotensin AT1 receptor antagonists.
Abstract: ACE inhibitors have achieved widespread usage in the treatment of cardiovascular and renal disease. ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and hypertrophic properties of angiotensin II (Ang II) and the vasodilatory and natriuretic properties of bradykinin and alter the metabolism of a number of other vasoactive substances. ACE inhibitors differ in the chemical structure of their active moieties, in potency, in bioavailability, in plasma half-life, in route of elimination, in their distribution and affinity for tissue-bound ACE, and in whether they are administered as prodrugs. Thus, the side effects of ACE inhibitors can be divided into those that are class specific and those that relate to specific agents. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have proved effective in the treatment of hypertension, they decrease mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction, and they delay the progression of diabetic nephropathy. Ongoing studies will elucidate the effect of ACE inhibitors on cardiovascular mortality in essential hypertension, the role of ACE inhibitors in patients without ventricular dysfunction after myocardial infarction, and the role of ACE inhibitors compared with newly available angiotensin AT1 receptor antagonists.
TL;DR: The results demonstrate that diazoxide targets mitochondrial but not sarcolemmal KATP channels and imply that mitochondrial KatP channels may mediate the protection from KATp channel openers.
Abstract: Background—Brief interruptions of coronary blood flow paradoxically protect the heart from subsequent prolonged ischemia. The basis of such endogenous cardioprotection, known as “ischemic precondit...
TL;DR: The effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure were determined.
Abstract: Background—The purpose of this study was to determine the effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure (CHF). Endothelial dysfunction is a key feature of CHF, contributing to increased peripheral vasoconstriction and impaired exercise capacity. Local handgrip exercise has previously been shown to enhance endothelium-dependent vasodilation in conduit and resistance vessels in CHF. Methods and Results—Twenty patients were prospectively randomized to a training group (n=10, left ventricular ejection fraction [LVEF] 24±4%) or a control group (n=10, LVEF 23±3%). At baseline and after 6 months, peak flow velocity was measured in the left femoral artery using a Doppler wire; vessel diameter was determined by quantitative angiography. Peripheral blood flow was calculated from average peak velocity (APV) and arterial cross-sectional area. After exercise training, nitroglycerin-induced endotheli...
TL;DR: The American Heart Association (AHA) has reclassified obesity as a major, modifiable risk factor for coronary heart disease and issues a “call to action” to the medical and research community, as well as the public.
Abstract: In response to the emerging body of scientific, medical, and behavioral data about the link between excess adiposity and coronary heart disease, the American Heart Association (AHA) has reclassified obesity as a major, modifiable risk factor for coronary heart disease.
In doing so, the AHA focuses more of its attention and resources on the role of obesity in cardiovascular disease and issues a “call to action” to the medical and research community, as well as the public. The actions that we request are listed below and begin with the need for more funding for research on obesity, particularly the interrelated roles of the biochemical and behavioral factors that underlie weight regulation. Only through such research can we better understand this disorder and develop more effective preventive strategies and treatments for obesity.
Obesity research today is in its infancy, at a stage comparable to lipid research 20 years ago. From epidemiology studies, we have learned that obesity is a serious risk factor for coronary heart disease, on a par with cigarette smoking, physical inactivity, and high blood cholesterol. Because the research on this “new” risk factor for heart disease is in its infancy, the solutions are less clear. Few drugs exist to prevent and treat obesity, and certainly there are no drugs comparable to the “statins” to reduce high blood cholesterol. The long-term effects of the few treatments available remain unknown. There are few tools …
TL;DR: A gas-filled microbubble with anti-ICAM-1 antibody on its shell specifically binds to activated ECs overexpressing ICam-1.
Abstract: Background—Preclinical atherosclerosis is associated with increased endothelial cell (EC) expression of leukocyte adhesion molecules (LAMs), which mediate monocyte adhesion during atherogenesis. Identification of cell-surface LAMs may uniquely allow assessment of endothelial function, but there are no in vivo methods for detecting LAMs. We tested a new microbubble designed to bind to and allow specific ultrasound detection of intercellular adhesion molecule-1 (ICAM-1). Methods and Results—A perfluorobutane gas–filled lipid-derived microsphere with monoclonal antibody to ICAM-1 covalently bound to the bubble shell was synthesized. Bubbles with either nonspecific IgG or no protein on the shell were synthesized as controls. Coverslips of cultured human coronary artery ECs were placed in a parallel-plate perfusion chamber and exposed to 1 of the 3 microbubble species, followed by perfusion with culture medium. Experiments were performed with either normal or interleukin-1β–activated ECs overexpressing ICAM-1,...
TL;DR: These studies suggest that pathophysiologically relevant concentrations of TNF-alpha are sufficient to mimic certain aspects of the phenotype observed in experimental and clinical models of heart failure.
Abstract: Background —Although patients with heart failure express elevated circulating levels of tumor necrosis factor-α (TNF-α) in their peripheral circulation, the structural and functional effects of circulating levels of pathophysiologically relevant concentrations of TNF-α on the heart are not known. Methods and Results —Osmotic infusion pumps containing either diluent or TNF-α were implanted into the peritoneal cavity of rats. The rate of TNF-α infusion was titrated to obtain systemic levels of biologically active TNF-α comparable to those reported in patients with heart failure (≈80 to 100 U/mL), and the animals were examined serially for 15 days. Two-dimensional echocardiography was used to assess changes in left ventricular (LV) structure (remodeling) and LV function. Video edge detection was used to assess isolated cell mechanics, and standard histological techniques were used to assess changes in the volume composition of LV cardiac myocytes and the extracellular matrix. The reversibility of cytokine-induced effects was determined either by removal of the osmotic infusion pumps on day 15 or by treatment of the animals with a soluble TNF-α antagonist (TNFR:Fc). The results of this study show that a continuous infusion of TNF-α led to a time-dependent depression in LV function, cardiac myocyte shortening, and LV dilation that were at least partially reversible by removal of the osmotic infusion pumps or treatment of the animals with TNFR:Fc. Conclusions —These studies suggest that pathophysiologically relevant concentrations of TNF-α are sufficient to mimic certain aspects of the phenotype observed in experimental and clinical models of heart failure.