Showing papers in "Circulation in 2004"
TL;DR: Although considerable improvement has occurred in the process of care for patients with ST-elevation myocardial infarction (STEMI), room for improvement exists as discussed by the authors, and the purpose of the present guideline is to focus on the numerous advances in the diagnosis and management of patients
Abstract: Although considerable improvement has occurred in the process of care for patients with ST-elevation myocardial infarction (STEMI), room for improvement exists.[1–3][1][][2][][3] The purpose of the present guideline is to focus on the numerous advances in the diagnosis and management of patients
8,352 citations
TL;DR: The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL, and confirm that older persons benefit from therapeutic lowering of LDL-C.
Abstract: The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.
6,944 citations
TL;DR: Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes, when diabetes becomes clinically apparent, CVD risk rises sharply.
Abstract: The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III)1 identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention. The cardiovascular community has responded with heightened awareness and interest. ATP III criteria for metabolic syndrome differ somewhat from those of other organizations. Consequently, the National Heart, Lung, and Blood Institute, in collaboration with the American Heart Association, convened a conference to examine scientific issues related to definition of the metabolic syndrome. The scientific evidence related to definition was reviewed and considered from several perspectives: (1) major clinical outcomes, (2) metabolic components, (3) pathogenesis, (4) clinical criteria for diagnosis, (5) risk for clinical outcomes, and (6) therapeutic interventions.
ATP III viewed CVD as the primary clinical outcome of metabolic syndrome. Most individuals who develop CVD have multiple risk factors. In 1988, Reaven2 noted that several risk factors (eg, dyslipidemia, hypertension, hyperglycemia) commonly cluster together. This clustering he called Syndrome X , and he recognized it as a multiplex risk factor for CVD. Reaven and subsequently others postulated that insulin resistance underlies Syndrome X (hence the commonly used term insulin resistance syndrome ). Other researchers use the term metabolic syndrome for this clustering of metabolic risk factors. ATP III used this alternative term. It avoids the implication that insulin resistance is the primary or only cause of associated risk factors. Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes. When diabetes becomes clinically apparent, CVD risk rises sharply. Beyond CVD and type 2 diabetes, individuals with metabolic syndrome seemingly are susceptible to other conditions, notably polycystic ovary syndrome, fatty liver, cholesterol gallstones, asthma, sleep disturbances, and some …
6,238 citations
TL;DR: Clinical trials have shown that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) improve endothelial dysfunction in patients with coronary risk factors beyond what could be attributed to their impact on plasma lipids.
Abstract: As the major regulator of vascular homeostasis, the endothelium exerts a number of vasoprotective effects, such as vasodilation, suppression of smooth muscle cell growth, and inhibition of inflammatory responses. Many of these effects are largely mediated by nitric oxide, the most potent endogenous vasodilator. Nitric oxide opposes the effects of endothelium-derived vasoconstrictors and inhibits oxidation of low-density lipoprotein. A defect in the production or activity of nitric oxide leads to endothelial dysfunction, signaled by impaired endothelium-dependent vasodilation. Accumulating evidence suggests that endothelial dysfunction is an early marker for atherosclerosis and can be detected before structural changes to the vessel wall are apparent on angiography or ultrasound. Many of the risk factors that predispose to atherosclerosis can also cause endothelial dysfunction, and the presence of multiple risk factors has been found to predict endothelial dysfunction. A number of clinical trials have shown that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) improve endothelial dysfunction in patients with coronary risk factors beyond what could be attributed to their impact on plasma lipids. Studies have elucidated several possible mechanisms by which statin therapy may improve endothelial dysfunction, including upregulation of nitric oxide production or activity and reduction of oxidative stress.
2,311 citations
TL;DR: A task force of the International Liaison Committee on Resuscitation (ILCOR) met in Melbourne, Australia, to review worldwide experience with the Utstein definitions and reporting templates as mentioned in this paper.
Abstract: Outcome after cardiac arrest and cardiopulmonary resuscitation is dependent on critical interventions, particularly early defibrillation, effective chest compressions, and advanced life support. Utstein-style definitions and reporting templates have been used extensively in published studies of cardiac arrest, which has led to greater understanding of the elements of resuscitation practice and progress toward international consensus on science and resuscitation guidelines. Despite the development of Utstein templates to standardize research reports of cardiac arrest, international registries have yet to be developed. In April 2002, a task force of the International Liaison Committee on Resuscitation (ILCOR) met in Melbourne, Australia, to review worldwide experience with the Utstein definitions and reporting templates. The task force revised the core reporting template and definitions by consensus. Care was taken to build on previous definitions, changing data elements and operational definitions only on the basis of published data and experience derived from those registries that have used Utstein-style reporting. Attention was focused on decreasing the complexity of the existing templates and addressing logistical difficulties in collecting specific core and supplementary (ie, essential and desirable) data elements recommended by previous Utstein consensus conferences. Inconsistencies in terminology between in-hospital and out-of-hospital Utstein templates were also addressed. The task force produced a reporting tool for essential data that can be used for both quality improvement (registries) and research reports and that should be applicable to both adults and children. The revised and simplified template includes practical and succinct operational definitions. It is anticipated that the revised template will enable better and more accurate completion of all reports of cardiac arrest and resuscitation attempts. Problems with data definition, collection, linkage, confidentiality, management, and registry implementation are acknowledged and potential solutions offered. Uniform collection and tracking of registry data should enable better continuous quality improvement within every hospital, emergency medical services system, and community.
2,277 citations
TL;DR: The purpose of this statement is to provide healthcare professionals and regulatory agencies with a comprehensive review of the literature on air pollution and cardiovascular disease and practical recommendations for healthcare providers and their patients are outlined.
Abstract: Air pollution is a heterogeneous, complex mixture of gases, liquids, and particulate matter. Epidemiological studies have demonstrated a consistent increased risk for cardiovascular events in relation to both short- and long-term exposure to present-day concentrations of ambient particulate matter. Several plausible mechanistic pathways have been described, including enhanced coagulation/thrombosis, a propensity for arrhythmias, acute arterial vasoconstriction, systemic inflammatory responses, and the chronic promotion of atherosclerosis. The purpose of this statement is to provide healthcare professionals and regulatory agencies with a comprehensive review of the literature on air pollution and cardiovascular disease. In addition, the implications of these findings in relation to public health and regulatory policies are addressed. Practical recommendations for healthcare providers and their patients are outlined. In the final section, suggestions for future research are made to address a number of remaining scientific questions.
2,213 citations
TL;DR: The findings suggest that autologous delivery of either native or transduced subcutaneous ASCs, which are regulated by hypoxia, may be a novel therapeutic option to enhance angiogenesis or achieve cardiovascular protection.
Abstract: Background— The delivery of autologous cells to increase angiogenesis is emerging as a treatment option for patients with cardiovascular disease but may be limited by the accessibility of sufficient cell numbers. The beneficial effects of delivered cells appear to be related to their pluripotency and ability to secrete growth factors. We examined nonadipocyte stromal cells from human subcutaneous fat as a novel source of therapeutic cells. Methods and Results— Adipose stromal cells (ASCs) were isolated from human subcutaneous adipose tissue and characterized by flow cytometry. ASCs secreted 1203±254 pg of vascular endothelial growth factor (VEGF) per 106 cells, 12 280±2944 pg of hepatocyte growth factor per 106 cells, and 1247±346 pg of transforming growth factor-β per 106 cells. When ASCs were cultured in hypoxic conditions, VEGF secretion increased 5-fold to 5980±1066 pg/106 cells (P=0.0016). The secretion of VEGF could also be augmented 200-fold by transfection of ASCs with a plasmid encoding VEGF (P<0...
2,174 citations
TL;DR: Lifetime risks for development of AF are 1 in 4 for men and women 40 years of age and older, even in the absence of antecedent congestive heart failure or myocardial infarction, and substantial lifetime risks underscore the major public health burden posed by AF.
Abstract: Background— Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated. Methods and Results— We included all participants in the Framingham Heart Study who were free of AF at index ages of 40 years and older. We estimated lifetime risks for AF (including atrial flutter) to age 95 years, with death free of AF as a competing event. We followed 3999 men and 4726 women from 1968 to 1999 (176 166 person-years); 936 participants had development of AF and 2621 died without prior AF. At age 40 years, lifetime risks for AF were 26.0% (95% CI, 24.0% to 27.0%) for men and 23.0% (21.0% to 24.0%) for women. Lifetime risks did not change substantially with increasing index age despite decreasing remaining years of life because AF incidence rose rapidly with advancing age. At age 80 years, lifetime risks for AF were 22.7% (20.1% to 24.1%) in men and 21.6% (19.3% to 22.7%) in women. In further analyses, counting only those who had development of AF without prior or concurrent congestive heart failure or myocardial infarction, lifetime risks for AF were approximately 16%. Conclusions— Lifetime risks for development of AF are 1 in 4 for men and women 40 years of age and older. Lifetime risks for AF are high (1 in 6), even in the absence of antecedent congestive heart failure or myocardial infarction. These substantial lifetime risks underscore the major public health burden posed by AF and the need for further investigation into predisposing conditions, preventive strategies, and more effective therapies.
1,950 citations
TL;DR: Recommendations for the initial evaluation, treatment in the acute phase, and long-term management of patients with Kawasaki disease are intended to assist physicians in understanding the range of acceptable approaches for caring for patients withawasaki disease.
Abstract: Background—Kawasaki disease is an acute self-limited vasculitis of childhood that is characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in 15% to 25% of untreated children and may lead to ischemic heart disease or sudden death. Methods and Results—A multidisciplinary committee of experts was convened to revise the American Heart Association recommendations for diagnosis, treatment, and long-term management of Kawasaki disease. The writing group proposes a new algorithm to aid clinicians in deciding which children with fever for 5 days and 4 classic criteria should undergo echocardiography, receive intravenous gamma globulin (IVIG) treatment, or both for Kawasaki disease. The writing group reviews the available data regarding the initial treatment for children with acute Kawasaki disease, as well for those who have persistent or recrudescent fever despite initial therapy with IVIG, including IVIG retreatment and treatment with corticosteroids, tumor necrosis factor- antagonists, and abciximab. Long-term management of patients with Kawasaki disease is tailored to the degree of coronary involvement; recommendations regarding antiplatelet and anticoagulant therapy, physical activity, follow-up assessment, and the appropriate diagnostic procedures to evaluate cardiac disease are classified according to risk strata. Conclusions—Recommendations for the initial evaluation, treatment in the acute phase, and long-term management of patients with Kawasaki disease are intended to assist physicians in understanding the range of acceptable approaches for caring for patients with Kawasaki disease. The ultimate decisions for case management must be made by physicians in light of the particular conditions presented by individual patients. (Circulation. 2004;110:2747-2771.)
1,854 citations
TL;DR: CHD, CVD, and total mortality are significantly higher in US adults with than in those without MetS, and MetS more strongly predicts CHD,CVD,and total mortality than its individual components.
Abstract: Background— Mortality resulting from coronary heart disease (CHD), cardiovascular disease (CVD), and all causes in persons with diabetes and pre-existing CVD is high; however, these risks compared with those with metabolic syndrome (MetS) are unclear. We examined the impact of MetS on CHD, CVD, and overall mortality among US adults. Methods and Results— In a prospective cohort study, 6255 subjects 30 to 75 years of age (54% female) (representative of 64 million adults in the United States) from the Second National Health and Nutrition Examination Survey were followed for a mean±SD of 13.3±3.8 years. MetS was defined by modified National Cholesterol Education Program criteria. From sample-weighted multivariable Cox proportional-hazards regression, compared with those with neither MetS nor prior CVD, age-, gender-, and risk factor–adjusted hazard ratios (HRs) for CHD mortality were 2.02 (95% CI, 1.42 to 2.89) for those with MetS and 4.19 (95% CI, 3.04 to 5.79) for those with pre-existing CVD. For CVD mortal...
1,720 citations
TL;DR: This study provides nationally representative prevalence estimates of PAD in the United States, revealing that PAD affects more than 5 million adults and disproportionately affects blacks.
Abstract: Background— Peripheral arterial disease (PAD) is associated with significant morbidity and mortality and is an important marker of subclinical coronary heart disease. However, estimates of PAD prevalence in the general US population have varied widely. Methods and Results— We analyzed data from 2174 participants aged 40 years and older from the 1999–2000 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial index <0.90 in either leg. The prevalence of PAD among adults aged 40 years and over in the United States was 4.3% (95% CI 3.1% to 5.5%), which corresponds to ≈5 million individuals (95% CI 4 to 7 million). Among those aged 70 years or over, the prevalence was 14.5% (95% CI 10.8% to 18.2%). In age- and gender-adjusted logistic regression analyses, black race/ethnicity (OR 2.83, 95% CI 1.48 to 5.42) current smoking (OR 4.46, 95% CI 2.25 to 8.84), diabetes (OR 2.71, 95% CI 1.03 to 7.12), hypertension (OR 1.75, 95% CI 0.97 to 3.13), hypercholesterolemia (OR 1.68, 95% CI 1....
TL;DR: The known pharmacokinetic elution profile of Cypher stents and the presence of polymer fragments surrounded by giant cells and eosinophils suggest that a reaction to the polymer may have caused late stent thrombosis.
Abstract: Background— The US Food and Drug Administration recently issued a warning of subacute thrombosis and hypersensitivity reactions to sirolimus-eluting stents (Cypher). The cause and incidence of these events have not been determined. Methods and Results— We present findings of a 58-year-old man who died of late stent thrombosis 18 months after receiving 2 Cypher stents for unstable angina. Although angiographic and intravascular ultrasound results at 8 months demonstrated the absence of neointimal formation, vessel enlargement was present. An autopsy showed aneurysmal dilation of the stented arterial segments with a severe localized hypersensitivity reaction consisting predominantly of T lymphocytes and eosinophils. Conclusions— The known pharmacokinetic elution profile of Cypher stents and the presence of polymer fragments surrounded by giant cells and eosinophils suggest that a reaction to the polymer may have caused late stent thrombosis. Careful long-term follow-up of patients with vessel enlargement af...
TL;DR: It is suggested that every minute of delay in primary angioplasty for STEMI affects 1-year mortality, even after adjustment for baseline characteristics, and all efforts should be made to shorten the total ischemic time.
Abstract: Background— Although the relationship between mortality and time delay to treatment has been demonstrated in patients with acute ST-segment elevation myocardial infarction (STEMI) treated by thrombolysis, the impact of time delay on prognosis in patients undergoing primary angioplasty has yet to be clarified. The aim of this report was to address the relationship between time to treatment and mortality as a continuous function and to estimate the risk of mortality for each 30-minute delay. Methods and Results— The study population consisted of 1791 patients with STEMI treated by primary angioplasty. The relationship between ischemic time and 1-year mortality was assessed as a continuous function and plotted with a quadratic regression model. The Cox proportional hazards regression model was used to calculate relative risks (for each 30 minutes of delay), adjusted for baseline characteristics related to ischemic time. Variables related to time to treatment were age >70 years (P<0.0001), female gender (P=0....
TL;DR: This study demonstrates, for the first time, that adipocytes and endothelial cells have a common progenitor, and highlights the concept that adipose lineage cells represent a suitable new cell source for therapeutic angiogenesis in ischemic disease.
Abstract: Background— Adipose tissue development and remodeling are closely associated with the growth of vascular network. We hypothesized that adipose tissue may contain progenitor cells with angiogenic potential and that therapy based on adipose tissue-derived progenitor cells administration may constitute a promising cell therapy in patients with ischemic disease. Methods and Results— In mice, cultured stromal-vascular fraction (SVF) cells from adipose tissue have a great proangiogenic potential, comparable to that of bone marrow mononuclear cells in the mouse ischemic hindlimb model. Similarly, cultured human SVF cells differentiate into endothelial cells, incorporate into vessels, and promote both postischemic neovascularization in nude mice and vessel-like structure formation in Matrigel plug. In vitro, these cells represent a homogeneous population of CD34- and CD13-positive cells, which can spontaneously express the endothelial cell markers CD31 and von Willebrand factor when cultured in semisolid medium. ...
TL;DR: Up to 25% of STEMI patients undergoing primary PCI with stenting are resistant to clopidogrel and therefore may be at increased risk for recurrent cardiovascular events.
Abstract: Background— Although clopidogrel reduces the risk of cardiovascular episodes after coronary events and stenting, a substantial number of incidents continue to occur. Methods and Results— The antiplatelet effect of clopidogrel was studied prospectively in 60 consecutive patients who underwent primary angioplasty (percutaneous coronary intervention [PCI]) with stenting for acute ST-segment–elevation myocardial infarction (STEMI) to determine whether variability in response to clopidogrel affects clinical outcomes. Patients were stratified into 4 quartiles according to the percentage reduction of ADP-induced platelet aggregation. Although patients in the first quartile were resistant to the effects of clopidogrel (ADP-induced platelet aggregation at day 6, 103±8% of baseline), ADP-induced aggregation was reduced to 69±3%, 58±7%, and 33±12% of baseline, respectively, in patients in quartiles 2 through 4 (P<0.01 for all). In addition, epinephrine-induced platelet aggregation and platelet aggregation under flow...
TL;DR: MSC injection improved limb function and appearance, reduced the incidence of auto-amputation, and attenuated muscle atrophy and fibrosis, suggesting MSCs can contribute to collateral remodeling through paracrine mechanisms.
Abstract: Background— Bone marrow cell therapy is reported to contribute to collateral formation through cell incorporation into new or remodeling vessels However, the possible role of a paracrine contribution to this effect is less well characterized Methods and Results— Murine marrow-derived stromal cells (MSCs) were purified by magnetic bead separation of cultured bone marrow The release of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and monocyte chemoattractant protein-1 (MCP-1) was demonstrated by analysis of MSC conditioned media (MSC-CM) MSC-CM enhanced proliferation of endothelial cells and smooth muscle cells in a dose-dependent manner; anti-VEGF and anti-FGF antibodies only partly attenuated these effects Balb/C mice (n=10) underwent distal femoral artery ligation, followed by adductor muscle injection of 1×106 MSCs 24 hours later Compared with controls injected with media (n=10) or mature endothelial cells (n=8), distal limb perf
TL;DR: This is the first demonstration of induction ofcardiomyocyte differentiation in hES cells that do not undergo spontaneous cardiogenesis and provides a model for the study of human cardiomyocytes in culture and could be a step forward in the development of cardiomeocyte transplantation therapies.
Abstract: A method for inducing cardiomyocyte differentiation of a hES cell, the method comprising co-culturing the hES cell with a cell excreting at least one cardiomyocyte differentiation inducing factor or with an extracellular medium therefrom, under conditions that induce differentiation, cells and cell populations so produced, and uses of the cells.
TL;DR: In randomized, controlled trials, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, in the form of statins, have been shown to provide effective therapy for lowering CRP, in conjunction with their lipid-lowering effects.
Abstract: Inflammation occurs in the vasculature as a response to injury, lipid peroxidation, and perhaps infection. Various risk factors, including hypertension, diabetes, and smoking, are amplified by the harmful effects of oxidized low-density-lipoprotein cholesterol, initiating a chronic inflammatory reaction, the result of which is a vulnerable plaque, prone to rupture and thrombosis. Epidemiological and clinical studies have shown strong and consistent relationships between markers of inflammation and risk of future cardiovascular events. Inflammation can potentially be detected locally by imaging techniques as well as emerging techniques, such as identification of temperature or pH heterogeneity. It can be detected systemically by measurement of inflammatory markers. Of these, the most reliable and accessible for clinical use is currently high-sensitivity C-reactive protein. A combination of methods may provide the best identification of persons at risk for cardiovascular events who would benefit from treatment. In randomized, controlled trials, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, in the form of statins, have been shown to provide effective therapy for lowering CRP, in conjunction with their lipid-lowering effects. Although the magnitude of risk reduction associated with statin use appears to be largest for those with the highest serum levels of CRP, whether CRP reduction per se lowers cardiovascular risk is unknown.
TL;DR: An “on-treatment” analysis of the relationship of survival to cardiac rhythm and treatment as they changed over time suggests that any beneficial antiarrhythmic effects of AADs are offset by their adverse effects.
Abstract: Background The AFFIRM Study showed that treatment of patients with atrial fibrillation and a high risk for stroke or death with a rhythm-control strategy offered no survival advantage over a rate-control strategy in an intention-to-treat analysis This article reports an "on-treatment" analysis of the relationship of survival to cardiac rhythm and treatment as they changed over time Methods and results Modeling techniques were used to determine the relationships among survival, baseline clinical variables, and time-dependent variables The following baseline variables were significantly associated with an increased risk of death: increasing age, coronary artery disease, congestive heart failure, diabetes, stroke or transient ischemic attack, smoking, left ventricular dysfunction, and mitral regurgitation Among the time-dependent variables, the presence of sinus rhythm (SR) was associated with a lower risk of death, as was warfarin use Antiarrhythmic drugs (AADs) were associated with increased mortality only after adjustment for the presence of SR Consistent with the original intention-to-treat analysis, AADs were no longer associated with mortality when SR was removed from the model Conclusions Warfarin use improves survival SR is either an important determinant of survival or a marker for other factors associated with survival that were not recorded, determined, or included in the survival model Currently available AADs are not associated with improved survival, which suggests that any beneficial antiarrhythmic effects of AADs are offset by their adverse effects If an effective method for maintaining SR with fewer adverse effects were available, it might be beneficial
Western Infirmary1, University of Gothenburg2, Cornell University3, Boston University4, Hannover Medical School5, University of Pittsburgh6, University of Copenhagen7, Alfred Hospital8, University of Toronto9, University of Helsinki10, University of Groningen11, Umeå University12, Amgen13, University of Washington14
TL;DR: The results of RENEWAL rule out a clinically relevant benefit of etanercept on the rate of death or hospitalization due to chronic heart failure.
Abstract: Background— Studies in experimental models and preliminary clinical experience suggested a possible therapeutic role for the soluble tumor necrosis factor antagonist etanercept in heart failure. Methods and Results— Patients with New York Heart Association class II to IV chronic heart failure and a left ventricular ejection fraction ≤0.30 were enrolled in 2 clinical trials that differed only in the doses of etanercept used. In RECOVER, patients received placebo (n=373) or subcutaneous etanercept in doses of 25 mg every week (n=375) or 25 mg twice per week (n=375). In RENAISSANCE, patients received placebo (n=309), etanercept 25 mg twice per week (n=308), or etanercept 25 mg 3 times per week (n=308). The primary end point of each individual trial was clinical status at 24 weeks. Analysis of the effect of the 2 higher doses of etanercept on the combined outcome of death or hospitalization due to chronic heart failure from the 2 studies was also planned (RENEWAL). On the basis of prespecified stopping rules, both trials were terminated prematurely owing to lack of benefit. Etanercept had no effect on clinical status in RENAISSANCE ( P =0.17) or RECOVER ( P =0.34) and had no effect on the death or chronic heart failure hospitalization end point in RENEWAL (etanercept to placebo relative risk=1.1, 95% CI 0.91 to 1.33, P =0.33). Conclusions— The results of RENEWAL rule out a clinically relevant benefit of etanercept on the rate of death or hospitalization due to chronic heart failure.
TL;DR: AIx and AP, noninvasively determined manifestations of arterial stiffening and increased wave reflections, are strong, independent risk markers for premature coronary artery disease.
Abstract: Background— Increased arterial stiffness, determined invasively, has been shown to predict a higher risk of coronary atherosclerosis. However, invasive techniques are of limited value for screening and risk stratification in larger patient groups. Methods and Results— We prospectively enrolled 465 consecutive, symptomatic men undergoing coronary angiography for the assessment of suspected coronary artery disease. Arterial stiffness and wave reflections were quantified noninvasively using applanation tonometry of the radial artery with a validated transfer function to generate the corresponding ascending aortic pressure waveform. Augmented pressure (AP) was defined as the difference between the second and the first systolic peak, and augmentation index (AIx) was AP expressed as a percentage of the pulse pressure. In univariate analysis, a higher AIx was associated with an increased risk for coronary artery disease (OR, 4.06 for the difference between the first and the fourth quartile [1.72 to 9.57; P<0.01]...
TL;DR: The definition of pediatric MetS, designed to be closely analogous to ATP III, found MetS is common in adolescents and has a similar racial/ethnic distribution to adults in this representative national sample.
Abstract: Background— Metabolic syndrome (MetS) is defined by the Third Report of the Adult Treatment Panel (ATP III) using criteria easily applied by clinicians and researchers. There is no standard pediatric definition. Methods and Results— We defined pediatric MetS using criteria analogous to ATP III as ≥3 of the following: (1) fasting triglycerides ≥1.1 mmol/L (100 mg/dL); (2) HDL 75th percentile for age and gender; and (5) systolic blood pressure >90th percentile for gender, age, and height. MetS prevalence in US adolescents was estimated with the Third National Health and Nutritional Survey 1988 to 1994. Among 1960 children aged ≥12 years who fasted ≥8 hours, two thirds had at least 1 metabolic abnormality, and nearly 1 in 10 had MetS. The racial/ethnic distribution was similar to adults: Mexican-Americans, followed by non-Hispanic w...
TL;DR: It is found that a strong association exists between OSA and AF, such that OSA is strikingly more prevalent in patients with AF than in high-risk patients with multiple other cardiovascular diseases.
Abstract: Background— Obstructive sleep apnea (OSA) is associated with recurrent atrial fibrillation (AF) after electrocardioversion. OSA is highly prevalent in patients who are male, obese, and/or hypertens...
Journal Article•
TL;DR: It is suggested that adjunctive CVD during CPVA significantly reduces recurrence of AF at 12 months, particularly in patients with reflexes and CVD, who were less likely to have recurrent AF than those without reflexes.
Abstract: Background— There are no data to evaluate the relationship between autonomic nerve function modification and recurrent atrial fibrillation (AF) after circumferential pulmonary vein ablation (CPVA). This study assesses the incremental benefit of vagal denervation by radiofrequency in preventing recurrent AF in a large series of patients undergoing CPVA for paroxysmal AF. Methods and Results— Data were collected on 297 patients undergoing CPVA for paroxysmal AF. Abolition of all evoked vagal reflexes around all pulmonary vein ostia was defined as complete vagal denervation (CVD) and was obtained in 34.3% of patients. Follow-up ended at 12 months. Heart rate variability attenuation, consistent with vagal withdrawal, was detectable for up to 3 months after CPVA, particularly in patients with reflexes and CVD, who were less likely to have recurrent AF than those without reflexes (P=0.0002, log-rank test). Only the percentage area of left atrial isolation and CVD were predictors of AF recurrence after CPVA (P<0...
TL;DR: In the wake of the reports of the Women’s Health Initiative and the Heart and Estrogen/Progestin Replacement Study, which unexpectedly showed that combination hormone therapy was associated with adverse CVD effects, there is a heightened need to critically review and document strategies to prevent CVD in women.
Abstract: Significant advances in our knowledge about interventions to prevent cardiovascular disease (CVD) have occurred since publication of the first female-specific recommendations for preventive cardiology in 1999.1 Despite research-based gains in the treatment of CVD, it remains the leading killer of women in the United States and in most developed areas of the world.2–3 In the United States alone, more than one half million women die of CVD each year, exceeding the number of deaths in men and the next 7 causes of death in women combined. This translates into approximately 1 death every minute.2 Coronary heart disease (CHD) accounts for the majority of CVD deaths in women, disproportionately afflicts racial and ethnic minorities, and is a prime target for prevention.1–2 Because CHD is often fatal, and because nearly two thirds of women who die suddenly have no previously recognized symptoms, it is essential to prevent CHD.2 Other forms of atherosclerotic/thrombotic CVD, such as cerebrovascular disease and peripheral arterial disease, are critically important in women. Strategies known to reduce the burden of CHD may have substantial benefits for the prevention of noncoronary atherosclerosis, although they have been studied less extensively in some of these settings.
In the wake of the reports of the Women’s Health Initiative and the Heart and Estrogen/Progestin Replacement Study (HERS), which unexpectedly showed that combination hormone therapy was associated with adverse CVD effects, there is a heightened need to critically review and document strategies to prevent CVD in women.4–7 These studies underscore the importance of evidence-based practice for chronic disease prevention. Optimal translation and implementation of science to improve preventive care should include a rigorous process of evaluation and clear communication about the quantity and quality of evidence used to support clinical recommendations. Recently, there has been an increase in the …
TL;DR: Contrast enhancement is a frequent finding in the clinical setting of suspected myocarditis and is associated with active inflammation defined by histopathology and is a valuable tool for the evaluation and monitoring of inflammatory heart disease.
Abstract: Background— Myocarditis can occasionally lead to sudden death and may progress to dilated cardiomyopathy in up to 10% of patients. Because the initial onset is difficult to recognize clinically and the diagnostic tools available are unsatisfactory, new strategies to diagnose myocarditis are needed. Methods and Results— Cardiovascular MR imaging (CMR) was performed in 32 patients who were diagnosed with myocarditis by clinical criteria. To determine whether CMR visualizes areas of active myocarditis, endomyocardial biopsy was taken from the region of contrast enhancement and submitted to histopathologic analysis. Follow-up was performed 3 month later. Contrast enhancement was present in 28 patients (88%) and was usually seen with one or several foci in the myocardium. Foci were most frequently located in the lateral free wall. In the 21 patients in whom biopsy was obtained from the region of contrast enhancement, histopathologic analysis revealed active myocarditis in 19 patients (parvovirus B19, n=12; human herpes virus type 6 [HHV 6], n=5). Conversely, in the remaining 11 patients, in whom biopsy could not be taken from the region of contrast enhancement, active myocarditis was found in one case only (HHV6). At follow-up, the area of contrast enhancement decreased from 9±11% to 3±4% of left ventricular mass as the left ventricular ejection fraction improved from 47±19% to 60±10%. Conclusions— Contrast enhancement is a frequent finding in the clinical setting of suspected myocarditis and is associated with active inflammation defined by histopathology. Myocarditis occurs predominantly in the lateral free wall. Contrast CMR is a valuable tool for the evaluation and monitoring of inflammatory heart disease.
TL;DR: A dose-response relation of ACEs to IHD and a relation between almost all individual ACEs and IHD is found and psychological factors appear to be more important than traditional risk factors in mediating the relation ofACEs to the risk of IHD.
Abstract: Background— The purpose of this study was to assess the relation of adverse childhood experiences (ACEs), including abuse, neglect, and household dysfunction, to the risk of ischemic heart disease (IHD) and to examine the mediating impact on this relation of both traditional IHD risk factors and psychological factors that are associated with ACEs. Methods and Results— Retrospective cohort survey data were collected from 17 337 adult health plan members from 1995 to 1997. Logistic regression adjusted for age, sex, race, and education was used to estimate the strength of the ACE–IHD relation and the mediating impact of IHD risk factors in this relation. Nine of 10 categories of ACEs significantly increased the risk of IHD by 1.3- to 1.7-fold versus persons with no ACEs. The adjusted odds ratios for IHD among persons with ≥7 ACEs was 3.6 (95% CI, 2.4 to 5.3). The ACE–IHD relation was mediated more strongly by individual psychological risk factors commonly associated with ACEs than by traditional IHD risk fac...
TL;DR: The present report summarizes a second conference devoted to clinical management of the metabolic syndrome, which was sponsored by the AHA in partnership with the NHLBI and cosponsored by the American Diabetes Association (ADA).
Abstract: The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III)1 identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention. Subsequently, the National Heart, Lung, and Blood Institute (NHLBI), in collaboration with the American Heart Association (AHA), convened a conference to examine scientific issues related to definition of the metabolic syndrome.2 The present report summarizes a second conference devoted to clinical management of the metabolic syndrome, which was sponsored by the AHA in partnership with the NHLBI and cosponsored by the American Diabetes Association (ADA). This latter conference considered the following issues: (1) pathogenesis and presentation of the metabolic syndrome, (2) management of underlying risk factors, (3) management of metabolic risk factors, and (4) unresolved issues and research challenges.
The conference on definition2 confirmed CVD as a major clinical outcome of metabolic syndrome and identified 6 major components of the syndrome: abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance ± glucose intolerance, a proinflammatory state, and a prothrombotic state. The follow-up conference on management was structured around therapies for these components. Clinical recognition of the metabolic syndrome is generally based on finding several well-recognized signs in clinical practice: abdominal obesity, elevated triglycerides, reduced HDL cholesterol, raised blood pressure, and elevated plasma glucose. In addition, research shows that other components not routinely measured commonly aggregate with the major components: elevated apolipoprotein B, small LDL particles, insulin resistance and hyperinsulinemia, impaired glucose tolerance (IGT), elevated C-reactive protein (CRP), and variation in coagulation factors (eg, plasminogen activator inhibitor [PAI]-1 and fibrinogen). The conference on definition2 also emphasized that risk for type 2 diabetes is higher in persons with metabolic syndrome and that diabetes is a major risk factor for CVD. It also examined various criteria for …
TL;DR: In this article, the American Heart Association Council on Nutrition, Physical Activity, and Metabolism reviewed the relationship between obesity and the cardiovascular system, evaluated the effect of weight loss on coronary heart disease risk factors, and provided practical weight management treatment guidelines for cardiovascular healthcare professionals.
Abstract: Obesity adversely affects cardiac function, increases the risk factors for coronary heart disease, and is an independent risk factor for cardiovascular disease. The risk of developing coronary heart disease is directly related to the concomitant burden of obesity-related risk factors. Modest weight loss can improve diastolic function and affect the entire cluster of coronary heart disease risk factors simultaneously. This statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism reviews the relationship between obesity and the cardiovascular system, evaluates the effect of weight loss on coronary heart disease risk factors and coronary heart disease, and provides practical weight management treatment guidelines for cardiovascular healthcare professionals. The data demonstrate that weight loss and physical activity can prevent and treat obesity-related coronary heart disease risk factors and should be considered a primary therapy for obese patients with cardiovascular disease.