Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Urinary Bisphenol A Concentration and Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women
- Predictors of Long-Term Survival After Coronary Artery Bypass Grafting Surgery: Results From the Society of Thoracic Surgeons Adult Cardiac Surgery Database (The ASCERT Study)
- Prediction of Long-Term Mortality After Percutaneous Coronary Intervention in Older Adults: Results From the National Cardiovascular Data Registry
- Effects of Catecholamine Stress on Diastolic Function and Myocardial Energetics in Obesity
- MicroRNA-21 Integrates Pathogenic Signaling to Control Pulmonary Hypertension: Results of a Network Bioinformatics Approach
- Endothelial Cells Overexpressing Interleukin-8 Receptors Reduce Inflammatory and Neointimal Responses to Arterial Injury
- Interleukin-1β Is Crucial for the Induction of Coronary Artery Inflammation in a Mouse Model of Kawasaki Disease
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Urinary Bisphenol A Concentration and Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women
Bisphenol A (BPA) is a synthetic molecule widely used in plastics and epoxy resins in can linings, from where it can leach to contaminate food and beverages. It is present in >95% of the population and is of public health concern because many studies have reported effects at low exposure levels as a hormone mimic in animal and laboratory investigations, although these effects are contested. There is little direct human evidence on BPA toxicokinetics, which appears to differ from that in laboratory models and may be influenced by concurrent food intake. A cross-sectional association between higher urinary BPA and cardiovascular disease was first noted in 2008 and was independently replicated in 2010 in the US population–representative National Health and Nutrition Examination Survey study. We show here for the first time that associations between higher BPA excretion and incident coronary artery disease during a 10.8-year follow-up show similar trends. Higher body mass index could represent higher food intakes and incidentally higher BPA exposure, but adjustment for or exclusion of those with obesity or high serum lipid concentrations has little effect on estimates. There are initial data that BPA may be associated with expression of estrogen related receptors in vivo and may be antiandrogenic, but a firm mechanism for the coronary artery disease association is unknown. Evidence on high BPA exposures from occupational studies is scarce. For clinicians, this study suggests that BPA is worth investigating further, especially given the feasibility of control and the limits of experimentation for potential hazards. The US Food and Drug Administration is already committed to reducing BPA residues in food and provides guidance on how to do so on its Web pages. See p 1482.
Predictors of Long-Term Survival After Coronary Artery Bypass Grafting Surgery: Results From the Society of Thoracic Surgeons Adult Cardiac Surgery Database (The ASCERT Study)
Most survival prediction models for coronary artery bypass grafting surgery are limited to in-hospital or 30-day end points. However, particularly as short-term mortality rates decrease, it is increasingly important for providers, patients, payers, and other stakeholders to better understand the likelihood of long-term survival. We linked broadly representative, real-world clinical data from the Society of Thoracic Surgeons Adult Cardiac Surgery Database and vital status from Medicare claims data to construct a robust, long-term coronary artery bypass grafting surgery survival prediction model. This study included 348 341 patients aged ≥65 years who underwent isolated coronary artery bypass grafting surgery between 2002 and 2007. Because of the large study cohort and clinical predictors, model performance is excellent. On the basis of the results of this study, late outcomes for patients who initially survive coronary artery bypass grafting surgery are less affected by traditional predictors of early mortality such as emergency status, shock, and reoperation. Conversely, late mortality is increasingly associated with chronic debilitating diseases such as insulin-dependent diabetes mellitus and dialysis-dependent renal failure and behaviors such as smoking. This is valuable information for shared decision making, comparative effectiveness research, quality improvement, patient counseling, and provider profiling. See p 1491.
Prediction of Long-Term Mortality After Percutaneous Coronary Intervention in Older Adults: Results From the National Cardiovascular Data Registry
Most survival prediction models for percutaneous coronary intervention are limited to in-hospital end points. Although short-term mortality rates remain low, multiple stakeholders, including providers, patients, and payers, will be more interested in long-term survival. We linked the broadly representative, real-world clinical data from the American College of Cardiology–National Cardiovascular Data Registry CathPCI Registry with vital statistics from the Medicare 100% denominator file to construct a robust, long-term percutaneous coronary intervention survival prediction model. This study included 343 466 patients aged ≥65 years who underwent percutaneous coronary intervention either with or without ST-segment elevation myocardial infarction between 2004 and 2007. Median follow-up was 15 months, with mortality of 2.97% at 30 days, and 8.58%, 13.4%, and 18.3% at 1, 2, and 3 years, respectively. Twenty-four demographic and clinical comorbidities, prior history of disease, and indices of disease severity and acuity were identified as being associated with mortality. Discrimination, calibration, and validation of the model were all excellent. The large sample size permitted precise estimates of the influence of clinical correlates on survival. Early mortality is predicted by variables related to acuteness of presentation, whereas longer-term mortality is associated with chronic debilitating diseases such as insulin-dependent diabetes mellitus and dialysis-dependent renal failure and behaviors such as cigarette smoking. The model may be used for shared medical decision making, quality improvement, and provider benchmarking and as a basis for developing comparative effectiveness research. See p 1501.
Effects of Catecholamine Stress on Diastolic Function and Myocardial Energetics in Obesity
Despite the fact that obesity is characterized by diastolic dysfunction, a condition associated with future heart failure, the mechanisms behind it are not known. In this study, we have demonstrated that myocardial energetics are impaired in obesity and that the phosphocreatine/ATP ratio is a predictor of diastolic function. This opens the possibility of a metabolic therapy aimed at improving myocardial energetics in obesity and potentially preventing the progression to heart failure. In addition, we have shown that during moderate inotropic stress, the already lower phosphocreatine/ATP ratio in obesity is further reduced, resulting in additional negative effects on diastolic function. Because the majority of the cardiovascular symptoms in obesity do not occur at rest and occur in subjects with normal left ventricular systolic and respiratory function, these changes in energetics and diastole provide a plausible explanation for exertional breathlessness in obesity. Myocardial energetics appear to be playing a central role in diastolic function in obesity; therefore, metabolic therapies aimed at improving myocardial energetics in obesity may become a means of targeting obesity-related shortness of breath and potentially preventing the development of heart failure. See p 1511.
MicroRNA-21 Integrates Pathogenic Signaling to Control Pulmonary Hypertension: Results of a Network Bioinformatics Approach
Pulmonary hypertension (PH) is a deadly disease with diverse etiologies resulting in pathological dysregulation in the pulmonary vasculature. This dysregulation involves numerous intersecting signaling pathways, the coordinate control of which may depend on master molecular effectors. MicroRNA molecules (miRNA) are small, noncoding RNA that may act as such regulators, but their importance in PH is still unclear. In the present study, a unique network biology–based approach was used to identify microRNA-21 (miR-21) as 1 of a select group of miRNA predicted to control expression of a convergent set of pathways in PH. Underscoring the biologic plausibility of this finding, miR-21 is upregulated by hypoxia and bone morphogenetic protein receptor 2 signaling, 2 important PH triggers. In turn, miR-21 targets an important vascular effector, RhoB, and induces molecular changes in pulmonary endothelial cells consistent with vasodilation and decreased angiogenesis. Furthermore, miR-21 is upregulated in lung from humans with PH and from multiple rodent models of PH. In 1 of these models, the genetic absence of miR-21 causes accelerated disease progression. Taken together, these data identify miR-21 as a coordinate regulator of PH pathology that acts as a homeostatic brake to stave off PH progression. This study reinforces the critical role for miRNA in PH and introduces the utility of a network-based method for identifying additional groups of disease-modifying miRNA. Because complex interactions among these miRNA with their common targets will dictate their individual impact on disease, the study of such miRNA networks may offer insight into their utility as therapeutic targets. See p 1520.
Endothelial Cells Overexpressing Interleukin-8 Receptors Reduce Inflammatory and Neointimal Responses to Arterial Injury
The endothelium is a functional component of the cardiovascular system that plays an important role in health and disease. Injury or dysfunction of endothelium can lead to many forms of cardiovascular disease, and the injured endothelium can serve as a therapeutic target in the prevention and treatment of cardiovascular disease. The cell-based therapies have been shown to alleviate tissue injury and organ dysfunction in animal models of cardiovascular disease. However, clinical trials with cell therapy for patients with cardiovascular disease have yielded inconsistent results and modest benefit overall. A major unsolved problem for cell-based therapy is how to home transplanted cells to damaged organs to improve their survival and to enhance tissue repair and organ function. We have developed an innovative strategy to overcome this hurdle by intravenously transfusing rat endothelial cells overexpressing the neutrophil interleukin-8 (IL-8) receptors IL8RA and IL8RB into rats with experimental endoluminal injury of the carotid artery. We have shown that, equipped with the IL8R homing device, endothelial cells mimic the behavior of neutrophils and compete with the binding of neutrophils to IL-8 overexpressed in injured vessels, thus inhibiting the neutrophil-induced inflammatory response and accelerating reendothelialization and vascular repair. This targeted delivery of endothelial cells to sites of cardiovascular injury provides a novel therapeutic strategy for cardiovascular disease. The results of the present study open the door to new therapeutic applications of cell therapy in patients with cardiovascular injury. See p 1533.
Interleukin-1β Is Crucial for the Induction of Coronary Artery Inflammation in a Mouse Model of Kawasaki Disease
Kawasaki disease (KD) is now recognized as the leading cause of acquired heart disease in children in the United States and developed world. The underlying cause of KD and the mechanisms leading to vessel inflammation, coronary artery lesions, and aneurysms, which are the hallmarks of KD, remain largely unknown. Standard therapy with intravenous immunoglobulin (IVIG) effectively reduces the incidence of coronary arterial lesions, but 10% to 20% of patients with KD fail to respond to IVIG and thus show a high prevalence of coronary lesions. There is no definitive treatment recommendation for patients who fail to respond to an initial course of IVIG treatment. Rescue treatment for IVIG resistance includes additional IVIG dose(s), steroids, anti–tumor necrosis factor monoclonal antibody, and cyclosporine A, but these approaches have shown mixed results, and the effectiveness of these therapies remains controversial. Development of an optimal alternative for IVIG-resistant KD patients is now an urgent matter. Using a well-established KD mouse model, we found that interleukin-1β is critically involved in the development of coronary arteritis and myocarditis in KD mice and that these lesions can be prevented by treatment with an interleukin-1 receptor antagonist. These observations provide mechanistic insights into the cellular and molecular understanding of the vasculitis and coronary arteritis in the KD mouse model and suggest that anti–interleukin-1β agents might prevent the development of coronary lesions in KD patients. Our findings provide justification for future prospective multicenter clinical trials to determine the efficacy of therapies designed to block interleukin-1β–dependent signaling in children with KD. See p 1542.
- © 2012 American Heart Association, Inc.
- Effects of Catecholamine Stress on Diastolic Function and Myocardial Energetics in Obesity
- Info & Metrics