Research Overview Comparative Effectiveness Research United States (US) healthcare expenditure has continued to grow over the past three decades, despite the promise that improved resource allocation, biomedical research and technology would improve both efficiency and outcomes. Current estimates from the United States Congressional Budget Office (CBO) estimate that 4 percent of the 2007 Gross Domestic Product (GDP) was allocated to Medicare and Medicaid. This amount is estimated to grow to up to 20 percent of the federal budget by 2050 if current projections remain true. Thus, healthcare expenditure is quickly becoming the most significant factor in the already strained United States federal budget. Payment for the treatment of peripheral arterial disease (PAD) represents a significant amount of healthcare resource allocation. In 2007, the United States spent 151 billion dollars in direct and indirect costs for the treatment of 12 million beneficiaries with PAD. It is clear that these current trends are untenable within the constraints of the economic system. Vascular care is likely to become increasingly important, as the overall population ages. It will become paramount to evaluate the appropriate treatment of each patient with vascular disease within the overall context of the national healthcare system. Comparative effectiveness research (CER) must provide the scientific basis for this process. Simply put, comparative effectiveness is the study of two or more treatment options to address a given medical condition. Within the domain of vascular disease, there is an ever-increasing array of options and modalities to address our patient’s disease processes. Many of these new modalities compete with either non-operative management or traditional operative techniques, and have not been fully evaluated with respect to efficacy and healthcare economics. The implementation of CER may be ideally suited for mechanisms such as Accountable Care Organizations. Within this construct, patients and providers use evidence-based medicine to decide on clinically and financially treatment courses, and both benefit from maximizing these factors. Within the vascular disease space, this is accomplished by choosing the safest, most efficacious and durable procedure. These factors have begun to translate into the federal regulatory process, as the Food and Drug Administration is now considering patient-centric outcomes for new device approvals. Dr. Stoner is actively involved in CER and value-based research, which is the scientific cornerstone of creating a sustainable healthcare framework. Research includes care process and value proposition optimization for aortic surgery (figure), and a critical analysis of evolving technologies. Cardiovascular Engineering Lab The University of Rochester Medical Center Cardiovascular Engineering Lab (CVEL) involves a cross-disciplinary, multi-institutional team working towards solving cardiovascular problems using engineering principles. The overall theme of this lab is solving little problems, using the expertise of staff and students from various backgrounds, in order to solve the bigger problems in this field. The cardiovascular system is governed by forces prevalent in engineering, and the team of clinicians and engineers work together on problems faced in the cardiovascular field which can be solved through the application of engineering. For more information, click here Vascular Biology Cullen Lab Dr. John Cullen's research focuses on the effects of 'moderate' and 'binge' patterns of alcohol consumption on the development of atherosclerosis. A biphasic effect of alcohol on the incidence of cardiovascular disease has been documented, where moderate consumption of ethanol exerts a protective effect while chronic alcohol abuse and/or binge drinking are associated with a higher incidence of cardiovascular disorders. It is thus increasingly apparent that in addition to the volume of consumption, the pattern of drinking must be considered. Our research involves investigating the precise cellular mechanisms whereby alcohol elicits these beneficial and/or deleterious effects. The investigation of the effects of alcohol consumption on two distinct processes, pivotal in the development and destabilization of the atherosclerotic plaque, are underway. Inflammation in the vessel wall is considered to be instrumental in the initiation and progression of atherosclerotic plaques and their destabilization. We are currently investigating the effects of 'moderate' and 'binge' alcohol consumption on monocyte infiltration and the expression of monocyte chemotactic protein-1, and it's receptor CCR2, as well as numerous other inflammatory mediators, in atherosclerotic plaques. Vascular remodeling, mediated in part by proteases and smooth muscle cell apoptosis, plays an important role in many pathophysiological processes including atherosclerosis. Studies are underway to define the effects of 'moderate' and 'binge' alcohol consumption on the expression of matrix metalloproteinases and plasminogen activators, as well as the degree of smooth muscle cell apoptosis, in the unstable atherosclerotic plaque. These studies utilize the genetically modified apolipoprotein E knockout (apo E k/o) mice, which after surgical intervention and a high fat diet, develops an unstable atherosclerotic plaque with many of the key characteristics seen in humans. We are also undertaking a detailed investigation of the effects of alcohol's primary metabolite, acetaldehyde, which has long been suggested to be involved in a number of alcohols pharmacological and behavioral effects, on vascular cell biology. As well as studying the effects of acetaldhyde on inflammation and vascular remodeling in the apoE k/o flow-cessation/hypocholesteromic model of atherosclerosis, we are also undertaking a detailed analysis of its effects on endothelial cells, smooth muscle cells and monocytes, in vitro. Given that 65% of the American population consume alcohol, with a 15% binge drinking rate among adults, and that cardiovascular disease remains the leading cause of death in the USA, deciphering the mechanisms mediating alcohols cardiovascular effects will provide significant new information to allow effective interventions to prevent mortality and morbidity associated with cardiovascular disease.