Research Agenda for Cardiovascular Aging: Humans to Molecules

Clinical manifestations of specific cardiovascular diseases, e.g., atherosclerosis and hypertension, that lead to heart failure and stroke likely become altered in older persons of advanced age because interactions occur between age-associated cardiovascular changes in health and specific pathophysiologic mechanisms that underlie cardiovascular diseases. The interactions result in a lower threshold for clinical symptoms, and greater severity and poorer prognosis of these diseases in older vs. younger persons. In this regard, cardiovascular changes that occur during aging in health ought not to be considered to reflect a "normal process"; rather these specific age-associated changes must be construed as specific "risk factors" for the aforementioned cardiovascular diseases and ought to become targets of interventions designed to prevent the epidemic of cardiovascular disease in later life. Such a strategy would thus advocate preventive treatment for what is now considered to be "normal cardiovascular aging." Effective and efficient prevention of the "risks" associated with cardiovascular aging in apparent health requires a fundamental understanding of these changes ranging in scope from humans to molecules. An opinion regarding specific directions for research aimed toward the achievement of this understanding is provided.     

Cell-based myocardial repair: how should we proceed?

Cell-based myocardial repair and regeneration heralds a new frontier in the treatment of cardiovascular disease. It provides an unprecedented opportunity to treat the underlying loss of cardiomyocytes that occurs after myocardial injury and that results in the cascade of events leading to heart failure. Yet, even as it progresses to the clinic, much remains to be understood about this technology. For example, controversies exist over the specific cells to be used, the cell dosages needed, how cells will impact the electrical activity of the myocardium, and even whether transplanted cells can actually improve myocardial function. We can perhaps answer these questions more quickly and more effectively - and thus benefit patients more rapidly - if we learn from the successes and failures of our gene therapy colleagues and take a prudent, step-wise approach from bench to bedside. To do so, we need only to promise what we can deliver, to do careful science, and then to deliver well on our promises. Although cellular cardiomyoplasty (cell transplantation for cardiac repair) shows great early clinical promise, its future as a new frontier in the treatment for cardiovascular disease will rest heavily on how we move forward in the next few years. Its success will heavily depend upon conducting carefully controlled, randomized double-blind clinical trials with appropriate endpoints, in the right patients. Choice of cell type, and mode of cell delivery, will also have to be considered, and may have to be matched to the patient. Irrespective of cell type, we can also be assured that cells offer both an opportunity for tissue repair and the potential for not yet understood outcomes. As with any frontier, there will be pitfalls and consequences to be considered that may surpass those of previous endeavors. But so too is the potential for previously unimagined success at treating the leading cause of death in the western world. In short, the promise for cardiovascular cell therapy is too great to be spoiled by ill-designed attempts that forget to account for both the natural propensities of cells and of the myocardium.     

Cardiovascular Disease Prevention During the COVID-19 Pandemic: Lessons Learned and Future Opportunities

The coronavirus disease 2019 (COVID-19) pandemic has been the defining healthcare issue since its outbreak, consuming healthcare systems and disrupting all aspects of human life throughout 2020 and continuing through 2021. When reviewing cardiovascular disease (CVD) prevention throughout the COVID-19 pandemic, the first tendency may be to focus on the negative disruption. Months of quarantine, isolation, and missed healthcare visits or delayed care may have exacerbated the epidemic of CVD in the United States. Looking back, however, perhaps it wasn’t a lost year as much as a health crisis that better prepared us for the battle to improve cardiovascular health. The pandemic brought new platforms for interacting with patients eager to engage, presenting a unique opportunity to reset how we approach preventive care.In this review, we discuss what the pandemic has taught us about caring for those vulnerable patients who were most afflicted—older adults, persons of color, and people facing adverse socioeconomic circumstances—and who continue to be impacted by CVD. We also identify opportunities for enhanced CVD prevention now boosted by the overnight adoption of telemedicine and other innovative cardiac care models. Lastly, we discuss how the COVID-19 pandemic has motivated physicians and patients alike to prioritize our health above all else, if only transiently, and how we can leverage this increased health awareness and investment into long-term, meaningful disease prevention.     

National Institutes of Health addresses the science of diversity

The US biomedical research workforce does not currently mirror the nation’s population demographically, despite numerous attempts to increase diversity. This imbalance is limiting the promise of our biomedical enterprise for building knowledge and improving the nation’s health. Beyond ensuring fairness in scientific workforce representation, recruiting and retaining a diverse set of minds and approaches is vital to harnessing the complete intellectual capital of the nation. The complexity inherent in diversifying the research workforce underscores the need for a rigorous scientific approach, consistent with the ways we address the challenges of science discovery and translation to human health. Herein, we identify four cross-cutting diversity challenges ripe for scientific exploration and opportunity: research evidence for diversity’s impact on the quality and outputs of science; evidence-based approaches to recruitment and training; individual and institutional barriers to workforce diversity; and a national strategy for eliminating barriers to career transition, with scientifically based approaches for scaling and dissemination. Evidence-based data for each of these challenges should provide an integrated, stepwise approach to programs that enhance diversity rapidly within the biomedical research workforce.     

Intrapartum practices to limit vertical transmission of HIV

The need to improve health services to HIV-positive women requires a specific focus on limiting mother-to-child transmission. Vertical transmission most often takes place during the intrapartum period; hence, it is essential to alert midwives to what constitutes safe or risky intrapartum practices. Midwives in the southern region of the North West Province of South Africa were surveyed for their knowledge of safe intrapartum practices that can limit vertical transmission of HIV, consequently indicating which intrapartum practices prevail in the region. We used a quantitative survey design and collected data by means of a questionnaire and checklist. A purposeful availability sample of 31 midwives who work in all four hospitals in the province was used and a random sample of 401 obstetric records was audited. Data were analysed by means of frequency analysis, effect sizes and cross-reference. A slight majority of the midwives had sufficient knowledge to distinguish between risky and safe practices. However, safe intrapartum practices are not always carried out and this raises concerns. Accordingly, we formulate general recommendations for nursing education, future research, and midwifery practice. In particular we suggest ways the national Guidelines for Maternity Care in South Africa may be adapted and better implemented to enhance safe intrapartum practices to limit vertical transmission of HIV.     

From the Cover: Increasing disparities between resource inputs and outcomes,as measured by certain health deliverables,in biomedical research

Society makes substantial investments in biomedical research, searching for ways to better human health. The product of this research is principally information published in scientific journals. Continued investment in science relies on society’s confidence in the accuracy, honesty, and utility of research results. A recent focus on productivity has dominated the competitive evaluation of scientists, creating incentives to maximize publication numbers, citation counts, and publications in high-impact journals. Some studies have also suggested a decreasing quality in the published literature. The efficiency of society’s investments in biomedical research, in terms of improved health outcomes, has not been studied. We show that biomedical research outcomes over the last five decades, as estimated by both life expectancy and New Molecular Entities approved by the Food and Drug Administration, have remained relatively constant despite rising resource inputs and scientific knowledge. Research investments by the National Institutes of Health over this time correlate with publication and author numbers but not with the numerical development of novel therapeutics. We consider several possibilities for the growing input-outcome disparity including the prior elimination of easier research questions, increasing specialization, overreliance on reductionism, a disproportionate emphasis on scientific outputs, and other negative pressures on the scientific enterprise. Monitoring the efficiency of research investments in producing positive societal outcomes may be a useful mechanism for weighing the efficacy of reforms to the scientific enterprise. Understanding the causes of the increasing input-outcome disparity in biomedical research may improve society’s confidence in science and provide support for growing future research investments.Few forces have transformed society more than science. Knowledge gained through the scientific method has lifted billions out of poverty, fueled industrialization and mass communication, eradicated smallpox, and placed human footprints on the moon. During the 20th century, science was increasingly funded by governments and corporations vying for military and economic advantage. Furthermore, the realization that investments in biomedical research translated into medical advances garnered strong societal support for the expenditure of public funds to support science. Today, science is a vast industry producing new knowledge, usually to address particular problems or questions facing humankind. Like any industry, the scientific enterprise uses tools and resources—scientists, money, and time—to produce an output: scientific knowledge, which can be represented by publications in the scientific literature.To remain competitive, corporations have long sought to maximize production efficiency, defined here as the ratio of output to input, by trimming waste and producing more (1). With increasing competition for research grants and jobs, funders and employers have turned to measures of efficiency and productivity to evaluate scientists (2). Such pressures have created well-documented incentives for scientists to maximize apparent productivity through publication numbers, citation counts, and publishing in high-impact journals (3, 4). Although this approach is designed to reward those who contribute most to the knowledge base, recent studies have raised questions about the quality of the biomedical literature (5–8). One such study found that only 11% of findings could be confirmed in 53 “landmark” hematology and oncology publications (6). Another study found that 43 of 67 published cardiovascular, oncological, and women’s health findings could not be reproduced (7). Recently, it was estimated that more than $28 billion is spent each year in the United States on irreproducible preclinical research and that the prevalence of these studies in the literature exceeds 50% (8). We note that this lack of reproducibility was identified by the National Institutes of Health (NIH) as a major problem and has led to initiatives for enhancing reproducibility and transparency (9). The irreproducibility of published data could potentially waste limited funding, years of work, and threatens to undermine public confidence in the scientific enterprise.A pure focus on scientific outputs can ignore the quality of those outputs. This is partially due to the fact that the quality and importance of scientific publications, unlike most human products, is subjective and difficult to assess in the present (10, 11). The true measure of a study’s quality would involve time-consuming and costly independent replication and an analysis of the work’s outcomes, including assessing its downstream utility to other applications and its effects on society. However, given the length of time needed and low probability of any given study generating substantial societal impact, it is very difficult to judge individual scientists or their work using simple outcome measures. Valid scientific research can have tremendous intrinsic societal value in producing information without the need for tangible outcomes. However, we also assume that all valid scientific research has some probability of generating tangible outcomes, even though such outcomes can be unpredictable and distant in both time and subject matter. For example, the theory of general relativity proposed in 1916 did not produce a useful outcome to the public until the late 20th century, when it provided a means to account for differences in clock rates under different gravitational influences, thereby enabling the global positioning systems found in a majority of modern cell phones and vehicles (12). Despite the intrinsic social value of biomedical knowledge, it is evident that public agencies, such as the NIH, support biomedical research with outcome-oriented goals, including benefitting health, preventing disease, and increasing return on investment (13). Although it is impractical to measure the outcomes generated by individual researchers, we believe that it is possible to estimate the outcomes of the biomedical research enterprise. In contrast to the production-based definition of efficiency (outputs ÷ inputs), we believe that evaluating research outcomes relative to inputs can be used to monitor the efficiency of biomedical innovation and the impact of research investments. Without studying outcomes, there is no way of knowing if society’s investment in research is paying off, and there is no way of evaluating the efficacy of systemic modifications to the scientific enterprise.     

Infection Prevention and the Medical Director: Uncharted Territory

Infections continue to be a major cause of disease and contributor to death in patients on dialysis. Despite our knowledge and acceptance that hemodialysis catheters should be avoided and eliminated, most patients who begin dialysis initiate treatment through a central vein hemodialysis catheter. Dialysis Medical Directors must be the instrument through which our industry changes. We must lead the charge to educate our dialysis staff and our dialysis patients. We must also educate ourselves so that we not only know that our facility policies are consistent with the best evidence available, but we must also know where local and federal regulations differ. When these differences impact on patient care, we must speak out and have these regulations changed. But it is not enough to know the rules and write them. We must lead by example and show our patients, our nephrology colleagues and our dialysis staff that we always follow these same policies. We need to practice what we preach and be willing and available to redirect those individuals who have difficulty following the rules. In order to effectively change process meaningful data must be collected, analyzed and acted upon. Dialysis Medical Directors must direct and lead the quality improvement process. We hope this review provides Dialysis Medical Directors with the necessary tools to effectively drive this process and improve care.     

Yentl syndrome. The underestimate of cardiovascular risk in women]

Cardiovascular diseases are the leading cause of death for women in all countries of the world. Aging of the population and the high prevalence of risk factors among young and middle-aged women allow to hypothesize that this situation will continue in the future. Differences exist between women and men in the impact of risk factors, symptoms and therapeutic response. However, the main problem limiting prevention and control of cardiovascular diseases among women is gender inequality in health care. Myocardial infarction and stroke continue to be seen as "male" diseases and this view has deeply limited research and clinical management improvements. Furthermore, factors related to the socioeconomic environment strongly influence the development of cardiovascular diseases. For women, the ability to stop smoking, have a healthy eating and regular physical activity and live in a supportive psychosocial environment is strongly influenced by their level of income, education, role, control over their lives, culture, religion, access to health care. For the majority of women these factors represent the main barriers to cardiovascular disease prevention. The promotion of cardiovascular health among women could be accomplished only by removing all the obstacles to women's active participation in public and private life allowing them to share a full and equal role in economic, social, cultural and political decision-making processes. This strategy will not only improve women's health, but also that of children and men.     

Strategies for Promoting Organizational and Practice Change by Advancing Implementation Research

BACKGROUND: The persistence of a large quality gap between what we know about how to produce high quality clinical care and what the public receives has prompted interest in developing more effective methods to get evidence into practice. Implementation research aims to supply such methods.
PURPOSE: This article proposes a set of recommendations aimed at establishing a common understanding of what implementation research is, and how to foster its development.
METHODS: We developed the recommendations in the context of a translation research conference hosted by the VA for VA and non-VA health services researchers.
IMPACTS: Health care organizations, journals, researchers and academic institutions can use these recommendations to advance the field of implementation science and thus increase the impact of clinical and health services research on the health and health care of the public.     

The North Dakota Mental Health and Aging Education Project: Curriculum Design and Training Outcomes for a Train-the-Trainer Model

A training curriculum on mental health and aging was developed and disseminated to 32 natural caregivers throughout a frontier state using a train-the-trainer model. Those certified as trainers included social workers, religious professionals, volunteers, long-term care employees, nurses, home health workers, and professional and informal caregivers. Trainers then utilized the materials assembled into toolkits to provide 1,813 hours of education in all eight regions of North Dakota. The purpose of this study was to evaluate the impact of the training on the preparation of trainers to provide mental health and aging education. Several points of evaluation, including a pre/posttest to assess the trainers' knowledge, an appraisal of the self-perceived value of the education to the trainers, and an applied case study to ascertain the trainers' ability to apply what they had learned, demonstrated the benefits of this model.     

Requirements and limits for life in the context of exoplanets

The requirements for life on Earth, its elemental composition, and its environmental limits provide a way to assess the habitability of exoplanets. Temperature is key both because of its influence on liquid water and because it can be directly estimated from orbital and climate models of exoplanetary systems. Life can grow and reproduce at temperatures as low as −15 °C, and as high as 122 °C. Studies of life in extreme deserts show that on a dry world, even a small amount of rain, fog, snow, and even atmospheric humidity can be adequate for photosynthetic production producing a small but detectable microbial community. Life is able to use light at levels less than 10⁻⁵ of the solar flux at Earth. UV or ionizing radiation can be tolerated by many microorganisms at very high levels and is unlikely to be life limiting on an exoplanet. Biologically available nitrogen may limit habitability. Levels of O₂ over a few percent on an exoplanet would be consistent with the presence of multicellular organisms and high levels of O₂ on Earth-like worlds indicate oxygenic photosynthesis. Other factors such as pH and salinity are likely to vary and not limit life over an entire planet or moon.The list of exoplanets is increasing rapidly with a diversity of masses, orbital distances, and star types. The long list motivates us to consider which of these worlds could support life and what type of life could live there. The only approach to answering these questions is based on observations of life on Earth. Compared with astronomical targets, life on Earth is easily studied and our knowledge of it is extensive––but it is not complete. The most important area in which we lack knowledge about life on Earth is its origin. We have no consensus theory for the origin of life nor do we know the timing or location (1). What we do know about life on Earth is what it is made of, and we know its ecological requirements and limits. Thus, it is not surprising that most of the discussions related to life on exoplanets focus on the requirements for life rather than its origin. In this paper we follow this same approach but later return briefly to the question of the origin of life.     

Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology

The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti-cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under-represent older patients and those with significant co-morbidities. The risk of adverse events may also increase when novel agents, which frequently modulate survival pathways, are used in combination with each other or with other conventional cytotoxic chemotherapeutics. The extent to which survival and growth pathways in the tumour cell (which we seek to inhibit) coincide with those in cardiovascular cells (which we seek to preserve) is an open question but one that will become ever more important with the development of new cancer therapies that target intracellular signalling pathways. It remains unclear whether potential cardiovascular problems can be predicted from analyses of such basic signalling mechanisms and what pre-clinical evaluation should be undertaken. The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients. This paper summarizes the deliberations of a cross-disciplinary workshop organized by the Heart Failure Association of the European Society of Cardiology (held in Brussels in May 2009), which brought together clinicians working in cardiology and oncology and those involved in basic, translational, and pharmaceutical science.     

Identification and management of cardiometabolic risk in Canada: a position paper by the cardiometabolic risk working group (executive summary)

With the objectives of clarifying the concepts related to "cardiometabolic risk," "metabolic syndrome" and "risk stratification" and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group presents an executive summary of a detailed analysis and position paper that offers a comprehensive and consolidated approach to the identification and management of cardiometabolic risk. The above concepts overlap and relate to the atherogenic process and development of type 2 diabetes. However, there is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider ethnicity-related risk factors in order to appropriately evaluate all individuals in their diverse patient populations.     

Complex actions of sex steroids in adipose tissue, the cardiovascular system, and brain: Insights from basic science and clinical studies

Recent publications describing the results of the Women's Health Initiative (WHI) and other studies reporting the impact of hormone therapy on aging women have spurred reexamination of the broad use of estrogens and progestins during the postmenopausal years. Here, we review the complex pharmacology of these hormones, the diverse and sometimes opposite effects that result from the use of different estrogenic and progestinic compounds, given via different delivery routes in different concentrations and treatment sequence, and to women of different ages and health status. We examine our new and growing appreciation of the role of estrogens in the immune system and the inflammatory response, and we pose the concept that estrogen's interface with this system may be at the core of some of the effects on multiple physiological systems, such as the adipose/metabolic system, the cardiovascular system, and the central nervous system. We compare and contrast clinical and basic science studies as we focus on the actions of estrogens in these systems because the untoward effects of hormone therapy reported in the WHI were not expected. The broad interpretation and publicity of the results of the WHI have resulted in a general condemnation of all hormone replacement in postmenopausal women. In fact, careful review of the extensive literature suggests that data resulting from the WHI and other recent studies should be interpreted within the narrow context of the study design. We argue that these results should encourage us to perform new studies that take advantage of a dialogue between basic scientists and clinician scientists to ensure appropriate design, incorporation of current knowledge, and proper interpretation of results. Only then will we have a better understanding of what hormonal compounds should be used in which populations of women and at what stages of menopausal/postmenopausal life.     

Patients' knowledge of risk and protective factors for cardiovascular disease

Coronary heart disease is the leading cause of death in the United States. The American Heart Association has proposed improving overall cardiovascular health by promoting 7 components of ideal cardiovascular health, including health behaviors (not smoking, regular exercise, and healthy diet) and health factors (ideal body mass index, cholesterol, blood pressure, and blood glucose). The patients' knowledge of these 7 components is unknown. We performed a cross-sectional survey of patients at 4 primary care and 1 cardiology clinic. The survey measured demographic data, personal behaviors/health factors, cardiovascular disease history, and knowledge about these 7 components. A multivariate model was developed to assess patient characteristics associated with high knowledge scores. Of the 2,200 surveys distributed, 1,702 (77%) were returned with sufficient responses for analysis. Of these, 49% correctly identified heart disease as the leading cause of death, and 37% (95% confidence interval [CI] 35% to 39%) correctly identified all 7 components. The average respondent identified 4.9 components (95% CI 4.7 to 5.0). The lowest recognition rates were for exercise (57%), fruit/vegetable consumption (58%), and diabetes (63%). In a multivariate model, knowledge of all 7 components was positively associated with high school education or greater (odds ratio 2.43, 95% CI 1.68 to 3.52) and white ethnicity (odds ratio 1.78, 95% CI 1.27 to 2.50), and negatively associated with attending an urban neighborhood clinic (odds ratio 0.60, 95% CI 0.44 to 0.82). In conclusion, just >1/3 of patients could identify all 7 components of ideal cardiovascular health. Educational efforts should target patients in low socioeconomic strata and focus on improving knowledge about healthy diet and regular exercise. Although patients with diabetes were more likely than those without diabetes to recognize their risk, 1 in 5 were not aware that diabetes is a risk factor for cardiovascular disease.     

What the Long Term Cohort Studies that Began in Childhood Have Taught Us about the Origins of Coronary Heart Disease

A limited number of observational studies were commenced in the 1970s and 1980s that have aimed to examine the child and adolescent origin of cardiovascular disease. These studies have provided, and continue to provide, critical evidence that have enhanced our understanding of the disease process, the early-life factors involved, and have informed public health and clinical guideline statements. Using data on preclinical markers of vascular health in adulthood, these studies have recently described the important role for youth lifestyle for later vascular health, provided information on the critical age in youth when risk factor associations with adult vascular health emerge, and have reported on the potential vascular benefits of resolving youth at-risk status in the transition from youth to adulthood. It is these works that we cover in detail in this review. Despite all the achievements from these studies, it is tantalizing that their most important contributions are still to come. That is, once sufficient clinical end points accrue so that analyses linking early life health to hard outcomes can be performed. These studies are a commodity and an invaluable resource that, with minimal re-investment, will provide increasing returns on cardiovascular health into the future.     

Cardiometabolic risk in Canada: a detailed analysis and position paper by the cardiometabolic risk working group

The concepts of "cardiometabolic risk," "metabolic syndrome," and "risk stratification" overlap and relate to the atherogenic process and development of type 2 diabetes. There is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. With the objectives of clarifying these concepts and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group reviewed the evidence related to emerging cardiovascular risk factors and Canadian guideline recommendations in order to present a detailed analysis and consolidated approach to the identification and management of cardiometabolic risk. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider risk factors related to ethnicity in order to appropriately evaluate everyone in their diverse patient populations.     

An ecosystem service perspective on urban nature,physical activity,and health

Nature underpins human well-being in critical ways, especially in health. Nature provides pollination of nutritious crops, purification of drinking water, protection from floods, and climate security, among other well-studied health benefits. A crucial, yet challenging, research frontier is clarifying how nature promotes physical activity for its many mental and physical health benefits, particularly in densely populated cities with scarce and dwindling access to nature. Here we frame this frontier by conceptually developing a spatial decision-support tool that shows where, how, and for whom urban nature promotes physical activity, to inform urban greening efforts and broader health assessments. We synthesize what is known, present a model framework, and detail the model steps and data needs that can yield generalizable spatial models and an effective tool for assessing the urban nature–physical activity relationship. Current knowledge supports an initial model that can distinguish broad trends and enrich urban planning, spatial policy, and public health decisions. New, iterative research and application will reveal the importance of different types of urban nature, the different subpopulations who will benefit from it, and nature’s potential contribution to creating more equitable, green, livable cities with active inhabitants.     

Role of genomics in cardiovascular medicine

As all branches of science grow and new experimental techniques become readily accessible, our knowledge of medicine is likely to increase exponentially in the coming years. Recently developed technologies have revolutionized our analytical capacities, leading to vast knowledge of many genes or genomic regions involved in the pathogenesis of congenital heart diseases, which are often associated with other genetic syndromes, coronary artery disease and non-ischemic cardiomyopathies and channelopathies. The knowledge-base of the genesis of cardiovascular diseases is likely going to be further revolutionized in this new era of genomic medicine. Here, we review the advances that have been made over the last several years in this field and discuss different genetic mechanisms that have been shown to underlie a variety of cardiovascular diseases.