Rural-Urban Differences in Vaccination and Hesitancy Rates and Trust: US COVID-19 Trends and Impact Survey on a Social Media Platform, May 2021-April 2022.

Objectives. To analyze rural-urban differences in COVID-19 vaccination uptake, hesitancy, and trust in information sources in the United States. Methods. We used data from a large survey of Facebook users. We computed the vaccination, hesitancy, and decline rates and the trust proportions among individuals hesitant toward COVID-19 information sources for rural and urban regions in each state from May 2021 to April 2022. Results. In 48 states with adequate data, on average, two thirds of states showed statistically significant differences in monthly vaccination rates between rural and urban regions, with rural regions having a lower vaccination rate at all times. Far fewer states showed statistically significant differences when comparing monthly hesitancy and decline rates for urban versus rural regions. Doctors and health professionals received the highest level of trust. Friends and family were also among the most trusted sources in rural areas where the vaccination uptake was low. Conclusions. Rural-urban difference in hesitancy rates among those still unvaccinated was much smaller than the rural-urban difference in vaccination rates, suggesting that access to vaccines may be another contributor to the lower vaccination rates in rural areas. (Am J Public Health. 2023;113(6):680-688. https://doi.org/10.2105/AJPH.2023.307274).

Bending the Curve in Cardiovascular Disease Mortality: Bethesda + 40 and Beyond.

More than 40 years after the 1978 Bethesda Conference on the Declining Mortality from Coronary Heart Disease provided the scientific community with a blueprint for systematic analysis to understand declining rates of coronary heart disease, there are indications the decline has ended or even reversed despite advances in our knowledge about the condition and treatment. Recent data show a more complex situation, with mortality rates for overall cardiovascular disease, including coronary heart disease and stroke, decelerating, whereas those for heart failure are increasing. To mark the 40th anniversary of the Bethesda Conference, the National Heart, Lung, and Blood Institute and the American Heart Association cosponsored the "Bending the Curve in Cardiovascular Disease Mortality: Bethesda + 40" symposium. The objective was to examine the immediate and long-term outcomes of the 1978 conference and understand the current environment. Symposium themes included trends and future projections in cardiovascular disease (in the United States and internationally), the evolving obesity and diabetes epidemics, and harnessing emerging and innovative opportunities to preserve and promote cardiovascular health and prevent cardiovascular disease. In addition, participant-led discussion explored the challenges and barriers in promoting cardiovascular health across the lifespan and established a potential framework for observational research and interventions that would begin in early childhood (or ideally in utero). This report summarizes the relevant research, policy, and practice opportunities discussed at the symposium.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Emerging Concepts in Precision Medicine and Cardiovascular Diseases in Racial and Ethnic Minority Populations.

Cardiovascular diseases remain the leading cause of mortality and a major contributor to preventable deaths worldwide. The dominant modifiable risk factors and the social and environmental determinants that increase cardiovascular risk are known, and collectively, are as important in racial and ethnic minority populations as they are in majority populations. Their prevention and treatment remain the foundation for cardiovascular health promotion and disease prevention. Genetic and epigenetic factors are increasingly recognized as important contributors to cardiovascular risk and provide an opportunity for advancing precision cardiovascular medicine. In this review, we explore emerging concepts at the interface of precision medicine and cardiovascular disease in racial and ethnic minority populations. Important among these are the lack of racial and ethnic diversity in genomics studies and biorepositories; the resulting misclassification of benign variants as pathogenic in minorities; and the importance of ensuring ancestry-matched controls in variant interpretation. We address the relevance of epigenetics, pharmacogenomics, genetic testing and counseling, and their social and cultural implications. We also examine the potential impact of precision medicine on racial and ethnic disparities. The National Institutes of Health's All of Us Research Program and the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine Initiative are presented as examples of research programs at the forefront of precision medicine and diversity to explore research implications in minorities. We conclude with an overview of implementation research challenges in precision medicine and the ethical implications in minority populations. Successful implementation of precision medicine in cardiovascular disease in minority populations will benefit from strategies that directly address diversity and inclusion in genomics research and go beyond race and ethnicity to explore ancestry-matched controls, as well as geographic, cultural, social, and environmental determinants of health.

Pharmacogenomics.

Genomic medicine, which uses DNA variation to individualise and improve human health, is the subject of this Series of papers. The idea that genetic variation can be used to individualise drug therapy-the topic addressed here-is often viewed as within reach for genomic medicine. We have reviewed general mechanisms underlying variability in drug action, the role of genetic variation in mediating beneficial and adverse effects through variable drug concentrations (pharmacokinetics) and drug actions (pharmacodynamics), available data from clinical trials, and ongoing efforts to implement pharmacogenetics in clinical practice.

Building evidence and measuring clinical outcomes for genomic medicine.

Human genomic sequencing has potential diagnostic, prognostic, and therapeutic value across a wide breadth of clinical disciplines. One barrier to widespread adoption is the paucity of evidence for improved outcomes in patients who do not already have an indication for more focused testing. In this Series paper, we review clinical outcome studies in genomic medicine and discuss the important features and key challenges to building evidence for next generation sequencing in the context of routine patient care.

Genomic medicine for undiagnosed diseases.

One of the primary goals of genomic medicine is to improve diagnosis through identification of genomic conditions, which could improve clinical management, prevent complications, and promote health. We explore how genomic medicine is being used to obtain molecular diagnoses for patients with previously undiagnosed diseases in prenatal, paediatric, and adult clinical settings. We focus on the role of clinical genomic sequencing (exome and genome) in aiding patients with conditions that are undiagnosed even after extensive clinical evaluation and testing. In particular, we explore the impact of combining genomic and phenotypic data and integrating multiple data types to improve diagnoses for patients with undiagnosed diseases, and we discuss how these genomic sequencing diagnoses could change clinical management.

Opportunities, resources, and techniques for implementing genomics in clinical care.

Advances in technologies for assessing genomic variation and an increasing understanding of the effects of genomic variants on health and disease are driving the transition of genomics from the research laboratory into clinical care. Genomic medicine, or the use of an individual's genomic information as part of their clinical care, is increasingly gaining acceptance in routine practice, including in assessing disease risk in individuals and their families, diagnosing rare and undiagnosed diseases, and improving drug safety and efficacy. We describe the major types and measurement tools of genomic variation that are currently of clinical importance, review approaches to interpreting genomic sequence variants, identify publicly available tools and resources for genomic test interpretation, and discuss several key barriers in using genomic information in routine clinical practice.

Use of the National Heart, Lung, and Blood Institute Data Repository.

BACKGROUND: Research on data sharing from clinical trials has focused on elucidating perceptions, barriers, and attitudes among trialists and study participants with respect to sharing data. However, little information exists regarding utilization or associated publication of articles once clinical trial data have been widely shared. METHODS: We analyzed administrative records of investigator requests for data access, linked publications, and bibliometrics to describe the use of the National Heart, Lung, and Blood Institute data repository. RESULTS: From January 2000 through May 2016, a total of 370 investigators requested data from 1 or more clinical trials. Requests for trial data have been increasing, with 195 investigators (53%) initiating requests during the last 4.4 years of the study period. The predominant reason for requesting data was post hoc secondary analysis of new questions (72%), followed by analytic or statistical approaches to clinical trials (9%) and meta-analyses or pooled study research (7%). Of 172 requests with online project descriptions, only 2 requests were initiated for reanalysis of primary-outcome findings. Data from 88 of 100 available clinical trials were requested at least once, and the median time from repository availability to first request was 235 days. A total of 277 articles were published on the basis of data from 47 trials. Citation metrics from 224 articles indicated that half of the publications have cumulative citations that rank in the top 34% normalized for subject category and year of publication. CONCLUSIONS: Demand for trial data for secondary analysis has been increasing. Requesting data for the a priori purpose of reanalysis or verification of original findings was rare.

Global, Regional, and National Burden of Rheumatic Heart Disease, 1990-2015.

BACKGROUND: Rheumatic heart disease remains an important preventable cause of cardiovascular death and disability, particularly in low-income and middle-income countries. We estimated global, regional, and national trends in the prevalence of and mortality due to rheumatic heart disease as part of the 2015 Global Burden of Disease study. METHODS: We systematically reviewed data on fatal and nonfatal rheumatic heart disease for the period from 1990 through 2015. Two Global Burden of Disease analytic tools, the Cause of Death Ensemble model and DisMod-MR 2.1, were used to produce estimates of mortality and prevalence, including estimates of uncertainty. RESULTS: We estimated that there were 319,400 (95% uncertainty interval, 297,300 to 337,300) deaths due to rheumatic heart disease in 2015. Global age-standardized mortality due to rheumatic heart disease decreased by 47.8% (95% uncertainty interval, 44.7 to 50.9) from 1990 to 2015, but large differences were observed across regions. In 2015, the highest age-standardized mortality due to and prevalence of rheumatic heart disease were observed in Oceania, South Asia, and central sub-Saharan Africa. We estimated that in 2015 there were 33.4 million (95% uncertainty interval, 29.7 million to 43.1 million) cases of rheumatic heart disease and 10.5 million (95% uncertainty interval, 9.6 million to 11.5 million) disability-adjusted life-years due to rheumatic heart disease globally. CONCLUSIONS: We estimated the global disease prevalence of and mortality due to rheumatic heart disease over a 25-year period. The health-related burden of rheumatic heart disease has declined worldwide, but high rates of disease persist in some of the poorest regions in the world. (Funded by the Bill and Melinda Gates Foundation and the Medtronic Foundation.).

National Heart, Lung, and Blood Institute cardiovascular clinical trial perspective.

The National Heart, Lung, and Blood Institute (NHLBI) has played an important role in funding the clinical science that supports many contemporary cardiology practice guidelines and in shaping the conduct of cardiovascular clinical trials. This Perspective outlines contemporary funding options as well as select important NHLBI policies, philosophy, and priorities.

Nutrition Disparities and Cardiovascular Health.

PURPOSE OF REVIEW: This review is an assessment of the state of the science on nutrition disparities and their contribution to disparities in cardiovascular health. RECENT FINDINGS: Nutrition disparities remain pervasive by race/ethnicity, sex/gender, socioeconomic status, and geography. They are rooted in differences in social, cultural, and environmental determinants of health, behavioral and lifestyle factors, and the impact of policy interventions. Systematic differences in diet quality, dietary patterns, and nutrient intakes contribute to cardiovascular disparities and are mediated by microbiota, and CVD risk factors including high levels of blood pressure, low density lipoprotein cholesterol (LDL), and glucose; oxidative stress, pro-inflammatory cytokines, and endothelial dysfunction. Despite the progress made in nutrition research, important gaps persist that signal the need for more effective interventions at multiple levels to reduce cardiovascular disparities. Research opportunities include (1) exploring the gene-nutrient-environment interactions in the context of ancestral diversity; (2) investigating the causal link between diet and gut microbiota and impact of social determinants of health; (3) understanding resilience; (4) testing the effectiveness of multi-level interventions that address social and environmental determinants; and (4) supporting intervention research informed by validated implementation science frameworks.

Reducing Cardiovascular Disparities Through Community-Engaged Implementation Research: A National Heart, Lung, and Blood Institute Workshop Report.

Cardiovascular disparities remain pervasive in the United States. Unequal disease burden is evident among population groups based on sex, race, ethnicity, socioeconomic status, educational attainment, nativity, or geography. Despite the significant declines in cardiovascular disease mortality rates in all demographic groups during the last 50 years, large disparities remain by sex, race, ethnicity, and geography. Recent data from modeling studies, linked micromap plots, and small-area analyses also demonstrate prominent variation in cardiovascular disease mortality rates across states and counties, with an especially high disease burden in the southeastern United States and Appalachia. Despite these continued disparities, few large-scale intervention studies have been conducted in these high-burden populations to examine the feasibility of reducing or eliminating cardiovascular disparities. To address this challenge, on June 22 and 23, 2017, the National Heart, Lung, and Blood Institute convened experts from a broad range of biomedical, behavioral, environmental, implementation, and social science backgrounds to summarize the current state of knowledge of cardiovascular disease disparities and propose intervention strategies aligned with the National Heart, Lung, and Blood Institute mission. This report presents the themes, challenges, opportunities, available resources, and recommended actions discussed at the workshop.

Socioeconomic Status and Cardiovascular Outcomes: Challenges and Interventions.

Socioeconomic status (SES) has a measurable and significant effect on cardiovascular health. Biological, behavioral, and psychosocial risk factors prevalent in disadvantaged individuals accentuate the link between SES and cardiovascular disease (CVD). Four measures have been consistently associated with CVD in high-income countries: income level, educational attainment, employment status, and neighborhood socioeconomic factors. In addition, disparities based on sex have been shown in several studies. Interventions targeting patients with low SES have predominantly focused on modification of traditional CVD risk factors. Promising approaches are emerging that can be implemented on an individual, community, or population basis to reduce disparities in outcomes. Structured physical activity has demonstrated effectiveness in low-SES populations, and geomapping may be used to identify targets for large-scale programs. Task shifting, the redistribution of healthcare management from physician to nonphysician providers in an effort to improve access to health care, may have a role in select areas. Integration of SES into the traditional CVD risk prediction models may allow improved management of individuals with high risk, but cultural and regional differences in SES make generalized implementation challenging. Future research is required to better understand the underlying mechanisms of CVD risk that affect individuals of low SES and to determine effective interventions for patients with high risk. We review the current state of knowledge on the impact of SES on the incidence, treatment, and outcomes of CVD in high-income societies and suggest future research directions aimed at the elimination of these adverse factors, and the integration of measures of SES into the customization of cardiovascular treatment.

HLBS-PopOmics: an online knowledge base to accelerate dissemination and implementation of research advances in population genomics to reduce the burden of heart, lung, blood, and sleep disorders.

Recent dramatic advances in multiomics research coupled with exponentially increasing volume, complexity, and interdisciplinary nature of publications are making it challenging for scientists to stay up-to-date on the literature. Strategies to address this challenge include the creation of online databases and warehouses to support timely and targeted dissemination of research findings. Although most of the early examples have been in cancer genomics and pharmacogenomics, the approaches used can be adapted to support investigators in heart, lung, blood, and sleep (HLBS) disorders research. In this article, we describe the creation of an HLBS population genomics (HLBS-PopOmics) knowledge base as an online, continuously updated, searchable database to support the dissemination and implementation of studies and resources that are relevant to clinical and public health practice. In addition to targeted searches based on the HLBS disease categories, cross-cutting themes reflecting the ethical, legal, and social implications of genomics research; systematic evidence reviews; and clinical practice guidelines supporting screening, detection, evaluation, and treatment are also emphasized in HLBS-PopOmics. Future updates of the knowledge base will include additional emphasis on transcriptomics, proteomics, metabolomics, and other omics research; explore opportunities for leveraging data sets designed to support scientific discovery; and incorporate advanced machine learning bioinformatics capabilities.

Global Burden of Stroke.

On the basis of the GBD (Global Burden of Disease) 2013 Study, this article provides an overview of the global, regional, and country-specific burden of stroke by sex and age groups, including trends in stroke burden from 1990 to 2013, and outlines recommended measures to reduce stroke burden. It shows that although stroke incidence, prevalence, mortality, and disability-adjusted life-years rates tend to decline from 1990 to 2013, the overall stroke burden in terms of absolute number of people affected by, or who remained disabled from, stroke has increased across the globe in both men and women of all ages. This provides a strong argument that "business as usual" for primary stroke prevention is not sufficiently effective. Although prevention of stroke is a complex medical and political issue, there is strong evidence that substantial prevention of stroke is feasible in practice. The need to scale-up the primary prevention actions is urgent.

Decline in Cardiovascular Mortality: Possible Causes and Implications.

If the control of infectious diseases was the public health success story of the first half of the 20th century, then the decline in mortality from coronary heart disease and stroke has been the success story of the century's past 4 decades. The early phase of this decline in coronary heart disease and stroke was unexpected and controversial when first reported in the mid-1970s, having followed 60 years of gradual increase as the US population aged. However, in 1978, the participants in a conference convened by the National Heart, Lung, and Blood Institute concluded that a significant recent downtick in coronary heart disease and stroke mortality rates had definitely occurred, at least in the US Since 1978, a sharp decline in mortality rates from coronary heart disease and stroke has become unmistakable throughout the industrialized world, with age-adjusted mortality rates having declined to about one third of their 1960s baseline by 2000. Models have shown that this remarkable decline has been fueled by rapid progress in both prevention and treatment, including precipitous declines in cigarette smoking, improvements in hypertension treatment and control, widespread use of statins to lower circulating cholesterol levels, and the development and timely use of thrombolysis and stents in acute coronary syndrome to limit or prevent infarction. However, despite the huge growth in knowledge and advances in prevention and treatment, there remain many questions about this decline. In fact, there is evidence that the rate of decline may have abated and may even be showing early signs of reversal in some population groups. The National Heart, Lung, and Blood Institute, through a request for information, is soliciting input that could inform a follow-up conference on or near the 40th anniversary of the original landmark conference to further explore these trends in cardiovascular mortality in the context of what has come before and what may lie ahead.