Access and adherence to prevention and therapeutic lifestyle change programs remain largely aspirational for many low resource and minority communities. Given the importance of prevention and the high cost of care in complex medical conditions such as cardiovascular kidney and metabolic syndrome (CKM), new models of care delivery that enhance value are needed. Community health workers (CHWs) may serve as an innovative link between healthcare systems and the community, improving last mile delivery of services for “at risk” community members through education, outreach, informal counseling, social service support, and advocacy. The impending new Center for Medicare Medicaid Services (CMS) reimbursements for Community Health Integration, Social Determinants of Health (SDOH) assessment, and Principal Illness Navigation services in medically necessary care, represents a major shift in reimbursement models. In this review, we explore four overarching barriers to widespread adoption of CHWs, current roles of CHWs in CKM care, including outcomes and data confirming economic viability and sustainability of engaging CHW's in CKM care. We explore problems with existing financial models for CHW involvement, and forthcoming reimbursement pathways and solutions. CHW's are frontline health workers who could be critical in enhancing value for CKM. However current reimbursement models and restructuring of payments needs to occur rapidly to embrace a new cadre of health workers in our fight against adverse CKM health.

BACKGROUND:Type 2 diabetes is a rapidly growing global health challenge in low- and middle-income countries (LMICs), and evidence suggests that air pollution exposure contributes. Household air pollution from burning solid fuels for cooking is a major burden in LMICs, but studies demonstrating associations between reductions in household air pollution and improvements in HbA1c, a biomarker of diabetes risk, are lacking. We previously reported substantial reductions in fine particulate matter with an aerodynamic diameter ≤2.5μm (PM2.5) and black carbon concentrations following an intervention in rural Honduras with the Justa cookstove, a wood-burning stove with an engineered combustion chamber and chimney. OBJECTIVE:In a stepped-wedge randomized controlled trial among 230 Honduran women using traditional wood-burning stoves at baseline, we evaluated the effect of the Justa intervention on HbA1c and characterized the longitudinal associations between air pollution exposures and HbA1c. METHODS:At each of six visits over 3 y, we measured 24-h PM2.5 and black carbon concentrations, and finger-stick HbA1c levels. We used linear mixed models in intent-to-treat (condition by assigned stove type), exposure-response (using 24-h measures and modeled estimates of long-term exposures), and "per protocol" self-reported stove use analyses. RESULTS:HbA1c was reduced for the Justa condition in comparison with the traditional stove condition, but estimates were small and not statistically significant [-0.03 percentage points, 95% confidence interval (CI): -0.13, 0.07, n=1,208 observations]. A slightly stronger effect was observed when using self-reported stove use in per protocol analyses. Exposure-response analyses demonstrated positive associations between HbA1c and air pollution [e.g., HbA1c was 0.22 percentage points higher (95% CI: 0.13, 0.30) per log-unit higher long-term average personal PM2.5]. DISCUSSION:Our study provides novel evidence of exposure-response associations between household air pollution and HbA1c within a randomized cookstove trial, contributing to the evidence base necessary to support clean cooking policy initiatives. https://doi.org/10.1289/EHP15095.

Background: Fine particulate matter <2.5 µm (PM2.5) air pollution increases cardio-pulmonary morbidity and mortality. To inform the public regarding local air quality and reduce short-term exposures to PM2.5, daily Air Quality Indices (AQIs) with activity guidance are issued across the United States (US). We aimed to estimate the cardio-pulmonary health benefits of the current AQI strategy. Methods: We estimated the number needed to treat (NNT) per county per day to avoid 1 atherosclerotic cardiovascular disease (ASCVD) or pulmonary event during each PM2.5 AQI action day (defined as a day with an AQI >100 for PM2.5) for 3 groups (healthy adults, ASCVD and pulmonary disease patients) in the US during 2022. The theoretical number of adverse events potentially prevented per county was estimated each day as the relevant county population divided by the corresponding NNT. These results were summed for all AQI action days among US counties to equal the potential total number of ASCVD and pulmonary events avoided nationwide. Results: There were 1081 AQI action days for PM2.5 (58.0 ± 32.4 µg/m3) across 236 counties in 2022, accounting for an estimated excess of 164 ASCVD and 3963 pulmonary events. Approximately 31 ASCVD and 796 pulmonary events could be theoretically avoided if all populations followed activity guidelines during every AQI action day. Conclusions: Daily AQI activity guidelines, as currently structured and implemented, likely prevent few cardio-pulmonary events per year in the US. Additional research is warranted to determine how to improve the overall approach to more effectively protect public health.

Hypertension is a multifactorial condition influenced by the intricate interplay of biological and genetic determinants. The growing field of Environmental Hypertensionology endorses the outsized role of environmental factors in the pathogenesis and exacerbation of hypertension. It provides a clinical approach to address these factors at the individual and societal levels. Environmental stressors contributing to blood pressure levels can be viewed within the mosaic model of hypertension, which offers a comprehensive framework for understanding blood pressure regulation through its connection with multiple other nodes causally related to the pathogenesis of hypertension. This review synthesizes growing evidence supporting the impact of several factors in the physical environment and adverse stressors embedded in key provisioning systems, including air, noise, and chemical pollution, along with aspects of the built environment, green spaces, food systems, on the global burden of hypertension. Although many factors may not be directly in the causal cascade of hypertension, the web of connections between many behooves an understanding of the important nodes for intervention. Public health strategies emphasizing the redesign of environments present an unprecedented opportunity to enhance global hypertension control rates. Future research should thus focus on integrating environmental risk assessment and interventions into clinical practice, optimizing urban planning, and public policy to achieve meaningful reductions in the global burden of hypertension. By understanding hypertension as a mosaic of interconnected causes, healthcare professionals are better equipped to individualize treatment, combining lifestyle interventions and multiple drug classes to target environmental and genetic factors driving high blood pressure.

Various studies indicated that pregnant women living near UONG sites may be more likely to give birth to infants with CHDs due to exposure to air, water, and soil pollution generated by these sites. We systematically searched three English-language databases-PubMed, Scopus, and the Web of Science Core Collection-from their inception until September 21, 2024 to include all types of epidemiological studies that explored the associations between maternal residential proximity to UONG sites and CHDs in the US. We screened a total of 282 unique studies and included six cohort and case-control studies conducted between 1996 and 2017 for evidence synthesis. These studies, conducted in Texas (two studies), Colorado (two), Ohio (one), and Oklahoma (one), encompassed almost 4.5 million births (including 88,638 CHDs cases). All risk estimates were adjusted for socioeconomic status and behavioral factors. Overall, the findings vary significantly across studies in relation to different exposure categories and buffer distances. Four studies reported significant positive associations between proximity to UONG sites and increased odds of CHDs in newborns compared to pregnant women with no recorded exposure to these sites, with adjusted ORs ranging from 1.04 (95 % CI: 1.01-1.07) to 2.62 (95 % CI: 2.48-2.77). The inconsistencies across the included studies make it challenging to pool effect sizes and determine the true impact of these sites on CHD risk in newborns. We also believe that further research is needed worldwide, particularly in regions where these sites are prevalent, as the included studies are limited to the U.S. Our study highlights the need for simple and practical interventions to reduce associated exposures in these communities, as our findings reveal that fetuses of mothers living in proximity to UONG sites are at an increased risk of CHDs.

BACKGROUND AND AIMS:We designed this study to investigate the mortality costs of cardiovascular disease (CVD) deaths associated with non-optimal, cold and hot temperatures-as an emerging environmental risk factor for CVD-globally, regionally, and nationally between 2000 and 2021. METHODS:We obtained disease burden estimates from the Global Burden of Disease (GBD) 2021 study and estimated the cost of CVD deaths linked to non-optimal, cold and hot temperatures using two valuation measures: the age-adjusted and age-invariant value of a statistical life (VSL). To identify key drivers of mortality costs, we performed multiple linear regression (MLR) analysis, examining the effects of climate, socio-economic, and demographic factors. RESULTS:The global mortality costs due to CVD increased by 51 %, rising from US$550.8 billion to US$833.2 billion using the age-adjusted VSL between 2000 and 2021. Cold temperatures accounted for the majority of the global mortality costs linked to non-optimal temperatures, between US$519.6 and US$745.5 billion over the study period. High-income GBD super-region demonstrated the greatest mortality costs, contributing 36-63 % of global mortality cost of CVD due to non-optimal temperatures over the study period. Among the top 5 countries (the USA, China, Russia, Japan, and Germany) with the greatest mortality cost of CVD deaths attributable to non-optimal temperatures, China experienced the most significant increase in mortality costs, rising by over 700 % during the study period and reaching nearly US$230 billion in 2021. Based on MLR findings, the primary factors influencing mortality costs were the age-standardized CVD death rate, gross domestic product (GDP) per capita, and population age structure. CONCLUSIONS:Our results underscore the importance of the growing global mortality costs from CVD associated with non-optimal temperatures. The findings should serve to alert the global community regarding the urgent need to develop policies that aim to protect the public, particularly in regions with the highest costs and aging populations.

BACKGROUND:More than one in three adults with hypertension in the United States are unaware of their condition, highlighting the importance of large-scale screening campaigns. Currently, the identification of hypertension is largely limited to medical settings. To help overcome this barrier, we developed a novel high-throughput screening protocol that measures blood pressure (BP) while patients remain seated in an automobile ("car-BP"). The aim of this study was to provide an initial assessment of the accuracy of car-BP. METHODS:Three BP readings were determined in a clinic exam room before and after three BP readings were taken while patients were seated in a parked car outside (n = 100 participants). The same validated device model (Omron HEM-907XL) and BP measurement methods adhering to guidelines were used in both scenarios. The average of all 6 clinic readings was compared to the average of the 3 car-BP readings in each individual. RESULTS:Mean clinic and car-BP readings were 120.9 ± 16.2/78.0 ± 9.9 and 118.9 ± 15.2/76.0 ± 10.0 mm Hg, respectively. The paired mean and absolute mean differences in systolic BP levels between methods were -1.92 mm Hg (95% confidence interval (CI) -3.2 to -0.7 mm Hg) and 4.8 mm Hg (95%CI 3.8 to 5.6 mm Hg), respectively. A total of 85% of participants had both systolic and diastolic BP levels ≤ 10 mm Hg different between measurement scenarios (meeting the a priori determined study primary outcome). CONCLUSIONS:Car-BP represents an innovative and accessible approach for potential large-scale hypertension screening campaigns.

The Global Burden of Disease assessment estimates that 20% of global type 2 diabetes cases are related to chronic exposure to particulate matter (PM) with a diameter of 2·5 μm or less (PM2·5). With 99% of the global population residing in areas where air pollution levels are above current WHO air quality guidelines, and increasing concern in regard to the common drivers of air pollution and climate change, there is a compelling need to understand the connection between air pollution and cardiometabolic disease, and pathways to address this preventable risk factor. This Review provides an up to date summary of the epidemiological evidence and mechanistic underpinnings linking air pollution with cardiometabolic risk. We also outline approaches to improve awareness, and discuss personal-level, community, governmental, and policy interventions to help mitigate the growing global public health risk of air pollution exposure.

HomeCirculationVol. 149, No. 10Cardiovascular and Planetary Health: Two Sides of the Same Planet Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBCardiovascular and Planetary Health: Two Sides of the Same Planet Sanjay Rajagopalan and Robert D. Brook Sanjay RajagopalanSanjay Rajagopalan Correspondence to: Sanjay Rajagopalan, MD, University Hospitals Harrington Heart and Vascular Institute, Case Western Reserve University School of Medicine, 11100 Euclid Ave, Cleveland, OH 44106. Email E-mail Address: [email protected] https://orcid.org/0000-0001-6669-8163 Harrington Heart and Vascular Institute, University Hospitals and Case Western Reserve University, Cleveland, OH (S.R.). and Robert D. BrookRobert D. Brook https://orcid.org/0000-0002-8521-7262 Division of Cardiovascular Diseases, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI (R.D.B.). Originally published4 Mar 2024https://doi.org/10.1161/CIRCULATIONAHA.123.065486Circulation. 2024;149:729–731Unassailable evidence for the interdependence of human and planetary well-being necessitates a fundamental shift away from believing that one's personal health is distinct and separable from that of the planet. Rather, we are now confronted with the reality that personal and planetary welfare are interdependent, with the environment and social systems playing critical roles. The Global Burden of Disease investigators estimates that 9.2 million deaths per year are attributable to known environmental pollutants, with more than half resulting from cardiovascular causes alone, including myocardial infarctions, strokes, and heart failure.1–3 Exposure to environmental pollution alone is thus a singularly important risk factor for cardiovascular disease worldwide. It is important to note that the full public health effect of pollution on health (eg, metabolic, mental, cancers, and other systems) is difficult to fully characterize and is likely much larger than estimated. The relationship between personal and planetary health is best visualized through the analogy of the "Raworth Donut" which combines 2 concentric circles to depict the social and ecological boundaries that ensconce human health.1 An increasingly archaic social-environmental-infrastructural system based on resource extraction and consumption has already resulted in the transgression of multiple planetary boundaries and ironically impinges on further improvements in cardiovascular outcomes. Seen in this light, returning to the safe space of planetary health within the Raworth Donut should be considered an existential imperative and may be one of the greatest opportunities to improve human health. This brief review aims to highlight the inextricable connection between planetary and human health and the potential opportunities to improve both.Air pollution, derived principally from fossil fuel combustion, is one of the key man-made factors that characterizes the "Anthropocene epoch," defined as when human activity has begun to alter the Earth's ecosystem. Air pollution contributes to more deaths per year than all wars, malaria, tuberculosis, HIV and other infectious disease combined, more than half of which are of cardiovascular origin.2 Robust evidence from animal and human studies has elucidated the mechanisms of air pollution–induced cardiovascular effects, which are mediated through diverse pathways involving hemodynamic, inflammatory, and thrombotic factors.4 An abundant body of evidence also implicates air pollution in the pathogenesis of traditional risk factors per se, most notably hypertension and diabetes. This impressive evidence base linking air pollution with cardiovascular disease was undoubtedly facilitated by the availability of a simple, standardizable, and scalable metric of air pollution, the mass of particulate matter ≤2.5 microns expressed as the micrograms per cubic meter of volume of ambient air. Despite the intrinsic complexity of its chemistry and sources, the measurement of particulate matter ≤2.5 microns using regional monitors, and eventually covering most of the global surface in 1×1 km grids using augmented information from satellite data, has allowed the derivation of integrated response exposure function and global burden estimates. Despite some limitations, this surrogate has been highly successful in robustly modeling health outcomes at regional, country, and global scales. However, because many additional environmental exposures, such as noise, nocturnal light, soil and waterborne chemical pollutants/toxins, and adverse features of the built environment (eg, lack of greenspaces) commonly cosegregate with air pollution, particularly in urban areas, alternate approaches that incorporate the sum of exposures and their effects or the aggregate, defined as the "exposome," have been proposed. The integration of large-scale climate, environmental, social, and health data into common platforms and the use of machine learning and artificial intelligence tools to explore climate and human health effects in these datasets provide an unprecedented new opportunity to health effect assessment, and to inform policy, as well. Growing evidence fortunately shows that reducing environmental exposures, especially to air pollutants, is a powerful strategy to reduce cardiovascular diseases, lower all-cause mortality, and increase overall life expectancy.1–3 Approaches that lower environmental pollution will therefore not only protect planetary health but also serve to improve human well-being.The concept of "residual environmental cardiovascular risk" may entail a framework that considers the entire exposome (ie, a myriad of exposures to "invisible" environmental and social factors) that contribute to global cardiometabolic health, after traditional risk factors have been addressed.3 Addressing the sum totality of exposures may warrant a departure from the current "one exposure at a time framework" to simultaneous examination of multiple exposures that affect humans throughout most locations in the modern world in a near-continuous fashion and interact in additive (or even synergistic) ways.Focusing on complex multisector exposures will not only facilitate a holistic understanding of the public health threats posed by environmental and social factors but may also help drive improvements to integrated societal systems (eg, transportation or health care industries) and thus accelerate attainment of sustainable development goals as a whole. Fossil fuels currently power 7 key provisioning systems (food, energy, mobility-connectivity, housing, green infrastructure, water, and waste management) that lie at the core of human health, well-being, and sustainability. Transforming provisioning systems to a net-zero electricity grid, enabled by renewable electricity, can help to achieve the dual attainment of climate and health goals.4 Such an approach has the potential to simultaneously mitigate multiple adverse exposures, especially when combined with urban spatial planning that addresses a 5-dimensional "5D" framework (density of population, housing, and jobs; diversity of land use; design for multiple transport modes; destination access; and distance to public transport and other noncar modes). Following this urban model has the potential to increase physical activity (eg, walkability) while also reducing motor traffic–related exposures such as air pollution and noise. Low-carbon strategies being considered throughout the world, such as innovations in active transportation, micromobility, energy-efficient buildings, urban food gardens, recreation areas, commuting infrastructure (eg, biking lanes, walking paths), and a revival of interest in an urban infrastructure to address social determinants of health, while encouraging and helpful in reducing pollution and greenhouse gases, represent important steps forward. However, they may not be enough to meet climate and planetary goals. Moving from low-carbon to deep decarbonization and net-zero strategies will entail far more extensive system changes, necessitating the transformation of complex sociotechnical systems dependent on linear "take-make-waste" models and breaking out of interrelated technological and behavioral lock-ins. A tripartite strategy has been recommended together with pathways within each strategy4: (1) Reducing demand (through spatial planning, single-sector efficiencies in buildings, transportation, and green infrastructure). (2) Switching supplies to net-zero carbon electricity, renewable fuels, and materials through carbon valorization. (3) Carbon capture technologies.Phasing out fossil fuels and reducing anthropogenic air pollution will have measurable and immediate effects on health that have already been shown to outweigh upfront investment costs.5 The positive marginal economic value of decarbonization is its profoundly beneficial rapid effect on health.6 As one example, dramatic reductions in air pollution–related morbidity and mortality would be a direct result, especially in regions of the world where the absolute levels of exposure are higher (eg, Asia, Africa). These benefits contrast with the vastly larger timescales (eg, decades) over which climate improvements may be expected. More than half of the immediate health effect of air pollution reduction may relate to reduction in cardiovascular mortality and reduced hospitalizations.2 The effect on susceptible populations, in particular, racial minorities and the socially disadvantaged, that contribute disproportionately to cost of care may be quite substantive. However, the most important effect on human health of decarbonization may be through yet unrealized synergies that it may deliver.7 These include: (1) the adoption of public or active forms of travel together with electrification of transportation, contributing to reduced noise pollution and increased physical activity; (2) reduction in cardiovascular disease related to increased intake of locally sourced and sustainable plant-based ingredients that will result from decarbonization in the agricultural sector; (3) massive reduction in chemical exposures due to elimination of petroleum-based products and the corresponding improvement in risk factors such as hypertension, obesity, and diabetes. Many of the most heavily polluted areas worldwide unfortunately are in developing countries facing the greatest concurrent risk from cardiovascular disease and climate change. They unfortunately also face substantial barriers to a successful transition to a green economy that can help mitigate the twin syndemic of climate and cardiovascular disease. Given that human and planetary health, especially climate change, are by definition global issues, this problem will require multifaceted coordinated political and governmental policy action efforts from the community of nations to solve what may be well beyond well-intentioned market-based strategies tethered to economic incentives alone.8,9To avert environmental collapse, we must cut carbon in every sector including health care. The US health care sector pollutes more than any other industrialized health system in the world, accounting for 27% of all global health care greenhouse gas emissions. A staggering 82% of health care emissions have indirect origins related to the supply chain, including pharmaceuticals, water and waste management, equipment services, medical supplies, among others. Physicians have a moral obligation to advocate for decarbonization on the basis of the profound health effect of a fossil fuel–based economy and articulate these links to their patients and constituents. The health care sector can lead the way in decarbonization efforts by holding their suppliers and manufacturers accountable and mandating that all health care–related products be manufactured using sustainable approaches and renewable energy sources. Our very health depends on it.ARTICLE INFORMATIONSources of FundingThis study was funded by National Institutes of Health Grants 1R35ES031702 and R01ES017290.Disclosures None.FootnotesThe American Heart Association celebrates its 100th anniversary in 2024. This article is part of a series across the entire AHA Journal portfolio written by international thought leaders on the past, present, and future of cardiovascular and cerebrovascular research and care. To explore the full Centennial Collection, visit https://www.ahajournals.org/centennialThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Sources of Funding and Disclosures, see page 731.Circulation is available at www.ahajournals.org/journal/circCorrespondence to: Sanjay Rajagopalan, MD, University Hospitals Harrington Heart and Vascular Institute, Case Western Reserve University School of Medicine, 11100 Euclid Ave, Cleveland, OH 44106. Email Sanjay.Rajagopalan@UHhospitals.orgREFERENCES1. Raworth K. A doughnut for the Anthropocene: humanity's compass in the 21st century.Lancet Planet Health. 2017; 1:e48–e49. doi: 10.1016/S2542-5196(17)30028-1CrossrefMedlineGoogle Scholar2. Rajagopalan S, Landrigan PJ. Pollution and the heart.N Engl J Med. 2021; 385:1881–1892. doi: 10.1056/NEJMra2030281CrossrefMedlineGoogle Scholar3. Al-Kindi S, Brook RD, Rajagopalan S. Residual environmental cardiovascular risk: an overlooked paradigm.Eur Heart J. 2023; 44:4612–4614. doi: 10.1093/eurheartj/ehad412CrossrefMedlineGoogle Scholar4. Seto KC, Churkina G, Hsu A, Keller M, Newman PWG, Qin B, Ramaswami A. From low- to net-zero carbon cities: the next global agenda.Annu Rev Environ Resour. 2021; 46:377–415. doi: 10.1146/annurev-environ-050120-113117CrossrefGoogle Scholar5. U.S. Environmental Protection Agency Office of Air and Radiation. The benefits and costs of the clean air act from 1990 to 2020, Final Report, Rev A.April 2011. Accessed July 1, 2023. https://www.epa.gov/sites/production/files/2015-07/documents/fullreport_rev_a.pdfGoogle Scholar6. Gallagher CL, Holloway T. Integrating air quality and public health benefits in U.S. decarbonization strategies.Front Public Health. 2020; 8:563358. doi: 10.3389/fpubh.2020.563358CrossrefMedlineGoogle Scholar7. van Daalen KR, Romanello M, Rocklov J, Semenza JC, Tonne C, Markandya A, Dasandi N, Jankin S, Achebak H, Ballester J, et al. The 2022 Europe report of the Lancet Countdown on health and climate change: towards a climate resilient future.Lancet Public Health. 2022; 7:e942–e965. doi: 10.1016/S2468-2667(22)00197-9CrossrefMedlineGoogle Scholar8. Bhattacharya A, Kharas H, McArthur JW. Developing countries are key to climate action.March 3, 2023. Accessed September 18, 2023. https://www.brookings.edu/articles/developing-countries-are-key-to-climate-action/Google Scholar9. Russell C, Greenspan Bell R. Environmental policy for developing countries.Issues Sci Technol. 2002; 18:No. 3. Accessed September 18, 2023. https://issues.org/greenspan-environmental-policy-developing-countries/Google Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. 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BACKGROUND: Persistent mineralocorticoid receptor activation is a pathologic response in type 2 diabetes and chronic kidney disease. Whereas mineralocorticoid receptor antagonists are beneficial in reducing cardiovascular complications, direct mechanistic pathways for these effects in humans are lacking. METHODS: The MAGMA trial (Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis) was a randomized, double-blind, placebo-controlled trial in patients with high-risk type 2 diabetes with chronic kidney disease (not receiving dialysis) on maximum tolerated renin-angiotensin system blockade. The primary end point was change in thoracic aortic wall volume, expressed as absolute or percent value (ΔTWV or ΔPWV), using 3T magnetic resonance imaging at 12 months. Secondary end points were changes in left ventricle (LV) mass; LV fibrosis, measured as a change in myocardial native T1; and 24-hour ambulatory and central aortic blood pressures. Tertiary end points included plasma proteomic changes in 7596 plasma proteins using an aptamer-based assay. RESULTS: A total of 79 patients were randomized to placebo (n=42) or 25 mg of spironolactone daily (n=37). After a modified intent-to-treat, including available baseline data of study end points, patients who completed the trial protocol were included in the final analyses. At the 12-month follow-up, the average change in PWV was 7.1±10.7% in the placebo group and 0.87±10.0% in the spironolactone group ( P =0.028), and ΔTWV was 1.2±1.7 cm 3 in the placebo group and 0.037±1.9 cm 3 in the spironolactone group ( P =0.022). Change in LV mass was 3.1±8.4 g in the placebo group and −5.8±8.4 g in the spironolactone group ( P =0.001). Changes in LV T1 values were significantly different between the placebo and spironolactone groups (26.0±41.9 ms in the placebo group versus a decrease of −10.1±36.3 ms in the spironolactone group; P =6.33×10 −4 ). Mediation analysis revealed that the spironolactone effect on thoracic aortic wall volume and myocardial mass remained significant after adjustment for ambulatory and central blood pressures. Proteomic analysis revealed a dominant effect of spironolactone on pathways involving oxidative stress, inflammation, and leukocyte activation. CONCLUSIONS: Among patients with diabetes with moderate to severe chronic kidney disease at elevated cardiovascular risk, treatment with spironolactone prevented progression of aortic wall volume and resulted in regression of LV mass and favorable alterations in native T1, suggesting amelioration of left-ventricular fibrosis. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02169089.

Background Exposure to fine particulate matter (<2.5 um, particulate matter with an aerodynamic diameter <2.5 microns [PM2.5]) has been implicated in atherogenesis. Limited data in animal studies suggest that PM2.5 exposure leads to myocardial fibrosis and increased incidence of heart failure (HF). Whether PM2.5 is associated with adverse outcomes in patients with preexisting HF has not been widely studied. Methods and Results In this retrospective cohort study, Medicare patients hospitalized with first HF between 2013 and 2020 were identified from the Medicare Provider Analysis and Review Part A 100% files. Patients were linked with integrated estimates of ambient PM2.5 obtained at 1×1 km using the zip code of participants' residence. The study outcomes were all‐cause death, HF, and all‐cause readmissions burden. A total of 2 599 525 patients were included in this study, with 6 321 731 person‐years of follow‐up. Mean PM2.5 was 7.3±1.7 μg/m3. Each interquartile range of PM2.5 was associated with 0.9% increased hazard of all‐cause death, 4.5% increased hazard of first HF readmission, 3.1% increased risk of HF hospitalization burden, and 5.2% increase in all‐cause readmission burden, after adjusting for 11 sociodemographic and medical factors. Subgroup analyses showed that the effects were more pronounced at levels <7 μg/m3 and in patients aged <75 years, Asians, and those residing in rural areas. Conclusions Ambient air pollution is associated with higher risk of adverse events in Medicare beneficiaries with established HF. These associations persist below the National Air Quality Standards (12 μg/m3), supporting that no threshold effect exists for health effects of air pollution exposure.

Background High blood pressure (BP) increases recurrent stroke risk. Methods and Results We assessed hypertension prevalence, treatment, control, medication adherence, and predictors of uncontrolled BP 90 days after ischemic or hemorrhagic stroke among 561 Mexican American and non‐Hispanic White (NHW) survivors of stroke from the BASIC (Brain Attack Surveillance in Corpus Christi) cohort from 2011 to 2014. Uncontrolled BP was defined as average BP ≥140/90 mm Hg at 90 days poststroke. Hypertension was uncontrolled BP or antihypertensive medication prescribed or hypertension history. Treatment was antihypertensive use. Adherence was missing zero antihypertensive doses per week. We investigated predictors of uncontrolled BP using logistic regression adjusting for patient factors. Median (interquartile range) age was 68 (59–78) years, 64% were Mexican American, and 90% of strokes were ischemic. Overall, 94.3% of survivors of stroke had hypertension (95.6% Mexican American versus 92.0% non‐Hispanic White; P =0.09). Of these, 87.9% were treated (87.3% Mexican American versus 89.1% non‐Hispanic White; P =0.54). Among the total population, 38.3% (95% CI, 34.4%–42.4%) had uncontrolled BP. Among those with uncontrolled BP prescribed an antihypertensive, 84.5% reported treatment adherence (95% CI, 78.8%–89.3%). Uncontrolled BP 90 days poststroke was less likely in patients with stroke who had a primary care physician (adjusted odds ratio [aOR], 0.45 [95% CI, 0.24–0.83]; P =0.01), greater stroke severity (aOR per‐1‐point‐higher National Institutes of Health Stroke Scale score, 0.96 [95% CI, 0.93–0.99]; P =0.02), or more depressive symptoms (aOR per‐1‐point‐higher Personal Health Questionnaire Depression Scale‐8 score, 0.95 [95% CI, 0.92–0.99] among those with a history of hypertension at baseline; P =0.009). Conclusions Greater than one third of survivors of stroke have uncontrolled BP at 90 days poststroke in this population‐based study. Interventions are needed to improve BP control after stroke.

Blood-based, observational, and cross-sectional epidemiological studies suggest that air pollutant exposures alter biological aging. In a single-blinded randomized crossover human experiment of 17 volunteers, we examined the effect of randomized 2-h controlled air pollution exposures on respiratory tissue epigenetic aging. Bronchial epithelial cell DNA methylation 24 h post-exposure was measured using the HumanMethylation450K BeadChip, and there was a minimum 2-week washout period between exposures. All 17 volunteers were exposed to ozone, but only 13 were exposed to diesel exhaust. Horvath DNAmAge [Pearson coefficient (r) = 0.64; median absolute error (MAE) = 2.7 years], GrimAge (r = 0.81; MAE = 13 years), and DNAm Telomere Length (DNAmTL) (r = -0.65) were strongly correlated with chronological age in this tissue. Compared to clean air, ozone exposure was associated with longer DNAmTL (median difference 0.11 kb, Fisher's exact P-value = .036). This randomized trial suggests a weak relationship of ozone exposure with DNAmTL in target respiratory cells. Still, causal relationships with long-term exposures need to be evaluated.

Background:The public health relevance of daily Air Quality Index (AQI) activity guidelines for the general adult public in the United States to prevent atherosclerotic cardiovascular disease (ASCVD) events is questionable. Objectives:The purpose of the study was to explore the utility of a policy tailoring activity guidance to calculated ASCVD risk rather than uniform recommendations to the general adult public as currently provided. Methods:We calculated the number needed to treat (NNT) to prevent one ASCVD event per day by following activity recommendations across 10-year ASCVD risk scores (1% to 20%). Second, we modeled the benefits of tailoring recommendations to ASCVD risk. Results:The NNT decreased as ASCVD risk and/or AQI levels increased. At AQIs up to 151 (68% of days with AQIs above moderate in the United States), the NNTs remained untenably high (>2.7-55.3 million) across ASCVD risk. Under unhealthy conditions (AQIs 151-200), 28% of elevated AQIs, NNTs <1 million could be achieved by current guidance (15% exposure reduction), but only among the highest-risk individuals (ASCVD 18% to 20%) on the most polluted days (AQIs 192-200). Tailoring guidance to ASCVD risk could yield NNTs <1 million at risk thresholds of 7.5% and 10% if activity restrictions were more stringent (35% to 50% exposure reductions) during unhealthy conditions. Conclusions:ASCVD risk has a major influence on the NNT to prevent cardiovascular events by following AQI guidance. It may be possible for a future policy to improve the utility of AQI activity guidance for the general adult public by tailoring activity recommendations to ASCVD risk.

Background: Prior studies have demonstrated a strong link between air pollution and type 2 diabetes including brown adipose tissue (BAT) dysfunction, common proximate regulators are poorly characterized. We hypothesized that exposure to ambient fine particulate matter (<2.5μm; PM2.5) modulates insulin resistance through its impact on epigenetic regulators of BAT function. Methods: Male C57BL/6 mice at the age of 4 weeks were fed a chow diet and exposed to concentrated PM2.5 or filtered air (n = 12 per group) for 24 weeks (6hr/day and 5 days in a week) using a VACES system, that allows chronic exposure to real world air pollution. Glucose and insulin tolerance tests, indirect calorimetry using metabolic cages and PET/CT using 18-FDG uptake were performed between 12-20 weeks following air pollution exposure. BAT was isolated for DNA methylation (DMRs), chromatin accessibility (DARs), and Differentially Expressed Genes (DEGs) analysis using bisulfite, ATAC and RNA-sequencing respectively. Results: BAT thermogenic activity was reduced by decreased FDG uptake (40%) with significant reduction in peak VO2 and VCO2 and RER at night time by PM2.5. Genome wide differential methylation indicates evidence for hypomethylation and hypermethylation, with widespread chromatin remodeling involving intronic and enhancer elements corresponding to multiple transcription factor binding sites including genes involved in thermogenesis, redox and circadian function. Integrated DAR-DEG-DMR analysis pointed to two targets, a histone deacetylase-9 (HDAC9) and KDM2B, a lysine demethylase. ChIP-qPCR of HDAC9 and KDM2B revealed binding and regulation of RORα, GST1α and PRDM16 with HDAC9 and UCP1 and NRF2 with KDM2B, respectively. Conclusion: Chronic air pollution exposure affects BAT function and induces insulin resistance through epigenetic regulation of key targets involved in redox function, thermogenesis and circadian function. Disclosure P. Rengasamy: None. J. Dazard: None. B. Park: None. A. Vergara-Martel: None. J. Edwards-Glenn: None. S. Nandikolmath: None. S.T. Moorthy: None. S.G. Al-Kindi: None. R.D. Brook: Advisory Panel; Alnylam Pharmaceuticals, Inc. S. Rajagopalan: Consultant; Novo Nordisk, Bayer Inc.