Mineralocorticoid Receptor Antagonism Prevents Aortic Plaque Progression and Reduces Left Ventricular Mass and Fibrosis in Patients With Type 2 Diabetes and Chronic Kidney Disease: The MAGMA Trial.

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 cm3 in the placebo group and 0.037±1.9 cm3 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.

Evaluation and management of hypertensive emergency.

Hypertensive emergencies cause substantial morbidity and mortality, particularly when acute organ injury is present. Careful and effective strategies to reduce blood pressure and diminish the effects of pressure-mediated injury are essential. While the selection of specific antihypertensive medications varies little across different forms of hypertensive emergencies, the intensity of blood pressure reduction to the target pressure differs substantially. Treatment hinges on balancing the positive effects of lowering blood pressure with the potential for negative effects of organ hypoperfusion in patients with altered autoregulatory mechanisms. When patients do not have acute organ injury in addition to severe hypertension, they benefit from a conservative, outpatient approach to blood pressure management. In all cases, long term control of blood pressure is paramount to prevent recurrent hypertensive emergencies and improve overall prognosis. This review discusses the current evidence and guidelines on the evaluation and management of hypertensive emergency.

Ambient Air Pollution Exposure and Adverse Outcomes Among Medicare Beneficiaries With Heart Failure.

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.

Air Pollution and Adverse Cardiovascular Events After Coronary Artery Bypass Grafting: A 10-Year Nationwide Study.

Background: Increased particulate matter <2.5 µm (PM2.5) air pollution is associated with adverse cardiovascular outcomes. However, its impact on patients with prior coronary artery bypass grafting (CABG) is unknown. Objectives: The purpose of this study was to evaluate the association between major adverse cardiovascular events (MACE) (defined as myocardial infarction, stroke, or cardiovascular death) and air pollution after CABG. Methods: We linked 26,403 U.S. veterans who underwent CABG (2010-2019) nationally with average annual ambient PM2.5 estimates using residential address. Over a 5-year median follow-up period, we identified MACE and fit a multivariable Cox proportional hazard model to determine the risk of MACE as per PM2.5 exposure. We also estimated the absolute potential reduction in PM2.5 attributable MACE simulating a hypothetical PM2.5 lowered to the revised World Health Organization standard of 5 µg/m3. Results: The observed median PM2.5 exposure was 7.9 µg/m3 (IQR: 7.0-8.9 µg/m3; 95% of patients were exposed to PM2.5 above 5 µg/m3). Increased PM2.5 exposure was associated with a higher 10-year MACE rate (first tertile 38% vs third tertile 45%; P < 0.001). Adjusting for demographic, racial, and clinical characteristics, a 10 µg/m3 increase in PM2.5 resulted in 27% relative risk for MACE (HR: 1.27, 95% CI: 1.10-1.46; P < 0.001). Currently, 10% of total MACE is attributable to PM2.5 exposure. Reducing maximum PM2.5 to 5 µg/m3 could result in a 7% absolute reduction in 10-year MACE rates. Conclusions: In this large nationwide CABG cohort, ambient PM2.5 air pollution was strongly associated with adverse 10-year cardiovascular outcomes. Reducing levels to World Health Organization-recommended standards would result in a substantial risk reduction at the population level.

Public Health Relevance of US EPA Air Quality Index Activity Recommendations.

Importance: Reducing exposure to fine particulate matter (<2.5 µm [PM2.5]) air pollution improves cardiopulmonary morbidity and mortality. However, the public health relevance of air quality index (AQI) activity guidelines under present-day environmental conditions in the US has not been critically assessed. Objective: To evaluate the public health relevance of following PM2.5 AQI activity guidance in preventing serious atherosclerotic cardiovascular disease (ASCVD) and pulmonary events among adults in the US. Design, Setting, and Participants: This cross-sectional modeling study involved the general adult population and sensitive individuals as designated by the US Environmental Protection Agency (EPA), including adults with preexisting ASCVD or lung disease (asthma or chronic obstructive pulmonary disease). The study was conducted between August 1, 2023, and January 31, 2024. Exposures: Daily AQI strata for PM2.5 and the corresponding activity recommendations. Main Outcomes and Measures: The main outcome was the number needed to treat (NNT) per day by following activity guidance across daily AQI strata to prevent 1 serious ASCVD or pulmonary event among relevant populations. To calculate PM2.5-induced excess disease event rates per day, estimated baseline disease-specific daily event rates for each group were multiplied by the increase in risks due to PM2.5 levels at each AQI stratum. The number of events prevented per day was calculated by multiplying each excess disease event rate by the percentage in exposure reduction plausibly incurred by following population-specific activity guidance at each AQI level. The NNT is the reciprocal of the number of events prevented. Results: The NNT to prevent ASCVD events was high for the general population and for patients with ASCVD across all AQI strata. The range of values was comparatively lower to prevent pulmonary events among adults with lung disease. During most days (96%) when activity recommendations were promulgated due to elevated PM2.5 (AQI, 101-200), the NNT to prevent a serious disease event remained very high for the general population (>18 million), patients with ASCVD (approximately 1.6-5 million), and adults with lung disease (approximately 66 000-202 000). Conclusions and Relevance: These findings suggest that existing PM2.5 AQI activity recommendations are of questionable public health relevance in present-day conditions and merit consideration for updating to improve their potential effectiveness.

The Urban Environment and Cardiometabolic Health.

Urban environments contribute substantially to the rising burden of cardiometabolic diseases worldwide. Cities are complex adaptive systems that continually exchange resources, shaping exposures relevant to human health such as air pollution, noise, and chemical exposures. In addition, urban infrastructure and provisioning systems influence multiple domains of health risk, including behaviors, psychological stress, pollution, and nutrition through various pathways (eg, physical inactivity, air pollution, noise, heat stress, food systems, the availability of green space, and contaminant exposures). Beyond cardiometabolic health, city design may also affect climate change through energy and material consumption that share many of the same drivers with cardiometabolic diseases. Integrated spatial planning focusing on developing sustainable compact cities could simultaneously create heart-healthy and environmentally healthy city designs. This article reviews current evidence on the associations between the urban exposome (totality of exposures a person experiences, including environmental, occupational, lifestyle, social, and psychological factors) and cardiometabolic diseases within a systems science framework, and examines urban planning principles (eg, connectivity, density, diversity of land use, destination accessibility, and distance to transit). We highlight critical knowledge gaps regarding built-environment feature thresholds for optimizing cardiometabolic health outcomes. Last, we discuss emerging models and metrics to align urban development with the dual goals of mitigating cardiometabolic diseases while reducing climate change through cross-sector collaboration, governance, and community engagement. This review demonstrates that cities represent crucial settings for implementing policies and interventions to simultaneously tackle the global epidemics of cardiovascular disease and climate change.

Toward Heart-Healthy and Sustainable Cities: A Policy Statement From the American Heart Association.

Nearly 56% of the global population lives in cities, with this number expected to increase to 6.6 billion or >70% of the world's population by 2050. Given that cardiometabolic diseases are the leading causes of morbidity and mortality in people living in urban areas, transforming cities and urban provisioning systems (or urban systems) toward health, equity, and economic productivity can enable the dual attainment of climate and health goals. Seven urban provisioning systems that provide food, energy, mobility-connectivity, housing, green infrastructure, water management, and waste management lie at the core of human health, well-being, and sustainability. These provisioning systems transcend city boundaries (eg, demand for food, water, or energy is met by transboundary supply); thus, transforming the entire system is a larger construct than local urban environments. Poorly designed urban provisioning systems are starkly evident worldwide, resulting in unprecedented exposures to adverse cardiometabolic risk factors, including limited physical activity, lack of access to heart-healthy diets, and reduced access to greenery and beneficial social interactions. Transforming urban systems with a cardiometabolic health-first approach could be accomplished through integrated spatial planning, along with addressing current gaps in key urban provisioning systems. Such an approach will help mitigate undesirable environmental exposures and improve cardiovascular and metabolic health while improving planetary health. The purposes of this American Heart Association policy statement are to present a conceptual framework, summarize the evidence base, and outline policy principles for transforming key urban provisioning systems to heart-health and sustainability outcomes.

Air pollution exposure and cardiometabolic risk.

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.

Lower Socioeconomic Status, Psychological Distress, and Self-reported Hypertension: A Longitudinal Moderated Mediation Analysis.

BACKGROUND: Lower socioeconomic status (SES) has been associated with hypertension; however, the mediators and moderators of this association remain understudied. We examined the mediation effect of psychological distress on the link between lower SES and self-reported hypertension and the racial and sex moderation effects. METHODS: We analyzed the data collected from 2009 to 2019 among adults from the Panel Study of Income Dynamics (PSID). Lower SES was defined as one of 3 indicators: education ≤12 years, unemployed, or individual annual income <$27,800. Psychological distress was assessed using the Kessler K6 scale. Cox proportional hazard regression was conducted. Mediation analyses were performed using the PROCESS macro. RESULTS: In the sample of heads of family who did not have self-reported hypertension in 2009 (N = 6,214), the mean age was 41 years, 30.6% were female, 32.9% were African American. The cumulative incidence of self-reported hypertension was 29.8% between 2009 and 2019. Cox proportional hazard regression analysis showed that after controlling for covariates, lower SES (score > 0 vs. score = 0) was associated with self-reported hypertension (hazard ratio = 1.27, 95% confidence interval = 1.14-1.42). SES had indirect effect on self-reported hypertension through psychological distress and the indirect effect (0.02 in females, 0.01 in males, P < 0.05) was moderated by sex but not by race. CONCLUSIONS: The association of SES and self-reported hypertension was mediated by psychological distress and sex moderated the mediation effect. Interventions focused on reducing contributors to SES and psychological stress should be considered to reduce hypertension risk.

Reduction of Outdoor and Indoor PM2.5 Source Contributions via Portable Air Filtration Systems in a Senior Residential Facility in Detroit, Michigan.

Background: The Reducing Air Pollution in Detroit Intervention Study (RAPIDS) was designed to evaluate cardiovascular health benefits and personal fine particulate matter (particulate matter < 2.5 µm in diameter, PM2.5) exposure reductions via portable air filtration units (PAFs) among older adults in Detroit, Michigan. This double-blind randomized crossover intervention study has shown that, compared to sham, air filtration for 3 days decreased 3-day average brachial systolic blood pressure by 3.2 mmHg. The results also showed that commercially available HEPA-type and true HEPA PAFs mitigated median indoor PM2.5 concentrations by 58% and 65%, respectively. However, to our knowledge, no health intervention study in which a significant positive health effect was observed has also evaluated how outdoor and indoor PM2.5 sources impacted the subjects. With that in mind, detailed characterization of outdoor and indoor PM2.5 samples collected during this study and a source apportionment analysis of those samples using a positive matrix factorization model were completed. The aims of this most recent work were to characterize the indoor and outdoor sources of the PM2.5 this community was exposed to and to assess how effectively commercially available HEPA-type and true HEPA PAFs were able to reduce indoor and outdoor PM2.5 source contributions. Methods: Approximately 24 h daily indoor and outdoor PM2.5 samples were collected on Teflon and Quartz filters from the apartments of 40 study subjects during each 3-day intervention period. These filters were analyzed for mass, carbon, and trace elements. Environmental Protection Agency Positive Matrix Factorization (PMF) 5.0 was utilized to determine major emission sources that contributed to the outdoor and indoor PM2.5 levels during this study. Results: The major sources of outdoor PM2.5 were secondary aerosols (28%), traffic/urban dust (24%), iron/steel industries (15%), sewage/municipal incineration (10%), and oil combustion/refinery (6%). The major sources of indoor PM2.5 were organic compounds (45%), traffic + sewage/municipal incineration (14%), secondary aerosols (13%), smoking (7%), and urban dust (2%). Infiltration of outdoor PM2.5 for sham, HEPA-type, and true HEPA air filtration was 79 ± 24%, 61 ± 32%, and 51 ± 34%, respectively. Conclusions: The results from our study showed that intervention with PAFs was able to significantly decrease indoor PM2.5 derived from outdoor and indoor PM2.5 sources. The PAFs were also able to significantly reduce the infiltration of outdoor PM2.5. The results of this study provide insights into what types of major PM2.5 sources this community is exposed to and what degree of air quality and systolic blood pressure improvements are possible through the use of commercially available PAFs in a real-world setting.

An updated systematic review and meta-analysis on portable air cleaners and blood pressure: Recommendations for users and manufacturers.

Fine particulate matter (PM2.5) air pollution is a leading contributor to the global burden of cardiovascular disease (CVD). One important underlying mechanism is an increase in blood pressure (BP). A growing number of studies have reported a beneficial effect of portable air cleaners (PACs) on systolic and diastolic BP; SBP and DBP. We conducted an updated systematic review and meta-analysis of studies using true versus sham mode filtration reporting the effects on BP. Of 214 articles identified up to February 5, 2023, seventeen (from China, USA, Canada, South Korea and Denmark) enrolling approximately 880 participants (484 female) met the inclusion criteria for meta-analyses. Aside from studies conducted in China, research on PACs and BP has been conducted in relatively low pollution settings. Mean indoor PM2.5 concentrations during the active and sham mode purification were 15.9 and 41.2 µg/m3, respectively. The mean efficiency of PACs against indoor PM2.5 was 59.8 % (ranging from 23 % to 82 %). True mode filtration was associated with a pooled mean difference of - 2.35 mmHg (95 % confidence interval [CI]: - 4.5, - 0.2) and - 0.81 mmHg (95 % CI: - 1.86, 0.24) in SBP and DBP, respectively. After removing the studies with high risk of bias, the magnitude of the pooled benefits on SBP and DBP increased to - 3.62 mmHg (95 % CI: - 6.69, - 0.56) and - 1.35 mmHg (95 % CI: - 2.29, - 0.41), respectively. However, there are several barriers to the use of PACs, specifically in low- and middle-income countries (LMICs), such as the initial purchase cost and filter replacements. There may be several avenues to help overcome these economic burdens and improve cost effectiveness, such as implementing government or other subsidized programs to distribute PACs targeting vulnerable and higher-risk individuals. We propose that environmental health researchers and healthcare providers should be better trained to educate the public regarding the use of PACs to reduce the impacts of PM2.5 on cardiometabolic diseases globally.