Faculty Bibliography

BACKGROUND:Fine-particulate-matter (i.e. with an aerodynamic diameter of ≤2.5 µm, PM2.5) air pollution is commonly treated as if it had 'equivalent toxicity', irrespective of the source and composition. We investigate the respective roles of fossil-fuel- and biomass-combustion particles in the PM2.5 relationship with cardiovascular morbidity and mortality using tracers of sources in Dhaka, Bangladesh. Results provide insight into the often observed levelling of the PM2.5 exposure-response curve at high-pollution levels. METHODS:A time-series regression model, adjusted for potentially confounding influences, was applied to 340 758 cardiovascular disease (CVD) emergency-department visits (EDVs) during January 2014 to December 2017, 253 407 hospital admissions during September 2013 to December 2017 and 16 858 CVD deaths during January 2014 to October 2017. RESULTS:Significant associations were confirmed between PM2.5-mass exposures and increased risk of cardiovascular EDV [0.27%, (0.07% to 0.47%)] at lag-0, hospitalizations [0.32% (0.08% to 0.55%)] at lag-0 and deaths [0.87%, (0.27% to 1.47%)] at lag-1 per 10-μg/m3 increase in PM2.5. However, the relationship of PM2.5 with morbidity and mortality effect slopes was less steep and non-significant at higher PM2.5 concentrations (during crop-burning-dominated exposures) and varied with PM2.5 source. Fossil-fuel-combustion PM2.5 had roughly a four times greater effect on CVD mortality and double the effect on CVD hospital admissions on a per-µg/m3 basis than did biomass-combustion PM2.5. CONCLUSION/CONCLUSIONS:Biomass burning was responsible for most PM2.5 air pollution in Dhaka, but fossil-fuel-combustion PM2.5 dominated the CVD adverse health impacts. Such by-source variations in the health impacts of PM2.5 should be considered in conducting ambient particulate-matter risk assessments, as well as in prioritizing air-pollution-mitigation measures and clinical advice.

Little information is available regarding the glycemic effects of inorganic arsenic (iAs) exposure in urban populations. We evaluated the association of total arsenic and the relative proportions of arsenic metabolites in urine with glycemia as measured by glycated blood hemoglobin (HbA1c) among 45 participants with prediabetes (HbA1c ≥ 5.7-6.4%), 65 with diabetes (HbA1c ≥ 6.5%), and 36 controls (HbA1c < 5.7%) recruited from an academic medical center in New York City. Each 10% increase in the proportion of urinary dimethylarsinic acid (DMA%) was associated with an odds ratio (OR) of 0.59 (95% confidence interval (CI): 0.28-1.26) for prediabetes, 0.46 (0.22-0.94) for diabetes, and 0.51 (0.26-0.99) for prediabetes and diabetes combined. Each 10% increase in the proportion of urinary monomethylarsonic acid (MMA%) was associated with a 1.13% (0.39, 1.88) increase in HbA1c. In contrast, each 10% increase in DMA% was associated with a 0.76% (0.24, 1.29) decrease in HbA1c. There was no evidence of an association of total urinary arsenic with prediabetes, diabetes, or HbA1c. These data suggest that a lower arsenic methylation capacity indicated by higher MMA% and lower DMA% in urine is associated with worse glycemic control and diabetes. Prospective, longitudinal studies are needed to evaluate the glycemic effects of low-level iAs exposure in urban populations.

OBJECTIVE:<0.05, |log2foldchange| >0.5) and analyzed using weighted gene co-expression network analysis. Weighted gene co-expression network analysis revealed blood modules enriched for immune activation, secretory granules, and coagulation in patients with PAD. Of these 127 differentially expressed transcripts, 40 were significantly associated with MACLE (log-rank false discovery rate <0.1). MicroRNA-4477b was significantly increased in patients with PAD with subsequent MACLE and in a mouse hindlimb ischemia model. CONCLUSIONS:A whole blood transcript signature identified patients with symptomatic PAD and PAD patients at increased risk of MACLE. A previously uncharacterized transcript microRNA-4477b was overexpressed in prevalent PAD, incident MACLE, and in a mouse hindlimb ischemia model. Our novel transcriptomic signature provides insight into potential mechanisms of patients with severe symptomatic PAD.

Thrombosis is a major concern in respiratory infections. Our aim was to investigate the magnitude and duration of risk for arterial and venous thrombosis following discharge after respiratory infection. Patients with respiratory infections were identified using the United States Nationwide Readmission Database from 2012 to 2014. Patients admitted with asthma or cellulitis served as comparators. Readmissions for acute myocardial infarction (MI) and venous thromboembolism (VTE) were evaluated at 30 to 180 days. The likelihood of a first thrombotic event after discharge was compared with a 30-day period prior to hospitalization. Among 5,271,068 patients discharged after a respiratory infection, 0.56% and 0.78% were readmitted within 30-days with MI and VTE, respectively. Relative to asthma and cellulitis, respiratory infection was associated with a greater age and sex-adjusted hazard of 30-day readmission for MI (adjusted HR [aHR] 1.48 [95% CI 1.42-1.54] vs. asthma; aHR 1.36 [95% CI 1.31-1.41] vs. cellulitis) and VTE (aHR 1.28 [95% CI 1.24-1.33] vs. asthma; aHR 1.26, [95% CI 1.22-1.30] vs. cellulitis). Risks of MI and VTE attenuated over time. In a crossover-cohort analysis, the odds of MI (OR 1.68 [95% CI 1.62-1.73]) and VTE (OR 3.30 [95% 3.19-3.41]) were higher in the 30 days following discharge after respiratory infection than during the 30-day baseline period. Hospitalization for respiratory infection was associated with increased risks of thrombosis that were highest in the first 30-days after discharge and declined over time.

Context/UNASSIGNED:Thyroid hormone plays a critical role in cardiovascular function. Severe hypothyroidism can be associated with "myxedema heart" characterized by relative bradycardia and pericardial effusion. Effusions associated with severe hypothyroidism can be large. Despite the large volume of effusions, tamponade is not a common consequence. However, with the incorporation of echocardiography into routine practice for evaluation of effusion, echocardiographic findings suggestive of clinical tamponade occur frequently. Case Description/UNASSIGNED:We report a series of 3 patients with large pericardial effusions secondary to severe hypothyroidism. These cases serve to demonstrate the discordance between echocardiographic signs consistent with tamponade with a patient's stable clinical hemodynamics. We also report the development of bronchial obstruction, a rare complication of a large effusion due to severe hypothyroidism. Conclusions/UNASSIGNED:While pericardial effusion associated with severe hypothyroidism has been described for decades, the echocardiographic findings may be less well known and may lead to unnecessary downstream testing or invasive management. We use our case series to facilitate a summary of what is known about the epidemiology, mechanism and physiology, and expected outcomes of myxedema associated pericardial effusion. Finally, in the setting of current paucity of clinical guidelines, we aim to familiarize clinicians with the phenomenon of pseudotamponade and suggest management strategies for myxedema associated pericardial effusion to guide clinicians to use conservative medical management in majority of cases.

INTRODUCTION/BACKGROUND:Sodium-glucose cotransporter-2 [SGLT2] inhibitors reduce cardiovascular events and mortality in patients with diabetes, particularly patients with established cardiovascular disease. Euglycemic diabetic ketoacidosis [euDKA], a complication of SGLT2 therapy, can be exacerbated by a low carbohydrate diet. CASE REPORT/METHODS:A 61-year-old man with a history of type 2 diabetes, taking a SGLT2 inhibitor empagliflozin 10 mg orally daily, presented to the emergency room with a 2-day history of nausea and chest pain. A week prior to presentation, he had started a ketogenic diet. He was initially admitted with a diagnosis of acute coronary syndrome. On initial assessment in the emergency room, his cardiac enzymes were normal and there were no ischemic changes in his ECG. As there was concern for unstable angina, he underwent cardiac catheterization, which showed a known total occlusion with collaterals and arteries with non-obstructive disease without evidence of acute plaque rupture. His baseline laboratory assessments revealed an elevated anion gap of 17, increased urinary and plasma ketones, and metabolic acidosis. His plasma glucose level was 84 mg/dL. The diagnosis of euDKA was made, and treatment with intravenous fluids and insulin was initiated. His chest pain and nausea subsequently resolved. CONCLUSION/CONCLUSIONS:We present a case of euDKA triggered by a ketogenic diet while on SGLT2 inhibitor therapy presenting as chest pain. The recognition of euDKA is important in the context of increased SGLT2 use for management of cardiovascular risk for patients with diabetes.

Fine particulate air pollution <2.5 μm in diameter (PM_2.5) is a major environmental threat to global public health. Multiple national and international medical and governmental organizations have recognized PM_2.5 as a risk factor for cardiopulmonary diseases. A growing body of evidence indicates that several personal-level approaches that reduce exposures to PM_2.5 can lead to improvements in health endpoints. Novel and forward-thinking strategies including randomized clinical trials are important to validate key aspects (e.g., feasibility, efficacy, health benefits, risks, burden, costs) of the various protective interventions, in particular among real-world susceptible and vulnerable populations. This paper summarizes the discussions and conclusions from an expert workshop, Reducing the Cardiopulmonary Impact of Particulate Matter Air Pollution in High Risk Populations, held on May 29 to 30, 2019, and convened by the National Institutes of Health, the U.S. Environmental Protection Agency, and the U.S. Centers for Disease Control and Prevention.