Short-term air pollution levels and sickle cell disease hospital encounters in South Carolina: A case-crossover analysis.

BACKGROUND: Sickle cell disease (SCD) is a genetic disorder and symptoms may be sensitive to environmental stressors. Although it has been hypothesized that exposure to outdoor air pollution could trigger acute SCD events, evidence is limited. METHODS: We obtained SCD administrative data on hospital encounters in South Carolina from 2002 to 2019. We estimated outdoor air pollutant (particulate matter<2.5 µm (PM2.5), ozone (O3), and PM2.5 elemental carbon (EC) concentrations at residential zip codes using spatio-temporal models. Using a random bi-directional, fixed-interval case-crossover study design, we investigated the relationship between air pollution exposure over 1-, 3-, 5-, 9-, and14-day periods with SCD hospital encounters. RESULTS: We studied 8410 patients with 144,129 hospital encounters. We did not observe associations among all patients with SCD and adults for PM2.5, O3, and EC. We observed positive associations among children for 9- and 14-day EC (OR: 1.05 (95% confidence interval (CI): 1.02, 1.08) and OR: 1.05 (95% CI: 1.02, 1.09), respectively) and 9- and 14-day O3 (OR: 1.04 (95%CI: 1.00, 1.08)) for both. CONCLUSIONS: Our findings suggest that short-term (within two-weeks) levels of EC and O3 and may be associated with SCD hospital encounters among children. Two-pollutant model results suggest that EC is more likely responsible for effects on SCD than O3. More research is needed to confirm our findings.

Statin Twitter: Human and Automated Bot Contributions, 2010 to 2022.

BACKGROUND: Many individuals eligible for statin therapy decline treatment, often due to fear of adverse effects. Misinformation about statins is common and drives statin reluctance, but its prevalence on social media platforms, such as Twitter (now X) remains unclear. Social media bots are known to proliferate medical misinformation, but their involvement in statin-related discourse is unknown. This study examined temporal trends in volume, author type (bot or human), and sentiment of statin-related Twitter posts (tweets). METHODS AND RESULTS: We analyzed original tweets with statin-related terms from 2010 to 2022 using a machine learning-derived classifier to determine the author's bot probability, natural language processing to assign each tweet a negative or positive sentiment, and manual qualitative analysis to identify statin skepticism in a random sample of all tweets and in highly influential tweets. We identified 1 155 735 original statin-related tweets. Bots produced 333 689 (28.9%), humans produced 699 876 (60.6%), and intermediate probability accounts produced 104 966 (9.1%). Over time, the proportion of bot tweets decreased from 47.8% to 11.3%, and human tweets increased from 43.6% to 79.8%. The proportion of negative-sentiment tweets increased from 27.8% to 43.4% for bots and 30.9% to 38.4% for humans. Manually coded statin skepticism increased from 8.0% to 19.0% for bots and from 26.0% to 40.0% for humans. CONCLUSIONS: Over the past decade, humans have overtaken bots as generators of statin-related content on Twitter. Negative sentiment and statin skepticism have increased across all user types. Twitter may be an important forum to combat statin-related misinformation.

Influenza vaccination and use of lipid lowering therapies in adults with atherosclerotic cardiovascular disease: An analysis of the Behavioral Risk Factor Surveillance System (BRFSS).

BACKGROUND: Influenza vaccination and lipid lowering therapy (LLT) are evidence-based interventions with substantial benefit for individuals with established atherosclerotic cardiovascular disease (ASCVD). However, levels of influenza immunization and LLT use are low, possibly due to pervasive fear-based misinformation uniquely targeting vaccines and LLT. Whether being unvaccinated for influenza predicts lower utilization of LLT is unknown. OBJECTIVES: We tested the hypothesis that American adults with ASCVD who are unvaccinated for influenza have lower use of LLT even after accounting for traditional factors associated with underuse of preventive therapies. METHODS: We pooled 2017, 2019, and 2021 survey data from the Behavioral Risk Factor Surveillance System (BRFSS), and selected respondents aged 40 to 75 years with self-reported ASCVD. We used logistic regression models adjusted for potential confounders to examine the association between influenza vaccination and self-reported LLT use. We performed a sensitivity analysis with multiple imputation to account for missing data. All analyses accounted for complex survey weighting. RESULTS: Of 66,923 participants with ASCVD, 55% reported influenza vaccination in the last year and 76% reported using LLT. Being unvaccinated for influenza was associated with lower odds of LLT use (OR 0.54; 95% CI 0.50, 0.58; P< .001). In a multivariable regression model adjusting for demographics and comorbidities, this association remained statistically significant (aOR 0.58, 95% CI 0.52, 0.64, P < .001). After additional adjustment for preventive care engagement, health care access, and use patterns of other cardiovascular medications this association persisted (aOR 0.66; 95% CI 0.60, 0.74; P < .001). There were no significant differences across subgroups, including those with and without hyperlipidemia. CONCLUSIONS: Unvaccinated status for influenza was independently associated with 34% lower odds of LLT use among American adults with ASCVD after adjustment for traditional factors linked to underuse of preventive therapies. This finding identifies a population with excess modifiable ASCVD risk, and supports investigation into nontraditional mechanisms driving underuse of preventive therapies, including fear-based misinformation.

Induction immunosuppression and post-transplant diabetes mellitus: a propensity-matched cohort study.

Introduction: Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain maintenance immunosuppressive drugs increase PTDM risk, it is unclear whether induction immunosuppression can do the same. Therefore, we evaluated whether induction immunosuppression with IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, or Alemtuzumab given in the peri-transplant period is associated with PTDM. Methods: We used the Scientific Registry of Transplant Recipients database to conduct a cohort study of US adults who received cardiac transplants between January 2008-December 2018. We excluded patients with prior or multiple organ transplants and those with a history of diabetes, resulting in 17,142 recipients. We created propensity-matched cohorts (n=7,412) using predictors of induction immunosuppression and examined the association between post-transplant diabetes and induction immunosuppression by estimating hazard ratios using Cox proportional-hazards models. Results: In the propensity-matched cohort, the average age was 52.5 (SD=13.2) years, 28.7% were female and 3,706 received induction immunosuppression. There were 867 incident cases of PTDM during 26,710 person-years of follow-up (32.5 cases/1,000 person-years). There was no association between induction immunosuppression and post-transplant diabetes (Hazard Ratio= 1.04, 95% confidence interval 0.91 - 1.19). Similarly, no associations were observed for each class of induction immunosuppression agents and post-transplant diabetes. Conclusion: The use of contemporary induction immunosuppression in cardiac transplant patients was not associated with post-transplant diabetes.

Politically related stress and low-birth-weight infants among Arab, Asian, Hispanic, non-Hispanic Black, and non-Hispanic White women in Michigan.

BACKGROUND: Despite the high cost of low birth weight and the persistent challenge of racial inequities affecting the Arab American community, there has been limited research to identify and examine risk factors for these inequities with validated data on Arab American ethnicity and recent population stressors. OBJECTIVES: This study examined whether the 2016 presidential election is associated with low birth weight among non-Hispanic White, Arab American, Hispanic, and non-Hispanic Black women. DESIGN: This population-based study of singleton births in Michigan (2008-2017) used an algorithm to identify mothers who were of Arab descent. METHODS: We used logistic regression to estimate odds ratios and 95% confidence intervals for the association between race/ethnicity and the odds of low birth weight. We examined whether these associations differed before and after the 2016 presidential election and according to maternal education. RESULTS: There were 1,019,738 births, including 66,272 (6.5%) classified as low birth weight. The odds of having a low-birth-weight infant were higher among all minority women compared to non-Hispanic White women. The association was similar before and after the 2016 presidential election and stronger among women with higher levels of education. CONCLUSION: This is the first study to estimate low birth weight among Arab American women in the context of political events. There are opportunities for future studies to discuss this issue in depth.

Racial disparities in post-transplant stroke and mortality following stroke in adult cardiac transplant recipients in the United States.

Black heart transplant recipients have a higher mortality rate than white recipients 6-12 months after transplant. Whether there are racial disparities in post-transplant stroke incidence and all-cause mortality following post-transplant stroke among cardiac transplant recipients is unknown. Using a nationwide transplant registry, we assessed the association between race and incident post-transplant stroke using logistic regression and the association between race and mortality among adults who survived a post-transplant stroke using Cox proportional hazards regression. We found no evidence of an association between race and the odds of post-transplant stroke (OR = 1.00, 95% CI: 0.83-1.20). The median survival time of those with a post-transplant stroke in this cohort was 4.1 years (95% CI: 3.0, 5.4). There were 726 deaths among the 1139 patients with post-transplant stroke, including 127 deaths among 203 Black patients and 599 deaths among 936 white patients. Among post-transplant stroke survivors, Black transplant recipients experienced a 23% higher rate of mortality compared to white recipients (HR = 1.23, 95% CI: 1.00-1.52). This disparity is strongest in the period beyond the first 6 months and appears to be mediated by differences in the post-transplant setting of care between Black and white patients. The racial disparity in mortality outcomes was not evident in the past decade. The improved survival of Black patients in the recent decade may reflect overall protocol improvements for heart transplant recipients irrespective of race, such as advancements in surgical techniques and immediate postoperative care as well as increased awareness about reducing racial disparities.

Impact of simulated flight conditions on supraventricular and ventricular ectopy.

Though billions of passengers and crew travel by air each year and are exposed to altitude equivalents of 7000-8000 feet, the health impact of cabin oxygenation levels has not been well studied. The hypoxic environment may produce ectopic heartbeats that may increase the risk of acute in-flight cardiac events. We enrolled forty older and at-risk participants under a block-randomized crossover design in a hypobaric chamber study to examine associations between flight oxygenation and both ventricular (VE) and supraventricular ectopy (SVE). We monitored participant VE and SVE every 5 min under both flight and control conditions to investigate the presence and rate of VE and SVE. While the presence of VE did not differ according to condition, the presence of SVE was higher during flight conditions (e.g. OR ratio = 1.77, 95% CI: 1.21, 2.59 for SVE couplets). Rates of VE and SVE were higher during flight conditions (e.g. RR ratio = 1.25, 95% CI: 1.03, 1.52 for VE couplets, RR ratio = 1.76, 95% CI: 1.39, 2.22 for SVE couplets). The observed higher presence and rate of ectopy tended to increase with duration of the flight condition. Further study of susceptible passengers and crew may elucidate the specific associations between intermittent or sustained ectopic heartbeats and hypoxic pathways.

Association of interpregnancy interval and gestational diabetes mellitus.

OBJECTIVE: To evaluate the association between interpregnancy interval (IPI) and risk for gestational diabetes mellitus (GDM). METHODS: We conducted a retrospective cohort study among singleton, non-anomalous, live birth pregnancies of 5,705,812 pregnant individuals in the United States from 2016 to 2018. We examined IPI of 4-<6 months, 6-11 months, 12-17 months, 24-35 months, 36-47 months, 48-59 months, 60-71 months, and ≥72 months in comparison to the reference interval of 18-23 months in relation to risk for GDM. We used logistic regression to evaluate the association between IPI and risk for GDM. RESULTS: There is a significantly increased risk for GDM associated with IPIs of 6-11 months and 12-17 months compared to the reference of 18-23 months (adjusted Odds Ratio [aOR] 1.05, 95% CI: 1.03-1.07; aOR 1.02, 95% CI: 1.01-1.03). The risk for GDM is greater for longer IPIs (36-47 months aOR 1.10, 95% CI: 1.05-1.08; 48-59 months aOR 1.11, 95% CI: 1.09-1.13; 60-71 months aOR 1.14, 95% CI: 1.12-1.16; ≥72 months aOR 1.31, 95% CI: 1.30-1.33). CONCLUSION: Our findings support the growing evidence that shorter and longer IPI increase the risk of GDM in pregnant individuals. Screening guidelines for detection of GDM may need to be re-evaluated and updated to include longer IPIs (≥36 months) as a risk factor for earlier screening prior to current recommendation of 24 weeks gestational age.

Incidence and risk factors of metabolic syndrome among Royal Thai Army personnel.

Metabolic Syndrome is a clustering of obesity, hyperglycemia/insulin resistance, dyslipidemia, and hypertension. We aimed to determine the incidence of metabolic syndrome among Royal Thai Army (RTA) personnel and its risk factors. We conducted a retrospective cohort study using data from 2017 to 2021. Metabolic syndrome was defined by NCEP ATP III (2005 Revision). A total of 98,264 participants were enrolled in the present study. The overall incidence rate of metabolic syndrome was 3.7 per 100 person-year (95% CI 3.7-3.8). The statistically significant risk factors for metabolic syndrome included male sex (aHR 1.40; 95% CI 1.29-1.51), age > 35 years, current alcohol consumption, and no exercise. When stratified by sex, the incidence rate of metabolic syndrome among participants aged ≥ 45 years was higher than those aged < 35 years with aHR 6.34; 95% CI 6.01-6.70 for males and aHR 9.59; 95% CI 7.55-12.19 for females. Our data demonstrated that metabolic syndrome is a common health issue, especially among RTA personnel over 35 years. Alcohol consumption and sedentary behavior played an essential role in facilitating metabolic syndrome in this study population and are potential targets for intervention to enhance primary prevention of the sequelae of metabolic syndrome.

Racial and Ethnic Disparities in Incidence and Prognosis of Perioperative Stroke Among Pediatric Cardiac Transplant Recipients.

Background In the general population, Black children have a higher incidence of stroke and all-cause mortality after stroke than White children. Beginning 6 months following cardiac transplantation, Black children have higher mortality than White children. However, whether there are racial and ethnic disparities in incidence and all-cause mortality following perioperative stroke among pediatric cardiac transplant recipients is unknown. Methods and Results Using the Scientific Registry of Transplant Recipients, we studied children who underwent their first heart transplant in the United States between January 1994 and September 2019. Using multivariable logistic regression, we assessed the association between race and ethnicity and perioperative stroke. We used multivariable piecewise Cox regression to examine the association between race and ethnicity and mortality among survivors of perioperative stroke. Among 8224 children who had a first cardiac transplant, 255 (3%) had a perioperative stroke. Black children had 32% lower odds of perioperative stroke compared with White children (adjusted odds ratio, 0.68 [95% CI, 0.46-0.996]). Following perioperative stroke, mortality rates were similar for Black and White children in the first 6 months (adjusted hazard ratio [HR], 0.99 [95% CI, 0.44-2.26]). However, Black children had a higher mortality rate than White children beyond 6 months (adjusted HR, 3.36 [95% CI, 1.22-9.22]). Conclusions Among pediatric cardiac transplant recipients, Black children have a lower incidence of perioperative stroke than White children. Among survivors of perioperative stroke, mortality is initially similar by race and ethnicity, but beyond 6 months, Black children have over a 3-fold higher mortality rate than White children. Identifying and intervening on potential differences in care is essential to addressing these disparities.

Post-transplant mortality and graft failure after induction immunosuppression among Black heart transplant recipients in the United States.

Black heart transplant recipients are more likely to receive induction immunosuppression compared to other races because of higher rates of acute rejection, graft failure, and mortality. However, it is not known whether contemporary induction immunosuppression improves their post-transplant outcomes. To evaluate whether Black patients who were prescribed induction immunosuppression therapy have lower all-cause mortality or graft-failure rates compared to those who were not, we studied Black U.S. adult heart transplant recipients in the Scientific Registry of Transplant Recipients database (2008-2018). We used multivariable Cox proportional hazards regression analysis to compare the hazards of all-cause mortality or graft failure as a composite, for patients who were prescribed induction immunosuppression and those who were not. Among 5160 recipients, 2787 (54.0%) were prescribed induction immunosuppression and 2373 (46.0%) were not. There was no evidence of survival differences according to induction immunosuppression for the composite of all-cause mortality or graft failure (aHR = 1.13, 95% CI 0.96-1.32), mortality (aHR = 1.14, 95% CI 0.97-1.34), graft failure (aHR = 1.05, 95% CI 0.82-1.34) and acute rejection (aHR = 1.00, 95% CI 0.89-1.12). Given the side effects of treatment, future guidelines should reconsider the recommendation for induction immunosuppression among Black patients.

The Association of Cannabis Use Disorder with Acute Limb Ischemia and Critical Limb Ischemia.

OBJECTIVES: Heavy cannabis use has been associated with the development of acute myocardial infarction and stroke. The objective of this study was to determine if heavy, chronic cannabis use is associated with the development of acute limb ischemia (ALI) or critical limb ischemia (CLI). METHODS: We conducted a retrospective cohort study within the National Inpatient Sample (2006-2015). Patients without cannabis use disorder (CUD) were matched to patients with CUD in a 2:1 ratio using propensity scores. Our primary outcomes were incidence of ALI and CLI. Secondary outcomes included incidence of acute mesenteric ischemia (AMI), chronic mesenteric ischemia (CMI), frequency of open or endovascular interventions, length of stay, and total costs. Sensitivity analyses were performed with alternative models, including in the entire unmatched cohort with regression models utilizing survey weights to account for sampling methodology. RESULTS: We identified a cohort of 46,297 857 unmatched patients. Patients with CUD in the unmatched cohort were younger, with less cardiovascular risk factors, but higher rates of smoking and substance abuse. The matched cohort included 824,856 patients with CUD and 1,610,497 controls. Those with CUD had a higher incidence of ALI (OR 1.20 95% CI: 1.04-1.38 P=.016). Following multiple sensitivity analyses, there was no robust association between CLI and CUD. We observed no robust association of CUD with AMI, CMI, procedures performed, frequency of amputation, costs, or total length of stay. CONCLUSIONS: Cannabis use disorder was associated with a significantly higher incidence of admission for acute limb ischemia. CUD was not associated with an increased risk of critical limb ischemia following sensitivity analysis. Given CUD is often seen in younger, less co-morbid patients it provides an important target for intervention in this population.

Effect of continuous positive airway pressure treatment on ambulatory blood pressures in high-risk sleep apnea patients: a randomized controlled trial.

STUDY OBJECTIVES: The long-term effect of continuous positive airway pressure (CPAP) on 24-hour blood pressure (BP) in patients at high risk with obstructive sleep apnea (OSA) is uncertain. We aimed to determine the effect of CPAP treatment on ambulatory BP in individuals with moderate or severe OSA and cardiovascular disease or multiple cardiovascular disease risk factors without severe sleepiness. METHODS: In this randomized, controlled, parallel group study, 169 participants were randomly assigned to CPAP treatment or the control group. The primary outcome was the change in mean 24-hour systolic BP between groups from baseline to the average of 6- and 12-month measurements using mixed-effect linear regression models. RESULTS: The 24-hour systolic BP did not significantly differ by group, although there was a trend of decrease in the CPAP group (treatment effect -2.7 mm Hg [95% confidence interval -5.9 to 0.6]; P = .105) compared with control. CPAP had the greatest effect on nighttime systolic BP (treatment effect -5.9 mm Hg [95% confidence interval -9.9 to -1.9]; P = .004). Similar improvements in other nocturnal BP indices were observed. CONCLUSIONS: In patients at high risk with moderate-severe OSA without severe sleepiness, CPAP resulted in modest BP improvements over 6 to 12 months of follow-up, with possibly larger effects for nocturnal BP. Use of office blood pressure may underestimate the effect of CPAP on BP profile in patients with OSA. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Sleep Apnea Intervention for Cardiovascular Disease Reduction; Identifier: NCT01261390; URL: https://clinicaltrials.gov/ct2/show/NCT01261390. CITATION: Zhao YY, Wang R, Gleason KJ, et al. Effect of continuous positive airway pressure treatment on ambulatory blood pressures in high-risk sleep apnea patients: a randomized controlled trial. J Clin Sleep Med. 2022;18(8):1899-1907.

Association of the 2020 US Presidential Election With Hospitalizations for Acute Cardiovascular Conditions.

Importance: Prior studies found a higher risk of acute cardiovascular disease (CVD) around population-wide psychosocial or environmental stressors. Less is known about acute CVD risk in relation to political events. Objective: To examine acute CVD hospitalizations following the 2020 presidential election. Design, Setting, and Participants: This retrospective cohort study examined acute CVD hospitalizations following the 2020 presidential election. Participants were adult members aged 18 years or older at Kaiser Permanente Southern California and Kaiser Permanente Northern California, 2 large, integrated health care delivery systems. Statistical analysis was performed from March to July 2021. Exposure: 2020 US presidential election. Main Outcomes and Measures: Hospitalizations for acute CVD around the 2020 presidential election were examined. CVD was defined as hospitalizations for acute myocardial infarction (AMI), heart failure (HF), or stroke. Rate ratios (RR) and 95% CIs were calculated comparing rates of CVD hospitalization in the 5 days following the 2020 election with the same 5-day period 2 weeks prior. Results: Among 6 396 830 adults (3 970 077 [62.1%] aged 18 to 54 years; 3 422 479 [53.5%] female; 1 083 128 [16.9%] Asian/Pacific Islander, 2 101 367 [32.9%] Hispanic, and 2 641 897 [41.3%] White), rates of hospitalization for CVD following the election (666 hospitalizations; rate = 760.5 per 100 000 person-years [PY]) were 1.17 times higher (95% CI, 1.05-1.31) compared with the same 5-day period 2 weeks prior (569 hospitalizations; rate = 648.0 per 100 000 PY). Rates of AMI were significantly higher following the election (RR, 1.42; 95% CI, 1.13-1.79). No significant difference was found for stroke (RR, 1.02; 95% CI, 0.86-1.21) or HF (RR, 1.18; 95% CI, 0.98-1.42). Conclusions and Relevance: Higher rates of acute CVD hospitalization were observed following the 2020 presidential election. Awareness of the heightened risk of CVD and strategies to mitigate risk during notable political events are needed.

Napping behavior in adults with episodic migraine: a six-week prospective cohort study.

STUDY OBJECTIVES: Patients with migraine commonly endorse napping as a strategy for headache pain relief, but also experience high rates of sleep disturbance. To elucidate the relationship between napping behavior and migraine, we evaluated the association between napping and headache frequency, severity, and intensity among adults with episodic migraine. We also examined the association between daily napping and that night's sleep. METHODS: In this six-week prospective cohort study, 97 adults with episodic migraine completed twice-daily headache and sleep electronic diaries and wore a wrist actigraph. We modeled the associations between napping (yes/no) and headaches with conditional logistic regression and daily napping and nighttime sleep with linear regression. RESULTS: Over 4,353 study days, participants reported 1,059 headache days and 389 days with naps. More than 80% of participants napped during the study, with mean nap duration of 76.7 ± 62.4 min. Naps were more likely to occur on day 2 of headache 35/242 (14.5%) than on nonheadache days 279/3294 (8.5%, OR 2.2 [95% CI 1.4, 3.4]). Mean nap onset time (14:40 ± 3.3 h) was later than headache onset (12:48 ± 5.3 h). In adjusted models, napping was associated with an additional 1.1 (95% CI -1.4, 3.6) headache days/month. Naps were not associated with worse self-reported or objective sleep that night. CONCLUSIONS: Our findings suggest that naps may be an uncommonly used behavioral strategy for prolonged migraine attacks and do not contribute to nightly sleep disturbance. Future studies are needed to examine the acute analgesic effects of daytime napping in patients with migraine.

Vascular remodeling of the small pulmonary arteries and measures of vascular pruning on computed tomography.

Pulmonary hypertension is characterized histologically by intimal and medial thickening in the small pulmonary arteries, eventually resulting in vascular "pruning." Computed tomography (CT)-based quantification of pruning is associated with clinical measures of pulmonary hypertension, but it is not established whether CT-based pruning correlates with histologic arterial remodeling. Our sample consisted of 138 patients who underwent resection for early-stage lung adenocarcinoma. From histologic sections, we identified small pulmonary arteries and measured the relative area comprising the intima and media (VWA%), with higher VWA% representing greater histologic remodeling. From pre-operative CTs, we used image analysis algorithms to calculate the small vessel volume fraction (BV5/TBV) as a CT-based indicator of pruning (lower BV5/TBV represents greater pruning). We investigated relationships of CT pruning and histologic remodeling using Pearson correlation, simple linear regression, and multivariable regression with adjustment for age, sex, height, weight, smoking status, and total pack-years. We also tested for effect modification by sex and smoking status. In primary models, more severe CT pruning was associated with greater histologic remodeling. The Pearson correlation coefficient between BV5/TBV and VWA% was -0.41, and in linear regression models, VWA% was 3.13% higher (95% CI: 1.95-4.31%, p < 0.0001) per standard deviation lower BV5/TBV. This association persisted after multivariable adjustment. We found no evidence that these relationships differed by sex or smoking status. Among individuals who underwent resection for lung adenocarcinoma, more severe CT-based vascular pruning was associated with greater histologic arterial remodeling. These findings suggest CT imaging may be a non-invasive indicator of pulmonary vascular pathology.

A self-controlled approach to survival analysis, with application to air pollution and mortality.

BACKGROUND: Many studies have reported that long-term air pollution exposure is associated with increased mortality rates. These investigations have been criticized for failure to control for omitted, generally personal, confounders. Study designs that are robust to such confounders can address this issue. METHODS: We used a self-controlled design for survival analysis. We stratified on each person in the Medicare cohort between 2000 and 2015 who died, and examined whether PM2.5, O3 and NO2 exposures predicted in which follow-up period the death occurred. We used conditional logistic regression stratified on person and controlled for nonlinear terms in calendar year and age. By design slowly varying covariates such as smoking history, BMI, diabetes and other pre-existing conditions, usual alcohol consumption, sex, race, socioeconomic status, and green space were controlled by matching each person to themselves. RESULTS: There were 6,452,618 deaths in the study population in the study period. We observed a 5.37% increase in the mortality rate (95% CI 4.67%, 6.08%) for every 5 µg/m3 increase in PM2.5, a 1.98% (95% CI 1.61%, 2.36%) increase for 5 ppb increment in O3, and a 2.10% decrease (95% CI 1.88%, 2.33%) for a 5 ppb increase in NO2. When restricted to persons whose PM2.5 exposure never exceeded 12 µg/m3 in any year between 2000 and 2015, the effect size increased for PM2.5 (12.71% (11.30, 14.15)), and the signs of O3 and NO2 reversed (-0.26% (-0.88, 0.35) for O3 and 1.77% increase (1.40, 2.13) for NO2). Effect sizes were larger for Blacks (e.g. 7.71% (5.46, 10.02) for PM2.5). CONCLUSION: There is strong evidence that the association between annual exposure to PM2.5 and mortality is not confounded by individual or neighborhood covariates, and continues below the standard. The effects of O3 and NO2 are difficult to disentangle.

The relationship between traffic-related air pollution exposures and allostatic load score among youth with type 1 diabetes in the SEARCH cohort.

OBJECTIVE: We investigated the effects of chronic exposures to particulate and traffic-related air pollution on allostatic load (AL) score, a marker of cumulative biological risk, among youth with type 1 diabetes. RESEARCH DESIGN AND METHODS: Participants were drawn from five clinical sites of the SEARCH for Diabetes in Youth (SEARCH) study (n = 2338). Baseline questionnaires, anthropometric measures, and a fasting blood test were taken at a clinic visit between 2001 and 2005. AL was operationalized using 10 biomarkers reflecting cardiovascular, metabolic, and inflammatory risk. Annual residential exposures to PM2.5 and proximity to heavily-trafficked major roadways were estimated for each participant. Poisson regression models adjusted for sociodemographic and lifestyle factors were conducted for each exposure. RESULTS: No significant associations were observed between exposures to PM2.5 or proximity to traffic and AL score, however analyses were suggestive of effect modification by race for residential distance to heavily-trafficked major roadways (p = 0.02). In stratified analyses, residing <100, 100-<200 and 200-<400 m compared to 400 m or more from heavily-trafficked major roadways was associated with 11%, 26% and 14% increases in AL score, respectively (95% CIs: -4, 29; 9, 45; -1, 30) for non-white participants compared to 6%, -2%, and -2% changes (95% CIs: -2, 15; -10, 7; -8, 6) for white participants. CONCLUSIONS: Among this population of youth with type 1 diabetes, we did not observe consistent relationships between chronic exposures to particulate and traffic-related air pollution and changes in AL score, however associations for traffic-related pollution exposures may differ by race/ethnicity and warrant further examination.

Ambient air pollution exposure and radiographic pulmonary vascular volumes.

Exposure to higher levels of ambient air pollution is a known risk factor for cardiovascular disease but long-term effects of pollution exposure on the pulmonary vessels are unknown. METHODS: Among 2428 Framingham Heart Study participants who underwent chest computed tomography (CT) between 2008 and 2011, pulmonary vascular volumes were calculated by image analysis, including the total vascular volume and small vessel volume (cross-sectional area <5 mm2; BV5 defined as small vessel volume). Using spatiotemporal models and participant home address, we assigned 1-year (2008) and 5-year (2004-2008) average concentrations of fine particulate matter (PM2.5), elemental carbon (EC), and ground-level ozone (O3), and distance to major roadway. We examined associations of 1- and 5-year exposures, and distance to road, with CT vascular volumes using multivariable linear regression models. RESULTS: There was a consistent negative association of higher O3 with lower small vessel volumes, which persisted after adjustment for distance to road. Per interquartile range (IQR) of 2008 O3, BV5 was 0.34 mL lower (95% confidence intervals [CI], -0.61 to -0.06; P = 0.02), with similar results for 5-year exposure. One-year EC exposure and closer proximity to road were weakly associated with small vessel volumes; BV5 was 0.18 mL higher per IQR of 2008 EC (95% CI, -0.05 to 0.42; P = 0.13) and 0.40 mL higher per IQR closer proximity to road (95% CI: -0.10 to 0.89; P = 0.12). PM2.5 was not associated with small vascular volumes; BV5 was 0.26 mL lower per IQR of 2008 PM2.5 (95% CI: -0.68 to 0.16; P = 0.22). CONCLUSIONS: Among community-dwelling adults living in the northeastern United States, higher exposure to O3 was associated with lower small pulmonary vessel volumes on CT.