Faculty Bibliography

BACKGROUND/UNASSIGNED:Higher relative risk for cardiovascular disease (CVD) events at lower blood pressure (BP) thresholds in female versus male adults suggest that hypertension thresholds should be sex-specific. METHODS/UNASSIGNED:We used the ARIC study (Atherosclerosis Risk in Communities) visit 1 (1987-1989) to compare the BP distribution, estimated risk (via the 10-year Predicting Risk of Cardiovascular Disease Events score), absolute risk, and relative risk of CVD according to BP thresholds, stratified by sex and hypertension treatment status, in participants without prior CVD. RESULTS/UNASSIGNED:=0.93). CONCLUSIONS/UNASSIGNED:In this middle-aged population, there were no consistent differences in BP distribution, risk factor burden, absolute risk, or relative risk of CVD between male and female adults. These findings do not support a sex-specific threshold for hypertension.

OBJECTIVE:Early-life exposure to phthalates, widely used in consumer products, may induce developmental lung adaptations and predispose to respiratory morbidity throughout childhood. We assessed the associations of fetal phthalate exposure with wheezing, asthma, and lung function from birth to adolescence. METHODS:We performed 1-stage individual participant data meta-analyses with data from six European birth cohorts (3,745 mother-child pairs) to assess associations of pregnancy-averaged maternal urinary concentrations of 7 phthalate metabolites and 3 phthalate groups (high- and low-molecular-weight phthalate metabolites and sum of di-2-ethylhexyl phthalate metabolites) with wheezing in infancy (0-1 years) and at preschool age (1-5 years), and asthma and lung function at school age (5-12 years). RESULTS:z-scores after multiple testing correction. CONCLUSION/CONCLUSIONS:Fetal exposure to higher phthalate concentrations is associated with lung function adaptations, while overall no consistent associations were observed with childhood wheezing or asthma. Future studies are needed to assess the causality of the observed associations, to identify the underlying mechanisms, and to assess potential respiratory consequences in adult life.

BACKGROUND:Exposure to particulate matter (PM) is a significant public health concern associated with respiratory, cardiovascular, and metabolic diseases. Oxidative stress is a key biological mechanism mediating the harmful effects of PM exposure. However, a comprehensive review of relating PM exposure to omics layers of oxidative stress has been lacking. We aimed to systematically review the current evidence on the associations between PM exposure and the multi-omics signatures of oxidative stress. METHODS:We conducted a systematic review of studies published between January 2021 and March 2024 in PubMed and Web of Science, following a registered protocol (PROSPERO ID: CRD42024617742). Eligible studies assessed the impact of PM exposure on oxidative stress-related omics in adult human populations. Data on exposure assessment, study characteristics, and omics outcomes were extracted, and the risk of bias was evaluated using the Newcastle-Ottawa Scale and Cochrane's. RESULTS:Seventy-seven studies were included. PM exposure was consistently associated with oxidative stress markers across multiple omics platforms. Studies on the analytes showed that PM was associated with an increase in oxidative markers. Metabolomics studies revealed alterations in pro-oxidant metabolites (e.g., eicosanoids, ceramides) and disruptions in antioxidant pathways (e.g., glutathione, vitamin C, and E metabolism). PM exposure was also linked to changes in energy metabolism, fatty acid oxidation, and detoxification pathways. Genomics studies reported differential methylation in genes involved in oxidative stress and inflammation. Microbiome studies suggest that PM exposure alters the composition of gut and nasal microbiota, favoring a pro-oxidative profile. However, some studies reported no significant associations, highlighting heterogeneity in findings. CONCLUSION/CONCLUSIONS:Our systematic review demonstrates that PM exposure affects multiple molecular pathways related to oxidative stress across diverse omics platforms. These findings highlight the complex responses to PM, underscoring the need for integrative multi-omics approaches to fully understand the health impacts of air pollution.

BACKGROUND:Dietary self-monitoring is central to effective personalized nutrition, providing critical data to inform tailored feedback and support behavior change. OBJECTIVE:To examine the impact of dietary self-monitoring adherence and the indirect effect of personalized scores to predict postprandial glycemic response (PPGR) on weight loss. METHODS:Post-hoc analysis of the Personal Diet Study that investigated the impact of a machine algorithm-based diet that integrates clinical and microbiome features (Personalized) compared to a standard, low-fat diet (Standardized) on weight loss. All participants received behavioral counseling and were encouraged to self-monitor dietary intake via a smartphone app. Personalized received algorithm-based scores (1 to 5) on predicted PPGR to foods logged (PPGR score; 1-2 indicating optimal; 3-5 suboptimal). Dietary self-monitoring adherence was the percentage of days logging ≥50% of target calories, classified as high or low. PPGR score quality was calculated by the proportion of optimal predicted PPGR scores per day; defined as "high-PPGR quality" days when this exceeded the group average. Mediation analysis assessed whether PPGR quality mediated the relationship between dietary self-monitoring adherence and weight loss. RESULTS:Participants with high self-monitoring adherence lost an average of 4.2% of their baseline weight, compared to 1.9% among those with low adherence (p=0.016). High self-monitoring adherence was associated with a greater likelihood of achieving ≥5% weight loss (aOR=3.67, 95% CI: 1.63-8.50). Within Personalized, high PPGR quality mediated 53.4% of the total effect of self-monitoring adherence on weight loss (p<0.001). CONCLUSION/CONCLUSIONS:Consistent self-monitoring coupled with personalized feedback may significantly enhance weight loss in a precision nutrition approach. CLINICAL TRIAL REGISTRATION/BACKGROUND:NCT03336411.

BACKGROUND:Little is known about the use of text messages to promote enrollment in smoking cessation treatment. RESEARCH QUESTION/OBJECTIVE:What is the impact of number of outreach messages and monetary incentives on enrollment in smoking cessation treatment among Latino adults? STUDY DESIGN AND METHODS/METHODS:This pragmatic randomized clinical trial used a 3x2 factorial design. The first factor, monetary incentives, consisted of three conditions: 1) receiving a small fixed amount ($5) when enrolling, 2) getting a chance to win a large amount ($200) when enrolling, and 3) no monetary incentive when enrolling. The second factor, number of cycles, consisted of two conditions: 1) one cycle of messages, and 2) four cycles of messages. Latino adults who smoke (n=2,826) were identified in electronic medical records. Participants were randomized in a 1:1:1 ratio to receive one of three monetary incentive conditions and in a 1:2 ratio to receive one or four cycles of messages. The main outcome was enrollment in a smoking cessation text messaging intervention. RESULTS:Enrollment rates ranged from 1.3% for the group that received no monetary incentive for enrollment and one cycle of messages to 5.4% for the group that received a fixed amount for enrollment and four cycles of messages. Receiving four cycles of messages was associated with a higher likelihood of enrollment compared to receiving one cycle of messages (OR 1.92 [95% CI, 1.22-3.01], p<0.01). Monetary incentives were not associated with enrollment. INTERPRETATION/CONCLUSIONS:Among Latino adults, enrollment in smoking cessation treatment increased significantly with increasing number of cycles. In contrast, monetary incentives did not increase enrollment. While modest, the 5.3% enrollment rate found among participants who received four cycles of messages and no monetary incentive can inform future population-level efforts to advance smoking cessation among Latino adults. CLINICAL TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT05722132.

BACKGROUND:Systematic profiling of plasma proteins in population studies offers a complementary approach to discovery of novel risk factors and may provide new insights into the causes of coronary heart disease. METHODS:To explore relationships between the circulating proteome and coronary heart disease (CHD), we evaluated associations of 4780 plasma proteins with incident CHD in the Cardiovascular Health Study (CHS, N=2856, 575 CHD events) and replicated significant associations in the Atherosclerosis Risk in Communities Study (ARIC, N = 10456; 1375 events). RESULTS:We find that 11 proteins significantly associate with incident CHD after adjusting for risk factors; and eight significantly replicated in ARIC. Several proteins correlate with carotid intimal medial thickness and CHD associations are attenuated in participants without subclinical atherosclerosis. Macrophage metalloelastase (MMP12) is the strongest observed association (Hazard Ratio, 1.31; 95% Confidence Interval, 1.19-1.44). Mendelian randomization (MR) identifies a causal relationship between higher MMP12 and lower CHD (Odds Ratio, OR 0.94) and ischemic stroke (OR 0.90) risk, while reverse MR found that genetic propensity to CHD increased MMP12. Taken together, multivariable MR confirms a direct protective effect of higher plasma MMP12 on CHD risk and a genetic effect of atherosclerosis and CHD on elevating MMP12. CONCLUSIONS:Proteomic analyses reveal associations with incident CHD and genomic evidence suggests that therapeutic MMP12 inhibition may confer adverse cardiovascular effects.

OBJECTIVES/OBJECTIVE:To identify stakeholder perceived challenges and facilitators for implementing a clean fuel and clean stove intervention to reduce household air pollution and hypertension in Lagos, Nigeria. DESIGN/METHODS:Qualitative study guided by the Exploration and Preparation phases of the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework, using focus group discussions and in-depth semi-structured interviews with inductive and deductive thematic analysis. SETTING/METHODS:Peri-urban communities across the five administrative divisions of Lagos State, Nigeria. PARTICIPANTS/METHODS:128 stakeholders from 32 communities, including community, religious, market and youth leaders, primary healthcare staff, and household decision makers. Approximately half were female. INTERVENTIONS/METHODS:This was a pre-implementation needs assessment that included demonstrations of the clean stove and fuel. PRIMARY AND SECONDARY OUTCOME MEASURES/METHODS:Thematic domains describing barriers and enablers to adoption and implementation, mapped to EPIS inner, outer, and bridging factors. RESULTS:Stakeholders reported barriers that included stove stacking, upfront stove cost, concerns about long-term fuel price and availability, equipment durability and maintenance, safety, mistrust of new technology, and uncertainty about stove performance for dishes requiring high heat and long cooking times. Reported facilitators included payment flexibility and subsidies, opportunities to test the stove, perceived benefits of cleaner and faster cooking with less soot, endorsement by community leaders, and interest in local retail and distribution to improve access. CONCLUSIONS:Implementation planning for clean fuel and clean stove programmes should address affordability, reliable fuel supply chains, durability and service, culturally relevant cooking needs, and trust building through community leadership. These findings inform adaptation strategies for scale-up in similar low-resource settings. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT05048147.

The objective of this systematic review was to identify the evidence of testicular cancer risk for people with intersex conditions. This assessment is hoped to help refine risk stratification tools for assessing gonadal malignancy risk and guide the development of more robust evidence-based management strategies. The literature was searched in Ovid MEDLINE, Embase, and Cumulative Index of Nursing and Allied Health using a search string developed by a multidisciplinary team. The protocol was registered at Prospective Register of Systematic Reviews as CRD42021231313. A total of 3608 articles were found. After selection, 301 publications were included (1215 individuals). The results identified significant evidence that pre-pubertal gonadectomy may be linked to lower rates of malignant gonadal changes for patients with partial gonadal dysgenesis, Turner's syndrome with Y-chromosome material, complete androgen insensitivity, partial androgen insensitivity, and patients with ovotestis/es. The evidence was not significant for patients with complete gonadal dysgenesis, Klinefelter syndrome, nor WT1-related syndromes. Specific cancer outcomes were unable to be assessed due to small sample sizes and thus it is unknown if clinically significant cancer outcomes are meaningfully altered by pre-pubertal gonadectomy. Importantly, the quality of data on the topic of gonadal malignancy in intersex patients with testicular tissue was determined to be poor overall. The quality was relatively more robust regarding the conditions of Complete Androgen Insensitivity, Klinefelter syndrome, and patients with ovotestis/es. More high-quality research is needed to draw specific conclusions on the risks and benefits of performing pre-pubertal gonadectomy for intersex patients. When counseling these patients, clinicians should be transparent regarding the paucity of data supporting pre-pubertal gonadectomy.