Publications

INTRODUCTION: Understanding how perceived interpersonal discrimination may affect women's cardiovascular health is key to informing prevention strategies, especially during mid-life when cardiovascular conditions emerge more frequently than in prior life stages.

METHODS: Participants are 451 women in Project Viva. In 2021-2022, participants completed the 9-item, race-neutral Williams Everyday Discrimination Scale (WEDS) via survey; total score ranged from 9 to 54, with higher scores indicating higher perceived discrimination. In 2022-2024, we collected in-person measures of body mass index (BMI), blood pressure and sleep duration (via actigraphy) and quality (via Patient-Reported Outcomes Measurement Information System sleep disturbance and sleep-related impairment forms). We defined obesity as BMI ≥30 kg/m2, hypertension as blood pressure ≥130/80 mm Hg or use of antihypertensive medications and short nightly sleep duration as sleep of <7 hours each night. We examined associations between WEDS (individual item and total scores) and cardiovascular outcomes using linear (continuous outcomes) or modified Poisson (binary outcomes) models.

RESULTS: At outcome measurement, women had a mean (SD) age of 55.8 (4.9) years and WEDS score of 14.9 (5.9); 74% self-identified as non-Hispanic White and 10% as non-Hispanic Black. After adjusting for age at outcome assessment, household income and education, a 10-point increment in total WEDS score was associated with a higher obesity risk (RR=1.40, 95% CI 1.10 to 1.79), higher BMI (β=1.62 kg/m2, 95% CI 0.50 to 2.74), shorter nightly sleep duration (β=-0.23 hours, 95% CI -0.41 to -0.06) and higher sleep disturbance (β=0.99, 95% CI -0.01 to 1.99) and sleep-related impairment t-scores (β=2.28, 95% CI 0.95 to 3.61). Most individual WEDS items were consistently associated with higher BMI and higher sleep impairment.

CONCLUSIONS: Higher perceived interpersonal discrimination was associated with higher BMI, risk of obesity, shorter sleep duration and poorer sleep quality among mid-life women. These findings underscore the association between interpersonal discrimination and cardiovascular health and highlight the importance of interventions aimed at reducing discrimination.

We investigated the associations of pregnancy levels of heavy metals and trace elements with the risk of gestational diabetes mellitus (GDM). Participating pregnant women were from the Boston Birth Cohort. We measured levels of mercury, lead, cadmium, selenium, and manganese in maternal red blood cells collected after delivery. We verified the GDM diagnosis using ICD codes, medication history, and plasma glucose profile abstracted from medical records. We used modified Poisson regression and Bayesian kernel machine regression models to examine associations of metals and elements, individually and as a mixture, with GDM. We stratified the analyses by race and ethnicity. Among 1256 pregnant women, 58% were non-Hispanic Black and 22% were Hispanic. Overall, each doubling of mercury and manganese levels was associated with 1.14 (95% CI: 1.01-1.28) and 0.65 (95% CI: 0.50-0.84) times the risk of GDM, respectively. In the race- and ethnicity-stratified analyses, the mercury-GDM association was stronger among Black women, and higher selenium levels were associated with higher GDM risk only among Hispanic women (Pinteraction = 0.01). In conclusion, women with higher mercury or lower manganese levels during pregnancy were more likely to develop GDM. An increased GDM risk associated with higher selenium levels was observed only in Hispanic women.

OBJECTIVE: To examine the prospective associations of metal mixtures during pregnancy with midlife adiposity and explore metal-folate interactions.

METHODS: In 500 participants from Project Viva, we measured six non-essential metals (arsenic, barium, cadmium, cesium, mercury, and lead) and five essential metals (copper, magnesium, manganese, selenium, and zinc) in red blood cells and folate in plasma collected during early pregnancy (mean gestational age: 10.0 weeks; mean age: 32.9 years). We assessed midlife (mean age: 51.2 years) adiposity using BMI and dual-energy X-ray absorptiometry (DXA) measures. We used multivariable-adjusted linear and multinomial logistic regression models to analyze individual exposures and Bayesian kernel machine regression to examine exposure mixtures.

RESULTS: Higher arsenic, cesium, and mercury levels were associated with lower midlife DXA percentage fat, total fat mass index, and/or trunk fat mass index, even after adjustments for diet in pregnancy. We observed an antagonistic interaction between folate and arsenic: arsenic was associated with higher obesity risk at lower folate levels but lower obesity risk at higher folate levels. The essential metal mixture tended to be associated with lower midlife BMI and obesity risk.

CONCLUSIONS: Higher pregnancy levels of arsenic, cesium, mercury, and the mixture of essential metals were associated with lower midlife adiposity.

BACKGROUND: Trial recruitment is a major determinant of study success, and participants' non-arrival at study visits represents a significant barrier to study completion. Little is known about the participant and study process characteristics associated with visit non-arrival.

OBJECTIVE: To investigate factors associated with non-arrival at initial in-person screening visits in two ongoing randomized controlled trials.

METHODS: The Groceries for Black Residents of Boston to Stop Hypertension trials (GoFresh and GoFreshRx) studied whether home-delivered, DASH-patterned groceries can reduce blood pressure among Black adults living in urban food priority areas. In this analysis, we examined sociodemographic and study-related factors associated with participant non-arrival at their initial study visit (defined as rescheduling or not showing up at all). Associations were determined using logistic regression with adjustment for age, estimated gender, and hypertension treatment status.

RESULTS: Among 2224 participants (mean age = 44.0 years, 72.5 % women), the non-arrival rate at screening visit 1 was 29.5 %. Older participants were more likely to arrive, while those with larger families and a longer duration between initial contact and visit were less likely to arrive. Participant's method of contacting the study, visit time, and season of visit were not associated with visit non-arrival.

CONCLUSION: In this large trial recruitment drive, older age, larger family size, and a longer time between initial contact and scheduled visit were associated with non-arrival at initial study visits. These factors represent potential targets for future interventions that either accommodate patient factors or intervene upon study process barriers to achieve timely recruitment goals.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) disproportionately affects Black adults and those with lower socioeconomic status in the United States. The aim of this study was to examine the associations between socioeconomic status and CKD, albuminuria/stage 1-2 CKD, and stage 3-5 CKD, and to assess differences between Black and White adults.

STUDY DESIGN: We used data from the 2017-2020 National Health and Nutrition Examination Survey. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 based on the race-free CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation (stage 3-5 CKD) and/or a urinary albumin-creatinine ratio of >30 mg/g (albuminuria/stage 1-2 CKD).

SETTING & PARTICIPANTS: Respondents to the 2017-2020 National Health and Nutrition Examination Survey with Black or White race.

EXPOSURE: Measures of socioeconomic status (income to poverty ratio, insurance status, education, employment status, and health care access).

ANALYTICAL APPROACH: We examined the relationship between measures of socioeconomic status and CKD, albuminuria/stage 1-2 CKD, and stage 3-5 CKD using survey-weighted Poisson regressions controlling for age, sex, and medical comorbid conditions.

RESULTS: The weighted sample (N = 182,622,525) was 52.2% women and 15.5% Black, with a mean age of 49.1 years. The prevalence of CKD was 15.6% in the overall sample, 20.9% among Black adults, and 14.7% among White adults. Higher income, higher education levels, and having health insurance were associated with a lower prevalence of CKD in the overall sample and among White adults, but not among Black adults. This pattern was consistent for those with albuminuria/stage 1-2 CKD, but not for those with stage 3-5 CKD.

LIMITATIONS: This study is limited by its cross-sectional design. In addition, data were based on single measurements and thus may be less precise in estimating the prevalence of chronic disease.

CONCLUSIONS: Higher socioeconomic status was inversely associated with albuminuria/stage 1-2 CKD and CKD among White but not Black adults. Future work should investigate the mechanisms by which albuminuria/stage 1-2 CKD remains independent of socioeconomic status among Black adults.

BACKGROUND: Prenatal per- and polyfluoroalkyl substance (PFAS) exposures may influence offspring blood pressure (BP), but long-term studies in diverse populations remain limited.

METHODS: Participants were from the Boston Birth Cohort. We measured PFAS in maternal plasma collected 24 to 72 hours after delivery and extracted children's BP from medical records. We calculated age-, sex-, and height-specific BP percentiles and defined elevated BP as systolic/diastolic BP ≥90th percentile (ages 3 to <13 years) or ≥120/80 mm Hg (ages 13 to <18 years). We used adjusted mixed-effects linear and modified Poisson models to examine associations of PFAS with BP percentiles and elevated BP. We used linear spline mixed-effects models to predict BP trajectories at ages 3 to 18 years by PFAS levels.

RESULTS: We included 13 404 BP measurements from 1094 children (median follow-up: 12 years [interquartile range, 9-15 years]; 61% Black and 22% Hispanic). Overall, higher perfluorodecanoic acid (PFDeA), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnA) were associated with higher systolic BP percentile. The associations differed by child life stage, sex, race and ethnicity. For example, associations of PFDeA with systolic BP percentile were stronger in older (β3-5y=0.40; β6-12y=1.06; β13-18y=2.55), male (βmale=1.51; βfemale=0.52), and Black (βBlack=1.75; βHispanic=0.45) children. In male children, each doubling of perfluoroheptanesulfonic acid (PFHpS) was associated with a 9% higher risk of elevated BP at ages 6 to 12 years and a 17% higher risk at 13 to 18 years, with no increased risk at 3 to 5 years. PFHpS was associated with a dose-dependent divergence in BP trajectories beginning at age 13 years.

CONCLUSIONS: Prenatal exposures to certain PFAS were associated with offspring BP, with stronger associations in adolescents, male children, and Black children. Prenatal PFAS exposures may have intergenerational, long-term, and latent hypertensive effects.

BACKGROUND: Orthostatic hypertension is an emerging risk factor for adverse events. Recent consensus statements combine an increase in blood pressure upon standing with standing hypertension, but whether these 2 components have similar risk associations with cardiovascular disease (CVD) is unknown.

METHODS: The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure during visit 1 (1987-1989). We defined systolic orthostatic increase (a rise in systolic blood pressure [SBP] ≥20 mm Hg, standing minus supine blood pressure) and elevated standing SBP (standing SBP ≥140 mm Hg) to examine the new consensus statement definition (rise in SBP ≥20 mm Hg and standing SBP ≥140 mm Hg). We used Cox regression to examine associations with incident coronary heart disease, heart failure, stroke, fatal coronary heart disease, and all-cause mortality.

RESULTS: Of 11 369 participants (56% female; 25% Black adults; mean age, 54 years) without CVD at baseline, 1.8% had systolic orthostatic increases, 20.1% had standing SBP ≥140 mm Hg, and 1.3% had systolic orthostatic increases with standing SBP ≥140 mm Hg. During up to 30 years of follow-up, orthostatic increases were not significantly associated with any of the adverse outcomes of interest, while standing SBP ≥140 mm Hg was significantly associated with all end points. In joint models comparing systolic orthostatic increases and standing SBP ≥140 mm Hg, standing SBP ≥140 mm Hg was significantly associated with a higher risk of CVD, and associations differed significantly from systolic orthostatic increases.

CONCLUSIONS: Unlike systolic orthostatic increases, standing SBP ≥140 mm Hg was strongly associated with CVD outcomes and death. These differences in CVD risk raise important concerns about combining systolic orthostatic increases and standing SBP ≥140 mm Hg in a consensus definition for orthostatic hypertension.

IMPORTANCE: Fertility status is a marker for future health, and infertility has been associated with risk for later cancer and diabetes, but associations with midlife cardiovascular health (CVH) in female individuals remain understudied.

OBJECTIVE: To evaluate the association of infertility history with CVH at midlife (approximately age 50 years) among parous individuals.

DESIGN, SETTING, AND PARTICIPANTS: Project Viva is a prospective cohort study of pregnant participants enrolled between 1999 and 2002 who delivered a singleton live birth in the greater Boston, Massachusetts, area. Infertility history was collected at a midlife visit between 2017 and 2021, approximately 18 years after enrollment. Data analysis was performed from January to June 2023.

EXPOSURES: The primary exposure was any lifetime history of infertility identified by self-report, medical record, diagnosis, or claims for infertility treatment.

MAIN OUTCOMES AND MEASURES: The American Heart Association's Life's Essential 8 (LE8) is a construct for ranking CVH that includes scores from 0 to 100 (higher scores denote better health status) in 4 behavioral (diet, physical activity, sleep, and smoking status) and 4 biomedical (body mass index, blood pressure, blood lipids, and glycemia) domains to form an overall assessment of CVH. Associations of a history of infertility (yes or no) with mean LE8 total, behavioral, biomedical, and blood biomarker (lipids and glycemia) scores were examined, adjusting for age at outcome (midlife visit), race and ethnicity, education, household income, age at menarche, and perceived body size at age 10 years.

RESULTS: Of 468 included participants (mean [SD] age at the midlife visit, 50.6 [5.3] years) with exposure and outcome data, 160 (34.2%) experienced any infertility. Mean (SD) LE8 scores were 76.3 (12.2) overall, 76.5 (13.4) for the behavioral domain, 76.0 (17.5) for the biomedical domain, and 78.9 (19.2) for the blood biomarkers subdomain. In adjusted models, the estimated overall LE8 score at midlife was 2.94 points lower (95% CI, -5.13 to -0.74 points), the biomedical score was 4.07 points lower (95% CI, -7.33 to -0.78 points), and the blood subdomain score was 5.98 points lower (95% CI, -9.71 to -2.26 points) among those with vs without history of infertility. The point estimate also was lower for the behavioral domain score (β = -1.81; 95% CI, -4.28 to 0.66), although the result was not statistically significant.

CONCLUSIONS AND RELEVANCE: This cohort study of parous individuals found evidence for an association between a history of infertility and lower overall and biomedical CVH scores. Future study of enhanced cardiovascular preventive strategies among those who experience infertility is warranted.

OBJECTIVE: There is a secular trend towards earlier age of menarche in the US and globally. Earlier age at menarche (AAM) has been associated with metabolic disorders that increase risk for preterm delivery (PTD), yet no studies in the US have investigated whether AAM influences risk of PTD. This study tested the hypothesis that AAM is associated with PTD.

DESIGN: A case-control study.

SETTING: The Boston Medical Center (BMC) in Boston, Massachusetts.

POPULATION OR SAMPLE: 8264 mother-newborn dyads enrolled at birth at BMC between 1998 and 2019, of which 2242 mothers had PTD (cases) and 6022 did not have PTD (controls).

METHODS: Multivariable-adjusted logistic regression models and restricted cubic splines were used to examine the association between AAM and risk of PTD. The combined impact of AAM and age at delivery on the risk of PTD was also examined.

MAIN OUTCOME MEASURES: Preterm delivery and gestational age (GA) was defined by maternal last menstrual period and early ultrasound documented in medical records.

RESULTS: Maternal age at delivery was 28.1 ± 6.5 years and AAM was 12.85 ± 1.86 years. Multivariable-adjusted cubic spline suggested an inverse dose-response association of AAM with odds of PTD and, consistently, a positive association with GA. A 1-year earlier AAM was associated with 5% (95% CI 2%-8%) higher odds of PTD, after adjustment for maternal year of birth, parity, maternal place of birth, education, smoking status and Mediterranean-style diet score. The association between AAM and PTD was stronger among older mothers whose age at delivery was ≥35 years.

CONCLUSIONS: Earlier AAM is associated with higher odds for PTD, and this association is stronger among women at advanced reproductive age.

INTRODUCTION: Metabolite signatures for blood pressure (BP) may reveal biomarkers, elucidate pathogenesis, and provide prevention targets for high BP. Knowledge regarding metabolites associated with BP in adolescence remains limited.

OBJECTIVES: Investigate the associations between metabolites and adolescent BP, both cross-sectionally (in early and late adolescence) and prospectively (from early to late adolescence).

METHODS: Participants are from the Project Viva prospective cohort. During the early (median: 12.8 years; N = 556) and late (median: 17.4 years; N = 501) adolescence visits, we conducted untargeted plasma metabolomic profiling and measured systolic (SBP) and diastolic BP (DBP). We used linear regression to identify metabolites cross-sectionally associated with BP at each time point, and to assess prospective associations of changes in metabolite levels from early to late adolescence with late adolescence BP. We used Weighted Gene Correlation Network Analysis and Spearman's partial correlation to identify metabolite clusters associated with BP at each time point.

RESULTS: In the linear models, higher androgenic steroid levels were consistently associated with higher SBP and DBP in early and late adolescence. A cluster of 59 metabolites, mainly composed of androgenic steroids, correlated with higher SBP and DBP in early adolescence. A cluster primarily composed of fatty acid lipids was marginally associated with higher SBP in females in late adolescence. Multiple metabolites, including those in the creatine and purine metabolism sub-pathways, were associated with higher SBP and DBP both cross-sectionally and prospectively.

CONCLUSION: Our results shed light on the potential metabolic processes and pathophysiology underlying high BP in adolescents.