Publications

BACKGROUND: Home blood pressure (BP) monitoring (HBPM) is increasingly used as an alternative to office BP. However, factors influencing agreement between office and home BP among very old adults remain unclear.

METHODS: During ARIC (Atherosclerosis Risk in Communities) visit 10, participants underwent 3 automated office BP (AOBP) measurements using an Omron HEM-907XL and performed HBPM twice daily for 8 days using an Omron BP7450. Discordance was defined as a systolic BP difference of ±10 mm Hg between mean AOBP and HBPM. Multivariable regression models evaluated demographic, anthropometric, and clinical factors associated with discordance.

RESULTS: Among 792 participants (58% female; mean age, 84±3.7 years), mean systolic BP was 130.6 mm Hg (AOBP) and 129.6 mm Hg (HBPM). Despite a minimal average difference (1.0±15.7 mm Hg), 49% had ≥10 mm Hg systolic BP discordance. Higher AOBP was associated with greater discordance. Compared with females, males had lower AOBP relative to HBPM (-4.69 mm Hg [95% CI, -6.86 to -2.51]). Smaller arm circumference was associated with higher discordance (β=14.4 mm Hg [95% CI, 4.78-24.04]). Frail adults had lower AOBP relative to HBPM (β, -5.1 mm Hg [95% CI, -11.0 to 0.9]). Baseline AOBP systolic BP ≥140 mm Hg strongly predicted discordance ≥+10 mm Hg (odds ratio, 8.27 [95% CI, 5.52-12.40]). Participants aged 91 to 100 years had lower AOBP than those aged 78 to 80 years (β, -5.0 mm Hg [95% CI, -10.06 to 0.001]).

CONCLUSIONS: Among very old adults, substantial BP discordance between AOBP and HBPM was common and influenced by higher BP, age, male sex, arm circumference, and frailty.

BACKGROUND: 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: 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: Of 13 418 participants (56% women, mean age [54±5.7 years]), 25% were treated for hypertension. Males had higher average 10-year CVD risk scores regardless of treatment. The distribution of BP and prevalence of CVD risk factors was similar for male and female adults. Incidence rates (per 10 000 person-years) comparing a systolic BP threshold of ≥140 versus <140 mm Hg for coronary heart disease were 30.9 and 12.0 among untreated male and female adults (P=0.07) and 27.4 versus 16.5 among treated male and female adults (P=0.63). HRs comparing a systolic BP threshold of ≥140 versus <140 mm Hg for coronary heart disease were 1.49 and 1.72 among untreated male and female adults (P=0.16) and 1.30 versus 1.40 among treated male and female adults (P=0.93).

CONCLUSIONS: 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.

BACKGROUND: There is growing interest in understanding the link between early life exposures to ambient air pollution and childhood blood pressure; however, existing findings, largely from single site/cohort studies, are inconclusive.

METHODS: We examined the association between exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) and blood pressure measured at age 5-12 years in 4863 U.S. children from 20 pregnancy cohorts of the NIH ECHO cohort. Point-based residential exposures were derived from spatiotemporal models with a biweekly resolution and averaged over each trimester, the whole pregnancy, and child age 0-2 years. We converted systolic (SBP) and diastolic blood pressure (DBP) to age-, sex-, and height-specific percentiles and classified children with SBP and/or DBP ≥ 90th percentile as high blood pressure (HBP). Associations of PM2.5 (per 5-μ g/m3) or NO2 (per 10-ppb) exposures with blood pressure outcomes were estimated using linear and Poisson regressions adjusted for sociodemographic, lifestyle, temporal, and spatial confounders.

RESULTS: Across windows, mean PM2.5 ranged from 7.6 to 7.9 μ g/m3, and mean NO2 ranged was 8.1-8.8 ppb. We found positive associations of PM2.5 in the first trimester with SBP percentile (β: 1.92, 95 %CI: 0.02, 3.83) and risk of HBP (RR: 1.16, 95 %CI: 1.02, 1.33). Higher PM2.5 exposures averaged over pregnancy and age 0-2 years were also related to elevated SBP percentiles and a higher risk of HBP, but with lower precision. Contrary to our hypotheses, inverse associations of pregnancy average NO2 with both SBP (β: -2.42, 95 %CI: -4.70, -0.14) and DBP (β: -1.94, 95 %CI: -3.81, -0.08) percentiles were suggested.

CONCLUSION: Results reinforce the detrimental effects of PM2.5 on childhood cardiometabolic health, even at low exposure levels. Such findings can inform regulatory policy on acceptable air pollution levels and appropriate controls. The inverse association between prenatal NO2 and blood pressure was counterintuitive and warrants further investigation.

BACKGROUND: Orthostatic hypotension (OH) is common among older adults actively prescribed hypertension pharmacotherapy. Associations between antihypertensives and OH are inconsistent, due to differences in drug classes and OH assessment protocols.

METHODS: Three supine and six standing blood pressures (BPs) were measured over 6 minutes, timed to initiate immediately (0 minutes) and 1, 2, 3, 4, and 5 minutes after standing. OH was defined as a drop of systolic/diastolic BP ≥ 20/10 mmHg upon standing from the supine position. OH phenotypes were initial (immediately after standing), early (within 3 minutes), late (after 3 minutes), and sustained (during 6 minutes of standing). Participants were asked about orthostatic symptoms experienced during OH assessment. We investigated associations of antihypertensive classes with OH phenotypes and orthostatic symptoms via multivariable logistic regression.

RESULTS: Of 863 participants (mean age 84 years), 41% had initial, 24% early, 18% late, and 17% sustained OH; 81% used antihypertensive medications. First-line antihypertensives (renin angiotensin aldosterone system blockers, dihydropyridine calcium channel blockers, and thiazide diuretics) were not associated with OH or orthostatic symptoms. Among non-first-line, alpha blockers were significantly associated with initial OH (OR 1.80, 95%CI 1.07, 3.01) and orthostatic symptoms during postural change (OR 2.64, 95%CI 1.34, 5.23), whereas combined alpha-beta blockers were significantly associated with early, late, or sustained OH (2.24 [1.15, 4.37], 2.50 [1.21, 5.17], 2.99 [1.41, 6.30], respectively) and experienced symptoms while standing (3.08 [1.10, 8.65]).

CONCLUSIONS: First-line antihypertensives are not associated with OH among older adults, which does not support their discontinuation in the setting of non-neurogenic OH.

BACKGROUND: Germ-free mice experiments indicate that human gut microbiota influence blood pressure (BP), but no studies have prospectively examined if infant gut microbiota affects their future childhood BP. We aim to investigate prospective associations of infant gut microbiota diversity and composition with childhood BP, examining effect measure modification by breastfeeding and mediation by a child's body mass index.

METHODS AND RESULTS: In the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort, we measured infant gut microbiota (16S rRNA V4) at 1 week, 1 month, and 1 year and child BP at 3 and 6 years. We assessed α diversity-BP, β diversity-BP, and microbe abundances-BP associations using linear regression, permutational multivariate analysis of variance, and beta-binomial count regression, respectively. Data from 526 children showed that α diversity and several Bifidobacterium spp. had protective associations with BP but only in children breastfed for ≥6 months. For instance, a 1-unit increment in 1 month Shannon index was associated with 1.86 mm Hg (95% CI, 0.66-3.05) lower 6-year systolic BP in children breastfed ≥6 months but a 0.73 (95% CI, -1.00 to 2.45) higher 6-year systolic BP in those breastfed <6 months (P-interaction=0.02). Greater abundance of 2 Bifidobacterium microbes at 1 week was negatively associated with 6-year systolic BP when breastfeeding ≥6 months (P-interaction<0.1). Further, abundance of 8 microbes at 1week or 1 month was linked to 3-year or 6-year BP (false discovery rate P<0.05), with 5 of them independent of a child's body mass index. Lastly, 1-week unweighted UniFrac distance and 1-year weighted UniFrac distance were associated with BP after adjustment (P<0.05).

CONCLUSIONS: Gut microbiota features at 1 week and 1 month of life were associated with BP at 6 years. Breastfeeding duration modified key associations including those for α diversity and Bifidobacteria.

BACKGROUND: Black adults are underrepresented in cardiovascular disease clinical trials. Individual and social circumstances may limit when they are available to complete trial prescreening requirements. Characterizing preferences related to callback times and the impact of calling during preferred times could inform strategies to improve the recruitment of Black adults into clinical research. Our objectives were to characterize prescreening call preferences and successfully reaching a potential participant among adults inquiring about participation in two trials for Black residents of Boston.

METHODS: The GoFreshRx and GoFresh trials examine the effect of a home-delivered Dietary Approaches to Stop Hypertension (DASH)-patterned grocery intervention on blood pressure among Black adults with or without hypertension treatment in Boston. With the exception of the study population, both trials were identical and used the same recruitment apparatus for outreach. Interested persons completed a common online form for both trials and indicated their preferred callback time. Staff call attempts and participant screening status were logged prospectively. Gender was estimated based on first name, using a published algorithm. Odds ratios (OR) were determined via logistic regression models with adjustment for estimated gender, recruitment source, method of inquiry, and first call during preferred callback time.

RESULTS: Of 2870 inquiries (September 2022-July 2023), 1740 participants were called and 1286 were reached. Out of the 1740 participants, 25% preferred to be called before noon and 22% after 4 pm, yet only 10% of the latter were called after 4 pm. Calling during preferred times significantly increased the odds of reaching participants (OR: 1.44; 95% CI: 1.12, 1.85) and completing a prescreening interview (OR: 1.39; 95% CI: 1.14, 1.71). Staff outreach 8-12 weeks (vs 0-4 weeks) after inquiry submission was significantly associated with lower odds of completing a prescreening interview (OR: 0.41; 95% CI: 0.23, 0.73). Participants who made inquiries via return mail were significantly less likely to be reached outside work hours (OR: 0.49; 95% CI: 0.27, 0.90) and in the afternoon (OR: 0.51; 95% CI: 0.30, 0.88). Participants recruited through community events were more likely to be reached in the afternoon (OR: 2.71; 95% CI: 1.06, 6.97).

CONCLUSION: Contacting participants during their preferred callback time was associated with reaching them and completing a prescreening interview. These data highlight the importance of study teams' flexibility in outreach time to enhance the recruitment of Black adults into cardiovascular clinical trials.

BACKGROUND: The long-term associations between metal mixtures in pregnancy and women's mid-life blood pressure (BP) and hypertension remain unclear.

METHODS: In Project Viva (enrolled 1999-2002), we measured nonessential (arsenic, barium, cadmium, cesium, mercury, lead) and essential metals (copper, magnesium, manganese, selenium, zinc) in red blood cells, along with folate and vitamin B12 in plasma, collected during pregnancy. We measured mid-life BP from 2017 to 2021 (median age, 51.2 years). We examined associations of individual metals with BP using linear regression and with hypertension (≥130/80 mm Hg or use of antihypertensive medication) using modified Poisson regression. We used Bayesian kernel machine regression to examine the mixture effects of metals and micronutrients.

RESULTS: The median follow-up time of the 493 women was 18.1 years (interquartile range, 17.8-18.6 years). After adjustment, a doubling of copper and manganese was associated with 0.75 (95% CI, 0.57-0.99) and 0.80 (95% CI, 0.71-0.91) times the risk of hypertension, respectively. Although higher cesium and selenium levels were associated with a slightly increased risk of hypertension, the 95% CIs were wide and crossed the null. A doubling of vitamin B12 was associated with a 3.64 (95% CI, 1.23-6.04) mm Hg lower systolic BP and a 2.52 (95% CI, 0.72-4.32) mm Hg lower diastolic BP. Bayesian kernel machine regression showed linear associations with no metal-metal or metal-micronutrient interactions. The essential metal mixture was monotonically associated with lower BP, while its association with hypertension showed threshold effects.

CONCLUSIONS: Optimizing essential metal levels during pregnancy, particularly copper and manganese, along with vitamin B12, may protect against higher BP and hypertension in mid-life women.

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.