Kara M. Whitaker

Using exercise stage-level mixed-effects models, we find that ACFE is associated with a distinct, intensity-dependent pattern of cardiovascular regulation where individuals with greater exposure exhibit blunted hemodynamic responses at lower workloads, but exaggerated reactivity as exercise intensity increases. These findings extend prior work by identifying a latent phenotype of stress-responsive cardiovascular dysfunction that is not apparent at rest, and that may represent an early pathophysiological signature of lifetime cardiovascular risk.

Background: Childhood obesity is a major public health concern that increases cardiovascular disease (CVD) risk. The Developmental Origins of Health and Disease theory posits that obesity and CVD risk is, in part, programmed in utero. A greater understanding of modifiable maternal factors that associate with offspring obesity and CVD risk in childhood could inform primordial prevention interventions during pregnancy. Maternal sedentary behavior, physical activity, and sleep during pregnancy are modifiable and plausible determinants of offspring obesity and CVD risk yet remain insufficiently studied. This protocol describes the design of the Pregnancy 24/7 Offspring Study (NCT07172880), developed to address this gap in knowledge. Methods: This study examines associations between device‐based maternal 24‐hour movement behavior (sedentary behavior, physical activity, and sleep) measured in each pregnancy trimester and analyzed via trajectories and as compositions with offspring obesity and CVD risk through 24 months of age. Maternal 24‐hour movement behavior data and birth outcomes were previously collected in the Pregnancy 24/7 Cohort Study (N=500, Iowa, Pennsylvania, and West Virginia). The Offspring study extends this cohort by enrolling up to 450 maternal‐offspring dyads and collecting new measures in the offspring, including body mass index z‐score from birth through 24 months obtained via medical record abstraction, anthropometry, indicators of CVD risk, and maternal questionnaires. The primary outcome is body mass index z‐score trajectory; secondary outcomes include adiposity, blood pressure, and brachial‐femoral pulse wave velocity. Conclusions: Findings from this study will advance understanding of how maternal 24‐hour activity associates with early‐life obesity and CVD risk, informing primordial prevention strategies during pregnancy.

Background/Objectives: Human breast milk (HM) is the gold-standard nutritional source for infants, delivering not only macro- and micronutrients but also bioactive components, including extracellular vesicles (EVs) enriched with microRNAs (miRNAs) that regulate immune, metabolic, and neurodevelopmental programming. Maternal lifestyle, including nutrition, is known to shape milk composition, yet it remains unknown whether maternal physical activity modulates the bioactive miRNA cargo of HM EVs. Methods: This pilot study examined associations between moderate-to-vigorous physical activity (MVPA; ≥3.0 metabolic equivalents) and prolonged sedentary behavior (SED60+; total sitting/lying minutes of bouts ≥60 min) with EV-enriched miRNA expression in HM collected in the early postnatal period (n = 11). Maternal activity was measured using a thigh-worn activPAL monitor across pregnancy trimesters and days 10–18 postnatal; HM was collected at day 18 postnatal. The EV-enriched fraction from skim milk was isolated and small RNA sequencing identified 691 unique miRNAs. Results: Principal component analysis showed that EV-enriched miRNA profiles were nominally most associated with prolonged sedentary behavior during the first two trimesters, though these associations did not survive correction for multiple testing. Differential expression analysis identified nine sedentary-associated miRNAs in trimester two, with smaller signals in trimesters one and three. Pathway enrichment revealed overrepresentation of genes involved in RNA regulation and post-transcriptional control, cell adhesion and cytoskeletal organization, and growth and nutrient signaling. Conclusions: Together, these findings suggest that maternal sedentary behavior during early and mid-pregnancy may be associated with candidate variation in HM EV-miRNA composition, offering a preliminary molecular link between prenatal behaviors and early-life programming that warrants replication in larger, independent cohorts.

Women who experienced gestational diabetes are at a high risk of developing cardiovascular disease later in life. This risk may be mediated, in part, by endothelial dysfunction after pregnancy. We demonstrate that endothelin-1 receptor type A antagonism with BQ-123 improves microvascular endothelial responses to local heating in otherwise healthy women with a history of gestational diabetes. These findings suggest that ET-1 contributes to microvascular endothelial dysfunction after gestational diabetes.

BACKGROUND: Accurate low-density lipoprotein cholesterol (LDL-C) assessment in young adulthood is critical for atherosclerotic cardiovascular disease (ASCVD) prevention, yet the optimal estimation equation remains uncertain. We compared the Friedewald, Martin-Hopkins, and Sampson equations for evaluating long-term ASCVD risks. METHODS: We included participants from 7 population-based cohorts within the International Childhood Cardiovascular Cohort Consortium who had LDL-C measurements in young adulthood (aged 20–39 years) and follow-up data for incident ASCVD. LDL-C levels were estimated using the Friedewald, Martin-Hopkins, and Sampson equations. For each pair of equations, participants were categorized into concordant (normal/normal, elevated/elevated) and discordant (normal/elevated, elevated/normal) groups based on LDL-C classifications (normal <130 mg/dL versus elevated ≥130 mg/dL). ASCVD events (myocardial infarction, stroke, transient ischemic attack, ischemic heart failure, angina, peripheral artery disease, carotid intervention, abdominal aortic aneurysm, coronary revascularization) were adjudicated from medical records. Associations between discordance and incident ASCVD were estimated using Fine-Gray regressions. RESULTS: Among 10 550 participants (56.8% females; mean baseline age [SD], 29.8 [4.3] years), 376 ASCVD events occurred over a mean follow-up of 22.7 years. Elevated LDL-C by all equations was associated with ASCVD events (subdistribution hazards ratio [95% CI]: Martin-Hopkins, 1.69 [1.35–2.12]; Sampson, 1.52 [1.22–1.90]; Friedewald, 1.47 [1.17–1.84]). Total discordance ranged from 2.3% to 2.9%. Compared with the concordant normal LDL-C group, normal LDL-C by Friedewald but elevated by Martin-Hopkins had higher ASCVD risks (3.32 [1.94–5.66]), with no excess risk in the reverse discordance (1.19 [0.47–3.05]). Normal Friedewald but elevated Sampson LDL-C had higher ASCVD risks (1.69 [0.93–3.05]); no participants had the reverse discordance. Normal Sampson LDL-C but elevated Martin-Hopkins LDL-C had higher ASCVD risks (3.94 [1.80–8.64]), whereas the reverse discordance showed no increased risk (0.86 [0.39–1.91]). CONCLUSIONS: The Martin-Hopkins equation provides more accurate LDL-C–based risk classification, identifying high-risk young adults missed by other equations and minimizing misclassification of those at normal risk.

Background: How prepregnancy body mass index (BMI) and pregnancy physical activity (PA) jointly shape postpartum cardiovascular risk remains unclear. This study evaluated whether joint trajectories of PA and sedentary behavior during pregnancy mediate the association between prepregnancy BMI and postpartum blood pressure (BP). Methods: Pregnancy 24/7 is a multisite observational cohort enrolling individuals <13 weeks' gestation, aged 18 to 45 years, without chronic hypertension, diabetes, sleep disorders, or severe mobility limitation (n=500). Participants with valid PA/sedentary behavior data for ≥1 trimester and a clinic BP reading 4 to 8 weeks postpartum were analyzed. Prepregnancy BMI was chart‐abstracted; PA/sedentary behavior were measured each trimester via the activPAL3 micro. Hypertensive postpartum BP was defined as systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg. Parallel‐process latent growth modeling and K‐means clustering identified PA trajectory groups; mediation analysis tested whether these groups explained the BMI‐BP association. Results: Among 388 participants (aged 30.9±4.5 years), 109 (28.4%) had hypertensive postpartum BP. Each 1‐unit increase in prepregnancy BMI was associated with 6.0% greater risk of hypertensive postpartum BP (risk ratio, 1.06 [95% CI, 1.04–1.09]), adjusting for demographic and pregnancy characteristics. Three trajectory groups emerged: active‐declining (n=142), active‐improving (n=103), and consistently sedentary (n=143). The active‐declining group had 37% lower risk than the consistently sedentary group, but this attenuated after BMI adjustment. Physical activity trajectories did not mediate the BMI‐BP relationship, which was largely explained by prepregnancy BMI alone. Conclusions: Prepregnancy BMI predicted hypertensive postpartum BP independent of activity patterns, underscoring the clinical value of prepregnancy weight optimization and vigilant postpartum monitoring for those entering pregnancy with elevated BMI. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04749849.

Was not provided for this article.

Background: Little is known about the negative impacts of the COVID‐19 pandemic on health behaviors among postpartum women. We aimed to assess self‐reported changes in physical activity, sitting time, and sleep among postpartum women early in the pandemic. Methods: We conducted an online survey of postpartum women in the United States ( n = 809) during May and June of 2020. Multiple logistic regression models were used to examine associations between socio‐demographic, medical, and COVID‐19‐related factors (e.g., COVID‐related worries and stressors) and self‐reported changes in health behaviors. Results: The prevalence of being less physically active, sitting for longer times, and sleeping less since the pandemic started were 57.4%, 64.9%, and 26.3%, respectively. Medicaid‐insured recipients reported more reduced physical activity and longer sitting time than privately insured women. Breastfeeding was associated with higher odds of being less physically active. Worse health status was strongly associated with adverse changes in the three behaviors (All P _trend < 0.05). A higher score on social connection with family members was associated with reduced physical activity and longer sitting time, while those with a higher social connection score with community/neighbors/friends were more physically active. COVID‐19‐related worries were associated with lower odds of being less physically active but greater likelihood of sitting longer and sleeping less. COVID‐19‐related stressors were associated with higher odds of sleeping less. Conclusions: Early in the COVID‐19 pandemic, adverse changes in health behaviors were prevalent among US postpartum women. Intervention programs optimizing multiple health behaviors among postpartum women and high‐risk groups are needed during pandemic situations.

Objectives: Hypertensive disorders of pregnancy (HDP) are primary antecedents of maternal cardiovascular morbidity during and after pregnancy. Despite evidence that 24-hour movement behaviours, including moderate-to-vigorous and light-intensity physical activity (MVPA, LPA), sedentary behaviour (SED) and sleep, relate to cardiovascular disease risk, associations with HDP are unknown. This study identified optimal 24-hour behavioural compositions across pregnancy associated with lower HDP risk. Methods: The Pregnancy 24/7 cohort study (N=500) quantified 24-hour movement behaviours in each trimester (10 ⁰ –12 ⁶ , 20 ⁰ –22 ⁶ and 32 ⁰ –34 ⁶ weeks gestation) and examined associations with HDP. Participants were enrolled between 2021–2024 from three US study sites. Movement behaviours were quantified from 7-day × 24-hour monitor wear using the activPAL3 micro (MVPA, LPA and SED) and Actiwatch Spectrum Plus (sleep). HDP (gestational hypertension and pre-eclampsia) was abstracted from medical records. Compositional binomial regression models predicted HDP risk based on isometric log-ratio transformation of 24-hour movement behaviours. Optimal overlapping behavioural compositions were identified by aggregating up to three repeated assessments of 24-hour data. Results: Among 470 participants with complete data, 86 (18.3%) developed HDP. The optimal overlapping daily composition (0–5th percentile) associated with the lowest HDP risk (7.2%) consisted of 5.9 (5.5–6.6) hours SED, 7.9 (6.4–8.9) hours LPA, 7 (2–22) minutes MVPA and 10.1 (8.5–11.3) hours sleep. Risk increased exponentially among participants with more than 10 hours/day of SED or less than 5 hours/day of LPA. Conclusion: SED and LPA were the strongest modifiable predictors of HDP, independent of trimester. These findings inform behavioural intervention targets to reduce the risk of HDP.

The purposes of this study were to determine whether adverse childhood family environment (ACFE) exposure is associated with altered hemodynamic responses to graded exercise in young adulthood, and whether this association was modified by sex and race in a large, population-based cohort. We hypothesized that ACFE exposure would be associated with an exaggerated exercise pressor response in young adulthood, independent of resting BP. We further hypothesized that the association between ACFE and the hemodynamic response to exercise would be stronger in females than males, and in Black versus White participants. Methods: Exercising blood pressure (BP) and heart rate (HR) responses were recorded during graded exercise testing and ACFE exposure was assessed among 3,417 young adults (mean age = 25 ± 4 y; 44% female; 46% Black). Linear mixed-effects models that included participant-specific random intercepts and random slopes were used to assess the relation between ACFE exposure and exercising systolic (SBP), diastolic, and mean BP, pulse pressure (PP), pulse pressure index (PPI), heart rate (HR), and rate pressure product (RPP). All models were adjusted for resting values of the hemodynamic outcome, as well as age, sex, race, study center, body mass index, current hypertension medication use, smoking status, and alcohol consumption. Results: Graded exercise hemodynamic responses were analyzed in 3,346-3,417 participants in the final models, providing 15,372-17,481 observations. Higher ACFE exposure was associated with lower SBP (β = -0.304 mmHg/ACFE, p = 0.033), HR (β = -0.485 bpm/ACFE, p-1 ·ACFE ^-1 , p=0.029), HR (β = 0.061 bpm·MET ^-1 ·ACFE ^-1 , p-1 ·ACFE ^-1 , p=0.025), and PP (β = 0.052 mmHg·MET ^-1 ·ACFE ^-1 , p=0.038) and PPI (β = 0.000232 units·MET ^-1 ·ACFE ^-1 , p=0.018). These findings were robust to additional adjustment for central adiposity, exercise capacity, and maximal heart rate and heart rate recovery. Conclusion: Our findings add nuanced evidence revealing that early adversity is associated with a demand-dependent shift in cardiovascular regulation, with attenuated responses at low demand, but more dramatic increases in pulsatile and myocardial load responses during progressive physiological stress.