Trajectories of Blood Pressure in Midlife Women: Does Menopause Matter?

Background: Whether changes in blood pressure (BP) over women's midlife are more driven by chronological aging or the menopause transition (MT) has been debated. We sought to determine whether women can be classified into distinct trajectory groups based on pattern and level of systolic (SBP), diastolic blood pressure, pulse pressure (PP), and mean arterial pressure (MAP) over the MT, and to assess whether menopause-related factors predict the group and/or level of BP measures. Methods: Participants were from the Study of Women's Health Across the Nation (SWAN). Group-based trajectory modeling was used to identify women who shared distinct BP trajectories over time relative to menopause onset and to assess associations of menopause-related factors with trajectory group and/or level of BP measures. An accelerated rise relative to menopause onset suggests a menopause contribution. Results: The study included 3,302 multi-racial/ethnic women with BP measures over 17 follow-up visits (baseline age[SD]: 46.3[2.7]). Women were classified into either low, medium, or high trajectory group in each BP measure. The low SBP, PP, and MAP trajectories (in 35%, 53%, and 28% of the cohort, respectively) were rising slowly before menopause but showed a significant accelerated rise 1 year after menopause, indicating a menopause contribution. The remaining BP trajectories were rising up until menopause and either continued with the same rise or declined after menopause. A younger menopause age predicted the low SBP, PP, and MAP trajectories. A greater follicle-stimulating hormone level predicted lower SBP and PP levels, while vasomotor symptoms occurrence predicted higher SBP, PP, and MAP levels over time. Estradiol did not predict trajectory or level of any BP measure. Conclusions: Distinct BP trajectories over the MT exist that revealed a group of women whose SBP, PP, and MAP trajectories are consistent with a menopause contribution. Our findings support frequent monitoring of BP during the MT.

Early Pregnancy Blood Pressure Patterns Identify Risk of Hypertensive Disorders of Pregnancy Among Racial and Ethnic Groups.

Background: Hypertensive disorders of pregnancy are a leading cause of severe maternal morbidity and mortality and 4-fold higher perinatal mortality in Black women. Early pregnancy blood pressure patterns may differentiate risk of hypertensive disorders of pregnancy. Methods: This study identified distinct blood pressure trajectories from 0 to 20 weeks’ gestation to evaluate subsequent pregnancy-related hypertension in a retrospective cohort of 174 925 women with no prior hypertension or history of preeclampsia, prenatal care entry ≤14 weeks, and a stillborn or live singleton birth delivered at Kaiser Permanente Northern California hospitals in 2009 to 2019. We used electronic health records to obtain clinical outcomes, covariables, and longitudinal outpatient blood pressure measurements ≤20 weeks’ gestation (mean 4.1 measurements). Latent class trajectory modeling identified 6 blood pressure groups: ultra-low-declining(referent), low-declining, moderate-fast-decline, low-increasing, moderate-stable, and elevated-stable. Multivariable logistic regression evaluated trajectory group-associations with odds of preeclampsia and gestational hypertension and effect modification by race-ethnicity and prepregnancy body size. Results: Compared with ultra-low-declining, adjusted odds ratios (95% CIs) for low-increasing, moderate-stable, and elevated-stable groups were 3.25 (2.7–3.9), 5.3 (4.5–6.3), and 9.2 (7.7–11.1) for preeclampsia, and 6.4 (4.9–8.3), 13.6 (10.5–17.7), and 30.2 (23.2–39.4) for gestational hypertension. Race/ethnicity, and prepregnancy obesity modified the trajectory-group associations with preeclampsia (interaction P <0.01), with highest risks for Black, then Hispanic and Asian women for all blood pressure trajectories, and with increasing obesity class. Conclusions: Early pregnancy blood pressure patterns revealed racial and ethnic differences in associations with preeclampsia risk within equivalent levels and patterns. These blood pressure patterns may improve individual risk stratification permitting targeted surveillance and early mitigation strategies.

Failure to Launch: Predictors of Unfavourable Physical Activity and Sedentary Behaviour Trajectories from Childhood to Adolescence: The Gateshead Millennium Study

In a previous study based on this cohort, only 15% of the participants belonged to a favourable physical activity/sedentary behaviour trajectory group (characterised by relatively high moderate–vigorous intensity physical activity and relatively low sedentary behaviour across childhood and adolescence). Since this favourable trajectory is protective against obesity, we aimed to identify factors associated with membership of this group. In this longitudinal study, 671 participants were assessed at ages 7, 9, 12 and 15 years. Participants’ demographics, socio-economic status (SES) and physical activity environment such as, sports club participation and commuting school were assessed at ages 7, 9 and 12 and analysed with favourable trajectory membership as an outcome using multinomial logistic regression. Sex (male) and SES (higher) were the non-modifiable factors associated with favourable trajectory group. Of the modifiable factors, commuting to school at age 7, a safe environment to play at age 7 and sports club participation at age 12 were all associated with more than 2.0 times increased probability of being in the most favourable trajectory. Future interventions to promote a favourable trajectory could focus on girls and participants with low SES. Promoting active commuting, safe local spaces to play and sports participation should also help lead to a favourable trajectory for physical activity and sedentary behaviour across childhood and adolescence.

Iron homeostasis pathway DNA methylation trajectories reveal a role for STEAP3 metalloreductase in patient outcomes after aneurysmal subarachnoid hemorrhage

Background Following aneurysmal subarachnoid hemorrhage (aSAH), the brain is susceptible to ferroptosis, a type of iron-dependent cell death. Therapeutic intervention targeting the iron homeostasis pathway shows promise for mitigating ferroptosis and improving recovery in animal models, but little work has been conducted in humans. DNA methylation (DNAm) plays a key role in gene expression and brain function, plasticity, and injury recovery, making it a potentially useful biomarker of outcomes or therapeutic target for intervention. Therefore, in this longitudinal, observational study, we examined the relationships between trajectories of DNAm in candidate genes related to iron homeostasis and acute (cerebral vasospasm and delayed cerebral ischemia) and long-term (Glasgow Outcome Scale [GOS, unfavorable = 1–3] and death) patient outcomes after aSAH. Results Longitudinal, genome-wide DNAm data were generated from DNA extracted from post-aSAH cerebrospinal fluid (n = 260 participants). DNAm trajectories of 637 CpG sites in 36 candidate genes related to iron homeostasis were characterized over 13 days post-aSAH using group-based trajectory analysis, an unsupervised clustering method. Significant associations were identified between inferred DNAm trajectory groups at several CpG sites and acute and long-term outcomes. Among our results, cg25713625 in the STEAP3 metalloreductase gene (STEAP3) stood out. Specifically, in comparing the highest cg25713625 DNAm trajectory group with the lowest, we observed significant associations (i.e., based on p-values less than an empirical significance threshold) with unfavorable GOS at 3 and 12 months (OR = 11.7, p = 0.0006 and OR = 15.6, p = 0.0018, respectively) and death at 3 and 12 months (OR = 19.1, p = 0.0093 and OR = 12.8, p = 0.0041, respectively). These results were replicated in an independent sample (n = 100 participants) observing significant associations with GOS at 3 and 12 months (OR = 8.2, p = 0.001 and OR = 6.3, p = 0.0.0047, respectively) and death at 3 months (OR = 2.3, p = 0.008) and a suggestive association (i.e., p-value < 0.05 not meeting an empirical significance threshold) with death at 12 months (OR = 2.0, p = 0.0272). In both samples, an additive effect of the DNAm trajectory group was observed as the percentage of participants with unfavorable long-term outcomes increased substantially with higher DNAm trajectory groups. Conclusion Our results support a role for DNAm of cg25713625/STEAP3 in recovery following aSAH. Additional research is needed to further explore the role of DNAm of cg25713625/STEAP3 as a biomarker of unfavorable outcomes, or therapeutic target to improve outcomes, to translate these findings clinically.

Trajectories of Emergency Department Use After Incident Functional Disability

Emergency department (ED) visits for older adults with functional disability may represent unmet needs and are often burdensome to patients and families. While it is known that older adults with functional disability use the ED at high rates, this does not capture the heterogeneity of experience after the onset of disability. Using NHATS, we identified a cohort of older adults with incident disability, or who reported they began to receive help with self-care and/or mobility in the prior year. Using the month that they report first receiving help, we linked to Medicare data to assess quarterly patterns of ED use. We used Group Based Trajectory Modeling to assess the trajectories of ED use after disability. We identified three distinct trajectories of ED use: persistently high, declining, and persistently low. We describe the clinical, household, and sociodemographic characteristics associated with likely membership in each trajectory group.

Blood Pressure Trajectory Groups and Outcome After Endovascular Thrombectomy: A Multicenter Study

Background and Purpose: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. Methods: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. Results: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days ( P <0.0001) after adjusting for potential confounders. Patients with high and high-to-moderate SBP trajectories had significantly greater odds of an unfavorable outcome (adjusted odds ratio, 3.5 [95% CI, 1.8–6.7], P =0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5–3.2], P <0.0001, respectively). Subjects in the high-to-moderate group had an increased risk of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.82 [95% CI, 1–3.2]; P =0.04). No significant association was found between trajectory group and hemorrhagic transformation. Conclusions: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

Trajectories of Depressive Symptoms and Incident Diabetes: A Prospective Study

Background Elevated depressive symptoms are associated with an increased risk for diabetes. Depression is a heterogeneous and chronic condition in which symptoms may remit, emerge, lessen, or intensify over time. Purpose The purpose of this study was to determine if trajectories of depressive symptoms measured at five time points over 8 years predicted incident diabetes over an 8-year follow-up in middle-aged and older adults. A secondary aim was to determine if trajectories of depressive symptoms predict incident diabetes, above and beyond depressive symptoms measured at a single time point. Methods Data came from the Health and Retirement Study (n = 9,233). Depressive symptoms were measured biennially from 1998 to 2006. Self-reported incident diabetes was measured during an 8-year follow-up. Results Five trajectories of depressive symptoms were identified (no depressive symptoms, low depressive symptoms, low-moderate depressive symptoms, moderate depressive symptoms, elevated and increasing depressive symptoms). Compared to the no depressive symptoms trajectory group (referent), all other trajectory groups were at higher risk of developing diabetes after adjusting for covariates. In most cases, trajectory group membership was associated with incident diabetes after controlling for depressive symptoms at a single time point. Conclusions Patterns of depressive symptoms over time were associated with incident diabetes. Patterns of depressive symptoms may be more predictive of diabetes incidence than depressive symptoms measured at a single time point.

Is Amyloid Burden Measured by 18F-Flutemetamol PET Associated with Progression in Clinical Alzheimer’s Disease?

Background: Patients with Alzheimer’s disease (AD) show heterogeneity in clinical progression rate, and we have limited tools to predict prognosis. Amyloid burden from 18F-Flutemetamol positron emission tomography (PET), as measured by standardized uptake value ratios (SUVR), might provide prognostic information. Objective: We investigate whether 18F-Flutemetamol PET composite or regional SUVRs are associated with trajectories of clinical progression. Methods: This observational longitudinal study included 94 patients with clinical AD. PET images were semi-quantified with normalization to pons. Group-based trajectory modeling was applied to identify trajectory groups according to change in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) over time. Multinomial logistic regression models assessed the association of SUVRs with trajectory group membership. Results: Three trajectory groups were identified. In the regression models, neither composite nor regional SUVRs were associated with trajectory group membership. Conclusion: There were no associations between CDR progression and 18F-Flutemetamol PET-derived composite SUVRs or regional SUVRs in clinical AD.

Developmental Trajectories of Justice System-Involved Friendship Proportion: Relevance for Predicting Continued Offending Risk in Emerging Adulthood

There is limited research which has examined the developmental nature of friendships and their relevance for offending. This study examined heterogeneity in the development of justice system-involved friendship proportionality and its relevance for predicting offending continuity in emerging adulthood. Having a greater proportion of such peers within a friendship collective as individuals exit adolescence may lead to continued risk of offending in adulthood. The Pathways to Desistance data were used in analyses. Group-based trajectory modeling was used to identify developmental patterns of justice system-involved friendship proportionality during adolescence and emerging adulthood. Logistic regression was used to assess the relevance of trajectory group assignment for predicting offending risk in emerging adulthood. Findings indicated that a six-group trajectory model best fit the data. All other trajectory groups in the model indicated a lower risk of offending in emerging adulthood than the High Chronic justice system-involved friendship proportionality group. Sensitivity analyses indicated that separation from criminal peers following adolescence may be a more conservative predictor of offending risk in emerging adulthood.

Association Between Longitudinal Blood Pressure Trajectory and the Progression of Chronic Kidney Disease: Results From the KNOW-CKD

Studies on the longitudinal temporal trend of blood pressure (BP) and its impact on kidney function are scarce. Here, we evaluated the association of dynamic changes in systolic blood pressure (SBP) over time with adverse kidney outcomes. We analyzed 1837 participants from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease). The main exposure was 3 distinct SBP trajectories determined by the latent class mixed model (decreasing, stable, and increasing) using 3 SBP measurements at 0, 6, and 12 months. The primary outcome was CKD progression, defined as a composite of halving estimated glomerular filtration rate from baseline value or onset of end-stage kidney disease. SBP declined from 144 to 120 mm Hg in the decreasing SBP trajectory group and rose from 114 to 136 mm Hg in the increasing trajectory group within 1 year. During 6576 person-years of follow-up (median, 3.7 years), the composite outcome occurred in 521 (28.4%) participants. There were fewer primary outcome events in the decreasing (30.6%) and stable (26.5%) SBP trajectory groups than in the increasing trajectory group (33.0%). In the multivariable-adjusted cause-specific hazards model, increasing SBP trajectory was associated with a 1.28-fold higher risk for adverse kidney outcome compared with stable SBP trajectory. However, the risk for the primary outcome did not differ between the decreasing and stable SBP trajectory groups. In this longitudinal CKD cohort study, compared with stable SBP trajectory, increasing SBP trajectory was associated with higher risk for adverse kidney outcome, whereas decreasing SBP trajectory showed similar risk.