Hypertension

BackgroundHypertensive disorders of pregnancy (HDP) are associated with future cardiovascular disease, predominantly through development of chronic hypertension, however the patterns of blood pressure recovery following a HDP are understudied. We sought to characterize the subtypes of hypertension (isolated systolic, isolated diastolic, systolic diastolic) and compare pregnancy and postpartum blood pressure trajectories among individuals with hypertensive disorders of pregnancy (HDP) who developed persistent hypertension at one year postpartum compared to individuals with normalization of blood pressure (BP). MethodsWe used data from a randomized controlled clinical trial of overweight and obese individuals with a physician adjudicated HDP conducted in the first year after delivery. Individuals with pre-pregnancy hypertension were excluded. Pregnancy BPs were obtained during prenatal visits, postpartum BPs were prospectively obtained through home BP monitoring, one week per month during the first year postpartum. Demographic characteristics and trajectories were compared based on whether or not individuals developed persistent hypertension (stage 1 or greater; systolic BP [&ge;]130, diastolic BP [&ge;]80 mmHg or use of anti-hypertensive medications) at one year. We further classified individuals with persistent hypertension as having isolated diastolic, isolated systolic and systolic diastolic hypertension. We used repeated BP measures to fit separate mixed-effects linear regression models for pregnancy and postpartum with participant identifier as random intercepts and weeks of pregnancy or months postpartum as a fixed effect expressed using restricted cubic splines. Models were compared using likelihood ratio test. ResultsWe included 129 individuals who contributed a mean of 95.4 (95%CI 76.7-115.1) BP readings during and following pregnancy. In total, 75 individuals (58%) progressed to stage 1 or stage 2 hypertension by 1 year postpartum. At one-year postpartum, among those with persistent hypertension, 43 (69%) had isolated diastolic hypertension, 2 (3%) had isolated systolic hypertension and 17 (27%) had systolic-diastolic hypertension. Individuals with persistent hypertension were about 2 years older, delivered at earlier gestational ages and tended to have a higher BMI at one year postpartum compared to those with BP normalization. There were no differences in BP at first prenatal visit or BP trajectories during pregnancy. Individuals with persistent hypertension had a more adverse BP trajectory (p<0.01 for systolic and diastolic BP) in the first year postpartum. These differences persisted in multivariable models after adjustment for pre-pregnancy BMI and type of HDP (p<0.01 for systolic and diastolic BP). ConclusionsBlood pressure trajectories in the first year postpartum, but not during pregnancy, may provide critical information for risk stratification after a HDP. In our study, a high proportion of individuals had ongoing hypertension, predominantly isolated diastolic hypertension. If confirmed in a larger cohort, this may provide insight into intervention development following a HDP. CLINICAL TRIALS REGISTRATION URL: https://clinicaltrials.gov/ct2/show/NCT03749746

BackgroundMaternal blood pressure (BP) varies greatly during pregnancy in response to hemodynamic changes, which has led to debate surrounding the use of a single diagnostic threshold. Previous studies have generated "reference ranges" of BP in pregnancy, yet they lack implementation and translation to clinical practice. This study aimed to generate gestational age-specific references and analyze BP Z-scores to further explore cardiovascular dynamics in pregnancy and their potential clinical implications. MethodsRepeated measurements of BP from 2 to 44 gestational weeks were extracted from the obstetric files of 1,875 mothers from the French EDEN cohort. Percentiles of systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP) were modeled using Generalized Additive Models for Location, Scale, and Shape (GAMLSS) as a function of gestational age. They were generated from a "low-risk" reference population defined by reduced cardiovascular risk factors and no hypertensive disorders. For each woman in the overall sample, Z-scores of BP were calculated relative to the "low-risk" percentiles, to assess how BP deviated from the expected trajectory across gestation. BP Z-score trajectories according to hypertensive disorders of pregnancy categories (chronic hypertension, gestational hypertension, and preeclampsia) were then plotted and compared. ResultsA U-shaped trend was observed in overall and "low-risk" percentiles of SBP and MAP, with a nadir around 25 weeks and an increase in the last trimester. In the overall sample, SBPs 95th percentile curve remained below the 140mmHg diagnostic threshold between 15 and 35 weeks of gestation. The Z-score trajectories of women presenting with hypertensive disorders start to diverge as early as the first 5 gestational weeks, well-before their diagnoses (median age: 35-36 weeks). BP evolution differed according to type of hypertensive disorder, for example, a steep increase (>1 standard deviation) from early in pregnancy among preeclamptic women. ConclusionThis percentiles-to-Z-score approach can position individual risk of mothers while considering the natural variation of blood pressure across pregnancy. Our results question the applicability of a non-time-specific threshold to these dynamics. Beyond their potential clinical applications, these references can be used in further research to examine "abnormal" cardiovascular trajectories and their consequences for future maternal and offspring health.

BackgroundThe digital transformation of medical data enables health systems to leverage real-world data (RWD) from electronic health records (EHR) to gain actionable insights for improving hypertension care. MethodsWe performed a serial cross-sectional analysis of outpatients of a large regional health system from 2010 to 2021. Hypertension was defined by systolic blood pressure (SBP) [&ge;] 140 mmHg or diastolic blood pressure (DBP) [&ge;] 90 mmHg) or recorded treatment with anti-hypertension medications. We evaluated four methods of using blood pressure measurements in the EHR to define hypertension. The primary outcomes were age-adjusted prevalence rates and age-adjusted control rates. Secondary outcomes were age-adjusted mean SBP and DBP and age-adjusted proportion of patients with a searchable diagnosis code of hypertension in the EHR. ResultsHypertension prevalence varied depending on the definition used, ranging from 36.5% to 50.9% initially and increasing over time by approximately 5%, regardless of the definition used. Control rates ranged from 61.2% to 71.3% initially, rose during 2018-2019 and fell during 2020-2021. The proportion of patients with a hypertension diagnosis ranged from 45.5% to 60.2% initially and improved during the study period. Non-Hispanic Black patients represented 25% of our regional population and consistently had higher prevalence rates, higher mean SBP and DBP and lower control rates compared with other racial and ethnic groups. ConclusionIn a large regional health system, we leveraged the EHR to provide real-world insights. The findings largely reflected national trends but showed distinctive regional demographics and findings. The findings have provided opportunities for improvement, with prevalence increasing, a quarter of the patients not controlled, and marked disparities. This approach could be emulated by regional health systems seeking to improve hypertension care. Key PointsQuestion: Can a large regional health system leverage the electronic health record to analyze hypertension trends and disparities to drive improvement? Findings: We analyzed 1,376,325 patients over 12 years and found that age-adjusted hypertension prevalence increased by approximately 5%. Age-adjusted hypertension control rates were in the 70% range and remained stable. Non-Hispanic Black patients represented 25% of our specific regional population and had 12-14% higher hypertension prevalence rates, higher mean age-adjusted systolic and diastolic blood pressure, and lower hypertension control rates compared with other racial groups. Meaning: Real world data can provide actionable insights about hypertension and disparities in a specific region that could inform regional system strategies and initiatives for improvement.

BackgroundThere are no recent estimates for hypertension-associated medical expenditures. This study aims to estimate hypertension-associated incremental medical expenditures among privately insured US adults. MethodsWe conducted a retrospective cohort study using IQVIAs Ambulatory Electronic Medical Records-US dataset linked with PharMetrics Plus claims data. Privately insured adults aged 18-64 years with [&ge;]1 blood pressure measurement in 2020-2021 were included. Hypertension was identified as having [&ge;]1 diagnosis code or [&ge;] 2 blood pressure measurements of [&ge;]140/90 mmHg, or [&ge;]1 antihypertensive medication in 2021. Annual total expenditures were estimated using a generalized linear model (GLM) with gamma distribution and log-link function. Out-of-pocket (OOP) expenditures were estimated using a two-part model that included logistic and GLM regression. Overlap propensity-score weights from logistic regression were used to obtain a balanced sample on hypertension status. ResultsAmong the 393,018 adults, 156556 (40%) were identified with hypertension. Compared to individuals without hypertension, those with hypertension had $2,926 (95% CI, $2,681-$3,170) higher total expenditures, and $328 (95% CI, $300-$355) higher OOP expenditures. Adults with hypertension had higher total inpatient ($3,272; 95% CI, $1,458-$5,086) and outpatient ($2,189; 95% CI, $2,009-$2,369) expenditures, when compared with those without hypertension. Hypertension-associated incremental total expenditures were higher for women ($3,242; 95% CI, $2,915-$3,569) than for men ($2,521; 95% CI, $2,139-$2,904). ConclusionsAmong privately insured US adults, hypertension was associated with higher medical expenditures, including higher inpatient and OOP expenditures. These findings may help assess the economic value of interventions effective in preventing hypertension.

IntroductionCardiovascular disease (CVD) is the leading cause of mortality for women. Timely diagnosis of hypertension after a hypertensive disorder of pregnancy (HDP) provides an opportunity for CVD prevention. We assessed the association between blood pressure (BP) 15-90 days postpartum and incident hypertension after an HDP. MethodsThis was a retrospective cohort study of women with an HDP between January 2014 and December 2017 at two health systems in the southeastern U.S. Cox proportional hazards models assessed the association of postpartum BP and incident hypertension 12 months postpartum. Covariates included type of HDP, gestational age at diagnosis, timing of measurement, comorbidities, and structural determinants of health. We excluded people with preexisting hypertension and without a BP measurement 15-90 days postpartum. ResultsOut of 5657 women, only 2514 (44%) met the inclusion criteria as almost 40% (2125) did not have a BP check at 15-90 days postpartum. The hazards of incident hypertension were significantly higher for those with elevated systolic postpartum BP (1.70, 95% CI: 1.37 - 2.12) and more severe HDPs. The estimated cumulative incidence of hypertension among participants with postpartum BP of 110/65 mmHg was 4.7% (CI, 2.0% - 7.4%) and for those with BP 140/90, it was 13.0% (CI 5.6% - 19.8%). ConclusionsThe risk of incident hypertension after an HDP is high in the first year postpartum. Despite this, for many participants, BP was not even measured within 15-90 days postpartum despite. Opportunities exist to improve care for individuals with HDPs.

BACKGROUNDSystemic arterial hypertension is a public health concern, and timely diagnosis and management are critical to mitigate long-term effects. Here, we evaluated prevalence trends and determinants of hypertension and its phenotypes in Mexican population over the last two decades. METHODSWe analyzed cross-sectional Mexican Health and Nutrition Surveys (2000-2023), including 141,668 adults aged [&ge;]20 years. Hypertension was defined as self-reported diagnosis or blood pressure (BP) [&ge;]140/90 mmHg; undiagnosed hypertension (UDH) as BP [&ge;]140/90 mmHg without prior diagnosis; and untreated hypertension (UTH) as prior diagnosis without treatment. UDH was classified as isolated systolic (ISH), isolated diastolic (IDH), or systolic-diastolic hypertension (SDH). We assessed prevalence trends with Poisson models, and determinants of UDH and UTH with logistic models. RESULTSWe observed an overall decrease in hypertension prevalence from 2000 to 2023, driven by increases in diagnosed (12.3% to 19.3%) and decreases in undiagnosed (20.7% to 11%) hypertension. IDH and SDH declined over time, while ISH increased, particularly among older adults. Among diagnosed cases, UTH decreased (31% to 19.5%) and BP control improved (40.5% to 69.5%). Despite these trends, by 2023 approximately 8.2 million Mexican adults still had UDH (36.3% of all hypertension cases), 2.8 million remained untreated, and 4.4 million uncontrolled. Lack of diagnosis and treatment were more likely among men, individuals with unhealthy lifestyles, and social disadvantage. CONCLUSIONSResults highlight evolving trends in hypertension diagnosis, treatment, and control in Mexico, with persistent challenges in UDH and UTH. Strengthening screening, treatment access, and equity is crucial to reduce hypertension-related cardiovascular risk.

ImportanceClinicians use blood pressure (BP) readings obtained during clinical encounters to detect hypertension and determine the adequacy of treatment. Variations in office-based BP measurements may obscure a hypertension diagnosis or overwhelm a signal of treatment response. ObjectivesTo quantify visit-to-visit variability (VVV) in BP values and its association with patient factors in real-world practice. Design, Setting and, ParticipantsRetrospective cohort analysis of adult patients (age [&ge;]18 years) with at least two outpatient visits in the Yale-New Haven Health System between January 1, 2014 to October 31, 2018. Main Outcome and MeasuresPatient-level measures of VVV included standard deviation (SD) and coefficient of variation (CV) of a given patients BP across visits. We introduced a metric to determine the VVV between any two visits (dyad) to characterize the BP information that clinicians have as they formulate their recommendations. Dyad-level measures of VVV included difference, absolute difference, standardized difference, and absolute standardized difference between the two visits of a dyad. ResultsThe study population included 537,245 adults, with a total of 7,721,864 BP measurements. The mean age was 53.4 years (SD of 19.0), 60.4% were women, 69.4% were non-Hispanic White, and 18.1% with hypertension treatment. At the patient level, the mean intra-individual SD and CV were 10.6 mmHg and 0.08 mmHg. At the dyad level, the mean difference, absolute difference, standardized difference, and absolute standardized difference were -0.7 mmHg, 11.6 mmHg, 0 mmHg, and 0.09 mmHg, respectively. Given the observed VVV, if an antihypertensive medication truly reduced a patients SBP by 10 mmHg (the average BP-lowering effect reported in previous review), clinicians would expect to observe a reduction of SBP < 5mm Hg at the next visit 36.9% of the time. In the multivariable linear regression model, only 2% of the variance in absolute standardized difference was attributable to patient characteristics. Conclusions and RelevanceThe large VVV poses challenges for diagnosis, treatment, and monitoring of patients with hypertension based on BP readings in outpatient settings, supporting recent guidelines recommending home BP monitoring and ambulatory BP monitoring as out-of-office alternatives to establish diagnosis of hypertension and BP control. KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat is the visit-to-visit variability (VVV) in blood pressure (BP) values and its association with patient factors in real-world practice? FindingsIn this retrospective cohort analysis that included 537,245 adults and 7,721,864 office-based BP measurements from a large health system, marked VVV was observed in BP values and the median absolute change between two consecutive visits was about 12 mmHg. The VVV was not significantly associated with patient demographic and clinical characteristics. MeaningThe large VVV poses challenges for diagnosis, treatment, and monitoring of patients with hypertension based on BP readings in outpatient settings, supporting recent guidelines recommending home BP monitoring and ambulatory BP monitoring as out-of-office alternatives to establish a new diagnosis of hypertension and BP control.

Dietary fibre fermentation produces short-chain fatty acids (SCFAs) that lower colonic luminal pH, influencing host responses that contribute to blood pressure (BP) regulation. Fibre intake also alters gastrointestinal transit time, which has been linked to hypertension prevalence. Here, we aimed to determine the gastrointestinal pH and transit time in patients with hypertension. Using the SmartPill Motility Testing System, we assessed gastrointestinal pH and transit time in 55 participants with normal and elevated BP measured by ambulatory BP monitoring. Participants with hypertension exhibited a higher colonic minimum pH than those with normal BP. This difference was not explained by antihypertensive medication use or BP control, gastrointestinal transit time, nutrient intake or circulating SCFA levels. These findings suggest a potential relationship between colonic pH profiles and BP regulation, underscoring the need for future research into gut pH dynamics as emerging contributors to cardiovascular disease risk and progression.

Background: Primary aldosteronism (PA) testing is recommended for patients with resistant hypertension but remains underused, and evidence linking aldosterone-targeted therapy to improved cardiovascular and renal outcomes is limited. Methods: In a nationwide cohort of patients with resistant hypertension between 2001 and 2022, we assessed PA testing and subsequent mineralocorticoid receptor antagonist (MRA) use and adrenalectomy. Among tested patients, time-dependent Cox models were used to assess associations between treatment exposure and mortality, major adverse cardiovascular events (MACE) and renal outcomes. Results: Among 254,338 patients, only 2.0% were tested for PA. Tested patients had a higher prevalence of hypokalemia and cardiometabolic comorbidities. In the overall tested population, MRA use was not associated with lower risks of cardiovascular or renal outcomes. However, when testing resulted in an established PA diagnosis, the use of both MRA (hazard ratio [HR] 0.60, 95% CI 0.42-0.86) and adrenalectomy (HR 0.33, 95% CI 0.20-0.54) were associated with a reduced risk of MACE compared with no aldosterone-targeted therapy. Similar results were observed regarding mortality. Adrenalectomy was associated with lower risk of MACE (HR 0.55, 95% CI 0.30-0.99), all-cause mortality (HR 0.52, 95% CI 0.29-0.93) and renal outcomes (HR 0.37, 95% CI 0.17-0.80) compared with MRA in patients with a diagnosis of PA. Conclusions: PA remains markedly underrecognized in resistant hypertension. Among patients with resistant hypertension who did undergo PA testing with establishment of a PA diagnosis, aldosterone-targeted therapy resulted in lower risk of adverse cardiorenal outcomes and death when compared to conventional antihypertensive therapy.

BackgroundAs the leading modifiable risk factor for death in the United States, hypertension requires timely and locally detailed surveillance. Current estimates of the high blood pressure (BP) care continuum are lagged national averages from sample surveys with low participation and unknown subnational variation. This study explores the use of self-service health kiosks in retail stores as an alternative source for subnational estimates of prevalence, awareness, and control. MethodsWe analyzed data from adult kiosk users (n = 1,270,485) across 1,892 counties in 49 States (except Massachusetts) and District of Columbia in a serial cross-sectional analysis from November 2017 to September 2024. High BP was defined as self-reported diagnosed or elevated BP (systolic [&ge;]140 mmHg or diastolic [&ge;]90 mmHg). Among those diagnosed, control was defined as BP <140/90 mmHg. Small area estimates for counties were calculated using multilevel regression and poststratification based on individual and areal socio-demographic covariates. We compared the prevalence of diagnosed hypertension with the Behavioral Risk Factor Surveillance System 2021. ResultsThe analytic sample had a mean age of 42.0 years (SD=15.6). Prevalence of high BP was 51.9% in 2017-2018 and 50.4% in 2023-2024. In 2023-2024, awareness and control were 73.7% and 61.8% and county-level prevalence ranged from 39.5% to 63.1%. Similar hotspots in the Southeast were identified in both kiosk and BRFSS (Spearmans {rho} = 0.52). ConclusionsHealth kiosk data reveal substantial spatial and socio-demographic variation in high BP. Near real-time sub-national surveillance of health kiosk users can provide insights to guide interventions and track progress. NOVELTY AND RELEVANCEO_ST_ABSWhat is New?C_ST_ABS- Self-service health kiosk data complement national surveys by offering direct BP measurements with wider geographic coverage and higher representation of vulnerable populations. - This study provides recent state- and county- level estimates of prevalence, awareness, and control of high BP for 1.3 million kiosk users. What is Relevant?- In 2023-2024, prevalence of high BP among kiosk users exceeded 50.0% with county- level variation ranging from 39.5% in the Mountain West to 63.1% in the Southeast. - National awareness and control were suboptimal at 73.7% and 61.8%. - These results highlight persistent gaps in high BP detection and management. Clinical/Pathophysiological Implications?- Near real-time kiosk-based BP surveillance can help identify high-risk populations and administer timely interventions to reduce cardiovascular risk.

BackgroundPrimary aldosteronism (PA) is a common, treatable cause of hypertension for which screening is widely recommended but rarely performed in clinical practice. However, real-world screening and diagnosis patterns across the entire hypertensive population remain unknown. This study aimed to delineate the 22-year state of nationwide PA screening and diagnosis rates among all hypertensive population in Taiwan MethodsIn this nationwide retrospective cohort study from 2001 to 2022, we identified all patients with hypertension using a national health insurance database. We calculated annual PA screening and diagnosis rates, with particular focus on high-risk subgroups, including patients with resistant hypertension, early-onset hypertension, hypokalemia, and other comorbidities warranting screening. ResultsAmong 7.8 million patients with hypertension, a total of 4.4% received PA screening during the study period. The annual PA screening rate increased from 0.26% in 2001 to 0.75% in 2022 (p < 0.001) yet remained markedly low. In 2022, only 1.0% of patients with resistant hypertension, 3.0% with early-onset hypertension, and 3.6% with hypokalemia underwent screening. The diagnostic yield of PA showed a slight decrease over time, fluctuating between 8.0% and 6.7% (p = 0.006). ConclusionsDespite an increase in PA screening over the past two decades, absolute rates remain critically low, falling far short of guideline recommendations, especially in high-risk groups. Our findings quantify a major implementation gap between evidence and clinical practice. As international guidelines are shifting towards broader and simpler screening protocols, there is an urgent need to improve the detection of this common and actionable condition. PerspectiveO_ST_ABSWhat is known?C_ST_ABSO_LIPrimary aldosteronism (PA) is a common, clinically important, and treatable cause of hypertension. Its adverse cardiovascular effects arise from renin independent aldosterone excess and chronic mineralocorticoid receptor overactivation. C_LIO_LICurrent guidelines historically recommended screening only in high-risk groups, but recent expert consensus and international guidelines increasingly support broader and even universal screening among all hypertensive patients. C_LIO_LIPrior epidemiologic studies have examined PA screening almost exclusively within selected high-risk subgroups. No study has comprehensively evaluated real-world screening patterns across an entire hypertensive population. C_LI What is new?O_LIUsing a 22-year nationwide cohort of nearly 8 million hypertensive patients, this is the first study to comprehensively quantify real-world trends in PA screening and diagnosis in Taiwan. C_LIO_LIAnnual screening rates nearly tripled but remained profoundly low (<4%), even in guideline-recommended high-risk groups such as resistant hypertension, early-onset hypertension, and hypokalemia. C_LIO_LIHypertensive patients receiving care at tertiary medical centers or in highly urbanized areas were more likely to undergo screening. C_LI What is next?O_LIThe persistent under-screening of PA represents a major implementation gap, resulting in missed opportunities for targeted treatment and long-term cardiovascular risk reduction. C_LIO_LIClosing this gap will require a paradigm shift that includes broader screening strategies, decentralizing testing to primary care, and adopting simplified diagnostic pathways aligned with contemporary guidelines. C_LIO_LIFuture efforts should evaluate the impact of these simplified approaches on diagnosis rates, treatment implementation, and cardiovascular outcomes, particularly as global practice moves toward earlier and more inclusive detection of renin-independent aldosteronism. C_LI

BackgroundHypertension is a major risk factor for cardiovascular and renal diseases, significantly contributing to morbidity and mortality. The COVID-19 pandemic has heightened concerns about the impact of hypertension on severe COVID-19 outcomes. MethodsWe conducted a cross-sectional analysis using the 2021 MarketScan Commercial and Health and Productivity Management databases. The study included adults aged 18-64 with continuous employer-sponsored private insurance, excluding those with pregnancy or capitated plans. We compared excess total medical costs, healthcare utilization (including the number of emergency department visits, inpatient admissions, outpatient visits, and outpatient prescription drugs), and productivity losses and related costs due to sick absences, short-term disability (STD), and long-term disability (LTD) between individuals with and without hypertension, further stratified by COVID-19 diagnosis. Multivariate regression models adjusted for demographics and comorbidities were used to estimate the differences in outcomes. ResultsAmong 1,612,398 adults aged 18-64 years, 13% had hypertension in 2021. Those with hypertension were older, were less likely to be female or live in urban areas, and exhibited a higher prevalence of comorbidities. The total excess medical costs associated with hypertension were $8723 per patient (95% CI, $8352-$9093), which was significantly higher by $6117 (95% CI, $4780-$7453) among individuals diagnosed with COVID-19. Persons with hypertension had higher health care utilization, including a higher number of ED visits (0.21 per patient; 95% CI, 0.21-0.22), inpatient admissions (0.11; 95% CI, 0.10-0.12), outpatient visits (5.42; 95% CI, 5.36-5.49), and outpatient prescription drugs (10.85; 95% CI, 10.75-10.94). Moreover, they experienced a greater number of sick absences (1.22 days; 95% CI, 1.07-1.36) and STD occurrences (3.68 days; 95% CI, 3.38-3.98) per patient compared to those without hypertension. These trends were further exacerbated among individuals diagnosed with COVID-19. ConclusionsHypertension markedly increases medical costs, healthcare utilization, and productivity losses, which are further exacerbated by COVID-19. These findings highlight the substantial economic burden of managing hypertension in the context of the COVID-19 pandemic and underscore the importance of targeted interventions.

BackgroundThe prognostic utility of NT-proBNP in the setting of hypertension has not been well-characterized in the general US adult population. MethodsWe measured NT-proBNP among adults aged 20 years who participated in the 1999-2004 National Health and Nutrition Examination Survey. In adults without a history of cardiovascular disease, we assessed the prevalence of elevated NT-pro-BNP by blood pressure (BP) treatment and control categories. We examined the extent to which NT-proBNP identifies participants at higher risk for mortality across BP treatment and control categories. ResultsThe number of US adults without CVD with elevated NT-proBNP ([&ge;]125 pg/ml) was 6.2 million among those with untreated hypertension, 4.6 million among those with treated controlled hypertension, and 5.4 million among those with treated uncontrolled hypertension. After adjusting for age, sex, body mass index, and race/ethnicity, participants with treated controlled hypertension and elevated NT-proBNP had increased risk of all-cause mortality (HR 2.29, 95% CI 1.79, 2.95) and increased risk of cardiovascular mortality (HR 3.83, 95% CI: 2.34, 6.29), compared to those without hypertension and with low levels of NT-proBNP (<125 pg/ml). Among those on antihypertensive medication, those with SBP 130-139 mm Hg and elevated NT-proBNP had increased risk of all-cause mortality, compared to those with SBP<120 mm Hg and low levels of NT-proBNP. ConclusionsAmong a general population of adults free of cardiovascular disease, NT-proBNP can provide additional prognostic information within and across categories of BP. Measurement of NT-proBNP may have potential for clinical use to optimize hypertension treatment.

BackgroundAssociations between blood urate levels, blood pressure (BP), and kidney function have previously been reported in observational studies. However, causal inference between these three traits is challenging due to potentially bidirectional relationships. Method: We applied bidirectional univariable Mendelian randomization (UVMR) to assess the causal relationships between urate levels, BP, and kidney function, proxied by estimated glomerular filtration rate (eGFR), using genetic associations from UK Biobank and CKDGen. We performed multivariable MR (MVMR) to assess the independent effects of urate and BP on eGFR. Effect estimates are presented as standard deviation (SD) change in outcome (95% confidence interval) per SD increase in exposure. ResultsThe UVMR analysis showed a bidirectional causal effect between urate and eGFR [urate on log(eGFR): beta=-0.10 (-0.22 to 0.02); log(eGFR) on urate: beta=-0.11 (-0.17 to -0.04)]. We also found bidirectional causal effects between urate and SBP [urate on SBP: beta=0.08 (0.04 to 0.11); SBP on urate: beta=0.13 (0.08 to 0.18)] and urate and DBP [urate on DBP: beta=0.09 (0.05 to 0.14); DBP on urate: beta=0.13 (0.08 to 0.18)]. However, there was weak evidence of a causal effect between BP and eGFR. MVMR results suggested the causal effect of urate on eGFR was independent of BP. ConclusionOur results provide evidence for bidirectional causal effects between urate and both eGFR and BP, suggesting urate control as a potential intervention to reduce BP and decline in kidney function in the general population, but little evidence of a causal relationship between BP and eGFR.

Preclinical models have been instrumental in defining the immunological mechanisms underlying hypertension, yet human studies remain comparatively limited, leaving a major gap in translational understanding. To address this, we investigated immune cell dynamics in human hypertension by profiling peripheral blood mononuclear cells from 48 normotensive and hypertensive participants, characterised using ambulatory blood pressure (BP) monitoring. High{square}dimensional spectral flow cytometry revealed strong positive correlations between night{square}time systolic BP and multiple CD8{square}T{square}cell subsets. Hypertensive participants also exhibited significantly elevated CD8{square}T cell subsets, a pattern that persisted even among those receiving anti{square}hypertensive medication with subsequently controlled BP. These findings suggest that BP control does not necessarily equate to biological control of hypertension and highlight a distinct CD8{square}T cell-driven signature that differentiates individuals with normal BP and hypertension.

Genetic predisposition is a risk factor for office hypertension. We tested whether genetic background could identify individuals with ambulatory daytime hypertension in a sample of white Europeans from Liechtenstein. We evaluated two measures of predisposition to hypertension: family history and polygenic risk scores (PRS). Our analytic sample contained 1444 participants aged 25 to 41. Of the participants, 12% had office hypertension, while 37% had out-of-office hypertension. The correlation between blood pressure PRS and family history of hypertension was low (R2 = 4.96x10-3), but both were strongly associated with ambulatory blood pressure (2.2 mmHg per 1 SD increase [95% CI: 1.6, 2.7] & 2.4 mmHg increase with positive family history [95% CI: 1.3, 3.4], respectively). The PRS provides incremental improvement in predicting ambulatory systolic blood pressure beyond a validated blood pressure prediction score ({Delta}AIC = - 33), whereas family history does not ({Delta}AIC = 1). However, the difference in performance between a baseline prediction algorithm for identifying ambulatory systolic daytime hypertension (positive likelihood ratio of 6.87 [95% CI: 5.56, 8.49]; negative likelihood ratio of 0.45 [95% CI: 0.39, 0.51]) and the same model with PRS integrated (positive likelihood ratio of 7.69 [95% CI: 6.18, 9.57]; negative likelihood ratio of 0.43 [95% CI: 0.37, 0.49]) was modest. In conclusion, in a white European sample from Liechtenstein, PRS and family history are distinct constructs that are associated with increased clinical and ambulatory blood pressure. Unlike family history, polygenic risk scores provide incremental information in the identification of individuals with ambulatory hypertension. However, these gains are modest and warrant further development to improve predictive utility at the point-of-care.

Hypertension is a silent killer, with over half of affected adults unaware of their condition1,2. This lack of awareness is a major concern, as early intervention is critical for preventing major adverse cardiovascular events3,4. While cuffless wearable blood pressure (BP) monitors offer comfort and convenience, their reliance on periodic calibration and inconsistent accuracy have limited their clinical adoption5,6. Here we show that applying artificial intelligence (AI) pre-trained on almost 500,000 hours of data to multimodal waveforms (photoplethysmography and accelerometry) recorded using a widely available consumer smartwatch (AI-PPG-ACC-HTN), without any cuff calibration, can detect hypertension with accuracy levels comparable to traditional cuffed BP devices in the existing clinical framework, including both initial and confirmatory screening. We validated AI-PPG-ACC-HTN in a prospective, multicenter study of 196 diverse participants free from known cardiovascular disease and antihypertensive medication against gold-standard 24-hour ambulatory BP monitoring. Over seven days of real-world monitoring, AI-PPG-ACC-HTN detected hypertension with a sensitivity of 65.8% (95% CI, 54.0%-76.3%), specificity of 90.0% (83.2-94.7), and positive predictive value (PPV) of 80.6% (68.6-89.6). In comparison, initial office BP screening achieved a sensitivity of 55.3% (43.4-66.7), specificity of 90.0% (83.2-94.7) and PPV of 77.8% (64.4-88.0). For confirmatory testing of participants with elevated BP identified by initial office BP screening (N=48), AI-PPG-ACC-HTN detected hypertension with a sensitivity of 78.4% (61.8-90.2), specificity of 90.9% (58.7-99.8) and PPV of 96.7% (82.8-99.9). Comparatively, repeat office BP achieved a sensitivity of 67.6% (50.2-82.0), specificity of 63.6% (30.8-89.1) and PPV of 86.2% (68.3-96.1); multiday home BP monitoring achieved a sensitivity of 89.2% (74.6-97.0), specificity of 81.8% (48.2-97.7) and PPV of 94.3% (80.8-99.3). These results highlight an opportunity for consumer smartwatches to facilitate population-level opportunistic hypertension screening, offering an accessible tool to address this major public health challenge.

BackgroundHypertensive disorders of pregnancy (HDP) affect up to 15% of pregnancies and are linked to adverse maternal and fetal outcomes. Primary aldosteronism (PA) affects up to 25% of hypertensive patients. We examined PA prevalence in women with prior HDP and its relationship to hypertension trajectory. MethodsAdults from across the U.S.A. meeting guideline-recommended screening criteria for PA were prospectively tested. Women with a self-reported history of HDP completed a questionnaire examining the relationship between PA and hypertension trajectory. ResultsOf 330 hypertensive parous women (62.4 {+/-} 9.8y; 32.1% non-white), 83 (25.2%) reported a history of HDP. Women with HDP were younger at hypertension diagnosis (38.8 vs. 47.9y; p <0.001). The prevalence of a positive PA test was similarly high in those with and without HDP (26.5% vs 32%; p = 0.35). Among women with HDP, 63 completed the follow-up questionnaire, of whom 15 (23.8%) tested positive for PA. Compared with PA-negative women, those with PA reported a higher proportion of pregnancies complicated by hypertension (76.5% vs. 60.9%, p = 0.11) and fetal complications (55.6% vs. 27.9%, p <0.01). Hypertension trajectories also differed: sustained hypertension, defined as persistently elevated blood pressure beyond the postpartum period, was nearly twice as frequent in women with a positive PA test (66.7 vs. 37.5%; p=0.047). ConclusionOver 25% of women with hypertension and a prior pregnancy screened positive for PA, highlighting its high prevalence, irrespective of history of HDP. Women with HDP remain at elevated cardiovascular risk, and PA may represent a targetable contributor.

ObjectiveHypertensive disorders of pregnancy are associated with future cardiovascular risk, however, the underlying mechanisms are unclear. We sought to test the feasibility of postpartum remote blood sampling following a hypertensive disorder of pregnancy and subsequently identify differentially expressed proteins in individuals who developed hypertension. Study designWe used data from a randomized clinical trial evaluating the feasibility of lifestyle intervention and home blood pressure monitoring of individuals with pre-pregnancy body mass index [&ge;]25 kg/m2 and new-onset hypertensive disorders of pregnancy. Blood pressure was measured at remote visits at 6 weeks and 1 year postpartum and blood microsamples were collected at the second remote visit. Mass spectrometry was used to quantify 381 proteins, from which differential expression and pathway enrichment analyses were performed to detect alterations with persistent hypertension. ResultsOf the 100 randomized individuals, 87 completed sample collection with 85 yielding usable proteomics data. 4 proteins were differentially expressed with false discovery rate < 0.05 in individuals not taking antihypertensive medications who developed Stage 2 hypertension: Complement C4-B (C4B) and inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) levels were elevated while Afamin (AFM) and myosin light chain 6 (MYL6) levels were decreased. Pathway enrichment analysis suggests a shared function of inhibition of endopeptidases (such as Neprilysin, which degrades natriuretic peptides) in upregulated proteins and ubiquitin-proteasome mediated proteolysis activity in downregulated proteins. ConclusionsHome microsampling is a promising methodology for postpartum sample collection. Serum proteomics using this approach suggest that protein homeostasis may be dysregulated in persistent hypertension following hypertensive disorders of pregnancy, providing novel candidates for future interventions. Condensation page1) Tweetable statement: a short condensation of the paper, consisting of no more than 210 characters, stating its essential point(s). Proteomic analysis reveals that de novo hypertension after hypertensive disorders of pregnancy correlates with dysregulated protein homeostasis. 3) AJOG at a Glance: This section only applies to Original Research and Systematic Review submissions. This section is limited to no more than 130 words, 1-3 short sentences or phrases in bullet form, briefly describing your study, its significance, and its contribution to the literature. Authors should minimize the use of abbreviations (only very commonly used abbreviations will be allowed) and define an abbreviation prior to use in this section. Responses should be listed in bullet form after the A., B., and C. headings as below (not in paragraph form). All responses are subject to minor editorial alterations and/or shortened without the authors approval, and published both in print and on the Journal website. A. Why was this study conducted?O_LIPrioritization of newborn care during the early postpartum months makes in-person research study visits challenging, necessitating improved methodologies. C_LIO_LIPersistent postpartum hypertension may mediate the established relationship between hypertensive disorders of pregnancy and future cardiovascular disease risk, yet its pathogenesis remains poorly understood. C_LI B. What are the key findings?O_LIHome microsampling is a promising methodology for postpartum sample collection. C_LIO_LISerum proteomics using this approach suggest that protein homeostasis may be dysregulated in persistent hypertension following hypertensive disorders of pregnancy. C_LI What does this study add to what is already known?O_LIOur findings suggest that certain known features of hypertensive disorders of pregnancy, such as coagulation cascade activation, alterations of serum Afamin and proteasome levels, and protease dysregulation, might persist and contribute to de novo postpartum hypertension. C_LIO_LISome of these pathways may be amenable to future intervention development to prevent persistent hypertension after a hypertensive disorder of pregnancy. C_LI

ObjectiveTo identify factors associated with persistent hypertension one-year postpartum after pregnancy complicated by gestational hypertension or preeclampsia. Study DesignA retrospective case-control study of postpartum patients who had a diagnosis of gestation hypertension or preeclampsia during a recent pregnancy and attended one-year postpartum annual exam and blood pressure check between 2014 and 2019 in a single academic medical center. Cases were defined as persons with persistent hypertension one year postpartum, using the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, defining stage I hypertension as systolic blood pressure [&ge;]130 mmHg or diastolic blood pressure [&ge;]80 mmHg. Controls were defined as non-pregnant persons with normal blood pressure (BP) at one year postpartum. Using bivariate and multivariate analyses, demographic, clinical and labor characteristics were compared between persons who had persistent hypertension one-year postpartum and controls. ResultsOf the 595 persons included in this analysis, 268 (45.0%) had persistent hypertension one year postpartum. Bivariate analyses demonstrated that older maternal age, higher body mass index (BMI) at first prenatal visit, at delivery, and one year postpartum, mild-range BP (compared to normal BP) prior to discharge, and patients with elevated BP at 6-week postpartum visit, were more likely to have persistent hypertension one-year postpartum. In contrast, nulliparity was associated with lower risk of having persistent hypertension at one-year postpartum. Multivariate logistic regression demonstrated that mild range BP prior to discharge (aOR 1.78, 95%CI 1.16-2.72), elevated BPs at 6 weeks postpartum (aOR 2.01, 95% CI 1.36-3.00), and higher BMI at one-year postpartum (aOR 1.07, 95%CI 1.00-1.14), remained to be significantly associated with higher odds of persistent hypertension one-year postpartum, while nulliparity remained to be associated with lower odds of persistent hypertension one-year postpartum (aOR 0.55, 95%CI 0.36-0.84) ConclusionIn this cohort, 45% of patients with gestational hypertension or preeclampsia had persistent hypertension one-year postpartum by the 2017 ACC/AHA hypertension definition. Patients that had mildly elevated BPs in the immediate postpartum period as well as at 6 weeks postpartum, and higher BMI one year postpartum, had higher risk of having at least stage I HTN one year following pregnancy complicated by gestational hypertension or preeclampsia.