BACKGROUND Nocturnal hypertension (NH) is associated with adverse cardiovascular outcomes beyond and even independent of daytime hypertension (DH). Although cohort studies have evaluated correlates of NH, there is comparably less data available from real-world clinical practice and for population subsets that tend to be under-represented in cohort studies.METHODS This retrospective cohort study included all patients who underwent ambulatory blood pressure monitor (ABPM) testing at a large US academic medical center from 1 January 2013 to 31 December 2023. We used multivariable-adjusted logistic regression to assess DH as a correlate of NH, covariates related to the co-occurrence of DH and NH, and correlates of isolated NH.RESULTS Of 1,566 patients, 812 (51.9%) had DH, 1,125 (71.8%) had NH, and 363 (23.2%) had isolated NH. A total of 762 (48.7%) patients had co-occurring daytime and NH. In multivariable analysis, significant correlates of NH included DH, male sex, age, Black race, and Hispanic ethnicity. By comparison, significant correlates of co-occurrent DH and NH included male sex, age, Asian race, Black race, and renal disease; coronary artery disease (CAD) was inversely associated with this co-occurrence. Among all covariates, only CAD was associated with isolated NH.CONCLUSIONS Our real-world study results highlight the generally under-recognized prominence of isolated NH, as well as the presence of NH among Hispanic and Asian-American populations. Further prospective investigations are needed to evaluate whether broader ABPM screening for NH is needed across all populations at risk, including but not limited to persons with more easily identified DH.

Resistant hypertension (RH) affects more than a tenth of adults and yet remains relatively underrecognized and undertreated. The electronic health record (EHR) now stands as a critical tool for overcoming barriers to the diagnosis and treatment of RH, specifically with respect to aiding in detection, excluding alternate diagnoses, and guiding clinical decision making. We review how the EHR has clarified the population level prevalence of RH and its impact on both quality of life and longevity. We examine how the EHR can be leveraged to identify relevant specific causes of elevated blood pressure such as medication non-adherence, clinical inertia, White Coat Effect, and hyperaldosteronism, among others. Additionally, we highlight the promises and potential pitfalls that warrant consideration when implementing novel EHR interventions to address clinical challenges such as RH. In particular, we discuss the importance of balancing augmented data availability with the need for streamlined data flow to clinicians, so that enhanced workflows can both maximize efficiency and improve quality of care. As the EHR continues to transform the practice of care delivery, RH represents a uniquely well-suited area for improving clinical identification and management in ways that could not be otherwise readily achieved in practice.

BACKGROUND:A deeper understanding of the association between blood pressure (BP) control and neighborhood-level social determinants of health (SDOH) may help elucidate nonclinical factors that contribute to hypertension disparities. We sought to evaluate patterns of BP elevations by neighborhood-level SDOH domains. METHODS:In this single-center retrospective cohort study at Cedars-Sinai Medical Center, adults with ≥2 outpatient visits/year in at least 2 consecutive years (each consecutive 2-year period forms a dyad) from 2018 to 2023 were linked to the Healthy Places Index (HPI), a measure of neighborhood SDOH. Among patients with normotensive BP (BP <130/80 mm Hg) in the first year of at least 1 dyad, we assessed for the development of high BP (systolic BP ≥ 130 or diastolic BP ≥ 80 mm Hg) in the following year. RESULTS:A total of 94,276 adults (median age 56.4 ± 18.8 years; 37.2% male) with BP <130/80 mm Hg, of whom 38,719 (41.1%) developed high BP. In analyses adjusting for demographic, clinical, and SDOH factors, risk of developing high BP was associated with living in a neighborhood with a HPI score in the lowest vs highest quartile (prevalence ratio [PR] 1.07, 95% CI: 1.05-1.10). This finding was primarily associated with the economic (1.04, 1.00-1.07) and educational attainment (1.05, 1.02-1.08) domains, captured as part of the HPI score. CONCLUSIONS:In a cohort of >94,000 adults starting with BP <130/80 mm Hg, an increase in BP above this threshold in the following year was associated with neighborhood-level SDOH status, particularly variations in economic and educational attainment.

BACKGROUND:Little is known about the initial dosing of loop diuretics among patients hospitalized for heart failure and its association with outcomes. METHODS:We identified patients admitted for heart failure at 24 hospitals across two health systems between January 1, 2017, and December 31, 2020. Initial diuretic dose was categorized relative to home dose in furosemide equivalents. The primary outcomes (length of stay) and secondary outcomes (rates of acute kidney injury, in-hospital mortality, and 30-day readmissions) were compared across categories of initial diuretic dose. RESULTS:Among 14 332 patients admitted for heart failure, the initial diuretic dose was lower-than-home dose in 1866 (13.0%) patients, equivalent-to-home dose in 3171 (22.1%) patients, and higher-than-home dose in 9295 (64.9%) patients. Compared with patients who received an equivalent or higher initial diuretic dose relative to home dose, risk-adjusted length of stay was longer among patients receiving a lower dose (4.9 days versus 4.0 days versus 4.0 days, P<0.01). Compared with equivalent-to-home dose, a higher initial diuretic dose was associated with a higher risk-adjusted rate of acute kidney injury (incident risk ratio [IRR], 1.17 [95% CI 1.04-1.31]; P=0.009) and a lower risk of 30-day readmission (IRR, 0.85 [95% CI, 0.78-0.93]; P=0.005). CONCLUSIONS:In a cohort of patients admitted for heart failure, more than 1 in 3 patients received an initial dose of intravenous loop diuretics that was lower than or equivalent to their home diuretic dose, and the initial dose was associated with length of hospital stay and acute kidney injury.

Background: Severe aortic stenosis (sAS) leads to high morbidity and mortality when left untreated. We sought to develop and validate an algorithm-based rules engine to identify patients with untreated sAS and to evaluate differences between those who did and did not subsequently receive guideline-concordant treatment with aortic valve replacement (AVR). Methods: We curated discrete and nondiscrete data from our echocardiography system, then created a rules engine to identify and grade aortic stenosis. We assessed sensitivity and specificity of the rules engine to identify sAS using manual adjudication. We additionally conducted a retrospective cohort analysis to identify demographic and socioeconomic factors associated with receipt of guideline-concordant AVR treatment for sAS. Results: The rules engine demonstrated 100% sensitivity and 95.4% specificity for identifying sAS across n ​= ​2162 echocardiographic studies from unique patients. Univariate analyses revealed patients with untreated sAS were more likely to be older and female, with no appreciated differences by race, ethnicity, insurance status, or neighborhood-level socioeconomic scores. In multivariable analyses, older individuals, women, and those with Medicare/Medicare advantage were less likely to undergo AVR. Among treated patients, those who underwent surgical AVR were more likely to be younger, male, and have lower socioeconomic neighborhood scores. Conclusions: Untreated sAS is prevalent but can be accurately identified at scale using an echocardiogram report-based rules engine. Disparities in the receipt of AVR persist, particularly among women, older adults, and patients with nonprivate insurance coverage. The systematic use of automated algorithmic protocols may facilitate valvular heart disease identification and reduction of treatment disparities.

Randomized controlled trials investigating colchicine for secondary prevention of cardiovascular events following acute myocardial infarction (AMI) have yielded conflicting results, and the real-world use and effectiveness of colchicine in this context remains unknown. As such, we sought to evaluate the use of colchicine following AMI in clinical practice and the associated outcomes. We performed a retrospective analysis of patients diagnosed with AMI and longitudinally followed in a large academic health system between 2018 and 2024 to describe the clinical use of colchicine for secondary prevention following AMI, as well as patient-level demographic and clinical characteristics associated with colchicine use. Next, using both multivariable logistic regression models with and without propensity matching, we examined the association between colchicine prescription following AMI and composite cardiovascular outcomes (comprised of recurrent AMI, any revascularization, stroke, and death). Kaplan-Meier Event-free Survival Analysis and Cox Proportional Hazards Models were performed. Of 1,796, 126 (7.0%) were prescribed colchicine after AMI. There was no association between use of colchicine and the composite cardiovascular events in either standard multivariable adjusted (Odds Ratio 1.00, 95% CI 0.66-1.50, p = 0.99) or propensity matched models (0.98, 0.57-1.66, p = 0.93). There was no difference in event-free survival between patients who were prescribed colchicine and those who were not. In summary, we report the first real-world data on the use and effectiveness of colchicine for prevention of cardiovascular events after AMI. Colchicine was infrequently prescribed for this indication and was not associated with lower rates of subsequent cardiovascular events.

While chronological age is a universal risk predictor across most populations and diseases, distinguishing between biologically older from younger individuals may identify individuals with accelerated or delayed cardiovascular aging. This study presents a deep learning model to predict age from echocardiogram videos, leveraging 2,610,266 videos from 166,508 studies from 90,738 patients. Leveraging multi-view echocardiography, our model achieved a mean absolute error (MAE) of 6.76 (6.65–6.87) years and a coefficient of determination (R2) of 0.732 (0.72–0.74) on Cedars-Sinai Medical Center test set. Consistent performance was observed across four external validation cohorts. Predictions were associated with increased risk of coronary artery disease, heart failure, and stroke, and captured discontinuities before and after a heart transplant. Guided back propagation highlighted the model’s focus on the mitral valve, mitral apparatus, and basal inferior wall, underscoring the potential of computer vision-based assessment of echocardiography in enhancing cardiovascular risk assessment and aging.

Background Health systems generate and store vast amounts of clinical data, requiring structured processes to ensure that secondary use of the data is available to researchers in an efficient, ethical, and secure manner. Objective We describe a process to provide data to health system researchers at a large, multi-hospital health system that balances efficiency with security and ethics. Methods The Honest Enterprise Research Broker (HERB) Committee has enacted a systematic process to deliver investigators requesting data, using pre-written SQL code, when possible, to increase efficiency, providing a suite of self-service tools for cohort size estimation, and assessing the security and privacy of data leaving the institution. We evaluated the number of extracts per year, the average time to delivery of the data extract, and user satisfaction with the process. Results From 2018 to 2023, the HERB Committee completed 487 data extracts. The number of requests increased from 51 in 2018 to 121 in 2023. Even as the number of extracts increased, the number of hours per extract decreased from 12.5 in 2018 to 9 in 2023. User satisfaction surveys found a high degree of satisfaction with the process. Conclusion Through a process of continuous improvement, the HERB Committee has developed an expedient process to support the research needs of a large academic multi-hospital health system.

BACKGROUND:A widely representative health system cohort with longitudinal specimen collection can serve as an efficient clinical biobank resource for multiple studies. Because the full scope of a health system cohort can include both health care workers and patients, enrollment and biobanking efforts may be designed to engage these specific participant populations. METHODS:For a multisite health system cohort that initially enrolled health care workers and then expanded to enroll patients, we evaluated the relative success of initiatives that specifically targeted enrollment of various health care worker and patient populations. We also compared enrollment rate success based on engagement type (active vs. passive), modality (in-person vs. virtual), and venue (clinical-based or community-based). Across each method of engagement, we compared the conversion rate from study consent to collected biospecimen. RESULTS:For recruitment activities involving health care workers, enrollment rates varied based on active versus passive (62% vs. 0.8%) and in-person versus virtual (9.6% vs. 0.8%) engagement as well as clinical-based versus community-based (65% vs. 3.9%) venues (p < 0.001 for all). For health care workers, the overall conversion rate from consent to biospecimen collection was 87%. For recruitment activities involving patients, enrollment rates also varied based on active versus passive (53% vs. 0.8%) and in-person versus virtual (62% vs. 0.8%) engagement, as well as clinical-based versus community-based (70% vs. 41%) venues (p < 0.001 for all). For patients, the overall conversion rate from consent to biospecimen collection was 75%. CONCLUSIONS:For studies aiming to build a biorepository resource involving both health care worker and patient participants, the active rather than passive engagement methods are likely to achieve not only a higher rate of contact to consented enrollment but also a higher rate of conversion from consent to biospecimen collection. Further studies are needed to guide resource planning around biorepository building capacity for specific study designs.

BACKGROUND:Longitudinal analysis of the circulating proteome after SARS-CoV-2 mRNA vaccination provides insights into immune adaptation, optimizing vaccination strategies, and understanding long-term molecular effects. METHODS:We analyzed 120 paired plasma samples from 114 healthy participants at six time points: pre-vaccination, 3 days and 7-21 days post-dose 1, 7-21 days post-dose 2, and at 8-, 16-, and 24-weeks post-dose 2. IgG antibody responses to SARS-CoV-2 structural proteins and autoantibody profiles were assessed using a multiplex platform, and plasma proteome changes were quantified by mass spectrometry. RESULTS:IgG antibodies against spike protein regions (RBD, S1, S2) produced sustained responses for up to 24 weeks, with no detection of nucleocapsid or membrane antibodies, confirming that there was no prior infection. Younger participants (<45 years) presented stronger responses, with no significant sex differences. Proteomics identified 342 proteins, of which 214 proteins were significantly altered, predominantly at 16-24 weeks. Key changes included upregulation of C1 complex proteins (C1R, C1QC, C1S) and downregulations of the C1 inhibitor SERPING1, indicating complement activation. Platelet-associated proteins showed minimal changes, suggesting a limited thrombosis risk. Altered proteins were enriched in carbohydrate metabolism, cofactors/vitamin metabolism, and thyroid hormone pathways. Autoantibody profiling showed stable responses for most self-antigens, with modest increased in several interleukin specific autoantibodies, including IL-1B, at later time points. CONCLUSIONS:Integrated plasma proteomics and autoantibody profiling demonstrated sustained immunogenicity and safety of SARS-CoV-2 mRNA vaccines, characterized by durable spike-specific antibody responses, late-onset complement activation, and limited autoantibody induction. These findings enhance our understanding of vaccine-induced immunity and inform long-term monitoring and optimization of mRNA vaccine strategies.

BACKGROUND: Women experience excess cardiovascular risk compared with men in the setting of similar metabolic disease burden. We aimed to examine sex differences in the vascular response to various forms of metabolic stress. METHODS: We conducted an observational study of 4299 adult participants (52% women, aged 59±13 years) of the National Health and Nutrition Examination Survey 2017 to 2018 cohort and 110 225 adult outpatients (55% women, aged 64±16 years) from the Cedars-Sinai Medical Center in 2019. We used natural splines to examine the association of systemic and organ-specific measures of metabolic stress including body mass index, hemoglobin A1c, hepatic FIB-4 score, and CKD-EPI estimated glomerular filtration rate with systolic blood pressure (SBP). Piecewise linear models were generated using normal value thresholds (body mass index <25 kg/m 2 , hemoglobin A1c <5.7%, FIB-4 <1.3, and estimated glomerular filtration rate ≥90 mL/min), which approximated observed spline break points. The primary outcome was an increase in SBP in association with increase in each metabolic measure. RESULTS: Women compared with men demonstrated larger magnitudes and an earlier onset of increase in SBP per increment increase across all metabolic stress measures. The slope of SBP increase per increment of each metabolic measure was greater for women than men particularly for metabolic measures within the normal range, with slope differences of 1.86 mm Hg per kg/m 2 of body mass index, 12.48 mm Hg per %hemoglobin A1c, 6.87 mm Hg per FIB-4 unit, and 0.44 mm Hg per mL/min decrement of estimated glomerular filtration rate in the National Health and Nutrition Examination Survey cohort ( P difference <0.05 for all). Overall results were consistent in the Cedars-Sinai Medical Center cohort. CONCLUSIONS: Women exhibited greater SBP alteration in the setting of multiple types of metabolic stress, particularly in periods representing the transition from metabolic health to disease. These findings suggest potential benefit of early metabolic health interventions as part of efforts to mitigate vascular risks in both women and men.

BACKGROUND:The complexity of patients undergoing cardiac surgery underscores the need to improve understanding of the factors that augment or predict risks of adverse postoperative outcomes. Our study set out to determine the extent to which postoperative fluid imbalance is related to clinically important outcomes following elective cardiac surgery. METHODS:In this retrospective cohort study, we studied 2557 elective coronary artery bypass graft (CABG) and/or valve surgery patients at an academic medical center from 2015 to 2020. We examined the relationship between cumulative fluid balance during intensive care unit (ICU) stay and subsequent clinical outcomes. We considered cumulative fluid balance as both a continuous and categorical variable based on cohort-based tertiles: negative (<less than ~500 mL negative), neutral (between ~500 mL negative and ~750 mL positive), or positive (more than ~750 mL positive). The primary outcome was a composite of 30-day mortality, ICU readmission, and postoperative hospital length of stay ≥30 days. RESULTS:The primary outcome occurred in 7.0% (n = 60), 2.3% (n = 20), and 9.3% (n = 79) of patients in the negative, neutral, and positive groups, respectively. In multivariable-adjusted analyses, cumulative fluid balance as a continuous variable demonstrated a U-shaped relationship with the primary outcome, with thresholds of significantly elevated risk observed at negative 1380 mL and positive 1700 mL. In multivariable-adjusted analyses of cumulative fluid balance as a categorical variable, patients who left the ICU with either negative (odds ratio 2.76 [95% confidence interval {CI}, 1.62-4.70]; P < .01) or positive cumulative fluid balance (3.53 [2.09-5.96]; P < .01) had higher risk for the primary outcome compared to those with a neutral cumulative fluid balance. CONCLUSIONS:A negative or positive cumulative fluid balance on the day of ICU discharge was associated with ~3 to 4 times greater odds of adverse postoperative outcomes, respectively, which was further elevated when fluid imbalance exceeded ~1.5 L. Our findings suggest that postoperative cumulative fluid balance in real-world practice, particularly for elective cardiac surgery patients, warrants greater attention.

BACKGROUND:Resistant hypertension (RH), in which blood pressure remains elevated on ≥3 medications or controlled on ≥4 medications, increases the risk of adverse cardiovascular events nearly 50% more than primary hypertension. We sought to identify genetic drivers of RH in a reliable and generalizable manner. METHODS:We utilized FinnGen (discovery) and UKBB (UK Biobank, replication) data sets to identify potential genetic drivers of RH. Using standard RH definitions, we developed cohorts in each data set and performed genome-wide (genome-wide association studies) and transcriptome-wide association studies, as well as Mendelian randomization analysis to evaluate potential causal associations. RESULTS:We replicated 5 genetic loci in CASZ1, WNT2B, KCNK3, LSP1, and near the EVX1/EVX1AS locus for RH. Of these, CASZ1 and WNT2B are strongly associated with aldosterone homeostasis, while KCNK3 and LSP1 are associated with pathways mediating vasodilation. EVX1/EVX1AS are involved in mesendodermal lineage differentiation during gastrulation. Gene- and pathway-based analyses identified associations with vascular and cardiac developmental pathways in addition to aldosterone synthesis and secretion pathways. Transcriptome-wide association study analyses identified 37 genes, of which the genetically regulated expression is associated with RH, with particularly strong tissue-specific associations with KCNK3. Finally, Mendelian randomization identified possible causal association for 4 vascular risk factors (CRP [C-reactive protein]), triglycerides, waist circumference, and body mass index) with RH, with strong associations with identified lead variants. CONCLUSIONS:We identified distinct genetic variants associated with RH, including those implicating the role of hyperaldosteronism, highlighting distinct pathways and targets for more effectively treating RH.

Many, though not all, studies suggest that contrast-associated acute kidney injury (CA-AKI) after percutaneous coronary intervention (PCI) rates are higher in women. The authors sought to clarify the presence of and factors contributing to possible sex differences. Among 2971 consecutive patients undergoing PCI, women experienced higher crude rates of CA-AKI. However, this association was significantly attenuated after adjusting for demographic and comorbid conditions, particularly pre-procedural anemia, which accounted for a substantial proportion of the excess risk. The study offers clarification regarding the higher post-PCI risks among women and underscores the role of anemia as a prevalent contributor to CA-AKI.

ABSTRACT Introduction Amidst highly transmissible SARS‐CoV‐2 variants that continue to circulate in the community, individuals with cancer exhibit variations in immunity and susceptibility for reasons that remain poorly understood. Methods In a longitudinal cohort study with ongoing SARS‐CoV‐2 serological and outcomes surveillance, we examined adults receiving cancer treatment (cases, n = 229) or who were free of cancer and other major comorbidities (controls, n = 800), prior to the Omicron era onset and onwards (September 24, 2021–March 10, 2024). The main outcomes were longitudinal SARS‐CoV‐2 anti‐spike receptor binding domain IgG (IgG‐SRBD) antibody response and Omicron and subvariant infection frequency and severity. Results Among the 229 participants with cancer (age 66 ± 12 years, 51% female), the most prevalent subtypes included nonmelanoma skin (23%), breast (20%), and hematologic (18%). In mixed‐effects linear models, hematologic cancer and B‐cell targeted agents were associated with reduced longitudinal IgG‐SRBD response (p < 0.05). In multivariable regression analyses, hematologic cancer (p = 0.037) and B‐cell targeted agents (p = 0.030) were associated with increased frequency of new infections. The frequency of new infections resulting in moderate illness was increased in patients with active/recent cancer treatment (44%) versus healthy controls (10%; p < 0.001); there were no severe or critical infections. Patients with hematologic, breast, prostate, or skin cancer (p < 0.01), treated with local therapy (odds ratio [OR] 1.82; 95% confidence interval [CI] 1.05–3.15; p = 0.032), B‐cell targeted therapy (OR 4.81; 95% CI 1.78–12.93; p = 0.002), or small molecule agents (OR 2.34; 95% CI 1.05–5.23; p = 0.037) were associated with increased infection severity. Conclusions Individuals with hematologic cancer or exposed to B‐cell‐targeted therapy had reduced humoral immunity and more frequent and severe infections. Active breast, prostate, or skin cancer, or treatment with local therapy or small molecule agents had elevated risk for more severe, but not more frequent, infections. Despite overall low rates of infection associated with lower respiratory disease, certain higher‐risk cancer patients may benefit from further protective measures.

Routinized pill-taking can enhance medication adherence but is difficult to achieve. In this pilot randomized controlled trial we assess the feasibility, acceptability, and preliminary efficacy of a novel behavioral economics-based approach to medication-adherence. We enrolled 60 hypertensive adults, who all received information on pill-routinization and selected an existing behavioral routine ('anchor') to assist with routinization of pill-taking. Participants were randomized into 3 groups: 1)'Control' receiving usual care (n = 20); 2)'Messages' receiving daily text messages (n = 20); and 3)'Incentives' receiving both text messages and rewards for medication adherence (n = 20). Interventions lasted 3 months, followed by a 6-month post-intervention period during which we assessed medication-adherence and conducted standardized assessments of acceptability. The study demonstrated high feasibility and acceptability, with 90% of participants willing to refer others to the study. Mean adherence during the extended follow-up period (months 7-9) was numerically higher in both intervention arms than the control arm (Control 75%, Messages 84%, and Incentives 77%) though this pilot study was not powered to detect a statistically significant difference (P = 0.73). While this pilot study was under-powered to detect between-group differences, the novel behavioral economics habit formation approach was feasible, acceptable, and yielded promising results, warranting completion of a fully-powered trial. Registration: URL:  https://www.clinicaltrials.gov ; Unique identifier: NCT04029883; registered 23/07/2019.