Publications

BACKGROUND: Orthostatic hypertension is an emerging risk factor for adverse events. Recent consensus statements combine an increase in blood pressure upon standing with standing hypertension, but whether these 2 components have similar risk associations with cardiovascular disease (CVD) is unknown.

METHODS: The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure during visit 1 (1987-1989). We defined systolic orthostatic increase (a rise in systolic blood pressure [SBP] ≥20 mm Hg, standing minus supine blood pressure) and elevated standing SBP (standing SBP ≥140 mm Hg) to examine the new consensus statement definition (rise in SBP ≥20 mm Hg and standing SBP ≥140 mm Hg). We used Cox regression to examine associations with incident coronary heart disease, heart failure, stroke, fatal coronary heart disease, and all-cause mortality.

RESULTS: Of 11 369 participants (56% female; 25% Black adults; mean age, 54 years) without CVD at baseline, 1.8% had systolic orthostatic increases, 20.1% had standing SBP ≥140 mm Hg, and 1.3% had systolic orthostatic increases with standing SBP ≥140 mm Hg. During up to 30 years of follow-up, orthostatic increases were not significantly associated with any of the adverse outcomes of interest, while standing SBP ≥140 mm Hg was significantly associated with all end points. In joint models comparing systolic orthostatic increases and standing SBP ≥140 mm Hg, standing SBP ≥140 mm Hg was significantly associated with a higher risk of CVD, and associations differed significantly from systolic orthostatic increases.

CONCLUSIONS: Unlike systolic orthostatic increases, standing SBP ≥140 mm Hg was strongly associated with CVD outcomes and death. These differences in CVD risk raise important concerns about combining systolic orthostatic increases and standing SBP ≥140 mm Hg in a consensus definition for orthostatic hypertension.

CONTEXT: The hospital discharge process is fraught for patients with serious illness and their caregivers.

OBJECTIVES: We sought to understand palliative care patient and caregiver concerns regarding the patient-centeredness of the hospital discharge process.

METHODS: We conducted semi-structured interviews with 11 patients receiving palliative care and 4 caregivers. Caregivers were interviewed with patient or alone, for a total of 13 interviews. Interviews were focused on the patient-centeredness of the discharge process, completeness of discharge education, and readmission. Transcripts were analyzed using an inductive approach with open coding.

RESULTS: We identified four themes: (i) symptoms, (ii) relationship to illness, (iii) variance in patient-provider alignment, and (iv) discharge readiness, including readmission. Physical and non-physical symptoms were common, though non-pain symptoms were more frequently concerns. Illness understanding and empowerment by the discharge process were low, with participants seeking more information. Alignment varied by provider with closer relationships with bedside nurses and outpatient providers, especially oncologists, than inpatient providers. Readmission was not perceived to be avoidable but was associated with symptom burden. Discharge readiness was mixed; common concerns included lack of clarity regarding next steps and post-discharge services. Up to 40% of participants reported incomplete education on given topics.

CONCLUSION: Our qualitative study of patients and caregivers receiving palliative care identified unmet needs in the discharge process: non-pain symptom burden, gaps in empowerment and illness understanding, and mixed discharge readiness. Relationship to care informs subsequent engagement with care and medical decision-making. Future interventions should focus on strengthening patient and caregiver empowerment and illness understanding.

OBJECTIVES: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.

DESIGN: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).

METHODS: To provide background and context, a review of delirium treatment randomized controlled trials (RCTs) published between 2003 and 2023 was conducted and evidence gaps were identified. The four panels addressed the identified subtopics. For each subtopic, research challenges were identified and recommendations to address each were proposed through virtual discussion before a live, full-day, and in-person conference. General agreement was reached for each proposed recommendation across the entire working group via moderated conference discussion. Recommendations were synthesized across panels and iteratively discussed through rounds of virtual meetings and draft reviews.

RESULTS: We identified key evidence gaps through a systematic literature review, yielding 43 RCTs of delirium treatments. From this review, eight unique challenges for delirium treatment trials were identified, and recommendations to address each were made based on panel input. The recommendations start with design of interventions that consider the multifactorial nature of delirium, include both pharmacological and nonpharmacologic approaches, and target pathophysiologic pathways where possible. Selecting appropriate at-risk patients with moderate vulnerability to delirium may maximize effectiveness. Targeting patients with at least moderate delirium severity and duration will include those most likely to experience adverse outcomes. Delirium severity should be the primary outcome of choice; measurement of short- and long-term clinical outcomes will maximize clinical relevance. Finally, plans for handling informative censoring and missing data are key.

CONCLUSIONS: By addressing key delirium treatment challenges and research gaps, our recommendations may serve as a roadmap for advancing delirium treatment research in older adults.

BACKGROUND: Delirium after cardiac surgery is common, morbid, and costly, but may be prevented with risk stratification and targeted intervention. In this study, we aimed to identify protein biomarkers and develop a predictive model for postoperative delirium in older patients undergoing cardiac surgery.

METHODS: SomaScan analysis of 1305 proteins in the plasma from 57 older adults undergoing cardiac surgery requiring cardiopulmonary bypass was conducted to define delirium-specific protein signatures at baseline (preoperative baseline timepoint [PREOP]) and postoperative day 2 (POD2). Selected proteins were validated in 115 patients using the Enzyme-Linked Lectin Assay (ELLA) multiplex immunoassay platform. Proteins were combined with clinical and demographic variables to build multivariable models that estimate the risk of postoperative delirium and bring light to the underlying pathophysiology.

RESULTS: Of the 115 patients, 21 (18.3%) developed delirium after surgery. The SomaScan proteome screening evidenced differential expression of 115 and 85 proteins in delirious patients compared to nondelirious preoperatively and at POD2, respectively ( P < .05). Following biological and methodological criteria, 12 biomarker candidates (Tukey's fold change [|tFC|] >1.4, Benjamini-Hochberg [BH]- P < .01) were selected for ELLA multiplex validation. Statistical analyses of model fit resulted in the combination of age, sex, and 3 proteins (angiopoietin-2; C-C motif chemokine 5; and metalloproteinase inhibitor 1; area under the curve [AUC] = 0.829) as the best performing predictive model for delirium. Analyses of pathways showed that delirium-associated proteins are involved in inflammation, glial dysfunction, vascularization, and hemostasis.

CONCLUSIONS: Our results support the identification of patients at higher risk of developing delirium after cardiac surgery using a multivariable model that combines demographic and physiological features, also bringing light to the role of immune and vascular dysregulation as underlying mechanisms.

BACKGROUND: Alcohol intake is associated with a higher risk of estrogen receptor-positive (ER+) breast cancer (BC), presumably through its confirmed ability to increase sex hormone levels. Whether consuming alcohol within the recommended limit of one serving per day increases sex hormone levels among postmenopausal women taking aromatase inhibitors (AI) to inhibit estrogen production remains unknown. Therefore, we compared sex hormone levels following white wine to levels following white grape juice among ER + BC survivors taking AIs.

METHODS: In this 10-week randomized controlled two-period crossover trial conducted from September 2022 to July 2023 among 20 postmenopausal women on AIs, we examined within-person changes in sex hormone levels following 3 weeks of 5 ounces of white wine daily versus 3 weeks of 6 ounces of white grape juice daily, with each drinking period preceded by two-week washouts and drinking period sequence allocated by randomization.

RESULTS: All 20 participants completed the trial. Compared to daily grape juice, daily wine led to decreases in total estradiol (11.1%, 95%confidence interval[CI] -49.8%,57.2%), free estradiol index (0.7%, 95%CI -2%,0.7%), and free estradiol concentration (7.7%, 95%CI -48%, 63.9%) but increases in estrone (13.8%, 95%CI -9.5%,43.1%), dehydroepiandrosterone sulfate (DHEAS; 11.4%, 95%CI -3.3%,28.4%), and testosterone (12.6%, 95%CI -0.8%,27.7%) and decreased sex hormone-binding globulin (SHBG; -2.7%, 95%CI -21.9%,21.2%).

CONCLUSIONS: Five ounces of white wine daily did not lead to statistically significant increases in estradiol, but it led to changes in other sex hormones suggesting higher BC risk. Whether this level of alcohol intake diminishes AI effectiveness warrants further investigation.

TRIALS REGISTRATION: Clinicaltrials.gov NCT05423730 registered June 14, 2022.

OBJECTIVES: Endovascular aneurysm repair (EVAR) for large infrarenal abdominal aortic aneurysms (AAAs) has been associated with worse outcomes compared with EVAR for smaller AAAs. Whether these findings apply to complex AAAs (cAAA) remains uncertain.

METHODS: We identified all intact complex EVAR (cEVAR) from 2012 to 2024 in the Vascular Quality Initiative. cEVAR was defined as having a proximal extent between zones 6 and 9 and at least one side branch/fenestration/chimney/parallel grafting. Aneurysm size was defined as follows: large: >65 mm (males), >60 mm (females); medium: 55 to 65 mm (males), 50 to 60 mm (females); and small: <55 mm (males), <50 mm (females). We assessed perioperative death, any complication, and in-hospital reintervention using logistic regression and midterm mortality using adjusted Kaplan-Meier methods and Cox regression analyses. Medium-sized aneurysms were compared with large and small aneurysms.

RESULTS: Of the 3426 patients, 22.6% had large, 60.4% medium, and 17.0% had small aneurysms. As compared with medium and small aneurysms, large aneurysms demonstrated higher rates of perioperative death (4.8% vs 2.6% vs 0.5%), any complication (33.3% vs 23.6% vs 19.4%), and in-hospital reintervention (6.2% vs 4.0% vs 2.6%) (all P < .05). The median follow-up was 445 days. One-year mortality rates were higher in large aneurysms (12.3% vs 7.8% vs 3.8%; P < .001). After adjustment, when compared with medium-sized aneurysms, large aneurysms were associated with a significantly higher risk of perioperative death (adjusted odds ratio [aOR], 1.73; 95% confidence interval [CI], 1.09-2.72), any complication (aOR, 1.44; 95% CI, 1.18-1.76), and midterm mortality (adjusted hazard ratio, 1.50; 95% CI, 1.19-1.88), but not in-hospital reintervention (aOR, 1.46; 95% CI, 0.99-2.13). Although small aneurysms, as compared with medium-sized aneurysms, did not demonstrate a difference in any complication (aOR, 0.87; 95% CI, 0.68-1.10), in-hospital reintervention (aOR, 0.77; 95% CI, 0.42-1.33), and midterm mortality (adjusted hazard ratio, 0.78; 95% CI, 0.57-1.08], they did demonstrate a lower risk of perioperative death (aOR, 0.26; 95% CI, 0.06-0.71).

CONCLUSIONS: In cEVAR for cAAA, large aneurysms, compared with medium-sized aneurysms, were associated with higher rates of perioperative death, any complication, and midterm mortality, with in-hospital reinterventions trending toward a statistically significant higher risk. Although these results align with expectations, they emphasize the importance of effectively managing patients with large cAAAs and highlight the need for future research to determine whether patients might benefit more from medical therapy or open repair.

BACKGROUND: Patients in the United States have recently gained federally mandated, free, and ready electronic access to clinicians' computerized notes in their medical records ("open notes"). This change from longstanding practice can benefit patients in clinically important ways, but studies show some patients feel judged or stigmatized by words or phrases embedded in their records. Therefore, it is imperative that clinicians adopt documentation techniques that help both to empower patients and minimize potential harms.

OBJECTIVE: At a time when open and transparent communication among patients, families, and clinicians can spread more easily throughout medical practice, this inquiry aims to develop informed guidelines for documentation in medical records.

METHODS: Through a series of focus groups, preliminary guidelines for documentation language in medical records were developed by health professionals and patients. Using a structured focus group decision guide, we conducted 4 group meetings with different sets of 27 participants: physicians experienced with writing open notes (n=5), patients accustomed to reviewing their notes (n=8), medical student educators (n=7), and resident physicians (n=7). To generate themes, we used an iterative coding process. First-order codes were grouped into second-order themes based on the commonality of meanings.

RESULTS: The participants identified 10 important guidelines as a preliminary framework for developing notes sensitive to patients' needs.

CONCLUSIONS: The process identified 10 discrete themes that can help clinicians use and spread patient-centered documentation.

IMPORTANCE: Nocturnal hypertension while asleep is associated with substantial increases in risk of cardiovascular disease (CVD) and death. Whether hypertension while supine is a risk factor associated with CVD independent of seated hypertension remains unknown.

OBJECTIVE: To investigate the association between supine hypertension and CVD outcomes and by hypertension treatment status.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from the Atherosclerosis Risk in Communities (ARIC) study, which was established in 1987 to examine cardiovascular risk factors among middle-aged adults from 4 communities in the US. Supine and seated blood pressure were measured in more than 13 000 middle-aged adults with longitudinal surveillance for CVD over 27 years. Participants with a history of coronary heart disease (CHD), heart failure, or stroke were excluded. Data were analyzed from May 2023 through December 2024.

EXPOSURES: Supine hypertension (supine systolic blood pressure ≥130 or diastolic blood pressure ≥80 mm Hg) with and without seated hypertension (seated systolic blood pressure ≥130 or diastolic blood pressure ≥80 mm Hg).

MAIN OUTCOMES AND MEASURES: Cox proportional hazard models with adjustment for CVD risk factors were performed to investigate the association of supine hypertension with and without seated hypertension with incident CHD, heart failure, stroke, fatal CHD, and all-cause mortality.

RESULTS: Of 11 369 participants without known CVD (6332 female [55.7%] and 5037 male [44.3%]; 2858 Black [25.1%] and 8511 White [74.9%]; mean [SD] age 53.9 [5.7] years]), 16.4% (95% CI, 15.5%-17.2%) of those without seated hypertension had supine hypertension and 73.5% (95% CI, 72.2%-74.8%) of those with seated hypertension had supine hypertension. Supine hypertension was associated with incident CHD (hazard ratio [HR], 1.60; 95% CI, 1.45-1.76), heart failure (HR, 1.83; 95% CI, 1.68-2.01), stroke (HR, 1.86; 95% CI, 1.63-2.13), fatal CHD (HR, 2.18; 95% CI, 1.84-2.59), and all-cause mortality (HR, 1.43; 95% CI, 1.35-1.52) during a median (25th, 75th percentile) follow-up of 25.7 (15.4, 30.4) years, 26.9 (17.6, 30.5) years, 27.6 (18.5, 30.6 years), 28.3 (20.5, 30.7) years, and 28.3 (20.5 years, 30.7) years, respectively. There were no meaningful differences by seated hypertension status. Results were similar by hypertension medication use. Participants with supine hypertension alone had risk associations similar to those of participants with hypertension in both positions and significantly greater than those of participants with seated hypertension alone with the exception of fatal CHD; seated vs supine HRs were 0.72 (95% CI, 0.61-0.85) for CHD, 0.72 (95% CI, 0.60-0.85) for heart failure, 0.66 (95% CI, 0.51-0.86) for stroke, and 0.83 (95% CI, 0.74-0.92) for all-cause mortality.

CONCLUSIONS AND RELEVANCE: Supine hypertension regardless of seated hypertension had a higher HR for CVD risk than seated hypertension alone. Future research should evaluate supine hypertension in the setting of nocturnal hypertension and as an independent target of blood pressure treatment.