Publications

2024

Morooka, Hikaru, Eirin B Haug, Vegard Malmo, Jan Pål Loennechen, Kenneth J Mukamal, Abhijit Sen, Imre Janszky, and Julie Horn. (2024) 2024. “Parity, Infertility, Age at First Birth and Risk of Atrial Fibrillation: Data from the HUNT Study”. European Journal of Preventive Cardiology. https://doi.org/10.1093/eurjpc/zwae215.

AIMS: Although parity, infertility, and age at first birth are important for later development of cardiovascular disease, research on their association with atrial fibrillation (AF) is limited.

METHODS: We linked data from the population-based HUNT study, the Medical Birth Registry of Norway (MBRN) and validated medical records from local hospitals. A total of 24,015 women aged 45 years or older were followed for verified incident AF. Parity and age at first birth were retrieved from the MBRN or from self-reported questionnaires in the HUNT. History of infertility was self-reported on the HUNT questionnaire. Cox-proportional hazard models were used to calculate hazard ratios (HR) for the multivariable-adjusted associations of parity, infertility, and age at first birth with risk of AF.

RESULTS: During a median follow-up of 12.8 years, 1,448 (6.0%) participants developed AF. Women with higher parity (four or more births vs. two births) were at 21% higher risk of AF (HR 1.21, 95% confidence interval (CI), 1.05-1.39). History of infertility was also associated with risk of AF (HR 1.20, 95% CI, 1.02-1.42). Among parous women, younger age at first birth (<20 years vs. 20-29 years) was associated with a 20% higher risk of AF (HR 1.20, 95% CI, 1.03-1.40).

CONCLUSION: Women with four or more births, or a history of infertility, or younger age at first birth have approximately a 20% higher risk of AF among women over 45 years old.

Salmi, Liz, Danielle Peereboom, David A Dorr, Leilani R Graham, Jennifer L Wolff, and Catherine M DesRoches. (2024) 2024. “Patient Portals Fail to Collect Structured Information About Who Else Is Involved in a Person’s Care”. Journal of Medical Internet Research 26: e49394. https://doi.org/10.2196/49394.

The US health care delivery system does not systematically engage or support family or friend care partners. Meanwhile, the uptake and familiarity of portals to personal health information are increasing among patients. Technology innovations, such as shared access to the portal, use separate identity credentials to differentiate between patients and care partners. Although not well-known, or commonly used, shared access allows patients to identify who they do and do not want to be involved in their care. However, the processes for patients to grant shared access to portals are often limited or so onerous that interested patients and care partners often circumvent the process entirely. As a result, the vast majority of care partners resort to accessing portals using a patient's identity credentials-a "do-it-yourself" solution in conflict with a health systems' legal responsibility to protect patient privacy and autonomy. The personal narratives in this viewpoint (shared by permission) elaborate on quantitative studies and provide first-person snapshots of challenges faced by patients and families as they attempt to gain or grant shared access during crucial moments in their lives. As digital modalities increase patient roles in health care interactions, so does the importance of making shared access work for all stakeholders involved-patients, clinicians, and care partners. Electronic health record vendors must recognize that both patients and care partners are important users of their products, and health care organizations must acknowledge and support the critical contributions of care partners as distinct from patients.

Hagglund, Maria, Anna Kharko, Annika Bärkås, Charlotte Blease, Åsa Cajander, Catherine DesRoches, Asbjørn Johansen Fagerlund, et al. (2024) 2024. “A Nordic Perspective on Patient Online Record Access and the European Health Data Space”. Journal of Medical Internet Research 26: e49084. https://doi.org/10.2196/49084.

The Nordic countries are, together with the United States, forerunners in online record access (ORA), which has now become widespread. The importance of accessible and structured health data has also been highlighted by policy makers internationally. To ensure the full realization of ORA's potential in the short and long term, there is a pressing need to study ORA from a cross-disciplinary, clinical, humanistic, and social sciences perspective that looks beyond strictly technical aspects. In this viewpoint paper, we explore the policy changes in the European Health Data Space (EHDS) proposal to advance ORA across the European Union, informed by our research in a Nordic-led project that carries out the first of its kind, large-scale international investigation of patients' ORA-NORDeHEALTH (Nordic eHealth for Patients: Benchmarking and Developing for the Future). We argue that the EHDS proposal will pave the way for patients to access and control third-party access to their electronic health records. In our analysis of the proposal, we have identified five key principles for ORA: (1) the right to access, (2) proxy access, (3) patient input of their own data, (4) error and omission rectification, and (5) access control. ORA implementation today is fragmented throughout Europe, and the EHDS proposal aims to ensure all European citizens have equal online access to their health data. However, we argue that in order to implement the EHDS, we need more research evidence on the key ORA principles we have identified in our analysis. Results from the NORDeHEALTH project provide some of that evidence, but we have also identified important knowledge gaps that still need further exploration.

Stull, April J, Aedín Cassidy, Luc Djousse, Sarah A Johnson, Robert Krikorian, Johanna W Lampe, Kenneth J Mukamal, et al. (2024) 2024. “The State of the Science on the Health Benefits of Blueberries: A Perspective”. Frontiers in Nutrition 11: 1415737. https://doi.org/10.3389/fnut.2024.1415737.

Mounting evidence indicates that blueberry consumption is associated with a variety of health benefits. It has been suggested that regular consumption of blueberries can support and/or protect against cardiovascular disease and function, pre-diabetes and type 2 diabetes, and brain and cognitive function in individuals with health conditions and age-related decline. Further, mechanistic investigations highlight the role of blueberry anthocyanins in mediating these health benefits, in part through interactions with gut microbiota. Also, nutritional interventions with blueberries have demonstrated the ability to improve recovery following exercise-induced muscle damage, attributable to anti-inflammatory effects. Despite these advancements in blueberry health research, research gaps persist which affects the generalizability of findings from clinical trials. To evaluate the current state of knowledge and research gaps, a blueberry health roundtable with scientific experts convened in Washington, DC (December 6-7, 2022). Discussions centered around five research domains: cardiovascular health, pre-diabetes and diabetes, brain health and cognitive function, gut health, and exercise recovery. This article synthesizes the outcomes of a blueberry research roundtable discussion among researchers in these domains, offering insights into the health benefits of blueberries and delineating research gaps and future research directions.

Barzilay, Joshua I, Petra Buzkova, Suzette J Bielinski, Mary Frances Cotch, Bryan Kestenbaum, Thomas R Austin, Laura Carbone, Kenneth J Mukamal, and Matthew J Budoff. (2024) 2024. “The Association of Microvascular Disease and Endothelial Dysfunction With Vertebral Trabecular Bone Mineral Density : The MESA Study”. Osteoporosis International : A Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. https://doi.org/10.1007/s00198-024-07152-y.

UNLABELLED: Retinopathy and albuminuria are associated with hip fracture risk. We investigated whether these disorders and endothelial dysfunction (which underlies microvascular diseases) were associated with low trabecular bone density. No significant associations were found, suggesting that microvascular diseases are not related to fracture risk through low trabecular bone density.

PURPOSE: Microvascular diseases of the eye, kidney, and brain are associated with endothelial dysfunction and increased hip fracture risk. To explore the basis for higher hip fracture risk, we comprehensively examined whether markers of microvascular disease and/or endothelial dysfunction are related to trabecular bone mineral density (BMD), a proximate risk factor for osteoporotic fractures.

METHODS: Among 6814 participants in the Multi-Ethnic Study of Atherosclerosis study (MESA), we derived thoracic vertebral trabecular BMD from computed tomography of the chest and measured urine albumin to creatinine ratios (UACR), retinal arteriolar and venular widths, flow mediated dilation (FMD) of the brachial artery after 5 min of ischemia; and levels of five soluble endothelial adhesion markers (ICAM-1, VCAM-1, L-selectin, P-selectin, and E-selectin). Linear regression models were used to examine the association of trabecular BMD with markers of microvascular disease and with markers of endothelial dysfunction.

RESULTS: We observed no significant associations of UACR, retinal arteriolar or venular widths, or FMD with BMD. We also observed no statistically significant association of spine trabecular BMD with levels of endothelial adhesion markers. Men and women had largely similar results.

CONCLUSION: We conclude that there is little evidence to connect thoracic spine trabecular BMD to microvascular disorders or to endothelial dysfunction among multi-ethnic middle-aged and older adults. Other factors beyond trabecular BMD (e.g., bone quality or predisposition to falling) may be responsible for the associations of microvascular disease with osteoporotic fractures.

Riffin, Catherine, Jessica Cassidy, Jamie M Smith, Erika Begler, Danielle Peereboom, Hillary D Lum, Catherine M DesRoches, and Jennifer L Wolff. (2024) 2024. “Care Partner Perspectives on the Use of a Patient Portal Intervention to Promote Care Partner Identification in Dementia Care”. Journal of Applied Gerontology : The Official Journal of the Southern Gerontological Society, 7334648241262649. https://doi.org/10.1177/07334648241262649.

Care partners are crucial to supporting the complex health needs of older adults with dementia, but they are not systematically identified in care delivery. As part of a real-world implementation project in geriatric primary care, we adapted a portal-based agenda setting intervention, OurNotes, by incorporating items to help care partners self-identify. Semi-structured interviews were conducted with care partners (N = 15) who completed the adapted OurNotes to explore their perceptions of the tool (usability, benefits, and challenges) and recommendations for refinement. The data were analyzed using thematic analysis. Benefits included enhancing care partners' preparedness for the visit and opening a direct channel to express concerns about patients' cognition and memory loss to clinicians. Challenges pertained to clinician responsiveness; recommendations focused on enabling the submitted OurNotes responses to be edited and updated by multiple care partners. Such refinements may help to maximize the impact of adapted OurNotes' and potential for future implementation and dissemination.

Caron, Elisa, Sai Divya Yadavalli, Mohit Manchella, Gabriel Jabbour, Tim J Mandigers, Jorge L Gomez-Mayorga, Randall A Bloch, et al. (2024) 2024. “Outcomes of carotid revascularization stratified by procedure in eGFR”. Journal of Vascular Surgery. https://doi.org/10.1016/j.jvs.2024.06.008.

OBJECTIVE: Renal failure is a predictor of adverse outcomes in carotid revascularization. There has been debate regarding the benefit of revascularization in patients with severe CKD or on dialysis.

METHODS: VQI patients undergoing TCAR, tfCAS, or CEA between 2016 and 2023 with eGFR <30 ml/min/1.73m2 or on dialysis were included. Patients were divided into cohorts based on procedure. Additional analyses were performed for patients on dialysis only and by symptomatology. Primary outcomes were perioperative stroke/death/MI (SDM). Secondary outcomes included perioperative death, stroke, MI, CNI and stroke/death. Inverse probability of treatment weighting (IPW) was performed based on treatment assignment to TCAR, tfCAS, and CEA patients and adjusted for demographics, comorbidities, and pre-op symptoms. Chi-square and multivariable logistic regression analysis were used to evaluate the association of procedure with perioperative outcomes in the weighted cohort. Five-year survival was evaluated using Kaplan-Meier and weighted Cox regression.

RESULTS: In the weighted cohort, 13,851 patients with eGFR of <30 (2,506 on dialysis) underwent TCAR (3,639, dialysis 704), tfCAS (1,975, 393) or CEA (8,237, 1,409) during the study period. Compared with TCAR, CEA had higher odds of stroke/death/MI (2.8% vs 3.6%, aOR 1.27 [1.00,1.61], p=.049), and MI (0.7% vs 1.5%, aOR 2.00 [1.31,3.05], p=.001)... Compared to TCAR, rates of SDM (2.8%vs5.8%), stroke (1.2%vs2.6%), death (0.9%vs2,4%)were all higher for tfCAS. In asymptomatic patients CEA patients had higher odds of MI (0.7% vs 1.3%, aOR 1.85[1.15, 2.97]p=.011) and CNI (0.3% vs 1.9%, aOR 7.23[3.28, 15.9] p<.001). Like the primary analysis, asymptomatic tfCAS patients demonstrated higher odds of death, and stroke/death. Symptomatic CEA patients demonstrated no difference in stroke, death or stroke/death. While tfCAS patients demonstrated higher odds of death, stroke, MI, stroke/death, and SDM. In both groups, 5-year survival was similar for TCAR and CEA (eGFR <30: 75.1% vs 74.2%, aHR1.06, p=.3) and lower for tfCAS (eGFR <30: 75.1% vs 70.4%, aHR1.44, p<.001) CONCLUSION: CEA and TCAR had similar odds of stroke and death and are both a reasonable choice in this population; however, TCAR may be better in patients with increased risk of MI. Additionally, tfCAS patients were more likely to have worse outcomes after weighting for symptom status. Finally, while patients with reduced eGFR have worse outcomes than their healthy peers, this analysis shows that the majority of patients survive long enough to benefit from the potential stroke risk reduction provided by all revascularization procedures.

Metlock, Faith E, Thomas Hinneh, Chitchanok Benjasirisan, Abeer Alharthi, Oluwabunmi Ogungbe, Ruth-Alma N Turkson-Ocran, Cheryl R Himmelfarb, and Yvonne Commodore-Mensah. (2024) 2024. “Impact of Social Determinants of Health on Hypertension Outcomes: A Systematic Review”. Hypertension (Dallas, Tex. : 1979). https://doi.org/10.1161/HYPERTENSIONAHA.123.22571.

Despite ample evidence linking social determinants of health (SDoH) and hypertension outcomes, efforts to address SDoH in the context of hypertension prevention and self-management are not commensurate with the burden and impact of hypertension. To provide valuable insights into the development of targeted and effective strategies for preventing and managing hypertension, this systematic review, guided by the Healthy People 2030 SDoH framework, aims to summarize the inclusion, measurement, and evaluation of SDoH in studies examining hypertension outcomes, with a focus on characterizing SDoH constructs and summarizing the current evidence of their influence on hypertension outcomes. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive search of electronic databases identified 10 608 unique records, from which 57 articles meeting inclusion criteria were analyzed. The studies, conducted nationally or regionally across the United States, revealed that higher educational attainment, health insurance coverage, income, and favorable neighborhood characteristics were associated with lower hypertension prevalence and better hypertension control among US adults. The findings underscore the importance of addressing SDoH such as education, health care access, economic stability, neighborhood environments, and social context to reduce hypertension disparities. Multilevel collaboration and community-engaged practices are necessary to tackle these disparities effectively.

Wolff, Jennifer L, Aleksandra Wec, Danielle Peereboom, Kelly T Gleason, Halima Amjad, Julia G Burgdorf, Jessica Cassidy, et al. (2024) 2024. “Care Partners and Consumer Health Information Technology: A Framework to Guide Systems-Level Initiatives in Support of Digital Health Equity”. Learning Health Systems 8 (Suppl 1): e10408. https://doi.org/10.1002/lrh2.10408.

INTRODUCTION: Consumer-oriented health information technologies (CHIT) such as the patient portal have a growing role in care delivery redesign initiatives such as the Learning Health System. Care partners commonly navigate CHIT demands alongside persons with complex health and social needs, but their role is not well specified.

METHODS: We assemble evidence and concepts from the literature describing interpersonal communication, relational coordination theory, and systems-thinking to develop an integrative framework describing the care partner's role in applied CHIT innovations. Our framework describes pathways through which systematic engagement of the care partner affects longitudinal work processes and multi-level outcomes relevant to Learning Health Systems.

RESULTS: Our framework is grounded in relational coordination, an emerging theory for understanding the dynamics of coordinating work that emphasizes role-based relationships and communication, and the Systems Engineering Initiative for Patient Safety (SEIPS) model. Cross-cutting work systems geared toward explicit and purposeful support of the care partner role through CHIT may advance work processes by promoting frequent, timely, accurate, problem-solving communication, reinforced by shared goals, shared knowledge, and mutual respect between patients, care partners, and care team. We further contend that systematic engagement of the care partner in longitudinal work processes exerts beneficial effects on care delivery experiences and efficiencies at both individual and organizational levels. We discuss the utility of our framework through the lens of an illustrative case study involving patient portal-mediated pre-visit agenda setting.

CONCLUSIONS: Our framework can be used to guide applied embedded CHIT interventions that support the care partner role and bring value to Learning Health Systems through advancing digital health equity, improving user experiences, and driving efficiencies through improved coordination within complex work systems.

Zhao, Longgang, Xinyuan Zhang, Brenda M Birmann, Christopher J Danford, Michelle Lai, Tracey G Simon, Andrew T Chan, et al. (2024) 2024. “Pre-Diagnostic Plasma Inflammatory Proteins and Risk of Hepatocellular Carcinoma in Three Population-Based Cohort Studies from the United States and the United Kingdom”. International Journal of Cancer. https://doi.org/10.1002/ijc.35054.

Previous studies suggest a role for inflammation in hepatocarcinogenesis. However, no study has comprehensively evaluated associations between circulating inflammatory proteins and risk of hepatocellular carcinoma (HCC) among the general population. We conducted a nested case-control study in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) with 56 pairs of incident HCC cases and controls. External validation was performed in the UK Biobank (34 HCC cases and 48,471 non-HCC controls). Inflammatory protein levels were measured in pre-diagnostic plasma using the Olink® Inflammation Panel. We used conditional logistic regression to calculate multivariable odds ratios (ORs) with 95% confidence intervals (CIs) for associations between a 1-standard deviation (SD) increase in biomarker levels and HCC risk, considering a statistically significant threshold of false discovery rate (FDR)-adjusted p < .05. In the NHS/HPFS, among 70 analyzed proteins with call rates >80%, 15 proteins had significant associations with HCC risk (pFDR < .05). Two proteins (stem cell factor, OR per SD = 0.31, 95% CI = 0.16-0.58; tumor necrosis factor superfamily member 12, OR per SD = 0.51, 95% CI = 0.31-0.85) were inversely associated whereas 13 proteins were positively associated with risk of HCC; positive ORs per SD ranged from 1.73 for interleukin (IL)-10 to 2.35 for C-C motif chemokine-19. A total of 11 proteins were further replicated in the UK Biobank. Seven of the eight selected positively associated proteins also showed positive associations with HCC risk by enzyme-linked immunosorbent assay, with ORs ranging from 1.56 for IL-10 to 2.72 for hepatocyte growth factor. More studies are warranted to further investigate the roles of these observed inflammatory proteins in HCC etiology, early detection, risk stratification, and disease treatment.