HIV, HIV-specific Factors and Myocardial Disease in Women

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In an effort to close the gap in research between men and women with HIV, NCIRE-supported Principal Investigators Drs. Phyllis Tien and Jorge Kizer recently co-authored the study “HIV, HIV-specific Factors and Myocardial Disease in Women”.

 

People with HIV (PWH) have an increased risk of cardiovascular disease. Cardiac magnetic resonance (CMR) has documented higher myocardial fibrosis, inflammation, and steatosis in PWH. However, studies have mostly relied on healthy volunteers as comparators and focused on men.

 

In their study, Drs. Tien and Kizer and their colleagues investigated the associations of HIV and HIV-specific factors with CMR phenotypes in female participants enrolled in the Women's Interagency HIV Study's New York and San Francisco sites. Primary phenotypes included myocardial native (n) T1 (fibro-inflammation), extracellular volume fraction (ECV, fibrosis) and triglyceride content (steatosis). Associations were evaluated with multivariable linear regression, and results pooled or meta-analyzed across centers.

 

Read more: https://pubmed.ncbi.nlm.nih.gov/38356158/

 

Phyllis Tien, MD is a clinical translational researcher who investigates chronic viral infections, specifically HIV and HCV, and their metabolic and inflammatory consequences on long term organ injury (e.g. liver, bone and vascular injury). As part of this work, she also studies novel non-invasive techniques to estimate steatosis and fibrosis using magnetic resonance (MR) imaging and ultrasound-based transient elastography as well as novel CT and MR imaging methods to measure bone and vascular injury.

 

Jorge Kizer, MD, MSc is the Chief of the Division of Cardiology for the San Francisco VA Health Care System. His research program seeks to advance the understanding of risk factors for heart disease and stroke in order to improve prevention, risk stratification, and treatment of these disorders. These investigations leverage molecular epidemiology and cardiovascular imaging to identify biochemical markers and endophenotypes involved in the initiation, development, and progression of cardiovascular diseases.

Addressing disparities in the global epidemiology of stroke

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Stroke, the second leading cause of death and the third leading cause of disability worldwide, has seen numbers of those impacted by the disease decrease significantly; yet not everyone can revel in this medical achievement.

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Co-authoring a recent article in Nature Reviews Neurology titled “Addressing disparities in the global epidemiology of stroke”, NCIRE-supported Principal Investigator and Board Member Dr. Bruce Ovbiagele highlights the rapid uptick in the burden of stroke in low- and middle-income countries (LMICs). The article sites that epidemiological, socioeconomic, and demographic shifts are the culprit for this desperate disparity, with increases to the incidence of stroke and other non-communicable diseases.

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While high-income countries (HICs) have boasted lower incidents of stroke than their LMIC counterparts, there is still disparities in stroke epidemiology along racial, ethnic, socioeconomic, and geographical lines.

 

Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, is a vascular neurologist, clinical epidemiologist, and health equity scholar, with a focus on reducing the burden of stroke. He is Professor of Neurology and Associate Dean at UCSF, as well as Chief of Staff at SFVAHCS, and serves a Statuary Director on the NCIRE Board.

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Learn more: https://www.nature.com/articles/s41582-023-00921-z

NCIRE is proud to announce the following exciting new developments for research conducted by NCIRE-supported Principal Investigators Drs. Michael Shlipak and Michelle Estrella:

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UCSF/SFVAHCS research collaboration reveals lack of albuminuria testing and describes treatment approaches in the real-world setting for patients with type 2 diabetes and chronic kidney disease

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University of California, San Francisco (UCSF), Kidney Health Research Collaborative (KHRC), and San Francisco VA Health Care System (SFVAHCS) has released 2 real-world evidence studies that are focused on helping appropriate patients with chronic kidney disease (CKD) access more timely treatment.

 

More than 1 in 7 American adults (14%) are estimated to have CKD, with diabetes and high blood pressure being the most common causes of CKD in American adults.(1) Many of these patients are unaware of their disease because there are typically no or few symptoms in the early stages of the disease and, historically, there is under-detection of CKD due to lack of testing. Treatment for CKD depends on the stage of disease and, while there is no cure, treatment can help slow its progression and lower the burden of associated heart disease complications.(2)

 

We are pleased to report the findings from the first 2 collaborative studies with UCSF and SFVAHCS.

 

• Prescription Patterns of Cardiovascular- and Kidney-Protective Therapies Among Patients with Type 2 Diabetes and Chronic Kidney Disease was undertaken to assess the prevalence and correlations of prescriptions for 2 drugs that protect against CKD progression and heart disease events, sodium-glucose cotransporter 2 inhibitors (SGLT2is) and/or glucagon-like peptide 1 receptor agonists (GLP1-RAs) in individuals with T2D with and without CKD. This was a cross-sectional analysis of SGLT2i and GLP1-RA prescriptions from 1 January 2019 to 31 December 2020 in the Veterans Health Administration (VHA) System. This study, which was published in Diabetes Care, demonstrated that patients with the greatest risk of cardiovascular disease (CVD) and kidney failure (ie, with severe albuminuria, elevated 10-year risk of atherosclerotic CVD, and 5-year risk of end-stage kidney disease >5%) were less likely to receive SGLT2is or GLP1-RAs.(3)

 

• Estimated Prevalence and Testing for Albuminuria in US Adults at Risk for Chronic Kidney Disease aimed to estimate the extent of albuminuria under-detection from lack of testing and evaluate its association with provision of common CKD treatments in patients with hypertension or diabetes. Using data from the 2007 to 2018 National Health and Nutrition Examination Surveys (NHANES), a model was created to predict abnormal albuminuria levels based on multiple predictor variables; this model was then applied to a 5% random sample of the Optum de-identified electronic health record dataset from 1 January 2017 to 31 December 2018 to predict the likelihood of abnormal albuminuria in untested patients in the clinical dataset. The results of these analyses, recently published in JAMA Network Open, estimate that two-thirds of patients with albuminuria were undetected due to lack of testing and that albuminuria testing was associated with greater likelihood of receiving CKD treatments.4 With improved identification of albuminuria, there would be a substantial opportunity to optimize care delivery for reducing kidney disease progression and cardiovascular complications.(4)

 

Drs. Estrella and Shlipak commitment to these research efforts, “We’re excited to continue these collaborative partnerships as it strongly aligns with the KHRC’s longstanding research dedication to optimize the prevention, early detection, and treatment of kidney disease and its associated cardiovascular complications. We believe that such academic-industry partnerships have the potential to close the gap between scientific discoveries and clinical care delivery, and additionally to accelerate research focused on early stages of kidney disease, which traditionally has lagged behind research into advanced stages of CKD.”

 

For more information, please contact Michelle.Estrella@ucsf.edu or Michael.Shlipak@ucsf.edu.

 

About UCSF and SFVAHCS’s Commitment in Kidney Disease

The University of California, San Francisco (UCSF) is one of the top hospitals in Northern California and the nation for kidney care.(5) The Kidney Health Research Collaborative (KHRC), based at UCSF and the San Francisco Veterans Affairs Health Care System (SFVAHCS), encompasses a group of leading scientists from multiple disciplines working to improve kidney health worldwide.(6) A non-profit research institute, the Northern California Institute for Research and Education (NCIRE) is a critical partner for the KHRC, as NCIRE provides outstanding administrative support for these awards from Bayer to KHRC. NCIRE promotes and supports the research of investigators who have joint faculty appointments at both UCSF and SFVAHCS, such as Drs. Estrella and Shlipak. San Francisco VA Health Care System (SFVAHCS) is a comprehensive network that provides health services to Veterans through the San Francisco VA Medical Center (SFVAMC) and nine community-based outpatient clinics in Santa Rosa, Oakland, Eureka, Ukiah, Clearlake, San Bruno and downtown San Francisco.

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Funding for this research was provided by Bayer Healthcare Pharmaceuticals.

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References

1. Centers for Disease Control and Prevention. Chronic kidney disease in the United States, 2023. May 30, 2023. Accessed July 24, 2023. https://www.cdc.gov/kidneydisease/publications-resources/CKD-national-facts.html

2. National Health Service. Chronic kidney disease – treatment. March 23, 2023. Accessed July 24, 2023. https://www.nhs.uk/conditions/kidney-disease/treatment/

3. Lamprea-Montealegre JA, Madden E, Tummalapalli SL, et al. Prescription patterns of cardiovascular- and kidney-protective therapies among patients with type 2 diabetes and chronic kidney disease. Diabetes Care. 2022;45:2900-2906.

4. Chu CD, Xia F, Yuxian D, et al. Estimated prevalence and testing for albuminuria in US adults at risk for chronic kidney disease. JAMA Network Open. 2023;6(7):e2326230. doi:10.1001/jamanetworkopen.2023.26230

5. UCSF. Kidney disease (nephrology). Accessed July 31, 2023. https://www.ucsfhealth.org/list-of-clinics/kidney-disease-nephrology

6. UCSF. Kidney Health Research Collaborative. Accessed July 31, 2023. https://khrc.ucsf.edu/

 

Geriatrics Team Publications Explore Aging Research Challenges, and Nursing Home Needs for Older Dementia patients

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Lead by University of California San Francisco (UCSF) Principal Investigator Dr. James Deardorff, several NCIRE-supported Investigators recently co-published two articles exploring research challenges in the geriatrics field and predicting the level of nursing home care needs for older adults with dementia.

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Published in the Journal of the American Geriatrics Society, the article “Around the EQUATOR with Clin-STAR: Prediction modeling opportunities and challenges in aging research” highlights methodologic challenges that aging-focused researchers will encounter when designing and reporting studies involving prediction models for older adults and provides guidance for addressing these challenges.

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NCIRE-supported Investigators Drs. Alexander Smith, John Boscardin, and Sei Lee joined Dr. Deardorff in suggesting that clinical prediction models are becoming increasingly popular and are often applied to populations involving older adults. Proper design and reporting of these studies are critical to ensure that they are developed and validated in a manner that does not misinform individuals or worsen healthcare inequities.

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Read the article here: https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18704

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In another article co-published by Dr. Deardorff and NCIRE-supported Investigators Drs. Deborah Barnes, John Boscardin, Kenneth Covinsky, Sei Lee, and Alexander Smith, the research team addressed the question: can need for nursing home level of care (NHLOC) in community-dwelling older adults with dementia be accurately predicted?

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Titled “Development and External Validation of Models to Predict Need for Nursing Home Level of Care in Community-Dwelling Older Adults With Dementia”, the prognostic study showed that relatively simple models using self-reported or proxy responses can predict need for NHLOC among older adults with probable dementia with moderate discrimination and excellent calibration. Given that most individuals with dementia ultimately need NHLOC, model estimates may help frame conversations between patients and families/caregivers regarding care planning.

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The study was published by the Journal of the American Medical Association (JAMA) Network-JAMA Internal Medicine, and may be read here:

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2812543

 

The Middle-Out Approach to reconceptualizing, assessing, and analyzing traumatic stress reactions

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NCIRE-supported Researchers, Drs. Shira Maguen and Sabra Inslicht co-published a paper with University of California, San Francisco and San Francisco VA Health Care System Principal Investigator Dr. Shane Adams that posits the importance of implementing the Middle-Out Approach to reconceptualizing, assessing, and analyzing traumatic stress reactions.

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Published in the International Society for Traumatic Stress Studies’ Journal of Traumatic Stress by Shane Adams et al., the paper introduces the Middle-Out Approach as a new integrative methodological framework for advancing the study and treatment of traumatic stress reactions to be increasingly representative of more individuals and contexts. This approach is differentiated from other practices by the assessments and data used as well as their application and analysis.

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The Middle-Out Approach aims to uncover unique theory- and data-driven phenotypes characterizing traumatic stress reactions that may have been previously obstructed by historical practices and restrictions of bottom-up, top-down, and variable centered-only designs and statistical approaches. This approach can help identify and explicate intra- and interindividual differences in traumatic stress reactions that can lead to increased empirical and diagnostic representations of unique experiences within diverse communities that meaningfully impact treatments.

 

Within the article, the research team provides a conceptual roadmap for integrating existing methods into new or existing studies to facilitate clear clinical applications and increased patient-centered care to address persisting research and clinical issues.

 

Sabra Inslicht, PhD, is a Staff Psychologist with the Mental Health Service with the San Francisco VA Health Care System (SFVAHCS), and Adjunct Professor of Psychiatry at the University of California, San Francisco (UCSF). Dr. Inslicht’s research focuses on identifying neurobiological mechanisms that underlie post-traumatic stress disorder (PTSD), fear conditioning models of PTSD, putative biomarkers that may explain sex differences in PTSD, and pharmacological and psychological interventions to ameliorate stress responding and insomnia.

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Shira Maguen, PhD is the Mental Health Director of the Post-9/11 Integrated Care Clinic and Staff Psychologist on the Posttraumatic Stress Disorder Clinical Team (PCT) at the SFVAHCS, and Vice Chair of SFVAHCS and Professor in the Department of Psychiatry and Behavioral Sciences, UCSF School of Medicine. Dr. Maguen was appointed to and served on the Creating Options for Veterans' Expedited Recovery (COVER) Commission. She is also the San Francisco site co-lead for the VA Women’s Practice Based Research Network (PBRN) and Director of the SFVAHCS PTSD MIRECC Postdoctoral Research Fellowship.

 

Read More: https://onlinelibrary.wiley.com/doi/10.1002/jts.23005