Browsing by Subject "CVD"

Now showing 1 - 5 of 5
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    Liver-specific in vivo base editing of Angptl3 via AAV delivery efficiently lowers blood lipid levels in mice
    (BMC, 2023-06-15) Zuo, Yuanbojiao; Zhang, Chen; Zhou, Yuan; Li, Haiwen; Xiao, Weidong; Herzog, Roland W.; Xu, Jie; Zhang, Jifeng; Chen, Y. Eugene; Han, Renzhi; Pediatrics, School of Medicine
    Background: Gene editing has emerged as an exciting therapeutic development platform for numerous genetic and nongenetic diseases. Targeting lipid-modulating genes such as angiopoietin-related protein 3 (ANGPTL3) with gene editing offers hope for a permanent solution to lower cardiovascular disease risks associated with hypercholesterolemia. Results: In this study, we developed a hepatocyte-specific base editing therapeutic approach delivered by dual adeno-associated virus (AAV) to enable hepatocyte-specific targeting of Angptl3 to lower blood lipid levels. Systemic AAV9-mediated delivery of AncBE4max, a cytosine base editor (CBE), targeting mouse Angptl3 resulted in the installation of a premature stop codon in Angptl3 with an average efficiency of 63.3 ± 2.3% in the bulk liver tissue. A near-complete knockout of the ANGPTL3 protein in the circulation were observed within 2-4 weeks following AAV administration. Furthermore, the serum levels of triglyceride (TG) and total cholesterol (TC) were decreased by approximately 58% and 61%, respectively, at 4 weeks after treatment. Conclusions: These results highlight the promise of liver-targeted Angptl3 base editing for blood lipid control.
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    Longitudinal Relationships Between Depressive Symptom Clusters and Inflammatory Biomarkers Implicated in Cardiovascular Disease in People with Depression
    (2021-12) Patel, Jay Sunil; Stewart, Jesse; Cyders, Melissa; Wu, Wei; Gupta, Samir
    Systemic inflammation is one potential mechanism underlying the depression to cardiovascular disease (CVD) relationship. In addition, somatic rather than cognitive/affective symptoms of depression may be more predictive of poorer CVD outcomes due to systemic inflammation. However, the small existing literature in this area has yielded mixed results. Therefore, the present study aimed to examine longitudinal associations between depressive symptom clusters and inflammatory biomarkers implicated in CVD (i.e., interleukin-6, IL-6; and C-reactive protein, CRP) using data from the eIMPACT trial. In addition, race was examined as a moderator given findings from two previous studies. The eIMPACT trial was a phase II, single-center randomized controlled trial comparing 12 months of the eIMPACT intervention to usual primary care for depression. Participants were 216 primary care patients aged ≥ 50 years with a depressive disorder and CVD risk factors but no clinical CVD from a safety net healthcare system (Mage = 58.7 years, 78% female, 50% Black, Meducation = 12.8 years). Depressive symptoms clusters (i.e., somatic and cognitive/affective clusters) were assessed using the Patient Health Questionnaire-9 (PHQ-9). IL-6 and high-sensitivity CRP were assessed by the local clinical research laboratory using R&D Systems ELISA kits. Change variables were modeled in MPlus using a latent difference score approach. The results of this study were largely null. Very few associations between depressive symptom clusters and inflammatory biomarkers implicated in CVD were observed, and the detected relationships may be due to type I error. Similarly, only one association was observed for race as a moderator, and the detected relationship may be due to type I error. The present findings do not provide strong support for the longitudinal associations between depressive symptom clusters and inflammatory biomarkers implicated in CVD nor the moderating effects of race. However, the present findings do not rule out the possibility of these relationships given important study limitations, such as study design and power. Future prospective cohort studies with multiple waves of data collection are needed to determine the longitudinal associations between depression facets and various inflammatory biomarkers implicated in CVD. In addition, a biologically-based approach to identifying facets of depression – e.g., the endophenotype model – may provide a clearer understanding of the depression-inflammation relationship.
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    Pregnancy as a Window to Future Cardiovascular Health: Design and Implementation of the nuMoM2b Heart Health Study
    (Oxford University Press, 2016-03-15) Haas, David M.; Ehrenthal, Deborah B.; Koch, Matthew A.; Catov, Janet M.; Barnes, Shannon E.; Facco, Francesca; Parker, Corette B.; Mercer, Brian M.; Bairey-Merz, C. Noel; Silver, Robert M.; Wapner, Ronald J.; Simhan, Hyagriv N.; Hoffman, Matthew K.; Grobman, William A.; Greenland, Philip; Wing, Deborah A.; Saade, George R.; Parry, Samuel; Zee, Phyllis C.; Reddy, Uma M.; Pemberton, Victoria L.; Burwen, Dale R.; Department of Obstetrics and Gynecology, IU School of Medicine
    The National Institute of Child Health and Human Development's Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study (HHS) was designed to investigate the relationships between adverse pregnancy outcomes and modifiable risk factors for cardiovascular disease. The ongoing nuMoM2b-HHS, which started in 2013, is a prospective follow-up of the nuMoM2b cohort, which included 10,038 women recruited between 2010 and 2013 from 8 centers across the United States who were initially observed over the course of their first pregnancies. In this report, we detail the design and study procedures of the nuMoM2b-HHS. Women in the pregnancy cohort who consented to be contacted for participation in future studies were approached at 6-month intervals to ascertain health information and to maintain ongoing contact. Two to 5 years after completion of the pregnancy documented in the nuMoM2b, women in the nuMoM2b-HHS were invited to an in-person study visit. During this visit, they completed psychosocial and medical history questionnaires and had clinical measurements and biological specimens obtained. A subcohort of participants who had objective assessments of sleep-disordered breathing during pregnancy were asked to repeat this investigation. This unique prospective observational study includes a large, geographically and ethnically diverse cohort, rich depth of phenotypic information about adverse pregnancy outcomes, and clinical data and biospecimens from early in the index pregnancy onward. Data obtained from this cohort will provide mechanistic and clinical insights into how data on a first pregnancy can provide information about the potential development of subsequent risk factors for cardiovascular disease.
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    Taking a Stand Against Air Pollution—The Impact on Cardiovascular Disease
    (Elsevier, 2021) Brauer, Michael; Casadei, Barbara; Harrington, Robert A.; Kovacs, Richard; Sliwa, Karen; Medicine, School of Medicine
    Although the attention of the world and the global health community specifically is deservedly focused on the COVID-19 pandemic, other determinants of health continue to have large impacts and may also interact with COVID-19. Air pollution is one crucial example. Established evidence from other respiratory viruses and emerging evidence for COVID-19 specifically indicates that air pollution alters respiratory defense mechanisms leading to worsened infection severity. Air pollution also contributes to co-morbidities that are known to worsen outcomes amongst those infected with COVID-19, and air pollution may also enhance infection transmission due to its impact on more frequent coughing. Yet despite the massive disruption of the COVID-19 pandemic, there are reasons for optimism: broad societal lockdowns have shown us a glimpse of what a future with strong air pollution measures could yield. Thus, the urgency to combat air pollution is not diminished, but instead heightened in the context of the pandemic.
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    Variation in statin prescription among veterans with HIV and known atherosclerotic cardiovascular disease
    (Elsevier, 2022) Erqou, Sebhat; Papaila, Alexa; Halladay, Christopher; Ge, Augustus; Liu, Michael A.; Jiang, Lan; Lally, Michelle; Menon, Anupama; Shah, Nishant R.; Miech, Edward; Virani, Salim S.; Zullo, Andrew R.; Shireman, Theresa I.; Longenecker, Christopher T.; Ross, David; Sullivan, Jennifer L.; Wu, Wen-Chih; Rudolph, James L.; Emergency Medicine, School of Medicine
    Background: People with HIV have increased atherosclerotic cardiovascular disease (ASCVD) risk, worse outcomes following incident ASCVD, and experience gaps in cardiovascular care, highlighting the need to improve delivery of preventive therapies in this population. Objective: Assess patient-level correlates and inter-facility variations in statin prescription among Veterans with HIV and known ASCVD. Methods: We studied Veterans with HIV and existing ASCVD, ie, coronary artery disease (CAD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD), who received care across 130 VA medical centers for the years 2018-2019. We assessed correlates of statin prescription using two-level hierarchical multivariable logistic regression. Median odds ratios (MORs) were used to quantify inter-facility variation in statin prescription. Results: Nine thousand six hundred eight Veterans with HIV and known ASCVD (mean age 64.3 ± 8.9 years, 97% male, 48% Black) were included. Only 68% of the participants were prescribed any-statin. Substantially higher statin prescription was observed for those with diabetes (adjusted odds ratio [OR] = 2.3, 95% confidence interval [CI], 2.0-2.6), history of coronary revascularization (OR = 4.0, CI, 3.2-5.0), and receiving antiretroviral therapy (OR = 3.0, CI, 2.7-3.4). Blacks (OR = 0.7, CI, 0.6-0.9), those with non-coronary ASCVD, ie, ICVD and/or PAD only, (OR 0.53, 95% CI: 0.48-0.57), and those with history of illicit substance use (OR=0.7, CI, 0.6-0.9) were less likely to be prescribed statins. There was significant variation in statin prescription across VA facilities (10th, 90th centile: 55%, 78%), with an estimated 20% higher likelihood of difference in statin prescription practice for two clinically similar individuals treated at two comparable facilities (adjusted MOR = 1.21, CI, 1.18-1.24), and a greater variation observed for Blacks or those with non-coronary ASCVD or history of illicit drug use. Conclusion: In an analysis of large-scale VA data, we found suboptimal statin prescription and significant interfacility variation in statin prescription among Veterans with HIV and known ASCVD, particularly among Blacks and those with a history of non-coronary ASCVD.