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Item Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus(Ovid Technologies Wolters Kluwer -American Heart Association, 2014-03-18) Patel, Kunjal; Wang, Jiajia; Jacobson, Denise L.; Lipshultz, Steven E.; Landy, David C.; Geffner, Mitchell E.; DiMeglio, Linda A.; Seage, George R.; Williams, Paige L.; Van Dyke, Russell B.; Siberry, George K.; Shearer, William T.; Young, Luciana; Scott, Gwendolyn B.; Wilkinson, James D.; Fisher, Stacy D.; Starc, Thomas J.; Miller, Tracie L.; Department of Pediatrics, IU School of MedicineBACKGROUND: Perinatally HIV-infected adolescents may be susceptible to aggregate atherosclerotic cardiovascular disease risk, as measured by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries and abdominal aorta risk scores, as a result of prolonged exposure to HIV and antiretroviral therapy. METHODS AND RESULTS: Coronary arteries and abdominal aorta PDAY scores were calculated for 165 perinatally HIV-infected adolescents, using a weighted combination of modifiable risk factors: dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. Demographic and HIV-specific predictors of scores ≥1 were identified, and trends in scores over time were assessed. Forty-eight percent and 24% of the perinatally HIV-infected adolescents had coronary arteries and abdominal aorta scores ≥1, representing increased cardiovascular disease risk factor burden. Significant predictors of coronary arteries scores ≥1 included male sex, history of an AIDS-defining condition, longer duration of use of a ritonavir-boosted protease inhibitor, and no prior use of tenofovir. Significant predictors of abdominal aorta scores ≥1 included suppressed viral load, history of an AIDS-defining condition, and longer duration of boosted protease inhibitor use. No significant changes in coronary arteries and abdominal aorta risk scores were observed over the 4-year study period. CONCLUSIONS: A substantial proportion of perinatally HIV-infected youth have high PDAY scores, reflecting increased aggregate atherosclerotic cardiovascular disease risk factor burden. High scores were predicted by HIV disease severity and boosted protease inhibitor use. PDAY scores may be useful in identifying high-risk youth who may benefit from early lifestyle or clinical interventions.Item Assessing identity, phenotype, and fate of endothelial progenitor cells(American Heart Association, 2008-09) Hirschi, Karen K.; Ingram, David A.; Yoder, Mervin C.; Department of Biochemistry & Molecular Biology, IU School of MedicineFrom the paradigm shifting observations of Harvey, Malpighi, and van Leeuwenhoek, blood vessels have become recognized as distinct and dynamic tissue entities that merge with the heart to form a closed circulatory system.1 Vessel structures are comprised predominantly of a luminal layer of endothelial cells that is surrounded by some form of basement membrane, and mural cells (pericytes or vascular smooth muscle cells) that make up the vessel wall. In larger more complex vessel structures the vessel wall is composed of a complex interwoven matrix with nerve components. Understanding the cellular and molecular basis for the formation, remodeling, repair, and regeneration of the vasculature have been and continue to be popular areas for investigation. The endothelium has become a particularly scrutinized cell population with the recognition that these cells may play important roles in maintaining vascular homeostasis and in the pathogenesis of a variety of diseases.2 Although it has been known for several decades that some shed or extruded endothelial cells enter the circulation as apparent contaminants in the human blood stream,3 only more recent technologies have permitted the identification of not only senescent sloughed endothelial cells,4 but also endothelial progenitor cells (EPCs), which have been purported to represent a normal component of the formed elements of circulating blood5 and play roles in disease pathogenesis.6–9 Most citations refer to an article published in 1997 in which Asahara and colleagues isolated, characterized, and examined the in vivo function of putative EPCs from human peripheral blood as a major impetus for generating interest in the field.10 This seminal article presented some evidence to consider emergence of a new paradigm for the process of neovascularization in the form of postnatal vasculogenesis. Since publication of that article, interest in circulating endothelial cells, and particularly EPCs, has soared, and one merely has to type the keyword search terms, endothelial progenitor cell, to recover more than 8984 articles including 1347 review articles in PubMed (as of June 2008). What can we possibly add in the form of another EPC review that will be considered of significant value for the reader? We will attempt to review some of the early article in the field and reflect on how information in those articles was gradually derivatized into perhaps more conflicting rather than unifying concepts. We will also attempt to concisely address some of the important determinants and principles that are now leading to a new understanding of what functionally constitutes an EPC and outline some of the current measures used to identify, enumerate, and quantify these cells. Finally, we give our opinion of the best definition for an EPC based on some comparative analyses performed primarily in human subjects.Item Assessing Information Congruence of Documented Cardiovascular Disease between Electronic Dental and Medical Records(2018) Patel, Jay; Mowery, Danielle; Krishnan, Anand; Thyvalikakath, ThankamDentists are more often treating patients with Cardiovascular Diseases (CVD) in their clinics; therefore, dentists may need to alter treatment plans in the presence of CVD. However, it’s unclear to what extent patient-reported CVD information is accurately captured in Electronic Dental Records (EDRs). In this pilot study, we aimed to measure the reliability of patient-reported CVD conditions in EDRs. We assessed information congruence by comparing patients’ self-reported dental histories to their original diagnosis assigned by their medical providers in the Electronic Medical Record (EMR). To enable this comparison, we encoded patients CVD information from the free-text data of EDRs into a structured format using natural language processing (NLP). Overall, our NLP approach achieved promising performance extracting patients’ CVD-related information. We observed disagreement between self-reported EDR data and physician-diagnosed EMR data.Item BP Components in Advanced CKD and the Competing Risks of Death, ESRD, and Cardiovascular Events(American Society of Nephrology (ASN), 2015-06-05) Sinha, Arjun D.; Agarwal, Rajiv; Department of Medicine, IU School of MedicineItem Effect of collaborative care for depression on risk of cardiovascular events: data from the IMPACT randomized controlled trial(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2014-01) Stewart, Jesse C.; Perkins, Anthony J.; Callahan, Christopher M.; Department of Psychology, School of ScienceOBJECTIVE: Although depression is a risk and prognostic factor for cardiovascular disease (CVD), depression trials involving cardiac patients have not observed the anticipated cardiovascular benefits. To test our hypothesis that depression treatment delivered before clinical CVD onset reduces risk of CVD events, we conducted an 8-year follow-up study of the Indiana sites of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) randomized controlled trial. METHODS: Participants were 235 primary care patients 60 years or older with major depression or dysthymia who were randomized to a 12-month collaborative care program involving antidepressants and psychotherapy (85 without and 35 with baseline CVD) or usual care (83 without and 32 with baseline CVD). Hard CVD events (fatal/nonfatal) were identified using electronic medical record and Medicare/Medicaid data. RESULTS: A total of 119 patients (51%) had a hard CVD event. As hypothesized, the treatment × baseline CVD interaction was significant (p = .021). IMPACT patients without baseline CVD had a 48% lower risk of an event than did usual care patients (28% versus 47%, hazard ratio = 0.52, 95% confidence interval = 0.31-0.86). The number needed to treat to prevent one event for 5 years was 6.1. The likelihood of an event did not differ between IMPACT and usual care patients with baseline CVD (86% versus 81%, hazard ratio = 1.19, 95% confidence interval, 0.70-2.03). CONCLUSIONS: Collaborative depression care delivered before CVD onset halved the excess risk of hard CVD events among older, depressed patients. Our findings raise the possibility that the IMPACT intervention could be used as a CVD primary prevention strategy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01561105.Item The Effects of Cinacalcet in Older and Younger Patients on Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial(American Society of Nephrology, 2015-05-07) Parfrey, Patrick S.; Drüeke, Tilman B.; Block, Geoffrey A.; Correa-Rotter, Ricardo; Floege, Jürgen; Herzog, Charles A.; London, Gerard M.; Mahaffey, Kenneth W.; Moe, Sharon M.; Wheeler, David C.; Kubo, Yumi; Dehmel, Bastian; Goodman, William G.; Chertow, Glenn M.; Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators; Department of Medicine, IU School of MedicineBACKGROUND AND OBJECTIVES: The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older (≥65 years, n=1005) and younger (<65 years, n=2878) patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified. RESULTS: Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were >3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. CONCLUSIONS: In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.Item Metabolic syndrome components and their response to lifestyle and metformin interventions are associated with differences in diabetes risk in persons with impaired glucose tolerance(Wiley Blackwell (Blackwell Publishing), 2014-04) Florez, Hermes; Temprosa, Marinella G.; Orchard, Trevor J.; Mather, Kieren J.; Marcovina, Santica M.; Barrett-Connor, Elizabeth; Horton, Edward; Saudek, Christopher; Pi-Sunyer, Xavier F.; Ratner, Robert E.; Goldberg, Ronald B.; Department of Medicine, IU School of MedicineAIMS: To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence. METHODS: We used the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2 years. RESULTS: In an intention-to-treat analysis, the demographic-adjusted hazard ratios (95% confidence interval) for diabetes in those with MetS (vs. no MetS) at baseline were 1.7 (1.3-2.3), 1.7 (1.2-2.3) and 2.0 (1.3-3.0) for placebo, metformin and lifestyle groups, respectively. Higher levels of fasting plasma glucose and triglycerides at baseline were independently associated with increased risk of diabetes. Greater waist circumference (WC) was associated with higher risk in placebo and lifestyle groups, but not in the metformin group. In a multivariate model, favourable changes in WC (placebo and lifestyle) and high-density lipoprotein cholesterol (placebo and metformin) contributed to reduced diabetes risk. CONCLUSIONS: MetS and some of its components are associated with increased diabetes incidence in persons with IGT in a manner that differed according to DPP intervention. After hyperglycaemia, the most predictive factors for diabetes were baseline hypertriglyceridaemia and both baseline and lifestyle-associated changes in WC. Targeting these cardiometabolic risk factors may help to assess the benefits of interventions that reduce diabetes incidence.Item Obstructive sleep apnoea in obese adolescents and cardiometabolic risk markers(Wiley Blackwell (Blackwell Publishing), 2014-12) Watson, S. E.; Li, Z.; Tu, W.; Jalou, H.; Brubaker, J. L.; Gupta, S.; Huber, J. N.; Carroll, A.; Hannon, T. S.; Department of Pediatrics, IU School of MedicineWHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: In paediatric patients, obstructive sleep apnoea is associated with adiposity, especially visceral adiposity. In adults, obstructive sleep apnoea is also associated with a higher prevalence of cardiovascular disease and type 2 diabetes. There are limited and conflicting paediatric studies examining the association between obstructive sleep apnoea and biomarkers of risk for cardiovascular disease and type 2 diabetes in youth. WHAT THIS STUDY ADDS: Obstructive sleep apnoea is linked with greater cardiometabolic risk markers in obese adolescents. Fasting insulin and homeostasis model assessment-insulin resistance may be especially linked with obstructive sleep apnoea among obese male Hispanic adolescents. The relationship between obstructive sleep apnoea and cardiometabolic abnormalities in obese adolescents should be considered when evaluating patients found to have obstructive sleep apnoea. BACKGROUND: Paediatric studies examining the association between obstructive sleep apnoea (OSA) and insulin sensitivity/cardiometabolic risk are limited and conflicting. OBJECTIVE: This study aims to determine if cardiometabolic risk markers are increased among obese youth with obstructive sleep apnoea as compared with their equally obese peers without OSA. METHODS: We performed a retrospective analysis of 96 patients (age 14.2 ± 1.4 years) who underwent polysomnography for suspected OSA. Fasting lipids, glucose, insulin and haemoglobin A1 c (HbA1 c) were performed as part of routine clinical evaluation. Patients were categorized into two groups by degree of OSA as measured by the apnoea-hypopnoea index (AHI): none or mild OSA (AHI < 5) and moderate or severe OSA (AHI ≥ 5). RESULTS: Despite the similar degrees of obesity, patients with moderate or severe OSA had higher fasting insulin (P = 0.037) and homeostasis model assessment-insulin resistance (HOMA-IR [P = 0.0497]) as compared with those with mild or no OSA. After controlling for body mass index, there was a positive association between the AHI and log HOMA-IR (P = 0.005). There was a positive relationship between arousals plus awakenings during the polysomnography and fasting triglycerides. CONCLUSIONS: OSA is linked with greater cardiometabolic risk markers in obese youth.Item Patient Race/Ethnicity and Patient-Physician Race/Ethnicity Concordance in the Management of Cardiovascular Disease Risk Factors for Patients With Diabetes(American Diabetes Association, 2010-03) Traylor, Ana H.; Subramanian, Usha; Uratsu, Connie S.; Mangione, Carol M.; Selby, Joe V.; Schmittdiel, Julie A.; Medicine, School of MedicineOBJECTIVE Patient-physician race/ethnicity concordance can improve care for minority patients. However, its effect on cardiovascular disease (CVD) care and prevention is unknown. We examined associations of patient race/ethnicity and patient-physician race/ethnicity concordance on CVD risk factor levels and appropriate modification of treatment in response to high risk factor values (treatment intensification) in a large cohort of diabetic patients. RESEARCH DESIGN AND METHODS The study population included 108,555 adult diabetic patients in Kaiser Permanente Northern California in 2005. Probit models assessed the effect of patient race/ethnicity on risk factor control and treatment intensification after adjusting for patient and physician-level characteristics. RESULTS African American patients were less likely than whites to have A1C <8.0% (64 vs. 69%, P < 0.0001), LDL cholesterol <100 mg/dl (40 vs. 47%, P < 0.0001), and systolic blood pressure (SBP) <140 mmHg (70 vs. 78%, P < 0.0001). Hispanic patients were less likely than whites to have A1C <8% (62 vs. 69%, P < 0.0001). African American patients were less likely than whites to have A1C treatment intensification (73 vs. 77%, P < 0.0001; odds ratio [OR] 0.8 [95% CI 0.7–0.9]) but more likely to receive treatment intensification for SBP (78 vs. 71%, P < 0.0001; 1.5 [1.3–1.7]). Hispanic patients were more likely to have LDL cholesterol treatment intensification (47 vs. 45%, P < 0.05; 1.1 [1.0–1.2]). Patient-physician race/ethnicity concordance was not significantly associated with risk factor control or treatment intensification. CONCLUSIONS Patient race/ethnicity is associated with risk factor control and treatment intensification, but patient-physician race/ethnicity concordance was not. Further research should investigate other potential drivers of disparities in CVD care.Item Presentation of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Third International Workshop(Endocrine Society, 2009-02) Silverberg, Shonni J.; Lewiecki, E. Michael; Mosekilde, Leif; Peacock, Munro; Rubin, Mishaela R.; Medicine, School of MedicineBACKGROUND: At the Third International Workshop on Asymptomatic Primary Hyperparathyroidism (PHPT) in May 2008, recent data on the disease were reviewed. We present the results of a literature review on issues arising from the clinical presentation and natural history of PHPT. METHODS: Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was reviewed, and the questions of the International Task Force were addressed by the Consensus Panel. CONCLUSIONS: 1) Data on the extent and nature of cardiovascular involvement in those with mild disease are too limited to provide a complete picture. 2) Patients with mild PHPT have neuropsychological complaints. Although some symptoms may improve with surgery, available data remain inconsistent on their precise nature and reversibility. 3) Surgery leads to long-term gains in spine, hip, and radius bone mineral density (BMD). Because some patients have early disease progression and others lose BMD after 8-10 yr, regular monitoring (serum calcium and three-site BMD) is essential in those followed without surgery. Patients may present with normocalcemic PHPT (normal serum calcium with elevated PTH concentrations; no secondary cause for hyperparathyroidism). Data on the incidence and natural history of this phenotype are limited. 4) In the absence of kidney stones, data do not support the use of marked hypercalciuria (>10 mmol/d or 400 mg/d) as an indication for surgery for patients. 5) Patients with bone density T-score -2.5 or less at the lumbar spine, hip, or distal one third radius should have surgery.