Harman S.M.,Phoenix Veterans Affairs Health Care System |
Black D.M.,University of California at San Francisco |
Naftolin F.,New York University |
Brinton E.A.,University of Utah |
And 12 more authors.
Annals of Internal Medicine | Year: 2014
Whether menopausal hormone therapy (MHT) protects against cardiovascular disease (CVD) remains unclear. Objective: To assess atherosclerosis progression and CVD risk factors after MHT initiated in early menopause. Design: Randomized, controlled trial. (ClinicalTrials.gov: NCT00154180) Setting: Nine U.S. academic centers. Participants: Healthy menopausal women aged 42 to 58 years between 6 and 36 months from last menses without prior CVD events who had a coronary artery calcium (CAC) score less than 50 Agatston units and had not received estrogen or lipid-lowering therapy for at least 90 days. Intervention: Oral conjugated equine estrogens (o-CEE), 0.45 mg/d, or transdermal 17β-estradiol (t-E2), 50 mcg/d, each with 200 mg of oral progesterone for 12 days per month, or placebo for 48 months. Measurements: Primary end point was annual change in carotid artery intima-media thickness (CIMT). Secondary end points included changes in markers of CVD risk. Results: Of 727 randomly assigned women, 89.3% had at least 1 follow-up CIMT and 79.8% had CIMT at 48 months. Mean CIMT increases of 0.007 mm/y were similar across groups. The percentages of participants in whom CAC score increased did not differ significantly across groups. No changes in blood pressure were observed with o-CEE or t-E2. Low- and high-density lipoprotein cholesterol levels improved and levels of C-reactive protein and sex hormone-binding globulin but not interleukin-6 increased with o-CEE. Insulin resistance decreased with t-E2. Serious adverse events did not differ by treatment. Limitation: Power to compare clinical events was insufficient. Conclusion: Four years of early MHT did not affect progression of atherosclerosis despite improving some markers of CVD risk. © 2014 American College of Physicians.
Migrino R.Q.,Medical College of Wisconsin |
Migrino R.Q.,Phoenix Veterans Affairs Health Care System |
Bowers M.,Medical College of Wisconsin |
Harmann L.,Medical College of Wisconsin |
And 3 more authors.
Journal of Cardiovascular Magnetic Resonance | Year: 2011
Background: Cardiovascular magnetic resonance (CMR) allows volumetric carotid plaque measurement that has advantage over 2-dimensional ultrasound (US) intima-media thickness (IMT) in evaluating treatment response. We tested the hypothesis that 6-month statin treatment in patients with carotid plaque will lead to plaque regression when measured by 3 Tesla CMR but not by IMT. Methods. Twenty-six subjects (67 2 years, 7 females) with known carotid plaque (> 1.1 mm) and coronary or cerebrovascular atherosclerotic disease underwent 3T CMR (T1, T2, proton density and time of flight sequences) and US at baseline and following 6 months of statin therapy (6 had initiation, 7 had increase and 13 had maintenance of statin dosing). CMR plaque volume (PV) was measured in the region 12 mm below and up to 12 mm above carotid flow divider using software. Mean posterior IMT in the same region was measured. Baseline and 6-month CMR PV and US IMT were compared. Change in lipid rich/necrotic core (LR/NC) and calcification plaque components from CMR were related to change in PV. Results: Low-density lipoprotein cholesterol decreased (86 6 to 74 4 mg/dL, p = 0.046). CMR PV decreased 5.8 2% (1036 59 to 976 65 mm 3, p = 0.018). Mean IMT was unchanged (1.12 0.06 vs. 1.14 0.06 mm, p = NS). Patients with initiation or increase of statins had -8.8 2.8% PV change (p = 0.001) while patients with maintenance of statin dosing had -2.7 3% change in PV (p = NS). There was circumferential heterogeneity in CMR plaque thickness with greatest thickness in the posterior carotid artery, in the region opposite the flow divider. Similarly there was circumferential regional difference in change of plaque thickness with significant plaque regression in the anterior carotid region in region of the flow divider. Change in LR/NC (R = 0.62, p = 0.006) and calcification (R = 0.45, p = 0.03) correlated with PV change. Conclusions: Six month statin therapy in patients with carotid plaque led to reduced plaque volume by 3T CMR, but ultrasound posterior IMT did not show any change. The heterogeneous spatial distribution of plaque and regional differences in magnitude of plaque regression may explain the difference in findings and support volumetric measurement of plaque. 3T CMR has potential advantage over ultrasound IMT to assess treatment response in individuals and may allow reduced sample size, duration and cost of clinical trials of plaque regression. © 2011 Migrino et al; licensee BioMed Central Ltd.
Pieper G.M.,Medical College of Wisconsin |
Shah A.,Medical College of Wisconsin |
Harmann L.,Medical College of Wisconsin |
Cooley B.C.,Medical College of Wisconsin |
And 3 more authors.
Journal of Heart and Lung Transplantation | Year: 2010
BACKGROUND: There remains no reliable non-invasive method to detect cardiac transplant rejection. Recently, speckle-tracking 2-dimensional strain echocardiography (2DSE) was shown to be sensitive in the early detection of myocardial dysfunction in various models of cardiomyopathy. We aim to determine if 2DSE-derived functional indices can detect cardiac transplant rejection. METHODS: Heterotopic rat cardiac transplantation was performed in histocompatible isografts or histoincompatible allografts. Histologic rejection scores were determined. Short-axis, mid-left ventricular (LV) echocardiography was performed on Day 6 after transplantation. Conventional measures of function were measured, (including LV fractional shortening and ejection fraction) as well as 2DSE parameters. RESULTS: Despite class IIIB rejection in allografts and no rejection in isografts, there was no difference between isografts vs allografts in fractional shortening (15% ± 3% vs 12% ± 3%) or ejection fraction (36% ± 5% vs 26% ± 6%; both not significant). In contrast, 2DSE revealed decreases between isografts and allografts in global radial strain (12.6% ± 5.6% vs 1.1% ± 0.2%, p < 0.05), peak radial systolic strain rate (3.10 ± 0.74/s vs 0.54 ± 0.13/s, p < 0.001), and peak circumferential systolic strain rate (-1.99 ± 0.55 vs -0.43 ± 0.11/s; p < 0.01). CONCLUSIONS: Systolic strain imaging using 2DSE differentiates myocardial function between experimental cardiac transplant rejection in allografts and non-rejection in isografts. Therefore, 2DSE may be useful in early non-invasive detection of transplant rejection. © 2010 International Society for Heart and Lung Transplantation All rights reserved.
Koska J.,Phoenix Veterans Affairs Health Care System |
Saremi A.,Phoenix Veterans Affairs Health Care System |
Bahn G.,Hines Veterans Affairs Cooperative Studies Program Coordinating Center |
Yamashita S.,Osaka University |
Reaven P.D.,Phoenix Veterans Affairs Health Care System
Diabetes Care | Year: 2013
OBJECTIVE-Intensive glucose-lowering therapy (INT) did not reduce macrovascular events in the recent randomized trials, possibly because it did not improve or worsen other traditional or novel cardiovascular risk factors. RESEARCH DESIGN AND METHODS-Standard plasma lipids, cholesterol content of lipoprotein sub fractions, and plasma inflammatory and prothrombotic markers were determined in a subgroup of the Veterans Affairs Diabetes Trial (VADT) participants (n = 266) at baseline and after 9 months of INT or standard therapy. RESULTS-INT lowered glycated hemoglobin (by a median of 2% vs. a median of 0.7% by standard treatment; P < 0.0001); increased BMI (4 vs. 1%; P < 0.001), total HDL (9 vs. 4%; P, 0.05), HDL2 (14 vs. 0%; P = 0.009), LDL2 (36 vs. 1%; P < 0.0001), and plasma adiponectin (130 vs. 80%; P < 0.01); and reduced triglycerides (213 vs. 24%; P = 0.02) and small, dense LDL4 (239 vs. 213%; P < 0.001), but had no effect on levels of plasma apolipoproteins B-100 and B-48, C-reactive protein, interleukin-6, lipoprotein-associated phospholipase A2, myeloperoxidase, fibrinogen, and plasminogen activator inhibitor 1. Incident macrovascular events were associated with baseline interleukin-6 (hazard ratio per each quartile increase 1.33 [95% CI 1.06-1.66]), total LDL (1.25 [1.01-1.55]), apolipoprotein B-100 (1.29 [1.01-1.65]), and fibrinogen (1.26 [1.01-1.57]) but not changes in any cardiovascular risk factors at 9 months. CONCLUSIONS-INT was associated with improved adiponectin, lipid levels, and a favorable shift in LDL and HDL subfractions after 9 months. These data suggest that the failure of INT to lower cardiovascular outcomes occurred despite generally favorable changes in standard and novel risk factors early in the study. © 2013 by the American Diabetes Association.
Epstein D.R.,Phoenix Veterans Affairs Health Care System |
Epstein D.R.,Arizona State University |
Sidani S.,Ryerson University |
Bootzin R.R.,University of Arizona |
Belyea M.J.,Arizona State University
Sleep | Year: 2012
Study Objective: Recently, the use of multicomponent insomnia treatment has increased. This study compares the effect of single component and multicomponent behavioral treatments for insomnia in older adults after intervention and at 3 months and 1 yr posttreatment. Design: A randomized, controlled study. Setting: Veterans Affairs medical center. Participants: 179 older adults (mean age, 68.9 yr ± 8.0; 115 women [64.2%]) with chronic primary insomnia. Interventions: Participants were randomly assigned to 6 wk of stimulus control therapy (SCT), sleep restriction therapy (SRT), the 2 therapies combined into a multicomponent intervention (MCI), or a wait-list control group. Measurements and Results: Primary outcomes were subjective (daily sleep diary) and objective (actigraphy) measures of sleep-onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), time in bed (TIB), and sleep efficiency (SE). Secondary outcomes were clinical measures including response and remission rates. There were no differences between the single and multicomponent interventions on primary sleep outcomes measured by diary and actigraphy. All treatments produced significant improvement in diary-reported sleep in comparison with the control group. Effect sizes for sleep diary outcomes were medium to large. Treatment gains were maintained at follow-up for diary and actigraph measured SOL, WASO, and SE. The MCI group had the largest proportion of treatment remitters. Conclusions: For older adults with chronic primary insomnia, the findings provide initial evidence that SCT, SRT, and MCI are equally efficacious and produce sustainable treatment gains on diary, actigraphy, and clinical outcomes. From a clinical perspective, MCI may be a preferred treatment due to its higher remission rate. Clinical Trial Information: Behavioral Intervention for Insomnia in Older Adults. NCT01154023. URL: http://clinicaltrials.gov/ct2/show/NCT01154023?term= Behavioral+Intervention+for+Insomnia+in+Older+Adults&rank=1.
Harman S.M.,Phoenix Veterans Affairs Health Care System
Fertility and Sterility | Year: 2014
Cardiovascular disease (CVD) is the most common cause of death in women. Before the Women's Health Initiative (WHI) hormone trials, evidence favored the concept that menopausal hormone treatment (MHT) protects against CVD. WHI studies failed to demonstrate CVD benefit, with worse net outcomes for MHT versus placebo in the population studied. We review evidence regarding the relationship between MHT and CVD with consideration of mechanisms and risk factors for atherogenesis and cardiac events, results of observational case-control and cohort studies, and outcomes of randomized trials. Estrogen effects on CVD risk factors favor delay or amelioration of atherosclerotic plaque development but may increase risk of acute events when at-risk plaque is present. Long-term observational studies have shown ∼40% reductions in risk of myocardial infarction and all-cause mortality. Analyses of data from randomized control trials other than the WHI show a ∼30% cardioprotective effect in recently menopausal women. Review of the literature as well as WHI data suggests that younger and/or more recently menopausal women may have a better risk-benefit ratio than older or remotely menopausal women and that CVD protection may only occur after >5 years; WHI women averaged 63 years of age (12 years postmenopausal) and few were studied for >6 years. Thus, a beneficial effect of long-term MHT on CVD and mortality is still an open question and is likely to remain controversial for the foreseeable future. © 2014 American Society for Reproductive Medicine, Published by Elsevier Inc. All rights reserved.
Bootzin R.R.,University of Arizona |
Epstein D.R.,Phoenix Veterans Affairs Health Care System
Annual Review of Clinical Psychology | Year: 2011
Sleep disturbance is intricately entwined with our sense of well-being, health, emotion regulation, performance and productivity, memory and cognitive functioning, and social interaction. A longitudinal perspective underscores the conclusion that persistent sleep disturbance, insomnia, at any time during the life span from infancy to old age has a lasting impact. We examine how insomnia develops, the evidence for competing explanations for understanding insomnia, and the evidence about psychological and behavioral treatments that are used to reduce insomnia and change daytime consequences. There are new directions to expand access to treatment for those who have insomnia, and thus a critical analysis of pathways for dissemination is becoming increasingly important. Copyright © 2011 by Annual Reviews. All rights reserved.
Segrin C.,University of Arizona |
Badger T.A.,University of Arizona |
Harrington J.,Phoenix Veterans Affairs Health Care System
Health Psychology | Year: 2012
Objective: Prostate cancer negatively influences quality of life (QOL) in survivors and the people with whom they are close. The purpose of this investigation was to assess the degree of dyadic interdependence in psychological QOL in dyads adjusting to prostate cancer and its treatment. Method: Participants were 70 prostate cancer survivors and their partners, most of whom were spouses. Assessments of psychological QOL (i.e., depression, anxiety, fatigue, and positive affect) were made at three points in time, each separated by 8 weeks. Results: Survivors' prostate specific function was associated with both their own and their partners' psychological QOL. There was evidence of longitudinal dyadic interdependence for psychological QOL, particularly from partners to survivors between the T2 and T3 assessments. Conclusions: Prostate cancer survivors' psychological QOL is affected substantially by their partners' psychological QOL, consistent with theories of emotional contagion. © 2011 American Psychological Association.
Dossett H.G.,Phoenix Veterans Affairs Health Care System |
Estrada N.A.,Veterans Affairs Salt Lake City Health Care System |
Swartz G.J.,Phoenix Veterans Affairs Health Care System |
LeFevre G.W.,Phoenix Veterans Affairs Health Care System |
Kwasman B.G.,Phoenix Veterans Affairs Health Care System
Bone and Joint Journal | Year: 2014
We have previously reported the short-term radiological results of a randomised controlled trial comparing kinematically aligned total knee replacement (TKR) and mechanically aligned TKR, along with early pain and function scores. In this study we report the two-year clinical results from this trial. A total of 88 patients (88 knees) were randomly allocated to undergo either kinematically aligned TKR using patient-specific guides, or mechanically aligned TKR using conventional instruments. They were analysed on an intention-to-treat basis. The patients and the clinical evaluator were blinded to the method of alignment. At a minimum of two years, all outcomes were better for the kinematically aligned group, as determined by the mean Oxford knee score (40 (15 to 48) versus 33 (13 to 48); p = 0.005), the mean Western Ontario McMaster Universities Arthritis index (WOMAC) (15 (0 to 63) versus 26 (0 to 73); p = 0.005), mean combined Knee Society score (160 (93 to 200) versus 137 (64 to 200); p= 0.005) and mean flexion of 121° (100 to 150) versus 113° (80 to 130) (p = 0.002). The odds ratio of having a pain-free knee at two years with the kinematically aligned technique (Oxford and WOMAC pain scores) was 3.2 (p = 0.020) and 4.9 (p = 0.001), respectively, compared with the mechanically aligned technique. Patients in the kinematically aligned group walked a mean of 50 feet further in hospital prior to discharge compared with the mechanically aligned group (p = 0.044). In this study, the use of a kinematic alignment technique performed with patient-specific guides provided better pain relief and restored better function and range of movement than the mechanical alignment technique performed with conventional instruments. © 2014 The British Editorial Society of Bone & Joint Surgery.
Koska J.,Phoenix Veterans Affairs Health Care System |
Sands M.,Phoenix Veterans Affairs Health Care System |
Burciu C.,Phoenix Veterans Affairs Health Care System |
Reaven P.,Phoenix Veterans Affairs Health Care System
Diabetes and Vascular Disease Research | Year: 2015
Cardiovascular (CV) disease is the leading cause of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM). However, improving glycaemic control alone has not decreased CV events. Therapies that improve glycaemic control, CV disease risk factors and CV function are more likely to be successful. Dipeptidyl peptidase-4 (DPP-4) inhibitors prevent breakdown of incretin hormones glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic peptide and improve glycaemic control in patients with T2DM. DPP-4 acts on other substrates, many associated with cardioprotection. Thus, inhibition of DPP-4 may lead to elevations in these potentially beneficial substrates. Data from animal studies and small observational studies in humans suggest that DPP-4 inhibitors may potentially reduce CV risk. However, recently completed CV outcome trials in patients with T2DM and CV disease or at high risk of adverse CV events have shown that the DPP-4 inhibitors saxagliptin and alogliptin neither increased nor decreased major adverse CV events. © The Author(s) 2015.