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Santago A.C.,Virginia Polytechnic Institute and State University | Santago A.C.,North Carolina State University | Vidt M.E.,University of Waterloo | Jordan J.H.,Section on Cardiovascular Medicine | And 2 more authors.
Annals of Biomedical Engineering | Year: 2015

The purpose of this study was to (1) develop and present a technique to quantitatively assess three-dimensional distribution and clustering of intramuscular fat and (2) use the technique to compare spatial characteristics of intramuscular fat in rotator cuff muscles of older adults with and without a supraspinatus tear. Moran’s Index (I), an existing quantitative measure of clustering, was extended for use with MRI to allow comparisons across individuals with different size muscles. Sixteen older adults (>60 years) with (N = 6) and without (N = 10) a degenerative supraspinatus tear participated. Following 3D Dixon MRIs of the shoulder, which separates fat from water, rotator cuff muscles were segmented and sectioned and fat% and Moran’s I were calculated to assess distribution and clustering, respectively. Moran’s I ranged was 0.40–0.92 and 0.39–0.76 for the tear and control subjects, respectively. Compared to uninjured controls, tear subjects demonstrated increased fat distribution (p = 0.036) and clustering (p = 0.020) distally in the supraspinatus. Tear subjects had more pronounced distribution (p < 0.001) and clustering distally (p < 0.001) than proximally. Other rotator cuff muscles exhibited different patterns of fat clustering and distribution. This technique, which we applied to quantify spatial characteristics of intramuscular fat, can be applied to assess clustering of fat in other pathologies and tissues. © 2015 Biomedical Engineering Society

Jordan J.H.,Section on Cardiovascular Medicine | Thwin S.S.,Boston University | Thwin S.S.,Massachusetts Veterans Epidemiology Research and Information Center | Lash T.L.,Emory University | And 10 more authors.
Breast Cancer Research and Treatment | Year: 2014

Five-year breast cancer survivors, diagnosed after 65 years of age, may develop more incident comorbidities than similar populations free of cancer. We investigated whether older breast cancer survivors have a similar comorbidity burden 6-15 years after cancer diagnosis to matched women free of breast cancer at start of follow-up and whether incident comorbidities are associated with all-cause mortality. In this prospective cohort study, 1,361 older 5-year early-stage breast cancer survivors diagnosed between 1990 and 1994 and 1,361 age- and health system-matched women were followed for 10 years. Adjudicated medical record review captured prevalent and incident comorbidities during follow-up or until death as collected from the National Death Index. Older 5-year breast cancer survivors did not acquire incident comorbidities more often than matched women free of breast cancer in the subsequent 10 years [hazard ratio (HR) 1.0, 95 % confidence interval (95 % CI) 0.93, 1.1]. Adjusted for cohort membership, women with incident comorbidities had a higher mortality rate than those without incident comorbidities (HR 4.8, 95 % CI 4.1, 5.6). A breast cancer history continued to be a hazard for mortality 6-15 years after diagnosis (HR 1.3, 95 % CI 1.1, 1.4). We found that older breast cancer survivors who developed comorbidities had an increased all-cause mortality rate even after adjusting for age and prevalent comorbidity burden. Additionally, survivors acquire comorbidities at a rate similar to older women free of breast cancer. These results highlight the association between comorbidity burden and long-term mortality risk among older breast cancer survivors and their need for appropriate oncology and primary care follow-up. © 2014 Springer Science+Business Media.

Shao Q.,Harbin Medical University | Cheng H.-J.,Section on Cardiovascular Medicine | Cheng H.-J.,Wake forest University | Kitzman D.W.,Section on Cardiovascular Medicine | And 2 more authors.
International Journal of Cardiology | Year: 2016

Background Altered nitric oxide synthase (NOS) has been implicated in the pathophysiology of heart failure (HF). Recent evidence links hypothyroidism to the pathology of HF. However, the precise mechanisms are incompletely understood. The alterations and functional effects of cardiac NOS in hypothyroidism are unknown. We tested the hypothesis that hypothyroidism increases cardiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism-induced depression of cardiomyocyte contractile properties, [Ca2 +]i transient ([Ca2+]iT), and β-adrenergic hyporesponsiveness. Methods and results We simultaneously evaluated LV functional performance and compared myocyte three NOS, β-adrenergic receptors (AR) and SERCA2a expressions and assessed cardiomyocyte contractile and [Ca2+]iT responses to β-AR stimulation with and without pretreatment of iNOS inhibitor (1400 W, 10- 5 mol/L) in 26 controls and 26 rats with hypothyroidism induced by methimazole (~ 30 mg/kg/day for 8 weeks in the drinking water). Compared with controls, in hypothyroidism, total serum T3 and T4 were significantly reduced followed by significantly decreased LV contractility (EES) with increased LV time constant of relaxation. These LV abnormalities were accompanied by concomitant significant decreases in myocyte contraction (dL/dtmax), relaxation (dR/dtmax), and [Ca2+]iT. In hypothyroidism, isoproterenol (10- 8 M) produced significantly smaller increases in dL/dtmax, dR/dtmax and [Ca2+]iT. These changes were associated with decreased β1-AR and SERCA2a, but significantly increased iNOS. Moreover, only in hypothyroidism, pretreatment with iNOS inhibitor significantly improved basal and isoproterenol-stimulated myocyte contraction, relaxation and [Ca2 +]iT. Conclusions Hypothyroidism produces intrinsic defects of LV myocyte force-generating capacity and relaxation with β-AR desensitization. Up-regulation of cardiomyocyte iNOS may promote progressive cardiac dysfunction in hypothyroidism. © 2015 Elsevier Ireland Ltd. All rights reserved.

Still C.H.,University Hospitals Case Medical Center | Still C.H.,Case Western Reserve University | Freedman B.I.,Section on Nephrology | Van Buren P.N.,University of Texas Southwestern Medical Center | And 11 more authors.
Journal of the American Society of Hypertension | Year: 2015

The Systolic Blood Pressure Intervention Trial (SPRINT) will compare treatment to a systolic blood pressure goal of <120 mm Hg to treatment to the currently recommended goal of <140 mm Hg for effects on incident cardiovascular, renal, and neurologic outcomes including cognitive decline. The objectives of this analysis are to compare baseline characteristics of African American (AA) and non-AA SPRINT participants and explore factors associated with uncontrolled blood pressure (BP) by race. SPRINT enrolled 9361 hypertensive participants aged older than 50 years. This cross-sectional analysis examines sociodemographics, baseline characteristics, and study measures among AAs compared with non-AAs. AAs made up 31% of participants. AAs (compared with non-AAs) were younger and less frequently male, had less education, and were more likely uninsured or covered by Medicaid. In addition, AAs scored lower on the cognitive screening test when compared with non-AAs. Multivariate logistic regression analysis found BP control rates to <140/90 mm Hg were higher for AAs who were male, had higher number of chronic diseases, were on diuretic treatment, and had better medication adherence. SPRINT is well poised to examine the effects of systolic blood pressure targets on clinical outcomes as well as predictors influencing BP control in AAs. © 2015 American Society of Hypertension.

Qureshi W.T.,Section on Cardiovascular Medicine | Nasir U.B.,University of Health Sciences, Lahore | Alqalyoobi S.,University of Missouri - Kansas City | Mawri S.,Ford Motor Company | And 5 more authors.
American Journal of Cardiology | Year: 2015

Atrial fibrillation (AF) is a significant health care problem for patients with obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) as a therapy for OSA is underused, and it is unknown if CPAP might reduce rates of AF. We systematically reviewed the published reports on CPAP use and risk of AF. MEDLINE, EMBASE, CINAHL, Web of Science, meeting abstracts, and Cochrane databases were searched from inception to June 2015. Studies needed to report the rates of AF in participants who were and were not on CPAP. Data were extracted by 2 authors. A total of 8 studies on OSA were identified (1 randomized controlled trial) with 698 CPAP users and 549 non-CPAP users. In a random effects model, patients treated with CPAP had a 42% decreased risk of AF (pooled risk ratio, 0.58; 95% confidence interval, 0.47 to 0.70; p <0.001). There was low heterogeneity in the results (I2 = 30%). In metaregression analysis, benefits of CPAP were stronger for younger, obese, and male patients (p <0.05). An inverse relationship between CPAP therapy and AF recurrence was observed. Results suggest that more patients with AF also should be tested for OSA. © 2015 Elsevier Inc.

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