Browsing by Author "Racette, Susan B."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Dietary nitrate's effects on exercise performance in heart failure with reduced ejection fraction (HFrEF)
    (Elsevier, 2018) Mulkareddy, Vinaya; Racette, Susan B.; Coggan, Andrew R.; Peterson, Linda R.; Kinesiology, School of Physical Education and Tourism Management
    Heart failure with reduced ejection fraction (HFrEF) is a deadly and disabling disease. A key derangement contributing to impaired exercise performance in HFrEF is decreased nitric oxide (NO) bioavailability. Scientists recently discovered the inorganic nitrate pathway for increasing NO. This has advantages over organic nitrates and NO synthase production of NO. Small studies using beetroot juice as a source of inorganic nitrate demonstrate its power to improve exercise performance in HFrEF. A larger-scale trial is now underway to determine if inorganic nitrate may be a new arrow for physicians' quiver of HFrEF treatments.
  • Thumbnail Image
    Item
    Relationship Between Age at Menopause, Obesity, and Incident Heart Failure: The Atherosclerosis Risk in Communities Study
    (American Heart Association, 2022) Ebong, Imo A.; Wilson, Machelle D.; Appiah, Duke; Michos, Erin D.; Racette, Susan B.; Villablanca, Amparo; Breathett, Khadijah; Lutsey, Pamela L.; Wellons, Melissa; Watson, Karol E.; Chang, Patricia; Bertoni, Alain G.; Medicine, School of Medicine
    Background: The mechanisms linking menopausal age and heart failure (HF) incidence are controversial. We investigated for heterogeneity by obesity on the relationship between menopausal age and HF incidence. Methods and Results: Using postmenopausal women who attended the Atherosclerosis Risk in Communities Study Visit 4, we estimated hazard ratios of incident HF associated with menopausal age using Cox proportional hazards models, testing for effect modification by obesity and adjusting for HF risk factors. Women were categorized by menopausal age: <45 years, 45 to 49 years, 50 to 54 years, and ≥55 years. Among 4441 postmenopausal women, aged 63.5±5.5 years, there were 903 incident HF events over a mean follow‐up of 16.5 years. The attributable risk of generalized and central obesity for HF incidence was greatest among women who experienced menopause at age ≥55 years: 11.09/1000 person‐years and 7.38/1000 person‐years, respectively. There were significant interactions of menopausal age with body mass index and waist circumference for HF incidence, P interaction 0.02 and 0.001, respectively. The hazard ratios of incident HF for a SD increase in body mass index was elevated in women with menopausal age <45 years [1.39 (1.05–1.84)]; 45–49 years [1.33, (1.06–1.67)]; and ≥55 years [2.02, (1.41–2.89)]. The hazard ratio of incident HF for a SD increase in waist circumference was elevated only in women with menopausal age ≥55 years [2.93, (1.85–4.65)]. Conclusions: As obesity worsened, the risk of developing HF became significantly greater when compared with women with lower body mass index and waist circumference, particularly among those who had experienced menopause at age ≥55 years.
  • Thumbnail Image
    Item
    Simultaneous Pharmacokinetic Analysis of Nitrate and its Reduced Metabolite, Nitrite, Following Ingestion of Inorganic Nitrate in a Mixed Patient Population
    (SpringerLink, 2020-11) Coggan, Andrew R.; Racette, Susan B.; Thies, Dakkota; Peterson, Linda R.; Stratford, Robert E., Jr.; Kinesiology, School of Health and Human Sciences
    Purpose: The pharmacokinetic properties of plasma NO3- and its reduced metabolite, NO2-, have been separately described, but there has been no reported attempt to simultaneously model their pharmacokinetics following NO3- ingestion. This report describes development of such a model from retrospective analyses of concentrations largely obtained from primary endpoint efficacy trials. Methods: Linear and non-linear mixed effects analyses were used to statistically define concentration dependency on time, dose, as well as patient and study variables, and to integrate NO3- and NO2- concentrations from studies conducted at different times, locations, patient groups, and several studies in which sample range was limited to a few hours. Published pharmacokinetic studies for both substances were used to supplement model development. Results: A population pharmacokinetic model relating NO3- and NO2- concentrations was developed. The model incorporated endogenous levels of the two entities, and determined these were not influenced by exogenous NO3- delivery. Covariate analysis revealed intersubject variability in NO3- exposure was partially described by body weight differences influencing volume of distribution. The model was applied to visualize exposure versus response (muscle contraction performance) in individual patients. Conclusions: Extension of the present first-generation model, to ultimately optimize NO3- dose versus pharmacological effects, is warranted.