AbstractObstructive sleep apnea (OSA), in which breathing is reduced or ceased during sleep, affects at least 10% of the population and is associated with numerous comorbidities. Current clinical diagnostic approaches characterize severity and treatment eligibility using the average respiratory event rate over total sleep time (apnea-hypopnea index). This approach, however, does not characterize the time-varying and dynamic properties of respiratory events that can change as a function of body position, sleep stage, and previous respiratory event activity. Here, we develop a statistical model framework based on point process theory that characterizes the relative influences of all these factors on the moment-to-moment rate of event occurrence. Our results provide new insights into the temporal dynamics of respiratory events, suggesting that most adults have a characteristic event pattern that involves a period of normal breathing followed by a period of increased probability of respiratory event occurrence, while significant differences in event patterns are observed among gender, age, and race/ethnicity groups. Statistical goodness-of-fit analysis suggests consistent and substantial improvements in our ability to capture the timing of individual respiratory events using our modeling framework. Overall, we demonstrate a more statistically robust approach to characterizing sleep disordered breathing that can also serve as a basis for identifying future patient-specific respiratory phenotypes, providing an improved pathway towards developing individualized treatments.
Megan M Marron, Stacy G Wendell, Robert M Boudreau
et al.
AbstractBackgroundLow walking ability is highly prevalent with advancing age and predicts major health outcomes. Metabolomics may help to better characterize differences in walking ability among older adults, providing insight into potentially altered molecular processes underlying age-related decline in functioning. We sought to identify metabolites and metabolic pathways associated with high versus low walking ability among 120 participants ages 79–95 from the CHS All Stars study.MethodsUsing a nested case–control design, 60 randomly selected participants with low walking ability were matched one-to-one on age, gender, race, and fasting time with 60 participants with high walking ability. High versus low walking ability was defined as being in the best versus worst tertiles for both gait speed (≥0.9 vs <0.7 m/s) and the Walking Ability Index (7–9 vs 0–1). Using liquid chromatography-mass spectrometry, 569 metabolites were identified in overnight-fasting plasma.ResultsNinety-six metabolites were associated with walking ability, where 24% were triacylglycerols. Triacylglycerols that were higher among those with high walking ability consisted mostly of polyunsaturated fatty acids, whereas triacylglycerols that were lower among those with high walking ability consisted mostly of saturated or monounsaturated fatty acids. Body composition partly explained associations between some metabolites and walking ability. Proline and arginine metabolism was a top pathway associated with walking ability.ConclusionThese results may partly reflect pathways of modifiable risk factors, including excess dietary lipids and lack of physical activity, contributing to obesity and further alterations in metabolic pathways that lead to age-related decline in walking ability in this older adult cohort.
The Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Eye Study Group and the Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Study Group
OBJECTIVES This study investigated whether the beneficial effects of intensive glycemic control and fenofibrate treatment of dyslipidemia in reducing retinopathy progression demonstrated in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study persisted beyond the clinical trial. RESEARCH DESIGN AND METHODS The ACCORD Study (2003–2009) randomized participants with type 2 diabetes to intensive or standard treatment for glycemia (A1C level at <6.0% [42 mmol/mol] vs. 7.0–7.9% [53–63 mmol/mol]), systolic blood pressure (<120 vs. 140 mmHg), and dyslipidemia (fenofibrate [160 mg] plus simvastatin or placebo plus simvastatin). ACCORD Eye Study participants, who had baseline and year 4 eye examinations and fundus photographs, were reexamined in the ACCORD Follow-On (ACCORDION) Eye Study (2010–2014) 4 years after the ACCORD trial closeout. The outcome measure was diabetic retinopathy progression of three or more steps on the Early Treatment Diabetic Retinopathy Study scale. RESULTS Diabetic retinopathy progressed in 5.8% with intensive glycemic treatment versus 12.7% with standard (adjusted odds ratio [aOR] 0.42, 95% CI 0.28–0.63, P < 0.0001), 7.5% with intensive blood pressure treatment versus 6.0% for standard (aOR 1.21, 95% CI 0.61–2.40, P = 0.59), and 11.8% with fenofibrate versus 10.2% with placebo (aOR 1.13, 95% CI 0.71–1.79, P = 0.60) in ACCORDION Eye participants (n = 1,310). CONCLUSIONS Prior intensive glycemic control continued to reduce diabetic retinopathy progression, despite similar A1C levels, when the ACCORD Study ended. This is the first study in people with type 2 diabetes of 10 years’ duration and established cardiovascular disease, unlike the newly diagnosed participants of the UK Prospective Diabetes Study, to demonstrate this effect. The benefit of fenofibrate, however, did not persist. Intensive blood pressure control had no effect.