Research Spotlights: July 2019

research spotlight

More years of education may reduce your risk of heart disease—A natural experiment

Researchers funded by NCATS, NHLBI, NIA, and NSF weighed in on the ongoing debate about whether education is a determinant of cardiovascular disease (CVD) or merely a correlation. In the United States, CVD is a leading cause of mortality. Education has been correlated with heart disease, but the exact mechanisms underlying this relationship are still unclear and could be due to both education and heart disease sharing common causes such as parental socioeconomic status and genetic factors.

The researchers evaluated a natural experiment, using the variation in U.S. state education policies (compulsory school laws) to estimate the population-level effects of education on heart disease and its risk factors. They used two large, national surveys: The National Health and Nutrition Examination Survey, (NHANES, serial cross-sectional data from the 1971 to 2012 waves, n = 44,732), and the Health and Retirement Study (HRS; cohort data from the 1992 to 2012 waves, n = 30,853) to identify people born from 1900 to 1950, when states required children to attend school between 0 and 12 years. They then used U.S. Census data on a group of similar individuals (n = approximately 5.4 million) to predict the number of years of required education for each person based on birth date and state. In order to determine heart disease status, self-reported outcome measures for CVD, related risk factors (smoking, depression, etc.), and relevant serum biomarkers (HDL, triglycerides, cholesterol, etc.) were examined.

Overall, approximately 33 percent of the study participants did not graduate from high school, while 34.5 percent reported CVD. Each additional year of education through high school was associated with a 2.5 percent reduction in CVD occurrence, as well as improvements in several cardiovascular risk factors, including an approximately 3 percent reduction in smoking and about 5 percent less depression.

This study provides additional evidence of the effects of education policies on CVD in the United States and highlights the importance of cross-sectoral interventions to address social factors like education to improve overall health.

Hamad R, Nguyen TT, Bhattacharya J, Glymour MM, Rehkopf DH. 2019. Educational attainment and cardiovascular disease in the United States: A quasi-experimental instrumental variables analysis. PLOS Medicine. 16(6): e1002834.

Assessing sleep to predict Alzheimer’s disease

Findings from recently published research supported by the NIA suggest a novel biomarker for predicting Alzheimer's pathology later in life. Recent research has linked sleep disruption to the progression of Alzheimer’s disease (AD). The two main pathological features of AD, tau and β-amyloid (Aβ), have been associated with both objective and subjective changes in sleep, however it is not known if late-life tau and Aβ burden are associated with distinct impairments in sleep physiology or changes in sleep across the lifespan.

The researchers combined positron emission tomography (PET) measures of Aβ and tau, electroencephalogram (EEG) sleep recordings, and retrospective sleep evaluations to investigate the potential utility of sleep measures in predicting in vivo AD pathology in male and female older adults. The study sample included 101 cognitively normal older adults from the Berkeley Aging Cohort Study (BACS), a longitudinal study of cognitive aging. A subset of (n = 31; 77 percent female) participants completed a sleep EEG assessment and the Berlin Questionnaire to assess sleep apnea risk, which was used as a covariate in EEG biomarker analyses. In another subset of the sample (n = 95; 59 percent female), subjects completed a retrospective questionnaire about sleep over their lifespan, including duration and sleep quality change.

Regression analyses showed that a decrease in slow oscillations/sleep spindle synchronization was associated with higher tau levels in the medial temporal lobe, while reduced slow-wave-activity amplitude was associated with higher β-amyloid levels. Additionally, the researchers found that a decrease in sleep quantity throughout aging, from the 50s through 70s, was associated with higher levels of β-amyloid and tau later in life.

This study shows that quantitative and qualitative markers of human sleep are sensitive to early tau and Aβ pathology. Importantly, utilizing EEG to assess changes in sleep may be a good, non-invasive tool for measuring AD pathophysiology.

Winer JR, Mander BA, Helfrich RF, Maass A, Harrison TM, Baker SL, Knight RT, Jagust WJ, Walker MP. 2019. Sleep as a potential biomarker of tau and β-amyloid burden in the human brain. J Neurosci. doi: 10.1523/JNEUROSCI.0503-19.2019.

"Nudges" to change palliative care

Researchers funded by the NCI and the University of Pennsylvania Health System are making strides in reducing unnecessary medical procedures. In the United States, approximately 250,000 patients annually with advanced cancer receive palliative radiotherapy to reduce symptoms such as pain or to improve quality of life. Daily imaging is often used in curative radiotherapy to ensure reproducible patient positioning; however, national guidelines recommend transitioning to weekly imaging for palliative radiotherapy since daily imaging unnecessarily increases the time of each session for patients who are often in pain or discomfort. Leveraging insights from the field of behavioral economics, default options have been shown to be able to change physician behavior but have focused more on adoption/implementation of high value care and less on de-adoption of unnecessary care.

The study took place across five radiation oncology practices and 21 radiation oncologists from 2016 to 2018 and included patients (n = 1019) undergoing palliative radiotherapy for cancers that had spread to other organs, including bone, soft tissue, and the brain. The researchers conducted a stepped-wedge cluster randomized clinical trial to test the effectiveness of introducing a default imaging order in the electronic health record (EHR) that specified no daily imaging during palliative radiotherapy versus the usual practice. Importantly, physicians could opt out and select another imaging frequency. Groups were randomly assigned to cross over to the intervention in two 4-month predefined wedges (analyses included 1-month washout periods).

The researchers found that adding the new default order “nudge” led to a reduction in daily imaging from 68 percent of the treatment regimens to 32 percent. With the reduction in unnecessary daily imaging, the average length of the radiotherapy sessions was reduced. This shows that a relatively simple nudge in the EHR can have a significant effect on medical practice and physician behavior, decreasing the use of unnecessary medical procedures and potentially saving healthcare costs.

Sharma S, Guttmann D, Small DS, Rareshide CAL, Jones J, Patel MS, Bekelman JE. 2019. Effect of Introducing a Default Order in the Electronic Medical Record on Unnecessary Daily Imaging During Palliative Radiotherapy for Adults with Cancer: A Stepped-Wedge Cluster Randomized Clinical Trial. JAMA Oncol. doi: 10.1001/jamaoncol.2019.1432.