Faculty Bibliography

RATIONALE: Overall validity of existing genetic biomarkers in the diagnosis of obstructive sleep apnea (OSA) remains unclear. The objective of this systematic genetic study is to identify "novel" biomarkers for OSA using systems biology approach. METHODS: Candidate genes for OSA were extracted from PubMed, MEDLINE, and Embase search engines and DisGeNET database. The gene ontology (GO) analyses and candidate genes prioritization were performed using Enrichr tool. Genes pertaining to the top 10 pathways were extracted and used for Ingenuity Pathway Analysis. RESULTS: In total, we have identified 153 genes. The top 10 pathways associated with OSA include (i) serotonin receptor interaction, (ii) pathways in cancer, (iii) AGE-RAGE signaling in diabetes, (iv) infectious diseases, (v) serotonergic synapse, (vi) inflammatory bowel disease, (vii) HIF-1 signaling pathway, (viii) PI3-AKT signaling pathway, (ix) regulation lipolysis in adipocytes, and (x) rheumatoid arthritis. After removing the overlapping genes, we have identified 23 candidate genes, out of which >30% of the genes were related to the genes involved in the serotonin pathway. Among these 4 serotonin receptors SLC6A4, HTR2C, HTR2A, and HTR1B were strongly associated with OSA. CONCLUSIONS: This preliminary report identifies several potential candidate genes associated with OSA and also describes the possible regulatory mechanisms.

ABSTRACT: A wealth of scientific knowledge is being generated in sleep and circadian science. In order for us to realize the return on investment for such scientific knowledge and to improve the health of the nation, we need to disseminate and implement research findings into practice. An implementation gap - termed a "quality chasm" by the Institutes of Medicine - separates the scientific knowledge we possess and the implementation of such knowledge into preventative interventions or healthcare treatments. It is frequently reported that a time lag of 17 years transpires before medical research reaches clinical practice. The rapid development of new therapies and devices for sleep and circadian disorders, the emergence of wearable devices and mobile health, combined with the mounting interest in sleep from the public and technology industries, present a transformative opportunity for sleep and circadian science researchers. In order to capitalize on this opportunity, the Sleep Research Society and the National Institutes of Health partnered to organize a workshop focused on the translation of evidence-based interventions for sleep and circadian disorders into practice strategies that benefit population health and patient outcomes. The workshop drew on the collective expertise of implementation scientists and sleep scientists in the areas of insomnia, sleep-disordered breathing, and adolescent sleep health. Together, they identified implementation gaps, effective interventions, implementation strategies and relevant outcomes and created a set of recommendations that could accelerate late-stage translation of sleep and circadian rhythms research findings to benefit public health. This white paper represents the proceedings and consensus developed at the workshop. The recommendations for high-priority implementation research are targeted at sleep and implementation researchers, educators, patients, professional societies, industry partners, funding-decision and policy makers. The major recommendations for implementation science in sleep and circadian sciences were to address the following high priority future research needs: (1) Costs and economic benefits associated with screening, diagnosing, treating insomnia across different systems (health care system, employers, etc.). (2) Promoting health literacy and education of patients, providers and community stakeholders regarding obstructive sleep apnea. (3) Increase the proportion of students in grades 9 through 12 who get sufficient sleep and (4) Perform trials aimed at improving adherence to treatments for sleep-disordered breathing (particularly evaluating cognitive therapy approaches). The fourth priority area was identified as an important barrier to implementation science efforts in sleep.

Sleep is important for regulating many physiologic functions that relate to metabolism. Because of this, there is substantial evidence to suggest that sleep habits and sleep disorders are related to diabetes risk. In specific, insufficient sleep duration and/or sleep restriction in the laboratory, poor sleep quality, and sleep disorders such as insomnia and sleep apnea have all been associated with diabetes risk. This research spans epidemiologic and laboratory studies. Both physiologic mechanisms such as insulin resistance, decreased leptin, and increased ghrelin and inflammation and behavioral mechanisms such as increased food intake, impaired decision-making, and increased likelihood of other behavioral risk factors such as smoking, sedentary behavior, and alcohol use predispose to both diabetes and obesity, which itself is an important diabetes risk factor. This review describes the evidence linking sleep and diabetes risk at the population and laboratory levels.

Novel ideas are needed to increase adherence to antihypertensive medication. The current study used data from the Counseling African Americans to Control Hypertension (CAATCH) study, a sample of 442 hypertensive African Americans, to investigate the mediating effects of expectation of hypertension care, social support, hypertension knowledge, and medication adherence, adjusting for age, sex, number of medications, diabetes, education, income, employment, insurance status, and intervention. Sixty-six percent of patients had an income of $20,000 or less and 56% had a high school education or less, with a mean age of 57 years. Greater expectation of care was associated with greater medication adherence (P=.007), and greater social support was also associated with greater medication adherence (P=.046). Analysis also showed that expectation of care mediated the relationship between hypertension knowledge and medication adherence (P<.05). Expectation of care and social support are important factors for developing interventions to increase medication adherence among blacks.

BACKGROUND/AIMS: Psychological conditions are increasingly linked with cardiovascular disorders. We aimed to examine the association between psychological distress and hypertension. METHODS: We used data from the National Health Interview Survey for 2004-2013. Hypertension was self-reported and the 6-item Kessler Psychological Distress Scale was used to assess psychological distress (a score >/=13 indicated distress). We used a logistic regression model to test the assumption that hypertension was associated with psychological distress. RESULTS: Among the study participants completing the survey (n = 288,784), 51% were female; the overall mean age (+/-SEM) was 35.3 +/- 0.02 years and the mean body mass index was 27.5 +/- 0.01. In the entire sample, the prevalence of psychological distress was 3.2%. The adjusted odds of reporting hypertension in psychologically distressed individuals was 1.53 (95% CI = 1.31-1.80, p = 0.01). CONCLUSION: The findings suggest that psychological distress is associated with higher odds of hypertension after adjusting for other risk factors for high blood pressure. Further studies are needed to confirm these findings and to elucidate the mechanisms by which stress increases hypertension risk.

BACKGROUND/AIMS: Stroke is a leading cause of premature death and disability, and increasing the proportion of individuals who are aware of stroke symptoms is a target objective of the Healthy people 2020 project. METHODS: We used data from the 2014 Supplement of the National Health Interview Survey (NHIS) to assess the prevalence of stroke symptom knowledge and awareness. We also tested, using a logistic regression model, the hypothesis that individuals who have knowledge of all 5 stroke symptoms will be have a greater likelihood to activate Emergency Medical Services (EMS) if a stroke is suspected. RESULTS: From the 36,697 participants completing the survey 51% were female. In the entire sample, the age-adjusted awareness rate of stroke symptoms/calling 911 was 66.1%. Knowledge of the 5 stroke symptoms plus importance of calling 911 when a stroke is suspected was higher for females, Whites, and individuals with health insurance. Stroke awareness was lowest for Hispanics, Blacks, and survey participants from Western US region. CONCLUSION: The findings allude to continuing differences in the knowledge of stroke symptoms across race/ethnic and other demographic groups. Further research will confirm the importance of increased health literacy for Stroke management and prevention in minority communities.

Background: The racial/ethnic differences in post-stroke blood pressure (BP) trajectory and mortality risk are not fully understood. The current paper investigated differences in average systolic BP (SBP) during the 6 months following stroke and effects of average post-stroke BP on mortality risk among Blacks and Hispanics. Hypothesis: Greater post-stroke BP levels will increase risk of mortality Methods:We examined BP measurements in 6,016 stroke survivors within the New York City Health and Hospitals Corporation (NYC HHC) during the 6 months following stroke. Based on the average of all SBP measurements in this period, patients were classified into three groups: (1) SBP =140 mm Hg and =150 mm Hg. We used inverse probability weighting (IPW) to control for group differences in demographic factors, comorbidity, and anti-hypertensive medication use. We examined whether 6 month SBP average was related to mortality following stroke, using Cox regression analysis. The mean duration of follow up after stroke was 2.6+/-1.5 years. Results: The mean age was 57.9+/-13.0 years, 57.4% of patients were female, 49.1% were Black and 37.3% were Hispanic. Blacks were more likely than Hispanics to have an average post-stroke SBP >=150mm Hg (27% versus 17%). Group 1 (SBP <140) and Group 3 (SBP>=150) had higher risks of mortality (Group 1 HR=1.26, 95%CI=1.13-1.41; Group 3 HR=1.29, 95%CI=1.13-1.48) when compared to Group 2 (SBP 140-150). When controlling for ethnicity, these differences are no longer significant. In stratified analyses, the increased hazard in Group 1 was maintained in the sub-sample of Blacks (HR=1.47, 95%CI=1.25-1.72) but not in Hispanics (HR=0.95, 95%CI=0.79-1.15). The difference between Group 2 and Group 3 was not significant in either Black or Hispanic sub-samples. Conclusion: Our findings demonstrate that having a post-stroke SBP below 140 mm Hg or above 150 mm Hg significantly increased individuals' mortality risk, adjusting for demographic factors, comorbidity, number of BP readings, and location of healthcare. Post-stroke BP trajectory differed between Blacks and Hispanics, and had different effects on mortality. These findings have important implications for post-stroke hypertension care

Background: In the United States, 40% of African Americans are disproportionately affected by hypertension leading to severe comorbidity and eventual mortality. Ethnic differences in hypertension among the various African American groups are not well documented. We evaluated the blood pressure control rates of Caribbean and West African born African Americans compared to US born African Americans attending New York City Health and Hospitals Corporation (NYC HHC) facilities. Methods: Data from NYC HHC clinical data warehouse were extracted for hypertensive patients seen between January 2004 and December 2009. Ethnic origin was based on self-reported country of birth (United States, the Caribbean, and West Africa). Blood pressure (BP) was scored by taking the average of 3 or more blood pressure measurements over the course of 3 months of HHC data. All BP measurements were made in the clinical setting and uncontrolled hypertension was defined as BP >140/90 mm Hg. All BPs were measured at least 4 months after hypertension diagnosis. We also extracted information regarding comorbid diagnoses, number of prescribed antihypertensive classes, number of medical visits, age, sex, BMI and mortality. We compared the groups using cox proportional hazard regression models. Results: The sample was composed of 25,142 African Americans of whom 13,778 (54.8%) were US born, 10,032 (39.9%) were Caribbean born, and 1,332 (5.3%) were West African born. The mean sample age was 51 (14.2) years, the mean BMI was 32.4 (11.0) and the sample was 61.4% (N=15,449) female. Compared to US born African Americans, Caribbean and West African born African Americans had higher levels of systolic blood pressure (3.8mmHg; p<.001 and 2.4mmHg; p<.001 respectively) and were more likely to have uncontrolled BP (OR=1.40;p<.001 and OR=1.21;p=.002, respectively). These differences were found in unadjusted models and after adjustment for age, sex, BMI, number of classes of antihypertensive medications prescribed, comorbidity, number of BP measurements, and length of HTN diagnosis. However, US born African Americans had higher rates of mortality (11.6%) compared to Caribbean born (6.0%) and West African born (2.5%) African Americans, which was confirmed by unadjusted and fully adjusted cox proportional hazards regression models. Conclusion: Ethnic differences in cardiovascular outcomes and mortality exist among hypertensive African Americans served by NYC HHC. US born African Americans have a lower survival rate despite lower BP and better BP control than Caribbean and West African born African Americans. Future studies on African Americans should take ethnic variations within these populations into account

Uncontrolled blood pressure (BP) is linked to increased risk of obstructive sleep apnea (OSA). However, few studies have assessed the impact of this relationship among blacks with metabolic syndrome (MetS). Data for this study were collected from 1035 blacks (mean age=62+/-13 years) enrolled in the Metabolic Syndrome Outcome study. Patients with a score 6 on the Apnea Risk Evaluation System were considered at risk for OSA. Of the sample, 77.1% were low-to-high OSA risk and 92.3% were hypertensive, of which 16.8% had uncontrolled BP levels. Analysis also showed that 60.4% were diabetic, 8.9% had a stroke history, 74.3% had dyslipidemia, 69.8% were obese and 30.9% had a history of heart disease. Logistic regression analyses were employed to investigate associations between uncontrolled BP and OSA risk, while adjusting for known covariates. Findings showed that uncontrolled BP independently increased the odds of OSA risk twofold (odds ratio=2.02, 95% confidence interval=1.18-3.48, P<0.05). In conclusion, our findings show that uncontrolled BP was associated with a twofold greater risk of OSA among blacks, suggesting that those with MetS and who have uncontrolled BP should be screened for the presence of OSA.Journal of Human Hypertension advance online publication, 6 August 2015; doi:10.1038/jhh.2015.78.