Faculty Bibliography

OBJECTIVES: Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer's disease (AD) is rapidly increasing. However, there is little or no evidence for a direct association between dietary nutrients and brain biomarkers of AD. This study identifies nutrient patterns associated with major brain AD biomarkers in a cohort of clinically and cognitively normal (NL) individuals at risk for AD. DESIGN: Cross-sectional study. SETTING: Manhattan (broader area). PARTICIPANTS: Fifty-two NL individuals (age 54+12 y, 70% women, Clinical Dementia Rating=0, MMSE>27, neuropsychological test performance within norms by age and education) with complete dietary information and cross-sectional, 3D T1-weighted Magnetic Resonance Imaging (MRI; gray matter volumes, GMV, a marker of brain atrophy), 11C-Pittsburgh compound-B (PiB; a marker of fibrillar amyloid-beta, Abeta) and 18F-fluorodeoxyglucose (FDG; a marker of glucose metabolism, METglc) Positron Emission Tomography (PET) scans were examined. MEASUREMENTS: Dietary intake of 35 nutrients associated with cognitive function and AD was assessed using the Harvard/Willet Food Frequency Questionnaire. Principal component analysis was used to generate nutrient patterns (NP) from the full nutrient panel. Statistical parametric mapping and voxel based morphometry were used to assess the associations of the identified NPs with AD biomarkers. RESULTS: None of the participants were diabetics, smokers, or met criteria for obesity. Five NPs were identified: NP1 was characterized by most B-vitamins and several minerals [VitB and Minerals]; NP2 by monounsaturated and polyunsaturated fats, including omega-3 and omega-6 PUFA, and vitamin E [VitE and PUFA]; NP3 by vitamin A, vitamin C, carotenoids and dietary fibers [Anti-oxidants and Fibers]; NP4 by vitamin B12, vitamin D and zinc [VitB12 and D]; NP5 by saturated, trans-saturated fats, cholesterol and sodium [Fats]. Voxel-based analysis showed that NP4 scores [VitB12 and D] were positively associated with METglc and GMV, and negatively associated with PiB retention in AD-vulnerable regions (p<0.001). In addition, both METglc and GMV were positively associated with NP2 scores [VitE and PUFA], and negatively associated with NP5 scores [Fats] (p<0.001), and METglc was positively associated with higher NP3 scores [Anti-oxidants and Fibers] (p<0.001). Adjusting for age, gender, ethnicity, education, caloric intake, BMI, alcohol consumption, family history and Apolipoprotein E (APOE) status did not attenuate these relationships. The identified 'AD-protective' nutrient combination was associated with higher intake of fresh fruit and vegetables, whole grains, fish and low-fat dairies, and lower intake of sweets, fried potatoes, high-fat dairies, processed meat and butter. CONCLUSION: Specific dietary NPs are associated with brain biomarkers of AD in NL individuals, suggesting that dietary interventions may play a role in the prevention of AD by modulating AD-risk through its effects on Abeta and associated neuronal impairment.

BACKGROUND: Black and Hispanic stroke survivors experience higher rates of recurrent stroke than whites. This disparity is partly explained by disproportionately higher rates of uncontrolled hypertension in these populations. Home blood pressure telemonitoring (HBPTM) and nurse case management (NCM) have proven efficacy in addressing the multilevel barriers to blood pressure (BP) control and reducing BP. However, the effectiveness of these interventions has not been evaluated in stroke patients. This study is designed to evaluate the comparative effectiveness, cost-effectiveness and sustainability of these two telehealth interventions in reducing BP and recurrent stroke among high-risk Black and Hispanic stroke survivors with uncontrolled hypertension. METHODS/DESIGN: A total of 450 Black and Hispanic patients with recent nondisabling stroke and uncontrolled hypertension are randomly assigned to one of two 12-month interventions: 1) HBPTM with wireless feedback to primary care providers or 2) HBPTM plus individualized, culturally-tailored, telephone-based NCM. Patients are recruited from stroke centers and primary care practices within the Health and Hospital Corporations (HHC) Network in New York City. Study visits occur at baseline, 6, 12 and 24 months. The primary outcomes are within-patient change in systolic BP at 12 months, and the rate of stroke recurrence at 24 months. The secondary outcome is the comparative cost-effectiveness of the interventions at 12 and 24 months; and exploratory outcomes include changes in stroke risk factors, health behaviors and treatment intensification. Recruitment for the stroke telemonitoring hypertension trial is currently ongoing. DISCUSSION: The combination of two established and effective interventions along with the utilization of health information technology supports the sustainability of the HBPTM + NCM intervention and feasibility of its widespread implementation. Results of this trial will provide strong empirical evidence to inform clinical guidelines for management of stroke in minority stroke survivors with uncontrolled hypertension. If effective among Black and Hispanic stroke survivors, these interventions have the potential to substantially mitigate racial and ethnic disparities in stroke recurrence. TRIAL REGISTRATION: ClinicalTrials.gov NCT02011685 . Registered 10 December 2013.

Environmental factors, such as noise exposure and air pollution, are associated with hypertension. These environmental factors also affect sleep quality. Given the growing evidence linking sleep quality with hypertension, the purpose of this review is to investigate the role of sleep as a key mediator in the association between hypertension and environmental factors. Through this narrative review of the extant literature, we highlight that poor sleep quality mediates the relationship between environmental factors and hypertension. The conceptual model proposed in this review offers opportunities to address healthcare disparities in hypertension among African Americans by highlighting the disparate impact that the predictors (environmental factors) and mediator (sleep) have on the African-American community. Understanding the impact of these factors is crucial since the main outcome variable (hypertension) severely burdens the African-American community.

Introduction: Many risk factors have been implicated in the pathophysiology of obstructive sleep apnea (OSA). Recent evidence suggests that medical risk factors, such as uncontrolled/high blood pressure (BP), high cholesterol, triglycerides, high body mass index, diabetes, and dyslipidemia (all indicators of metabolic syndrome) are highly comorbid with OSA. However, data on the relationships between these risk factors and OSA among blacks with metabolic syndrome are lacking. Methods: Data for the present study were collected from 340 participants from the Metabolic Syndrome Outcome (MetSO) study, a NIHfunded cohort study of 1,035 blacks with metabolic syndrome (mean age = 62 + 13 years, 69% female, and 43% with annual family income < $10K). During initial interviews, patients provided sociodemographic, health risks, and history of chronic diseases. Patients with a score > 6 on the Apnea Risk Evaluation System (ARES) were considered at high OSA risk. Logistic regression analyses were employed to investigate whether metabolic syndrome indicators, particularly uncontrolled blood pressure, increased the odds of OSA. Results: Of the sample, 77.1% was at risk for OSA and 16.8% had uncontrolled BP. Analysis also showed 60.4% were diabetic, 8.9% had a stroke history, 74.3% had dyslipidemia, 91.1% were either overweight or obese and 30.9% had heart disease. Mean systolic BP was 134.8 + 18.4; diastolic BP was 75.6 + 11.9; LDL cholesterol was 105.6 + 36.9; HDL cholesterol was 48.0 + 17.3; triglycerides was 135.8 + 81.2; glucose was 138.4 + 68.3; and HbA1c was 7.93 + 1.63. Logistic regression analysis showed that uncontrolled BP independently increased the odds of OSA risk (OR = 1.94, 95% CI = 1.12-3.32, p < 0.01). Conclusion: Our indings suggest that uncontrolled BP was associated with a twofold greater risk of OSA in blacks. The clinical implication of this inding is that blacks with metabolic syndrome and who have uncontrolled BP should be screened for the presence of OSA

We tested the hypothesis that racial differences in vitamin D levels are associated with racial disparities in insulin resistance between blacks and whites. Among 3628 non-Hispanic black and white adults in the National Health and Nutrition Examination Survey from 2001 to 2006, we examined the association between race and insulin resistance using the homeostasis assessment model for insulin resistance. We conducted analyses with and without serum 25-hydroxyvitamin D (25[OH]D). We adjusted for age, sex, educational level, body mass index, waist circumference, physical activity, alcohol intake, smoking, estimated glomerular filtration rate, and urinary albumin/creatinine ratio. Blacks had a lower mean serum 25(OH)D level compared with whites (14.6 [0.3] ng/mL vs 25.6 [0.4] ng/mL, respectively; P < .0001). Blacks had a higher odds ratio (OR) for insulin resistance without controlling for serum 25(OH)D levels (OR, 1.67; 95% confidence interval, 1.26-2.20). The association was not significant (OR, 1.28; 95% confidence interval, 0.90-1.82) after accounting for serum 25(OH)D levels. The higher burden of insulin resistance in blacks compared with whites may be partially mediated by the disparity in serum 25(OH)D levels.

Background: Biomarker discovery studies may fail to translate to the clinic because the study population does not match the intended clinical use or because hidden preanalytic variability in the discovery samples contaminates the apparent disease specific information in the biomarkers. This can arise from differences in blood sample processing between study sites or in samples collected differently at the same study site. Methods: To better understand the effect of different blood sample processing procedures, we evaluated protein measurement bias in a large multi-center lung cancer study using the >1000 protein SOMAscan assay. These analyses revealed that perturbations in serum collection and processing result in changes to families of proteins from known biological pathways. We subsequently developed protein biomarker signatures of cell lysis, platelet activation and complement activation and assembled these preanalytic signatures into quantitative multi-dimensional Sample Mapping Vector (SMV) scores. Results: The SMV score provides critical evaluation of the quality of every blood-based sample used in discovery and also enables the evaluation of candidate protein biomarkers for resistance to preanalytic variability. Despite uniform processing protocols for each clinic, the SMV analysis revealed unexpected case/control bias arising from collecting case and control serum from different clinics at the same academic centers, an effect that created false or bias-contaminated disease markers. We therefore used the SMV score to remove bias-susceptible analytes and to define a well-collected, unbiased training set. An improved classifier was developed, resistant to common artifacts in serum processing. Conclusions: . The performance of this classifier to detect lung cancer in a high-risk population is more likely to represent real-world diagnostic results. We believe this approach is generally applicable to clinical investigations in all fields of biomarker discovery and translational medicine