Thomas O. Obisesan

Moderate wine consumption is associated with decreased odds of developing age-related macular degeneration in NHANES-1

OBJECTIVE: To determine the association between alcohol intake and the risk of developing age‐related macular degeneration (AMD).

A comprehensive genetic association study of Alzheimer disease in African Americans.

OBJECTIVES To evaluate the association of genetic variation with late-onset Alzheimer disease (AD) in African Americans, including genes implicated in recent genome-wide association studies of whites. DESIGN We analyzed a genome-wide set of 2.5 million imputed markers to evaluate the genetic basis of AD in an African American population. SUBJECTS Five hundred thirteen well-characterized African American AD cases and 496 cognitively normal African American control subjects. SETTING Data were collected from multiple sites as part of the Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study and the Henry Ford Health System as part of the Genetic and Environmental Risk Factors for Alzheimer Disease Among African Americans (GenerAAtions) Study. RESULTS Several significant single-nucleotide polymorphisms (SNPs) were observed in the region of the apolipoprotein E gene (APOE). After adjusting for the confounding effects of APOE genotype, one of these SNPs, rs6859 in PVRL2, remained significantly associated with AD (P = .0087). Association was also observed with SNPs in CLU, PICALM, BIN1, EPHA1, MS4A, ABCA7, and CD33, although the effect direction for some SNPs and the most significant SNPs differed from findings in data sets consisting of whites. Finally, using the African American genome-wide association study data set as a discovery sample, we obtained suggestive evidence of association with SNPs for several novel candidate genes. CONCLUSIONS Some genes contribute to AD pathogenesis in both white and African American cohorts, although it is unclear whether the causal variants are the same. A larger African American sample will be needed to confirm novel gene associations, which may be population specific.

High Blood Pressure, Hypertension, and High Pulse Pressure Are Associated with Poorer Cognitive Function in Persons Aged 60 and Older: The Third National Health and Nutrition Examination Survey

OBJECTIVES: To test the hypothesis that hypertension, high blood pressure, and high pulse pressure (PP) are independently associated with lower cognitive function.

C-Reactive Protein Genotypes Affect Baseline, but not Exercise Training–Induced Changes, in C-Reactive Protein Levels

Objective—The goal of this study is to determine whether C-reactive protein (CRP) gene variants affect baseline and training-induced changes in plasma CRP levels. Methods and Results—Sixty-three sedentary men and women aged 50 to 75 years old underwent baseline testing (Vomax, body composition, CRP levels). They repeated these tests after 24 weeks of exercise training while on a low-fat diet. The CRP +219G/A variant significantly associated with CRP levels before and after training after accounting for the effects of demographic and biological variables. CRP −732A/G genotype was significantly related on a univariate basis to CRP levels after training. The CRP +29T/A variant did not affect CRP levels before or after training. In regression analyses, the +219 and −732 variants each had significant effects on CRP levels before and after training. Subjects homozygous for the common A/G −732/+219 haplotype exhibited the highest CRP levels, and having the rare allele at either site was associated with significantly lower CRP levels. CRP levels decreased significantly with training (−0.38±0.18 mg/L; P=0.03). However, none of the CRP variants was associated with the training-induced CRP changes. Conclusion—CRP +219G/A and −732A/G genotypes and haplotypes and exercise training appear to modulate CRP levels. However, training-induced CRP reductions appear to be independent of genotype at these loci.

Relationship between circulating progenitor cells, vascular function and oxidative stress with long-term training and short-term detraining in older men

Exercise may contribute to the maintenance of vascular function via enhanced liberation and action of bone-marrow-derived progenitor cells. Activity related changes in oxidative stress may also influence the number and function of these cells. In the present study, we sought to determine (i) whether adaptations in reactive hyperaemic FBF (forearm blood flow) response associated with long-term endurance exercise and short-term detraining were related to resting putative progenitor cell number and function, and (ii) whether oxidative stress affected these factors. Participants included men with a history of more than 30 years of moderate-to-high intensity exercise (HI group) and healthy low-active age- and BMI (body mass index)-matched control subjects (LO group). Vascular reactive hyperaemic FBF response, resting CD34+ and CD34+/VEGFR2+ (vascular endothelial growth factor receptor 2+] cell number, CFU-EC (colony forming unit-endothelial cell) count and CFU-EC senescence were evaluated. Oxidative stress measures included OxLDL (oxidized low-density lipoprotein) and TAC (total antioxidant capacity).These measures were assessed following 10 days of detraining in the HI group. The HI group had greater peak reactive hyperaemic FBF responses compared with the LO group, despite no difference in resting CD34+ cell number, CD34+/VEGFR2+ cell number, CFU-EC colonies or CFU-EC senescence. With detraining in the HI group, CD34+ cells declined 44 %, and the percentage change in CD34+/VEGFR2+ cells was positively correlated with the change in FBF response to reactive hyperaemia. The percentage change in CD34+/VEGFR2+ cells and the percentage change in EPC (endothelial progenitor cell) senescence with detraining were related to the percentage change in TAC. These results reveal that changes in reactive hyperaemic FBF are closely related to activity dependent dynamic changes in CD34+/VEGFR2+ cell number, which may be influenced by alterations in oxidative stress.

Ethnic and Geographic Variation in Stroke Mortality Trends

Background and Purpose— Magnitude, geographic, and ethnic variation in trends in stroke within the United States require updating for health services and health disparities research. Methods— Data for stroke were analyzed from the US mortality files for 1999 to 2007. Age-adjusted death rates were computed for non-Hispanic African Americans and European Americans aged ≥45 years. Results— Between 1999 and 2007, the age-adjusted death rate per 100 000 for stroke declined both in African Americans and in European Americans of both genders. Among African American females, European American females, and European American males, rates declined by at least 2% annually in every division. Among African American males, rates declined little in the East and West South Central divisions where disparities in trends by urbanization level were found. Conclusions— Between 1999 and 2007, the rate of decline in stroke mortality varied by geographic region and ethnic group.

Racial and geographic variation in coronary heart disease mortality trends

BackgroundMagnitudes, geographic and racial variation in trends in coronary heart disease (CHD) mortality within the US require updating for health services and health disparities research. Therefore the aim of this study is to present data on these trends through 2007.MethodsData for CHD were analyzed using the US mortality files for 1999–2007 obtained from the US Centers for Disease Control and Prevention. Age-adjusted annual death rates were computed for non-Hispanic African Americans (AA) and European Americans (EA) aged 35–84 years. The direct method was used to standardize rates by age, using the 2000 US standard population. Joinpoint regression models were used to evaluate trends, expressed as annual percent change (APC).ResultsFor both AA men and women the magnitude in CHD mortality is higher compared to EA men and women, respectively. Between 1999 and 2007 the rate declined both in AA and in EA of both sexes in every geographic division; however, relative declines varied. For example, among men, relative average annual declines ranged from 3.2% to 4.7% in AA and from 4.4% to 5.5% in EA among geographic divisions. In women, rates declined more in later years of the decade and in women over 54 years. In 2007, age-adjusted death rate per 100,000 for CHD ranged from 93 in EA women in New England to 345 in AA men in the East North Central division. In EA, areas near the Ohio and lower Mississippi Rivers had above average rates. Disparities in trends by urbanization level were also found. For AA in the East North Central division, the APC was similar in large central metro (−4.2), large fringe metro (−4.3), medium metro urbanization strata (−4.4), and small metro (−3.9). APC was somewhat higher in the micropolitan/non-metro (−5.3), and especially the non-core/non-metro (−6.5). For EA in the East South Central division, the APC was higher in large central metro (−5.3), large fringe metro (−4.3) and medium metro urbanization strata (−5.1) than in small metro (−3.8), micropolitan/non-metro (−4.0), and non-core/non-metro (−3.3) urbanization strata.ConclusionsBetween 1999 and 2007, the level and rate of decline in CHD mortality displayed persistent disparities. Declines were greater in EA than AA racial groups. Rates were greater in the Ohio and Mississippi River than other geographic regions.

Incorporating ethnicity into genetic risk assessment for Alzheimer disease: The REVEAL study experience

Purpose: To describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants.Methods: The following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicity-specific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease.Results: Review of epidemiological data suggested notable differences in risk between African Americans and whites and that Apolipoprotein E genotype predicts risk in both groups. Discussions about the benefits and risks of stratified risk assessments reached consensus that estimates based on data from whites should not preclude enrolling African Americans, but population-specific risk curves should be created if feasible. Risk models specific to ethnicity, gender, and Apolipoprotein E genotype were subsequently developed for the randomized clinical trial that oversampled African Americans.Conclusion: The Risk Evaluation and Education for Alzheimer Disease study provides an instructive example of a process to develop risk assessment protocols that are sensitive to the implications of genetic testing for multiple ethnic groups with differing levels of risk.

Living with companion animals, physical activity and mortality in a U.S. national cohort.

Living with a canine companion is postulated to increase physical activity. We test the hypotheses that adults living with a canine companion have a higher level of physical activity and reduced mortality risk compared to those not living with a companion animal. A U.S. national health survey with longitudinal mortality follow-up studied 11,394 American men and women aged 40 years and over examined in 1988–1994 followed an average 8.5 years. Measurements at baseline included self-reported companion animals in the household, socio-demographics, health status, physical and biochemical measurements. Outcome measures were leisure-time physical activity (LTPA), and death from all causes. Death during follow-up occurred in 3,187 persons. In bivariate cross-sectional analyses living with a dog was associated with more frequent LTPA and higher survival. In proportional hazards regression analysis, no significant interaction of age, gender or ethnicity with animals was found. After adjusting for confounding by baseline socio-demographics and health status at ages 40+, the hazards ratio (95% confidence limits) for living with a canine companion compared to no animals was 1.21(1.04–1.41, p < 0.001). After also controlling for health behaviors, blood pressure and body mass, C-reactive protein and HDL-cholesterol, the HR was 1.19 (0.97–1.47, NS). In a nationwide cohort of American adults, analyses demonstrated no lower risk of death independent of confounders among those living with canine or feline companions, despite positive association of canine companions with LTPA.

Hypertension and Cognitive Function

Cumulative evidence implicates hypertension in the pathogenesis of Alzheimer disease. Although it may not presently be possible to completely differentiate the effects of treatment and control of hypertension itself from those of the medication used to achieve such treatment goals, efforts directed at the treatment and control of hypertension can have significant public health impact.