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The association between socioeconomic status (SES) and subclinical cardiovascular disease is not well understood. Using data from the Atherosclerosis Risk in Communities Study, we sought to evaluate the cross-sectional and prospective associations of SES, measured by annual income and educational level, with elevated high-sensitivity cardiac troponin T (hs-cTnT) concentrations (≥14 ng/L) using Poisson and multinomial logistic regressions, respectively. We used Cox proportional hazard models to compare the risks of coronary heart disease, heart failure, and mortality according to SES, stratified by baseline hs-cTnT concentration. Our study baseline was 1990-1992, with follow-up through 2011. We found an independent association between SES and hs-cTnT. When comparing participants in the lowest educational level group to those in the highest, the adjusted prevalence ratios for elevated hs-cTnT were 1.36 (95% confidence interval: 1.05, 1.75) overall, 1.83 (95% confidence interval: 1.23, 2.71) in blacks, and 1.05 (95% confidence interval: 0.73, 1.52) in whites (P for interaction = 0.08). Among participants with nonelevated hs-cTnT concentrations, when comparing those in the lowest income groups to those in the highest, the adjusted hazard ratios were strongest for heart failure and death. Having elevated baseline hs-cTnT doubled the risk of heart failure and death. Persons with low SES and elevated hs-cTnT concentrations have the greatest risk of cardiovascular events, which suggests that this group should be aggressively targeted for cardiovascular risk reduction., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: A single measurement of 25-hydroxyvitamin D (25 [OH] D) may not accurately reflect long-term vitamin D status. Little is known about change in 25(OH)D levels over time, particularly among blacks., Objective: The objective of the study was to determine the longitudinal changes in 25(OH)D levels among Atherosclerosis Risk in Communities (ARIC) study participants., Design: This was a longitudinal study., Setting: The study was conducted in the general community., Participants: A total of 9890 white and 3222 black participants at visit 2 (1990-1992), 888 whites and 876 blacks at visit 3 (1993-1994), and 472 blacks at the brain visit (2004-2006) participated in the study., Main Outcome Measure: The 25(OH)D levels were measured, and regression models were used to assess the associations between clinical factors and longitudinal changes in 25(OH)D., Results: Vitamin D deficiency (<50 nmol/L [<20 ng/mL]) was seen in 23% and 25% of whites at visits 2 and 3, and in 61%, 70%, and 47% of blacks at visits 2, 3, and the brain visit, respectively. The 25(OH)D levels were correlated between visits 2 and 3 (3 y interval) among whites (r = 0.73) and blacks (r = 0.66). Among blacks, the correlation between visit 2 and the brain visit (14 y interval) was 0.33. Overall, increases in 25(OH)D levels over time was associated with male gender, use of vitamin D supplements, greater physical activity, and higher high-density lipoprotein-cholesterol (P < .001). Decreases in 25(OH)D levels over time were associated with current smoking, higher body mass index, higher education, diabetes, and hypertension (all P < .05)., Conclusions: Among US blacks and whites, 25(OH)D levels remained relatively stable over time. Certain modifiable lifestyle factors were associated with change in 25(OH)D levels over time.

Photosensitivity is a heritable abnormal cortical response to flickering light, manifesting as particular electroencephalographic changes, with or without seizures. Photosensitivity is prominent in a very rare epileptic encephalopathy due to de novo CHD2 mutations, but is also seen in epileptic encephalopathies due to other gene mutations. We determined whether CHD2 variation underlies photosensitivity in common epilepsies, specific photosensitive epilepsies and individuals with photosensitivity without seizures. We studied 580 individuals with epilepsy and either photosensitive seizures or abnormal photoparoxysmal response on electroencephalography, or both, and 55 individuals with photoparoxysmal response but no seizures. We compared CHD2 sequence data to publicly available data from 34 427 individuals, not enriched for epilepsy. We investigated the role of unique variants seen only once in the entire data set. We sought CHD2 variants in 238 exomes from familial genetic generalized epilepsies, and in other public exome data sets. We identified 11 unique variants in the 580 individuals with photosensitive epilepsies and 128 unique variants in the 34 427 controls: unique CHD2 variation is over-represented in cases overall (P = 2.17 × 10(-5)). Among epilepsy syndromes, there was over-representation of unique CHD2 variants (3/36 cases) in the archetypal photosensitive epilepsy syndrome, eyelid myoclonia with absences (P = 3.50 × 10(-4)). CHD2 variation was not over-represented in photoparoxysmal response without seizures. Zebrafish larvae with chd2 knockdown were tested for photosensitivity. Chd2 knockdown markedly enhanced mild innate zebrafish larval photosensitivity. CHD2 mutation is the first identified cause of the archetypal generalized photosensitive epilepsy syndrome, eyelid myoclonia with absences. Unique CHD2 variants are also associated with photosensitivity in common epilepsies. CHD2 does not encode an ion channel, opening new avenues for research into human cortical excitability., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Aim: Clinical cardiovascular disease is a major risk factor for cognitive impairment and dementia. However, less is known about the association of subclinical myocardial damage with cognition and dementia. We sought to examine the associations of high-sensitivity cardiac troponin T (hs-cTnT) with cognition and dementia., Methods and Results: Cross-sectional analysis of cognition (baseline 1996-98) and prospective analysis of dementia (follow-up through 2010) in 9472 participants in the Atherosclerosis Risk in Communities study. High-sensitivity cardiac troponin T was measured using a novel highly sensitive assay with a lower limit of the blank of 3 ng/L. Cognitive function was assessed by three tests: the delayed word recall test (DWRT), the digit symbol substitution test (DSST), and the word fluency test (WFT). Dementia was defined using ICD-9 codes. Linear regression and Cox models were adjusted for traditional cardiovascular risk factors. The mean age of participants was 63 years, 59% were female, 21% were black, and 66% had hs-cTnT ≥3 ng/L. In cross-sectional analyses, higher hs-cTnT was associated with lower scores on the DSST (P-trend < 0.001) and the WFT (P-trend = 0.002), but not on the DWRT (P-trend = 0.089). Over a median of 13 years, there were 455 incident dementia hospitalizations. In prospective analyses, higher baseline concentrations of hs-cTnT were associated with an increased risk for dementia hospitalizations overall (P-trend < 0.001) and for vascular dementia (P-trend = 0.029), but not for Alzheimer's dementia (P-trend = 0.212)., Conclusion: Elevations in baseline concentrations of hs-cTnT were associated with lower cognitive test scores at baseline and increased dementia hospitalization risk during the follow-up. Our results suggest that subclinical myocardial injury is associated with cognition and dementia., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Low concentrations of 25-hydroxyvitamin D have been consistently associated with cardiovascular disease (CVD) in many observational studies. In an analysis published in this issue of the American Journal of Epidemiology, Welles et al. (Am J Epidemiol. 2014;179(11):1279-1287) used data from 946 participants with stable CVD who were enrolled in the Heart and Soul Study (San Francisco Bay Area, 2000-2012) and found that the association of low 25-hydroxyvitamin D with increased secondary CVD event risk was attenuated after adjustment for parathyroid hormone level, suggesting that parathyroid hormone may mediate this association. They used observational data to gain insight into potential mechanisms underlying the association between vitamin D and CVD risk. Their study focused on secondary CVD events, whereas many previous observational studies have focused on incident CVD events among persons without a history of CVD. In this commentary, we place the study by Welles et al. in context with the existing literature and propose future directions for vitamin D research. We highlight a number of methodological concepts that are important in analyzing vitamin D data, including racial differences in vitamin D concentrations and adjustment for seasonal variation in vitamin D concentrations. We agree that randomized controlled trials should be conducted before making guidelines for screening and treating vitamin D deficiency for the prevention of CVD events., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Studies of long-term cognitive change should account for the potential effects of education on the outcome, since some studies have demonstrated an association of education with dementia risk. Evaluating cognitive change is more ideal than evaluating cognitive performance at a single time point, because it should be less susceptible to confounding. In this analysis of 14,020 persons from a US cohort study, the Atherosclerosis Risk in Communities (ARIC) Study, we measured change in performance on 3 cognitive tests over a 20-year period, from ages 48-67 years (1990-1992) through ages 70-89 years (2011-2013). Generalized estimating equations were used to evaluate the association between education and cognitive change in unweighted adjusted models, in models incorporating inverse probability of attrition weighting, and in models using cognitive scores imputed from the Telephone Interview for Cognitive Status for participants not examined in person. Education did not have a strong relationship with change in cognitive test performance, although the rate of decline was somewhat slower among persons with lower levels of education. Methods used to account for selective dropout only marginally changed these observed associations. Future studies of risk factors for cognitive impairment should focus on cognitive change, when possible, to allow for reduction of confounding by social or cultural factors.

The objective of this study was to assess the validity of prevalent and incident self-reported diabetes compared with multiple reference definitions and to assess the reliability (repeatability) of a self-reported diagnosis of diabetes. Data from 10,321 participants in the Atherosclerosis Risk in Communities (ARIC) Study who attended visit 4 (1996-1998) were analyzed. Prevalent self-reported diabetes was compared with reference definitions defined by fasting glucose and medication use obtained at visit 4. Incident self-reported diabetes was assessed during annual follow-up telephone calls and was compared with reference definitions defined by fasting glucose, hemoglobin A1c, and medication use obtained during an in-person visit attended by a subsample of participants (n = 1,738) in 2004-2005. The sensitivity of prevalent self-reported diabetes ranged from 58.5% to 70.8%, and specificity ranged from 95.6% to 96.8%, depending on the reference definition. Similarly, the sensitivity of incident self-reported diabetes ranged from 55.9% to 80.4%, and specificity ranged from 84.5% to 90.6%. Percent positive agreement of self-reported diabetes during 9 years of repeat assessments ranged from 92.7% to 95.4%. Both prevalent self-reported diabetes and incident self-reported diabetes were 84%-97% specific and 55%-80% sensitive as compared with reference definitions using glucose and medication criteria. Self-reported diabetes was >92% reliable over time.

Physiological reactions to psychological stress are positively associated with several important chronic conditions including cardiovascular and neurodegenerative diseases and are linked to increased mortality. As such, the identification of cellular and molecular pathways that act to reduce stress responding may represent important targets for therapeutic intervention. Here we report that acute treatment with the peroxisome-proliferator activated receptor-γ (PPARγ) agonist rosiglitazone (RSG) blunts systemic responses to acute psychological stress in rats. Rats that had previously received oral RSG for 5 d exhibited a 40% reduction in the initial heart rate response to an acute restraint stress, compared with vehicle-treated controls, suggesting that increased PPARγ signaling blunts the acute autonomic response to stress. Rats previously treated with RSG likewise had a blunted hormonal response to this stressor, exhibiting a 30% reduction in peak corticosterone levels compared with controls. Moreover, stress-induced expression of c-Fos, a marker of early neuronal activation, was similarly reduced in the paraventricular hypothalamus, a key site for brain stress integration, facilitating both autonomic and hypothalamic-pituitary-adrenocortical responses to stress. Taken as a whole, these data suggest that PPARγ stimulation potently inhibits physiological responses to psychological stress, prescribing a novel role for PPARγ signaling in the regulation of brain stress integration.