Indiana University-Purdue University Indianapolis (IUPUI) / While insomnia/sleep disturbance has been identified as an independent predictor of cardiovascular disease in the general population, no studies have examined whether insomnia contributes to the elevated cardiovascular disease (CVD) risk in people with human immunodeficiency virus (HIV). Thus, the current study examined whether insomnia symptoms predict incident atherosclerotic CVD in the Veterans Aging Cohort Study 9 (VACS9), a prospective cohort of HIV-infected (n = 3,138) and uninfected (n = 3,010) Veterans utilizing self-report measures and administrative data. In partial support of my hypotheses, I found that HIV-infected Veterans bothered a lot by difficulty falling or staying asleep have greater CVD risk than HIV-infected Veterans without these symptoms. This study failed to replicate previous findings that insomnia symptoms are predictive of incident CVD in uninfected adults, which may be due to issues related to the validity of the insomnia symptoms assessment. A number of methodological issues are identified and considered in the interpretation of the current study results. Given the novelty of examining insomnia as a predictor of incident CVD in HIV-infected adults and the limitations of the present study, future research is needed to better elucidate the association between insomnia and future CVD in this population.

Indiana University-Purdue University Indianapolis (IUPUI) / Depressed adults are at increased risk of developing atherosclerotic cardiovascular disease (CVD). However, heterogeneity in the depressed population engenders a key question: Are there subgroups of depressed adults at greater risk of developing CVD? Because other affective traits – i.e., anxiety, hostility/anger, and low trait positive affect – have also been associated with increased CVD risk, depressed adults with higher levels of these co-occurring affective traits may have an elevated risk of developing CVD. Consequently, the present study’s first aim was to examine, in depressed adults, which affective traits (depression, anxiety, hostility/anger, or low positive affect) are associated with endothelial function, a marker of cumulative CVD risk. In addition, because the other affective traits overlap with depressive symptom severity, this study’s second aim was to investigate which components of pairs of affective traits (shared versus unique) are related to endothelial function. Finally, given that the mechanisms underlying affective trait-endothelial function relationships in depressed adults are unknown, this study’s third aim was to explore traditional CVD risk status as a candidate mediator of observed relationships. To achieve these aims, I combined pre-treatment, cross-sectional data from three randomized controlled trials involving 138 depressed primary care patients with no history of clinical CVD. Assessments included validated self-report questionnaires for affective traits, brachial artery flow-mediated dilation (FMD) for endothelial function, and 10-year Framingham risk score for traditional CVD risk status. I conducted structural equation modeling (SEM) with confirmatory factor analysis to examine the relationships of interest after adjusting for age, sex, race/ethnicity, education, and baseline arterial diameter. Although the shared variance between each affective trait pair could not be modeled due to poor fit, adequate fitting models revealed that hostility/anger and the unique components of hostility/anger were associated with poorer endothelial function (standardized coefficients = -.18 and -.22, respectively). All of the other affective traits and their components (depression, anxiety, positive affect, unique depression, unique anxiety, and unique positive affect) were not related to endothelial function (all ps > .08). Traditional CVD risk status did not partially explain the relationship between the unique components of hostility/anger and endothelial function (standardized coefficient for the indirect effect = .00; p = .89). If my results are supported by future findings, it would suggest that depressed adults with hostility/anger (a) may be a subgroup of the depressed population at greater risk of developing CVD and (b) may be in need of earlier, more intense, and/or different CVD primary prevention efforts. Future studies are needed to confirm this relationship and identify underlying mechanisms.

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no / The National Audit Office (NAO) has produced prescribing indicators that Primary Care Trusts (PCTs) can use to judge their performance. One of the indicators is for the antiplatelet clopidogrel, measured as defined daily dose (DDD) per cardiovascular Specific Therapeutic Age Related Prescribing Unit (STAR-PU). Clopidogrel is used as an indicator because it is a more expensive medicine than the alternative (aspirin) and there may be scope for cost reduction. We aimed to establish if the NAO indicator for clopidogrel prescribing is a valid measure of prescribing performance. Methods Prescribing data for 152 PCTs and a range of explanatory variables were obtained. Correlation between variables was determined. A regression analysis was conducted to compare the dependent variable (prescribing) with the explanatory variables identified. Results The percentage of patients on the coronary heart disease register and Index of Multiple Deprivation explained 30% of the variation in prescribing (DDD/STAR-PU) between PCTs. Even though DDD/STAR-PU is adjusted for age and sex other measures of need still have an impact on prescribing. Conclusions Using DDD/STAR-PU alone as a prescribing indicator might misidentify some PCTs, which are under- and over-using clopidogrel. Poor ranking against other PCTs using the NAO indicator should be fully explored taking into account other variables (cardiovascular morbidity and deprivation) before any corrective action is taken.

No / To provide an insight into the process of patients receiving Health Checks and to determine the extent to which patients were supported to reduce the risks of developing cardiovascular disease through behaviour change. Semi-structured qualitative interviews were undertaken with 45 patients about their initial experiences of undertaking a Health Check. They were followed up 1 year later to assess whether the behavioural changes reported after the Health Check had been maintained. Patients expressed a need for individualized support in order to stay motivated and to adopt long-term diet and lifestyle changes. Those involved in the delivery of the programme need to adopt a consistent approach in terms of explaining the purpose of the Health Check, communicating risk and consider the challenges and the barriers that influence behaviour change. / National Institute for Health Research' Research for Patient Benefit Programme. Grant Number: PB-PG-0609-19169. University of York

Yes / MicroRNAs are short, non-coding RNAs that target messenger RNAs for degradation. miR-145 is a vascular-enriched microRNA that is important for smooth muscle cell (SMC) differentiation. Under healthy circumstances, SMC exist in a contractile, differentiated phenotype promoted by miR-145. In cases of disease or injury, SMC can undergo reversible dedifferentiation into a synthetic phenotype, accompanied by inhibition of miR-145 expression. Vascular disorders such as atherosclerosis and neointimal hyperplasia are characterised by aberrant phenotypic switching in SMC. This review will summarise the physiological roles of miR-145 in vascular SMC, including the molecular regulation of differentiation, proliferation and migration. Furthermore, it will discuss the different ways in which miR-145 can be dysregulated and the downstream impact this has on the progression of vascular pathologies. Finally, it will discuss whether miR-145 may be suitable for use as a biomarker of vascular disease.

Paraoxonase-1 (PON1) has an anti-oxidative function in preventing the formation of oxidized lipoproteins (LDL and HDL) and hydrolyzing the active metabolites of some organophosphate insecticides (e.g., paraoxon and diazoxon) and other non-physiological substrates. PON1Q192R affects PON1 hydrolytic activity and its protective role against oxidative stress, thereby influencing susceptibility to cardiovascular disease among individuals. The objectives of this study were to determine the effect of race, gender, and age on PON1 activities and PON1192 genotypes in Caucasian and African American Southerners. Serum samples from 200 individuals (equally distributed race and gender classes, ages 25-55) were assayed spectrophotometrically for paraoxon and diazoxon hydrolysis. Data indicate a positive correspondence between PON1192 genotypes and race and PON1 activity and race. Data do not indicate an influence of gender and age on PON1 activities or PON1192 genotypes. These results are useful in explaining the increased risk of cardiovascular disease in African Americans compared to Caucasians

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