Autonomic correlates of ocular accommodation and cardiovascular function

PURPOSE: To evaluate the hypothesis that objective measures of open- and closed-loop ocular accommodation are related to systemic cardiovascular function, and ipso facto autonomic nervous system activity. METHODS: Sixty subjects (29 male; 31 female) varying in age from 18 to 33 years (average: 20.3 +/- 2.9 years) with a range of refractive errors [mean spherical equivalent (MSE): -7.12 to +1.82 D] participated in the study. Five 20-s continuous objective recordings of the accommodative response, measured with an open-view IR autorefractor (Shin-Nippon SRW-5000), were obtained for a variety of open- and closed-loop accommodative demands while simultaneous continuous measurement of heart rate was recorded with a finger-mounted piezo-electric pulse transducer for 5 min. Fast Fourier Transformation of cardiovascular function allowed the absolute and relative power of the autonomic components to be assessed in the frequency-domain, whereas heart period gave an indication of the time-domain response. RESULTS: Increasing closed-loop accommodative demand led to a concurrent increase in heart rate of approximately 2 beats/min for a 4.0 D increase in accommodative demand. The increase was attributable to a reduction in the absolute (p < 0.05) and normalised (p < 0.001) input of the systemic parasympathetic nervous system, and was unaffected by refractive group. The interaction with refractive group failed to reach significance. CONCLUSIONS: For sustained accommodation effort, the data demonstrate covariation between the oculomotor and cardiovascular systems which implies that a near visual task can significantly influence cardiovascular behaviour. Accommodative effort alone, however, is not a sufficient stimulus to induce autonomic differences between refractive groups. The data suggest that both the oculomotor and cardiovascular systems are predominantly attributable to changes in the systemic parasympathetic nervous system.

Does cardiovascular therapy affect the onset and recurrence of preretinal and vitreous haemorrhage in diabetic eye disease?

Aims To review the role of cardiovascular disease and therapy in the onset and recurrence of preretinal/vitreous haemorrhage in diabetic patients. Methods Retrospective case note analysis of diabetic patients with vitreous haemorrhage from the Diabetic Eye Clinic at Birmingham Heartlands Hospital. Results In total, 54 patients (mean age 57.1, 37 males, 20 type I vs34 type II diabetic patients) were included. The mean (SD) duration of diagnosed diabetes at first vitreous haemorrhage was significantly longer, 21.9 (7.6) years for type I and 14.8 (9.3) years for type II diabetic patients (P<0.01, unpaired t-test, two-tailed). Aspirin administration was not associated with a significantly later onset of vitreous haemorrhage. Four episodes were associated with ACE-inhibitor cough. There was a trend towards HMGCoA reductase inhibitor (statin) use being associated with a delayed onset of vitreous haemorrhage: 21.4 years until vitreous haemorrhage (treatment group) vs 16.2 years (nontreatment group) (P=0.09, two-tailed, unpaired t-test, not statistically significant). During follow-up 56 recurrences occurred, making a total of 110 episodes of vitreous haemorrhage in 79 eyes of 54 patients. The mean (range) follow-up post haemorrhage was 1067 (77–3842) days, with an average of 1.02 recurrences. Age, gender, diabetes type (I or II) or control, presence of hypertension or hypercholesterolaemia, and macrovascular complications were not associated with a significant effect on the 1-year recurrence rate. Aspirin (and other antiplatelet or anticoagulant agents) and ACE- inhibitors appeared to neither increase nor decrease the 1-year recurrence rate. However, statin use was significantly associated with a reduction in recurrence (Fisher exact P<0.05; two-tailed) with an odds ratio (95% CI) of 0.25 (0.1–0.95). Conclusion In this retrospective analysis, the onset of preretinal/vitreous haemorrhage was not found to be accelerated by gender, hypertension, hypercholesterolaemia, evidence of macrovascular disease, or HbA1c. Neither aspirin nor ACE-inhibitor administration accelerated the onset or recurrence of first vitreous haemorrhage. Statins may have a protective role, both delaying and reducing the recurrence of haemorrhage.

Pharmacogenetics and the print media:what is the public told?

Background: Pharmacogenetics is a rapidly growing field that aims to identify the genes that influence drug response. This science can be used as a powerful tool to tailor drug treatment to the genetic makeup of individuals. The present study explores the coverage of the topic of pharmacogenetics and its potential benefit in personalised medicine by the UK newsprint media. Methods: The LexisNexis database was used to identify and retrieve full text articles from the 10 highest circulation national daily newspapers and their Sunday equivalents in the UK. Content analysis of newspaper articles which referenced pharmacogenetic testing was carried out. A second researcher coded a random sample (21%) of newspaper articles to establish the inter-rater reliability of coding. Results: Of the 256 articles captured by the search terms, 96 articles (with pharmacogenetics as a major component) met the study inclusion criteria. The majority of articles over-stated the benefits of pharmacogenetic testing while paying less attention to the associated risks. Overall beneficial effects were mentioned 5.3 times more frequently than risks (p < 0.001). The most common illnesses for which pharmacogenetically based personalised medicine was discussed were cancer, cardiovascular disease and CNS diseases. Only 13% of newspaper articles that cited a specific scientific study mentioned this link in the article. There was a positive correlation between the size of the article and both the number of benefits and risks stated (P < 0.01). Conclusion: More comprehensive coverage of the area of personalised medicine within the print media is needed to inform public debate on the inclusion of pharmacogentic testing in routine practice.

Hypertension, poor glycemic control, and microalbuminuria in Cuban Americans with type 2 diabetes

Purpose: To investigate to what degree the presence of hypertension (HTN) and poor glycemic control (GC) influences the likelihood of having microalbuminuria (MAU) among Cuban Americans with type 2 diabetes (T2D).Methods: A cross-sectional study conducted in Cuban Americans (n = 179) with T2D. Participants were recruited from a randomly generated mailing list purchased from KnowledgeBase Marketing, Inc. Blood pressure (BP) was measured twice and averaged using an adult size cuff. Glycosylated hemoglobin (A1c) levels were measured from whole blood samples with the Roche Tina-quant method. First morning urine samples were collected from each participant to determine MAU by a semiquantitative assay (ImmunoDip).Results: MAU was present in 26% of Cuban Americans with T2D. A significantly higher percentage of subjects with MA had HTN (P = 0.038) and elevated A1C (P = 0.002) than those with normoalbuminuria. Logistic regression analysis showed that after controlling for covariates, subjects with poor GC were 6.76 times more likely to have MAU if they had hypertension compared with those without hypertension (P = 0.004; 95% confidence interval [CI]: 1.83, 23.05). Conclusion: The clinical significance of these findings emphasizes the early detection of MAU in this Hispanic subgroup combined with BP and good GC, which are fundamentals in preventing and treating diabetes complications and improving individuals’ renal and cardiovascular outcomes.

Television Watching, Diet Quality, and Physical Activity and Diabetes among Three Ethnicities in the United States

Diabetes is a world-wide epidemic associated with multiple environmental factors. Prolonged television viewing (TV) time has been related to increased risk of obesity and type 2 diabetes in several studies. TV viewing has been positively associated with cardiovascular disease risk factors, lower energy expenditure, over-eating high-calorie and high-fat foods. The objective of this study was to assess the associations of hours of TV viewing with dietary quality, obesity and physical activity for three ethnic minorities with and without type 2 diabetes. Diet quality and physical activity were inversely related to prolonged TV viewing. African Americans and participants with type 2 diabetes were more likely to watch more than 4 hours of TV per day as compared to their counterparts. Diet quality was inversely associated with physical activity level. Future studies are needed to establish the risk factors of prolonged TV watching in adult populations for the development of diabetes or diabetes-related complications. Although strategies to reduce TV watching have been proven effective among children, few trials have been conducted in adults. Intervention trials aimed at reducing TV viewing targeting people with type 2 diabetes may be beneficial to improve dietary quality and physical activity, which may reduce diabetes complications.

The impact of maternal inflammation and maternal stress in the regulation of neurodevelopment and physiological function

The mechanisms governing fetal development follow a tightly regulated pattern of progression such that interference at any one particular stage is likely to have consequences for all other stages of development in the physiological system that has been affected thereafter. These disturbances can take the form of many different events but two of the most common and widely implicated in causing detrimental effects to the developing fetus are maternal immune activation (MIA) and maternal stress. MIA has been shown to cause an increase in circulating proinflammatory cytokines in both the maternal and fetal circulation. This increase in proinflammatory mediators in the fetus is thought to occur by fetal production rather than through exchange between the maternal-fetal interface. In the case of maternal stress it is increased levels of stress related hormones such as cortisol/corticosterone which is thought to elicit the detrimental effects on fetal development. In the case of both maternal infection and stress the timing and nature of the insult generally dictates the severity and type of effects seen in affected offspring. We investigated the effect of a proinflammatory environment on neural precursor cells of which exposure resulted in a significant decrease in the normal rate of proliferation of NPCs in culture but did not have any effect on cell survival. These effects were seen to be age dependent. Using a restraint stress model we investigated the effects of prenatal stress on the development of a number of different physiological systems in the same cohort of animals. PNS animals exhibited a number of aberrant changes in cardiovascular function with altered responses to stress and hypertension, modifications in respiratory responses to hypercapnic and hypoxic challenges and discrepancies in gastrointestinal innervation. Taken together these findings suggest that both maternal infection and maternal stress are detrimental to the normal development of the fetus.

Heart failure in sub-Saharan Africa: review of the aetiology of heart failure and the role of point-of-care biomarker diagnostics

Within Africa, the burden of heart failure is significant. This arises from the increase in cardiovascular disease and associated risk factors such as hypertension and diabetes, as well as causes of heart failure which are particular to sub-Saharan Africa, such as endomyocardial fibrosis. The lack of access to echocardiography and other imaging modalities, from a cost and technical perspective, combined with the predominantly rural nature of many countries with poor transport links, means that the vast majority of people never obtain an appropriate diagnosis. Similarly, research has been limited on the causes and treatment of heart failure in Africa and in particular endemic causes such as EMF and rheumatic heart disease. This review outlines the burden of heart failure in Africa and highlights the opportunity to expand diagnosis through the use of biomarkers, in particular natriuretic peptides. This builds on the success of point-of-care testing in human immunodeficiency virus and tuberculosis which have been extensively deployed in community settings in Africa.

Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium

AIMS: Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively.

METHODS AND RESULTS: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, we analysed individual level data from 10 prospective population-based studies including 74 738 participants. We investigated the value of adding troponin I levels to conventional risk factors for prediction of cardiovascular disease by calculating measures of discrimination (C-index) and net reclassification improvement (NRI). We further tested the clinical implication of statin therapy based on troponin concentration in 12 956 individuals free of cardiovascular disease in the JUPITER study. Troponin I remained an independent predictor with a hazard ratio of 1.37 for cardiovascular mortality, 1.23 for cardiovascular disease, and 1.24 for total mortality. The addition of troponin I information to a prognostic model for cardiovascular death constructed of ESC SCORE variables increased the C-index discrimination measure by 0.007 and yielded an NRI of 0.048, whereas the addition to prognostic models for cardiovascular disease and total mortality led to lesser C-index discrimination and NRI increment. In individuals above 6 ng/L of troponin I, a concentration near the upper quintile in BiomarCaRE (5.9 ng/L) and JUPITER (5.8 ng/L), rosuvastatin therapy resulted in higher absolute risk reduction compared with individuals <6 ng/L of troponin I, whereas the relative risk reduction was similar.

CONCLUSION: In individuals free of cardiovascular disease, the addition of troponin I to variables of established risk score improves prediction of cardiovascular death and cardiovascular disease.

The Cardiovascular Pathology of Stimulant Overdose Decedents in King County, Washington

Thesis (Master's)--University of Washington, 2016-09

Exercise and Lifestyle Therapy Improves Weight Maintenance in Young People With Psychosis: A Service Evaluation

INTRODUCTION Young people with psychosis typically have higher rates of premature cardiovascular disease and metabolic disorders compared to non-psychotic peers. This has been primarily due to a sedentary lifestyle, poor diet composition, misuse of harmful substances and higher rates of obesity and smoking. When prescribed obesogenic antipsychotic medication, a weight gain of >12 kg within 2 years is typical. PURPOSE: To examine the benefits of a 12 wk exercise and lifestyle intervention entitled ‘Supporting Health and Promoting Exercise’ (SHAPE) for young people recently diagnosed with psychosis. METHODS Participants (n=26; 8 females; mean age 27.7 ± 5.1) engaged in weekly 45’ education sessions on healthy lifestyle behaviors, including: managing anxiety and depression, mindfulness and relaxation training, substance misuse, smoking cessation, healthy eating and nutritional advice, dental and sexual health care. This was followed by a 45’ exercise session including activities such as circuit and resistance training, yoga, and badminton, led by qualified exercise instructors. Anthropometric data were measured at baseline, 12 wk and 12 month post-intervention. Lifestyle behaviors and clinical measurements, including resting heart rate, blood pressure, total cholesterol, triglycerides, HbA1c and prolactin, were assessed at baseline and 12 months post-intervention as part of their routine clinical care plan. Significant differences over time were assessed using Paired Sample t-tests. RESULTS SHAPE participants (n=26) presented with first episode psychosis (n=11), schizophrenia (n=11), bipolar disorder (n=2), at risk mental state (n=1), and persistent delusion disorder (n=1) of which 52% were prescribed highly obesogenic antipsychotic medications (Clozapine and Olanzepine). Mean baseline data suggests participants were at an increased health risk due to elevated values in mean BMI (70% were overweight or obese), waist circumference, resting heart rate, and triglycerides (see Table 1 & 2). Over 50% reported smoking daily and 85% had elevated resting blood pressure (>120/80 mm Hg). At 12 wk post-intervention, no changes were observed in mean BMI or waist circumference (see Table 1); 19 participants either maintained (mean 0.5 kg: range ± 2 kg) or decreased (mean -5.7 kg: range 2-7 kg) weight; 7 participants increased weight (mean 4.9 kg: range 2.0-9.6 kg). At 12 month post-intervention (n=16), no change was evident in mean BMI, waist circumference, or any other clinical variable (see Table 2). Positive impacts on lifestyle behaviors included 7 participants eating ~400g of fruit/vegetables daily, 2 ceased substance use, 2 ceased alcohol use, 4 ceased smoking and 5 were less sedentary. CONCLUSION At the start of the programme, participants were already at an increased risk for cardiometabolic disorders. Findings suggest that SHAPE supported young people with psychosis to: -attenuate their physical health risk following a 12 wk exercise and lifestyle intervention which were sustained at 12 months follow up. -make positive lifestyle behavior changes leading to sustained improvements in weight maintenance and physical health.

Epidemiology and genetic architecture of blood pressure: a family based study of Generation Scotland

Hypertension is a major risk factor for cardiovascular disease and mortality, and a growing global public health concern, with up to one-third of the world’s population affected. Despite the vast amount of evidence for the benefits of blood pressure (BP) lowering accumulated to date, elevated BP is still the leading risk factor for disease and disability worldwide. It is well established that hypertension and BP are common complex traits, where multiple genetic and environmental factors contribute to BP variation. Furthermore, family and twin studies confirmed the genetic component of BP, with a heritability estimate in the range of 30-50%. Contemporary genomic tools enabling the genotyping of millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, has transformed hypertension genetics research. This is accompanied by the presence of international consortia that have offered unprecedentedly large sample sizes for genome-wide association studies (GWASs). While GWAS for hypertension and BP have identified more than 60 loci, variants in these loci are associated with modest effects on BP and in aggregate can explain less than 3% of the variance in BP. The aims of this thesis are to study the genetic and environmental factors that influence BP and hypertension traits in the Scottish population, by performing several genetic epidemiological analyses. In the first part of this thesis, it aims to study the burden of hypertension in the Scottish population, along with assessing the familial aggregation and heritialbity of BP and hypertension traits. In the second part, it aims to validate the association of common SNPs reported in the large GWAS and to estimate the variance explained by these variants. In this thesis, comprehensive genetic epidemiology analyses were performed on Generation Scotland: Scottish Family Health Study (GS:SFHS), one of the largest population-based family design studies. The availability of clinical, biological samples, self-reported information, and medical records for study participants has allowed several assessments to be performed to evaluate factors that influence BP variation in the Scottish population. Of the 20,753 subjects genotyped in the study, a total of 18,470 individuals (grouped into 7,025 extended families) passed the stringent quality control (QC) criteria and were available for all subsequent analysis. Based on the BP-lowering treatment exposure sources, subjects were further classified into two groups. First, subjects with both a self-reported medications (SRMs) history and electronic-prescription records (EPRs; n =12,347); second, all the subjects with at least one medication history source (n =18,470). In the first group, the analysis showed a good concordance between SRMs and EPRs (kappa =71%), indicating that SRMs can be used as a surrogate to assess the exposure to BP-lowering medication in GS:SFHS participants. Although both sources suffer from some limitations, SRMs can be considered the best available source to estimate the drug exposure history in those without EPRs. The prevalence of hypertension was 40.8% with higher prevalence in men (46.3%) compared to women (35.8%). The prevalence of awareness, treatment and controlled hypertension as defined by the study definition were 25.3%, 31.2%, and 54.3%, respectively. These findings are lower than similar reported studies in other populations, with the exception of controlled hypertension prevalence, which can be considered better than other populations. Odds of hypertension were higher in men, obese or overweight individuals, people with a parental history of hypertension, and those living in the most deprived area of Scotland. On the other hand, deprivation was associated with higher odds of treatment, awareness and controlled hypertension, suggesting that people living in the most deprived area may have been receiving better quality of care, or have higher comorbidity levels requiring greater engagement with doctors. These findings highlight the need for further work to improve hypertension management in Scotland. The family design of GS:SFHS has allowed family-based analysis to be performed to assess the familial aggregation and heritability of BP and hypertension traits. The familial correlation of BP traits ranged from 0.07 to 0.20, and from 0.18 to 0.34 for parent-offspring pairs and sibling pairs, respectively. A higher correlation of BP traits was observed among first-degree relatives than other types of relative pairs. A variance-component model that was adjusted for sex, body mass index (BMI), age, and age-squared was used to estimate heritability of BP traits, which ranged from 24% to 32% with pulse pressure (PP) having the lowest estimates. The genetic correlation between BP traits showed a high correlation between systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (G: 81% to 94%), but lower correlations with PP (G: 22% to 78%). The sibling recurrence risk ratio (λS) for hypertension and treatment were calculated as 1.60 and 2.04 respectively. These findings confirm the genetic components of BP traits in GS:SFHS, and justify further work to investigate genetic determinants of BP. Genetic variants reported in the recent large GWAS of BP traits were selected for genotyping in GS:SFHS using a custom designed TaqMan® OpenArray®. The genotyping plate included 44 single nucleotide polymorphisms (SNPs) that have been previously reported to be associated with BP or hypertension at genome-wide significance level. A linear mixed model that is adjusted for age, age-squared, sex, and BMI was used to test for the association between the genetic variants and BP traits. Of the 43 variants that passed the QC, 11 variants showed statistically significant association with at least one BP trait. The phenotypic variance explained by these variant for the four BP traits were 1.4%, 1.5%, 1.6%, and 0.8% for SBP, DBP, MAP, and PP, respectively. The association of genetic risk score (GRS) that were constructed from selected variants has showed a positive association with BP level and hypertension prevalence, with an average effect of one mmHg increase with each 0.80 unit increases in the GRS across the different BP traits. The impact of BP-lowering medication on the genetic association study for BP traits has been established, with typical practice of adding a fixed value (i.e. 15/10 mmHg) to the measured BP values to adjust for BP treatment. Using the subset of participants with the two treatment exposure sources (i.e. SRMs and EPRs), the influence of using either source to justify the addition of fixed values in SNP association signal was analysed. BP phenotypes derived from EPRs were considered the true phenotypes, and those derived from SRMs were considered less accurate, with some phenotypic noise. Comparing SNPs association signals between the four BP traits in the two model derived from the different adjustments showed that MAP was the least impacted by the phenotypic noise. This was suggested by identifying the same overlapped significant SNPs for the two models in the case of MAP, while other BP traits had some discrepancy between the two sources