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Port Glasgow, United Kingdom

Preiss D.,University of Glasgow | Packard C.J.,Glasgow Clinical Research Facility
Current Cardiology Reports | Year: 2014

Statins are safe, efficacious and the cornerstone of cardiovascular disease prevention strategies. A number of add-on therapies with complementary actions on the plasma lipid profile have been tested in large scale trials to see if they give incremental benefit. In particular, the 'HDL hypothesis' - that raising this lipoprotein will promote reverse cholesterol transport and reduce cardiovascular risk - has been examined using drugs such as dalcetrapib and niacin. So far, results have been negative, and this has raised questions over the nature of the association of HDL with atherosclerosis, and whether statins reduce cardiovascular risk through multiple mechanisms. There is still an unmet clinical need especially in those patients who cannot tolerate statins and those with severe hyperlipidemia, and so new therapeutic approaches have been developed. These show significant promise in terms of LDL-cholesterol lowering but significant challenges include cost, route of administration (subcutaneous injection) and side effects. Testing in major outcome trials will be required to demonstrate their clinical utility. © 2014 Springer Science+Business Media. Source

Krishnadas R.,University of Glasgow | Kim J.,University of Glasgow | McLean J.,University of Glasgow | David Batty G.,Medical Research Council Social and Public Health science Unit | And 5 more authors.
Frontiers in Human Neuroscience | Year: 2013

Complex cognitive functions are widely recognized to be the result of a number of brain regions working together as large-scale networks. Recently, complex network analysis has been used to characterize various structural properties of the large-scale network organization of the brain. For example, the human brain has been found to have a modular architecture i.e., regions within the network form communities (modules) with more connections between regions within the community compared to regions outside it. The aim of this study was to examine the modular and overlapping modular architecture of the brain networks using complex network analysis. We also examined the association between neighborhood level deprivation and brain network structure-modularity and gray nodes. We compared network structure derived from anatomical MRI scans of 42 middle-aged neurologically healthy men from the least (LD) and the most deprived (MD) neighborhoods of Glasgow with their corresponding random networks. Cortical morphological covariance networks were constructed from the cortical thickness derived from the MRI scans of the brain. For a given modularity threshold, networks derived from the MD group showed similar number of modules compared to their corresponding random networks, while networks derived from the LD group had more modules compared to their corresponding random networks. The MD group also had fewer gray nodes-a measure of overlapping modular structure. These results suggest that apparent structural difference in brain networks may be driven by differences in cortical thicknesses between groups. This demonstrates a structural organization that is consistent with a system that is less robust and less efficient in information processing. These findings provide some evidence of the relationship between socioeconomic deprivation and brain network topology. © 2013 Krishnadas, Kim, McLean, Batty, McLean, Millar, Packard and Cavanagh. Source

Preiss D.,University of Glasgow | Lloyd S.M.,University of Glasgow | Ford I.,University of Glasgow | McMurray J.J.,University of Glasgow | And 5 more authors.
The Lancet Diabetes and Endocrinology | Year: 2014

Background: Metformin reduces cardiovascular risk in patients with type 2 diabetes seemingly independent of lowering blood glucose concentration. We assessed the cardiovascular effects of metformin in individuals without type 2 diabetes. Methods: We did a single-centre, double-blind, placebo-controlled trial at the Glasgow Clinical Research Facility (Glasgow, UK). We enrolled patients taking statins who did not have type 2 diabetes but who did have coronary heart disease and large waist circumferences. Participants were randomly assigned (1:1) by computer to either metformin (850 mg twice daily) or matching placebo in block sizes of four. Patients, investigators, trial staff, and statisticians were masked to treatment allocation. The primary endpoint was progression of mean distal carotid intima-media thickness (cIMT) over 18 months in the modified intention-to-treat population. Secondary endpoints were changes in carotid plaque score (in six regions), measures of glycaemia (HbA1c, fasting glucose, and insulin concentrations, and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and concentrations of lipids, high sensitivity C-reactive protein, and tissue plasminogen activator. The trial was registered at ClinicalTrials.gov, number NCT00723307. Findings: We screened 356 patients, of whom we enrolled 173 (86 in the metformin group, 87 in the placebo group). Average age was 63 years. At baseline, mean cIMT was 0·717 mm (SD 0·129) and mean carotid plaque score was 2·43 (SD 1·55). cIMT progression did not differ significantly between groups (slope difference 0·007 mm per year, 95% CI -0·006 to 0·020; p=0·29). Change of carotid plaque score did not differ significantly between groups (0·01 per year, 95% CI -0·23 to 0·26; p=0·92). Patients taking metformin had lower HbA1c, insulin, HOMA-IR, and tissue plasminogen activator compared with those taking placebo, but there were no significant differences for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high sensitivity C-reactive protein, or fasting glucose. 138 adverse events occurred in 64 patients in the metformin group versus 120 in 60 patients in the placebo group. Diarrhoea and nausea or vomiting were more common in the metformin group than in the placebo group (28 vs 5). Interpretation: Metformin had no effect on cIMT and little or no effect on several surrogate markers of cardiovascular disease in non-diabetic patients with high cardiovascular risk, taking statins. Further evidence is needed before metformin can be recommended for cardiovascular benefit in this population. Funding: Chief Scientist Office (Scotland). © 2014 Preiss et al. Source

Packard C.J.,Glasgow Clinical Research Facility | Weintraub W.S.,Christiana Care Health System | Laufs U.,Universitatsklinikum des Saarlandes
Vascular Pharmacology | Year: 2015

Short-term absolute cardiovascular event rates in young/middle-aged people are low even if they have risk factors, and parameters such as number-needed-to-treat over 5. years are inadequate to visualize and to communicate the lifelong benefit of interventions such as statin therapy to individuals and to healthcare providers. To understand more fully the impact of risk factors, and lifestyle and pharmacological interventions, there is a need to focus on disease trajectory over a lifetime and to develop new metrics of success. A shift to primordial ('true') prevention of the formation of atherosclerotic lesions will require new tools and approaches in the interaction between physicians and patients as individuals or populations. © 2015 Elsevier Inc.. Source

Krishnadas R.,Southern Research Institute | Mclean J.,Southern Research Institute | Batty G.D.,Medical Research Council Social and Public Health science Unit | Batty G.D.,University College London | And 12 more authors.
Psychosomatic Medicine | Year: 2013

OBJECTIVE: Neighborhood-level socioeconomic deprivation has been associated with poor cognitive function pertaining to language and the executive control. Few studies have explored the cortical morphology of regions most commonly associated with these functions. The aim of this study was to examine the association between neighborhood-level deprivation and the morphology of cortical regions associated with language and executive control in adults. METHODS: Using a cross-sectional study design, we compared the cortical morphology of 42 neurologically healthy adult men from the least deprived and most deprived neighborhoods of Glasgow. We performed surface-based morphometry on 3-T structural magnetic resonance imaging (MRI) images to extract the cortical morphology - volume, thickness (CT), and surface area (SA) of regions commonly associated with language and executive control. Cortical morphology was compared between the two groups. We used mediation analysis to examine whether cardiometabolic risk factors mediated the relationship between deprivation status and cortical morphology. RESULTS: Intracranial volume and mean total CT did not differ between groups. The deprived group had significantly smaller left posterior parietal cortex SA (Cohen d = 0.89) and fusiform cortex SA (Cohen d = 1.05). They also had thinner left Wernicke's area (Cohen d =0.93) and its right homologue (Cohen d = 1.12). Among the cardiometabolic markers, a composite factor comprising inflammatory markers mediated the relationship between deprivation status and Wernicke's area CT. CONCLUSIONS: A group of neurologically healthy men from deprived neighborhoods showed significantly smaller cortical morphology - both SA and CT - in regions of the brain pertaining to language and executive function. We provide additional evidence of a relationship between socioeconomic deprivation and cortical morphology. Copyright © 2013 by the American Psychosomatic Society. Source

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